bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of potential molecular markers in renal cell carcinoma: impact on clinicopathological outcomes in patients undergoing radical nephrectomy
Authors: Sakai Iori , Miyake Hideaki , Takenaka Atsushi , Fujisawa Masato
Published: April 2009

OBJECTIVES

To evaluate the expression levels of several potential molecular markers in renal cell carcinoma (RCC), to clarify the significance of these markers as prognostic predictors in patients undergoing radical nephrectomy (RN).

PATIENTS AND METHODS

The study included 153 patients with clinically organ‐confined RCC undergoing RN. Expression levels of 12 proteins, including Aurora‐A, Bcl‐2, Bcl‐xL, clusterin, heat‐shock protein 27 (HSP27), HSP70, HSP90, Ki‐67, matrix metalloproteinase (MMP)‐2 and ‐9, p53 and vascular endothelial growth factor, in RN specimens obtained from these 153 patients were measured by immunohistochemical staining.

RESULTS

Of the 12 markers, clusterin, HSP27, Ki‐67, MMP‐2 and ‐9 expression were significantly associated with several conventional prognostic factors. Univariate analysis also identified these five markers as significant predictors of disease recurrence, while mode of presentation, pathological stage, grade and microvascular invasion were also significant. Of these significant factors, Ki‐67 expression, pathological stage and microvascular invasion appeared to be independently related to disease recurrence. Furthermore, there were significant differences in recurrence‐free survival according to positive numbers of these three independent factors, i.e. disease recurred in four of 56 patients who were negative for risk factors (7%), 17 of 71 positive for one risk factor (24%), and 20 of 26 positive for two or three risk factors (77%).

CONCLUSIONS

Combined evaluation of Ki‐67 expression, pathological stage and microvascular invasion would be particularly useful for further refinement of the system for predicting the outcome after RN for patients with RCC.
Retrospective analysis of the distance between the neurovascular bundle and prostate cancer foci in radical prostatectomy specimens: its clinical implication in nerve‐sparing surgery
Authors: Inoue Shogo , Shiina Hiroaki , Hiraoka Takeo , Mitsui Yozo , Sumura Masahiro , Urakami Shinji , Igawa Mikio
Published: April 2009

OBJECTIVE

To analyse the distance between the ipsilateral neurovascular bundles (NVBs) and foci of prostate cancer (N‐T distance) in specimens removed by radical prostatectomy (RP) and identify the predictor for N‐T distance for preserving the ipsilateral NVB, as an accurate understanding of the anatomical relationship between prostate cancer foci and the NVB is necessary for establishing the indications for the appropriate use of nerve‐sparing (NS) modifications of RP.

PATIENTS AND METHODS

The study included 245 patients with prostate cancer who had RP through the perineal or retropubic approach between June 2000 and November 2006. The analysis focused on 302 foci of prostate cancer (192 cases), which involved at least the posterolateral region of the prostate. The N‐T distance was separately measured in the apex, middle and base of the prostate, and was correlated with the maximum diameter and Gleason score of the foci, and the preoperative prostate‐specific antigen (PSA) level.

RESULTS

The mean N‐T distance was 2.98, 2.95 and 3.03 mm in the apex (216 foci), middle (195 foci) and base (80 foci), respectively. In the apex, the N‐T distance was related to both tumour size and preoperative PSA value (P < 0.001 and P < 0.05, respectively). In the base, tumour size was related to the N‐T distance (P < 0.01), but the preoperative PSA level was not related to the N‐T distance. In the middle, the association of tumour size with N‐T distance was of borderline significance (P = 0.07). Irrespective of tumour location, the Gleason score did not contribute to the N‐T distance.

CONCLUSIONS

These findings show the basic information necessary when making a decision to perform NS‐RP in patients with localized prostate cancer. The application of N‐T distance could provide a better strategy for determining indications that warrant the use of NS RP than with the conventional tactile feedback approach.
Survival outcomes in men receiving androgen‐deprivation therapy as primary or salvage treatment for localized or advanced prostate cancer: 20‐year single‐centre experience
Authors: DiBlasio Christopher J. , Malcolm John B. , Hammett Jessica , Wan Jim Y. , Aleman Michael A. , Patterson Anthony L. , Wake Robert W. , Derweesh Ithaar H.
Published: April 2009

OBJECTIVES

To evaluate the overall survival (OS) and disease‐specific survival (DSS) in men receiving primary androgen‐deprivation therapy (PADT) or salvage medical ADT (SADT) for prostate cancer.

PATIENTS AND METHODS

After Institutional Review Board approval, we retrospectively reviewed patients receiving ADT for prostate cancer between July 1987 and June 2007. Variables included age at diagnosis and ADT induction, race, PSA level before ADT, ADT schedule (continuous/intermittent), clinical/pathological stage, hormone‐refractory prostate cancer (HRCP) status, PADT or SADT, and deaths.

RESULTS

In all, 548 men were analysed. The mean age at diagnosis and ADT induction were 70.1 and 72.3 years, respectively, and 321 (58.6%) were African‐American. The median PSA level before ADT was 16.3 ng/mL. ADT was administered continuously in 497 (90.7%) patients; 342 (62.4%) received PADT while 206 (37.6%) received SADT. At mean (range) follow‐up of 81.8 (2.1–445) months, 98 (17.9%) deaths occurred; 31 (31.6%) were cancer‐specific. The OS and DSS in the PADT and SADT groups were not significantly different (P = 0.36 and P = 0.81, respectively). Mortality rates/distributions were similar between groups (P = 0.68). Multivariate predictors of OS and DSS included age at diagnosis (P = 0.03) and ADT induction (P = 0.009), tumour stage (P < 0.001), and PSA level at ADT induction (P = 0.01). Progression to HRPC worsened OS and DSS (both P < 0.001).

CONCLUSION

PADT and SADT prolong survival in men with prostate cancer. HRPC portends a poor DSS. Age at diagnosis and ADT induction, PSA level before ADT, and disease stage predict both OS and DSS in this population. However, most men died from causes unrelated to prostate cancer, thus questioning the true value of ADT in prolonging patient survival.
Transient co‐expression for fast and high‐yield production of antibodies with human‐like N‐glycans in plants
Authors: Vézina Louis‐P. , Faye Loïc , Lerouge Patrice , D’Aoust Marc‐André , Marquet‐Blouin Estelle , Burel Carole , Lavoie Pierre‐Olivier , Bardor Muriel , Gomord Véronique
Published: April 2009

Plant‐based transient expression is potentially the most rapid and cost‐efficient system for the production of recombinant pharmaceutical proteins, but safety concerns associated with plant‐specific N‐glycosylation have hampered its adoption as a commercial production system. In this article, we describe an approach based on the simultaneous transient co‐expression of an antibody, a suppressor of silencing and a chimaeric human β1,4‐galactosyltransferase targeted for optimal activity to the early secretory pathway in agroinfiltrated Nicotiana benthamiana leaves. This strategy allows fast and high‐yield production of antibodies with human‐like N‐glycans and, more generally, provides solutions to many critical problems posed by the large‐scale production of therapeutic and vaccinal proteins, specifically yield, volume and quality.
Comparative sequence analyses of the major quantitative trait locus phosphorus uptake 1 (Pup1) reveal a complex genetic structure
Authors: Heuer Sigrid , Lu Xiaochun , Chin Joong Hyoun , Tanaka Juan Pariasca , Kanamori Hiroyuki , Matsumoto Takashi , De Leon Teresa , Ulat Victor Jun , Ismail Abdelbagi M. , Yano Masahiro , Wissuwa Matthias
Published: April 2009

The phosphorus uptake 1 (Pup1) locus was identified as a major quantitative trait locus (QTL) for tolerance of phosphorus deficiency in rice. Near‐isogenic lines with the Pup1 region from tolerant donor parent Kasalath typically show threefold higher phosphorus uptake and grain yield in phosphorus‐deficient field trials than the intolerant parent Nipponbare. In this study, we report the fine mapping of the Pup1 locus to the long arm of chromosome 12 (15.31–15.47 Mb). Genes in the region were initially identified on the basis of the Nipponbare reference genome, but did not reveal any obvious candidate genes related to phosphorus uptake. Kasalath BAC clones were therefore sequenced and revealed a 278‐kbp sequence significantly different from the syntenic regions in Nipponbare (145 kb) and in the indica reference genome of 93‐11 (742 kbp). Size differences are caused by large insertions or deletions (INDELs), and an exceptionally large number of retrotransposon and transposon‐related elements (TEs) present in all three sequences (45%–54%). About 46 kb of the Kasalath sequence did not align with the entire Nipponbare genome, and only three Nipponbare genes (fatty acid α‐dioxygenase, dirigent protein and aspartic proteinase) are highly conserved in Kasalath. Two Nipponbare genes (expressed proteins) might have evolved by at least three TE integrations in an ancestor gene that is still present in Kasalath. Several predicted Kasalath genes are novel or unknown genes that are mainly located within INDEL regions. Our results highlight the importance of sequencing QTL regions in the respective donor parent, as important genes might not be present in the current reference genomes.
The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes
Authors: Jia J.‐J. , Zhang X. , Ge C.‐R. , Jois M.
Published: April 2009

Uncoupling proteins (UCPs) belong to the family of mitochondrial transporter proteins that may uncouple the transport of protons across the inner mitochondrial membrane from electron transport and the synthesis of ATP from ADP, hence generating heat rather than energy. In mammals, more than five family members have been identified, including UCP1, UCP2, UCP3, UCP4 (or BMCP1/UCP5) and UCP5. The UCPs may play an important role in energy homeostasis and have become prominent in the fields of thermogenesis, obesity, diabetes and free‐radical biology and have been considered candidate genes for obesity and insulin resistance. They have been as important potential targets for treatment of aging, degenerative diseases, diabetes and obesity. Recently, a series of studies showed the polymorphisms of UCPs gene association with the fat metabolism, obesity and diabetes. This review summarizes data supporting the roles of UCP2 and UCP3 in energy dissipation, as well as the genetic variety association with fat metabolism, obesity and diabetes in humans.
Obesity and overweight in Canada: an updated cost‐of‐illness study
Authors: Anis A. H. , Zhang W. , Bansback N. , Guh D. P. , Amarsi Z. , Birmingham C. L.
Published: April 2009

This study is to update the estimates of the economic burden of illness because of overweight and obesity in Canada by incorporating the increase in prevalence of overweight and obesity, findings of new related comorbidities and rise in the national healthcare expenditure. The burden was estimated from a societal perspective using the prevalence‐based cost‐of‐illness methodology. Results from a literature review of the risks of 18 related comorbidities were combined with prevalence of overweight and obesity in Canada to estimate the extent to which each comorbidity is attributable to overweight and obesity. The direct costs were extracted from the National Health Expenditure Database and allocated to each comorbidity using weights principally from the Economic Burden of Illness in Canada. The study showed that the total direct costs attributable to overweight and obesity in Canada were $6.0 billion in 2006, with 66% attributable to obesity. This corresponds to 4.1% of the total health expenditures in Canada in 2006. The inclusion of newly identified comorbidities increased the direct cost estimates of obesity by 25%, while the rise in national healthcare expenditure accounted for a 19% increase. Policies to reduce being overweight and obese could potentially save the Canadian healthcare system millions of dollars.
Reflections from a systematic review of dietary energy density and weight gain: is the inclusion of drinks valid?
Authors: Johnson L. , Wilks D. C. , Lindroos A. K. , Jebb S. A.
Published: April 2009

The association between dietary energy density, increased energy intake and weight gain is supported by experimental evidence, but confirmation of an effect in free‐living humans is limited. Experimental evidence supports a role of energy density in obesity through changes in food composition, not drinks consumption. The inclusion of drinks in the calculation creates a variable of questionable validity and has a substantive impact on the estimated energy density of the diet. We posit, based on the experimental evidence, that calculating the energy density of diets by excluding drinks and including calories from drinks as a covariate in the analysis is the most valid and reliable method of testing the relationship between energy density and weight gain in free‐living humans. We demonstrate, by systematically reviewing existing observational studies of dietary energy density and weight gain in free‐living humans, how current variation in the method for calculating energy density hampers the interpretation of these data. Reaching an a priori decision on the appropriate methodology will reduce the error caused by multiple comparisons and facilitate meaningful interpretation of epidemiological evidence to inform the development of effective obesity prevention strategies.
The effect of pharmaceutical intervention on lipid profile in polycystic ovary syndrome
Authors: Diamanti‐Kandarakis E. , Kandaraki E. , Christakou C. , Panidis D.
Published: April 2009

The polycystic ovary syndrome (PCOS), a prevalent endocrinopathy of women, has been associated with a clustering of adverse metabolic features, which co‐exist with reproductive dysfunction. Lipid abnormalities are very common in lean as well as obese women with PCOS and should be cautiously considered in the therapeutic management of the syndrome. Clinicians should also critically assess the lipidemic effect of pharmaceutical intervention, primarily aimed at hyperandrogenism, anovulation or insulin resistance. Because dyslipidemia may contribute to long‐term cardiometabolic and reproductive sequelae in PCOS, it should be considered as an additional therapeutic target when these patients are assigned to appropriate pharmaceutical treatment.
Non‐alcoholic fatty liver disease is associated with cardiovascular disease risk markers
Authors: Edens M. A. , Kuipers F. , Stolk R. P.
Published: April 2009

Recognition of the link between non‐alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) has boosted research in this area. The main objective of this paper is to review the literature on NAFLD in the context of CVD, focussing on underlying mechanisms and treatment. Besides excessive fatty acid influx, etiologic factors may include components of the metabolic syndrome, cytokines and mitochondrial dysfunction. NAFLD is associated with both hepatic and systemic insulin resistance. In the case of NAFLD, the liver overproduces several atherogenic factors, notably inflammatory cytokines, glucose, lipoproteins and coagulation factors, and factors increasing blood pressure. Intervention studies on diet and laparoscopic surgery revealed improvements of hepatic fat content and CVD risk profile. Pharmacological approaches with potential benefit have been developed as well, but effects are often confounded by weight change. NAFLD is associated with an increased CVD risk profile (and hepatic risk). In order to improve CVD risk profile, prevention and treatment of NAFLD seem advisable. However, well‐designed intervention studies, randomized clinical trials and long‐term follow‐up studies are scarce.
WHAT ‘EMPIRICAL TURN IN BIOETHICS’?
Authors: HURST SAMIA
Published: April 2009

Uncertainty as to how we should articulate empirical data and normative reasoning seems to underlie most difficulties regarding the ‘empirical turn’ in bioethics. This article examines three different ways in which we could understand ‘empirical turn’. Using real facts in normative reasoning is trivial and would not represent a ‘turn’. Becoming an empirical discipline through a shift to the social and neurosciences would be a turn away from normative thinking, which we should not take. Conducting empirical research to inform normative reasoning is the usual meaning given to the term ‘empirical turn’. In this sense, however, the turn is incomplete. Bioethics has imported methodological tools from empirical disciplines, but too often it has not imported the standards to which researchers in these disciplines are held. Integrating empirical and normative approaches also represents true added difficulties. Addressing these issues from the standpoint of debates on the fact‐value distinction can cloud very real methodological concerns by displacing the debate to a level of abstraction where they need not be apparent. Ideally, empirical research in bioethics should meet standards for empirical and normative validity similar to those used in the source disciplines for these methods, and articulate these aspects clearly and appropriately. More modestly, criteria to ensure that none of these standards are completely left aside would improve the quality of empirical bioethics research and partly clear the air of critiques addressing its theoretical justification, when its rigour in the particularly difficult context of interdisciplinarity is what should be at stake.
REFLECTIVE EQUILIBRIUM AND EMPIRICAL DATA: THIRD PERSON MORAL EXPERIENCES IN EMPIRICAL MEDICAL ETHICS
Authors: DE VRIES MARTINE , VAN LEEUWEN EVERT
Published: April 2009

In ethics, the use of empirical data has become more and more popular, leading to a distinct form of applied ethics, namely empirical ethics. This ‘empirical turn’ is especially visible in bioethics. There are various ways of combining empirical research and ethical reflection. In this paper we discuss the use of empirical data in a special form of Reflective Equilibrium (RE), namely the Network Model with Third Person Moral Experiences. In this model, the empirical data consist of the moral experiences of people in a practice. Although inclusion of these moral experiences in this specific model of RE can be well defended, their use in the application of the model still raises important questions. What precisely are moral experiences? How to determine relevance of experiences, in other words: should there be a selection of the moral experiences that are eventually used in the RE? How much weight should the empirical data have in the RE? And the key question: can the use of RE by empirical ethicists really produce answers to practical moral questions?

In this paper we start to answer the above questions by giving examples taken from our research project on understanding the norm of informed consent in the field of pediatric oncology. We especially emphasize that incorporation of empirical data in a network model can reduce the risk of self‐justification and bias and can increase the credibility of the RE reached.
WHEN SPEED TRULY MATTERS, OPENNESS IS THE ANSWER
Authors: MARTURANO ANTONIO
Published: April 2009

In this paper I analyse the ethical implications of the two main competing methodologies in genomic research. I do not aim to provide another contribution from the mainstream legal and public policy perspective; rather I offer a novel approach in which I analyse and describe the patent‐and‐publish regime (the proprietary regime) led by biologist J. Craig Venter and the ‘open‐source’ methodologies led by biotechnology Nobel laureate John Sulston. The ‘open‐source methodologies’ arose in biotechnology as an alternative to the patent‐and‐publish regime in the wake of the explosion in computer technology. Indeed, the tremendous increase in computer technology has generated a corresponding increase in the pace of genomics research. I conclude this paper by arguing that while the patent‐and‐publish method is a transactional method based on the exchange of extrinsic goods (patents in exchange for research funds), the free and open‐source methodology (FLOSS)1 is a transformational method based on a visionary ideal of science, which leads to prioritizing intrinsic goods in scientific research over extrinsic goods.
637. FRITILLARIA YUMINENSIS
Authors: Leon Christine , Fay Michael F. , Rix Martyn
Published: April 2009

Fritillaria yuminensis X.Z. Duan (Liliaceae) is described and illustrated; the species in the Fritillaria verticillata complex are listed and their relationship to the rest of the genus, as revealed by DNA studies, is described. The cultivation of Fritillaria (bei mu) for medicine and its conservation in China are summarised.
638. TULIPA LEHMANNIANA
Authors: Wilford Richard , Zarrei Mehdi
Published: April 2009

An Iranian form of Tulipa lehmanniana Mercklin is described and illustrated. The history, classification, natural range and cultivation of this species are discussed and detailed observations on its occurrence and habitat in Iran are provided.
639. PTEROCACTUS GONJIANII
Authors: Kiesling Roberto , Márquez Justo , Taylor Nigel
Published: April 2009

The cactus geophyte, Pterocactus gonjianii, an endemic from San Juan province in the Andes of Argentina, is illustrated and its habitat and morphological details are described. Botanical and horticultural notes on this unusual genus of opuntioid cacti are also provided.
640. QUERCUS CASTANEIFOLIA
Authors: Rix Martyn , Kirkham Tony
Published: April 2009

Quercus castaneifolia C.A. Mey. is described and illustrated from a tree growing at Kew. Its habitat, distribution, variation in the wild and its relationships with similar species, are discussed. A summary of the history and conservation of some of the oldest trees at Kew is included.
642. SAXIFRAGA GRANULATA
Authors: Fay Michael F. , Rankou Hassan , Wilford Richard
Published: April 2009

Saxifraga granulata L. (Saxifragaceae) is a characteristic plant of semi‐natural grasslands at Kew. The literature relating to its occurrence in the UK and its use in medicine is summarised, and a description, cultivation requirements, colour plate and line drawings are given.
643. OXALIS MASSONIANA
Authors: Duncan Graham
Published: April 2009

The South African Oxalis massoniana T.M.Salter is illustrated and described, and its cultivation requirements are discussed. A brief account of Francis Masson's journeys of exploration at the Cape is given.
644. MERTENSIA MARITIMA
Authors: Alton Steve , FitzGerald Ro
Published: April 2009

The Mertensia maritima aggregate is discussed, with the primary focus on M. maritima (L.) Gray sensu stricto which is illustrated and described. Its highly specialised habitat is examined and some unusual physical adaptations noted, together with its history, occurrence in ethnobotanical records, and reported performance in cultivation. Some problems encountered in attempting to clarify the nomenclature and taxonomy of the aggregate are discussed, notably those concerning the segregates M. maritima subsp. asiatica Takeda, and Mertensia simplicissima G.Don.
646. CYLINDROCLINE LORENCEI
Authors: Hind Nicholas , Sánchez Michèle , Magdalena Carlos
Published: April 2009

Cylindrocline lorencei A. J. Scott, a ‘Plant in Peril’, is described and illustrated, and its cultivation requirements provided. The species' conservation status is commented on: once declared extinct in the wild, attempts have now been made to re‐introduce the species into Mauritius. The relationships of Cylindrocline are discussed.
Bottom‐up processing and reading comprehension in experienced adult readers
Authors: Holmes Virginia M.
Published: April 2009

Previous research has indicated a weak to moderate role for word recognition skill in contributing to reading comprehension efficiency in highly experienced adult readers. The goal of this study was to re‐evaluate the strength of this association, including assessment of the contribution of skill in discriminating unfamiliar shapes and identifying letters. Unexpectedly, the results revealed a very strong association between efficiency in reading connected text and word recognition skill, as measured by efficiency of access to the orthographic lexicon. Ability to identify letters rapidly and accurately also contributed to orthographic access skill. These associations were only minimally reduced by controlling for skill in discriminating unfamiliar shapes. The results were interpreted in terms of the verbal‐efficiency theory, according to which rapid and accurate lower‐level processing liberates resources for equally crucial higher‐level comprehension processing, ultimately resulting in more efficient text comprehension.
Literacy skills in Maltese–English bilingual children
Authors: Xuereb Rachael
Published: April 2009

This research considers aspects of literacy in Maltese–English bilingual children. The study examined the reading and phonological awareness skills in English and Maltese of children whose home language is Maltese and second language English. A sample of 50 typically developing Maltese pupils aged 8 years 0 months to 10 years 5 months was selected. Since commencing school at the age of 5 years, the children have been learning to read in Maltese and also in English. For the purpose of this study, Maltese reading and reading‐related tests were constructed to parallel the UK and US standardised assessments. The novel tests and the standardised tests were administered to all the children. Results showed that Maltese children read better in their first language (Maltese) than in English, the language of instruction. Findings also showed that phonological awareness measures correlated across first and second languages. The results are discussed in terms of L1 and L2 transfer, whereby the transparency of Maltese orthography and English phonological processing skills facilitate performance on phonological tasks in both Maltese and English.
Identification of Multivariate Responders and Non-Responders by using Bayesian Growth Curve Latent Class Models
Authors: Leiby Benjamin E. , Sammel Mary D. , Ten Have Thomas R. , Lynch Kevin G.
Published: April 2009

We propose a multivariate growth curve mixture model that groups subjects on the basis of multiple symptoms measured repeatedly over time. Our model synthesizes features of two models. First, we follow Roy and Lin in relating the multiple symptoms at each time point to a single latent variable. Second, we use the growth mixture model of Muthén and Shedden to group subjects on the basis of distinctive longitudinal profiles of this latent variable. The mean growth curve for the latent variable in each class defines that class’s features. For example, a class of ‘responders’ would have a decline in the latent symptom summary variable over time. A Bayesian approach to estimation is employed where the methods of Elliott and co-workers are extended to estimate simultaneously the posterior distributions of the parameters from the latent variable and growth curve mixture portions of the model. We apply our model to data from a randomized clinical trial evaluating the efficacy of bacillus Calmette–Guerin in treating symptoms of interstitial cystitis. In contrast with conventional approaches using a single subjective global response assessment, we use the multivariate symptom data to identify a class of subjects where treatment demonstrates effectiveness. Simulations are used to confirm identifiability results and to evaluate the performance of our algorithm.
Spatial Prediction of Weed Intensities From Exact Count Data and Image-Based Estimates
Authors: Guillot Gilles , Lorén Niklas , Rudemo Mats
Published: April 2009

Collecting weed exact counts in an agricultural field is easy but extremely time consuming. Image analysis algorithms for object extraction applied to pictures of agricultural fields may be used to estimate the weed content with a high resolution (about 1 m2), and pictures that are acquired at a large number of sites can be used to obtain maps of weed content over a whole field at a reasonably low cost. However, these image-based estimates are not perfect and acquiring exact weed counts also is highly useful both for assessing the accuracy of the image-based algorithms and for improving the estimates by use of the combined data. We propose and compare various models for image index and exact weed count and we use them to assess how such data should be combined to obtain reliable maps. The method is applied to a real data set from a 30-ha field. We show that using image estimates in addition to exact counts allows us to improve the accuracy of maps significantly. We also show that the relative performances of the methods depend on the size of the data set and on the specific methodology (full Bayes versus plug-in) that is implemented.
Stability Analysis of an Additive Spline Model for Respiratory Health Data by Using Knot Removal
Authors: Binder Harald , Sauerbrei Willi
Published: April 2009

In many settings with possibly non-linear influence of covariates, such as in the present application with children’s respiratory health data, generalized additive models are an attractive choice. Although techniques for fitting these have been extensively investigated, there are fewer results on stability of replication, i.e. stability of fitted model components with respect to perturbations in the data. Nevertheless, this aspect is essential for judging how useful the present model is for understanding predictors of lung function. We therefore investigate existing tools for stability analysis based on bootstrap samples, such as quantities for variability and bias, for our application. Furthermore, as the focus is on models based on B-splines, knot removal techniques are available. These can help to provide more insight into the stability of local features that are fitted in bootstrap samples. We analyse the bootstrap result matrix via log-linear models. Specifically, the relationship with respect to local features between the influence functions of potential lung function predictors is investigated.
WORKERS' BEHAVIOR AND LABOR CONTRACT: AN EVOLUTIONARY APPROACH
Authors: Hiller Victor
Published: April 2009

This paper investigates the co‐evolution of labor relationships and workers' preferences. The workforce is composed by cooperative and non‐cooperative workers, while firms offer either explicit or implicit contracts. Both the distribution of preferences and the nature of labor contract are endogenized: firms invest in corporate culture in order to change workers' preferences and the proportion of each type of contract is driven by an evolutionary process. The complementarity between the transmission of cooperation and the implementation of implicit contracts leads to multiple equilibria and path dependence phenomenon. This property is illustrated by historical evolutions of American and Japanese labor contracts.
Screening for childhood mental health problems: outcomes and early identification
Authors: Essex Marilyn J. , Kraemer Helena C. , Slattery Marcia J. , Burk Linnea R. , Thomas Boyce W. , Woodward Hermi R. , Kupfer David J.
Published: April 2009

Background:  Many childhood psychiatric problems are transient. Consequently, screening procedures to accurately identify children with problems unlikely to remit and thus, in need of intervention, are of major public health concern. This study aimed to develop a universal school‐based screening procedure based on the answers to three questions: (1) What are the broad patterns of mental health problems from kindergarten to grade 5? (2) What are the grade 5 outcomes of these patterns? (3) How early in school can children likely to develop the most impairing patterns be identified accurately?

Methods:  Mothers and teachers reported on a community sample (N = 328) of children’s internalizing and externalizing symptoms in kindergarten and grades 1, 3, and 5. In grade 5, teachers reported on children’s school‐based functional impairments, physical health problems, and service use; mothers reported on children’s specialty mental health care.

Results:  Four patterns distinguished children who (1) never evidenced symptoms; (2) evidenced only isolated symptoms; or evidenced recurrent symptoms, either (3) without or (4) with comorbid internalizing and externalizing. By grade 5, children with recurrent comorbid symptoms had the greatest impairments, physical health problems, and service use. These children can be identified quite accurately by grade 1.

Conclusions:  Universal screening at school entry can effectively identify children likely to develop recurrent comorbid symptoms, and would provide a basis for developing optimal targeted intervention programs.
Can captivity lead to inter‐species mating in two Mesocricetus hamster species?
Authors: DelBarco‐Trillo J. , Gulewicz K. , Segal A. , McPhee M. E. , Johnston R. E.
Published: April 2009

In two closely related species, females generally prefer conspecific males over heterospecific males. We found that estrous (but not diestrous) female Syrian hamsters Mesocricetus auratus prefer the odors of conspecific males to odors of Turkish hamsters Mesocricetus brandti. However, female Syrian hamsters are not aggressive toward male Turkish hamsters and will readily mate with them. We hypothesize that many generations in captivity led to a reduction in females' ability to avoid inter‐species mating, possibly related to the heightened sexual receptivity observed in Mesocricetus hamsters in captivity. To test this hypothesis, we replicated a study carried out with female Turkish hamsters soon after the current laboratory stock of this species was established. In that study, female Turkish hamsters showed lordosis toward male Syrian hamsters in only 20% of interactions and attacked heterospecific males in 80% of the pairings. Using animals descended from that original colony (after many generations in captivity and certain episodes of inbreeding), 100% of female Turkish hamsters mated with heterospecific males and none showed aggression toward heterospecific males. Thus female avoidance of inter‐specific mating may be affected by captive rearing conditions.
Prospects for microbeam radiation therapy of brain tumours in children to reduce neurological sequelae
Authors: Laissue JA , Blattmann H , Wagner H P , Grotzer M A , Slatkin D N
Published: April 2009

Microbeam radiation therapy (MRT), a form of experimental radiosurgery of tumours using multiple parallel, planar, micrometres‐wide, synchrotron‐generated X‐ray beams (‘microbeams’), can safely deliver radiation doses to contiguous normal animal tissues that are much higher than the maximum doses tolerated by the same normal tissues of animals or patients from any standard millimetres‐wide radiosurgical beam. An array of parallel microbeams, even in doses that cause little damage to radiosensitive developing tissues, for example, the chick chorioallantoic membrane, can inhibit growth or ablate some transplanted malignant tumours in rodents. The cerebella of 100 normal 20 to 38g suckling Sprague‐Dawley rat pups and of 13 normal 5 to 12kg weanling Yorkshire piglets were irradiated with an array of parallel, synchrotron‐wiggler‐generated X‐ray microbeams in doses overlapping the MRT‐relevant range (about 50‐600Gy) using the ID17 wiggler beamline tangential to the 6GeV electron synchrotron ring at the European Synchrotron Radiation Facility in Grenoble, France. Subsequent favourable development of most animals over at least 1 year suggests that MRT might be used to treat children's brain tumours with less risk to the development of the central nervous system than is presently the case when using wider beams.
Sensory evaluation of the hands in children with brachial plexus birth injury
Authors: Palmgren Tove , Peltonen Jari , Linder Tove , Rautakorpi Sanna , Nietosvaara Yrjänä
Published: April 2009

The aim of this study was to examine sensory changes of the hand in brachial plexus birth injury (BPBI). Ninety‐five patients (43 females, 52 males) comprising two age groups, 6 to 8 years (mean age 7y 6mo) and 12 to 14 years (mean age 13y 2mo), were included. Sixty‐four had upper (cervical [C] 5–6), 19 upper and middle (C5‐7), and 12 had total (C5‐thoracic (Th)1) plexus injury. Obstetric plexus surgery had been performed on 14 patients at the age of 1 to 6 months. The sensibility of 32 palmar areas of both hands was tested with Semmes‐Weinstein filaments (calibres 2.83, 3.61, 4.31, 4.56, and 6.65). In upper plexus injuries, abnormal values (4.31‐4.56) were recorded in seven out of 64 affected hands. In C5‐7 and total plexus‐involvement, decreased sensibility was found in five out of 19 (4.31‐6.65) and in four out of 12 (4.31‐no sensation) affected hands respectively. Conservatively treated patients had better sensation than those treated surgically. Sensory recovery of the hands in BPBI is generally good, especially in upper plexus injuries. Impairment of fine sensation is not uncommon in more extensive permanent BPBI. In total injuries, protective sensation of the hand is not always restored.
Increased inflammatory markers are associated with early periventricular leukomalacia
Authors: Tsukimori Kiyomi , Komatsu Hajime , Yoshimura Takazumi , Hikino Shunji , Hara Toshiro , Wake Norio , Nakano Hitoo
Published: April 2009

The aim of the study was to investigate whether inflammatory markers are associated with the occurrence of periventricular leukomalacia (PVL). Superoxide (O2‐) production of neutrophils and plasma antioxidative superoxide dismutase (SOD) activity in umbilical cord blood were studied. Participants were preterm infants with early PVL (n=6; three males, three females; mean birthweight 1458g [SD 517], range 620–2040g; mean gestational age 29.8wks [SD 2.9], range 27–34wks); and preterm control infants without PVL (n=10; five males, five females; mean birthweight 1838g [SD 664], range 925–2748g; mean gestational age 30.6wks [SD 3.1], range 26–34wks). In addition, pro‐inflammatory cytokine levels were measured in the umbilical cord blood. N‐formyl‐methionyl‐leucyl‐phenylalanine‐induced O2‐ production by neutrophils in infants with early PVL was significantly higher than that in the control group. In contrast, there was no significant difference in concentrations of copper/zinc‐SOD and SOD activity between groups. Concentrations of interleukin (IL)‐1β and tumour necrosis factor‐α (but not IL‐6, IL‐8, or granulocyte‐colony stimulating factor) were significantly higher in infants with early PVL than in control infants. The excess O2‐ produced by activated neutrophils with increased pro‐inflammatory cytokine production could play a role in the molecular cascade leading to white matter damage in PVL.
The Functional Mobility Scale: ability to detect change following single event multilevel surgery
Authors: Harvey Adrienne , Graham H Kerr , Morris Meg E , Baker Richard , Wolfe Rory
Published: April 2009

The aim of this study was to examine the ability of the Functional Mobility Scale (FMS) to detect change in children with cerebral palsy (CP) undergoing single event multilevel surgery (SEMLS). A retrospective study was conducted of gait laboratory records and video assessments for a consecutive sample of children with CP aged 4 to 18 years who were managed by multilevel surgery. FMS ratings and Gross Motor Function Classification System (GMFCS) levels were recorded preoperatively and at regular postoperative time points. The sample comprised 66 children (32 females, 34 males) with spastic diplegia, GMFCS Levels I (n=18), II (n=24), and III (n=24). The mean age at surgery was 10 years (SD 2y 6mo, range 6–16y). For each FMS distance (5, 50, and 500m) odds ratios showed significant deterioration in mobility at 3 and 6 months postoperatively. Mobility then improved to baseline levels by 12 months and improved further by 24 months postoperatively. GMFCS level remained stable throughout most of the postoperative period for children classified as GMFCS Level III preoperatively but not for children classified as Levels I or II. The FMS was found to be a clinically feasible tool for quantifying change after SEMLS in children with CP.
Quantitative reference curves for associated movements in children and adolescents
Authors: Gasser Theo , Rousson Valentin , Caflisch Jon , Largo Remo
Published: April 2009

Intensity of contralateral associated movements (AMs) is a measure of movement quality assessed using frequency and degree of AMs. A sample of 593 right‐handed participants without disability (286 males, 307 females; aged 5y‐18y 6mo) was studied with the Zurich Neuromotor Assessment (ZNA). The ZNA is a standardized testing procedure which assesses performance on standardized motor tasks according to timed performance and frequency and degree of AMs. In contrast to frequency and degree, intensity of AMs allowed the calculation of centiles which were quasi‐continuous. Centile curves of contralateral AMs for the ZNA and data on inter‐ and intraobserver reliability are presented. The significance of age, sex, and side differences are discussed. Intensity of AMs offers clinical and scientific advantages for measurement of movement quality. There is a decrease of AMs with age depending on the complexity of tasks. Females showed consistently fewer AMs than males, whereas only minor side differences were shown.
Childhood myasthenia: clinical subtypes and practical management
Authors: Parr J R , Jayawant S
Published: April 2009

In recent years, understanding of the pathogenesis and clinical presentation of distinct myasthenia subtypes has increased significantly. This article reviews the clinical manifestations of autoimmune myasthenia gravis (including myasthenia associated with anti‐muscle‐specific kinase antibodies), ocular myasthenia, and antibody negative myasthenia. The following treatments are examined: cholinesterase inhibitors, immunosuppressants, and thymectomy. Inherited congenital myasthenic syndromes (CMS) are now increasingly recognized, and most commonly present during childhood. This article outlines the presynaptic, synaptic basal lamina‐associated, and postsynaptic classification of CMS and the clinical presentation and aetiology of individual syndromes. Relevant investigations and treatment options (including the role of pyridostigmine, 3,4‐diaminopyridine, fluoxetine, and ephedrine) are discussed.
Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very‐low‐birthweight preterm children
Authors: ROSE JESSICA , BUTLER ERIN E , LAMONT LAUREN E , BARNES PATRICK D , ATLAS SCOTT W , STEVENSON DAVID K
Published: April 2009

The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term‐equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel−Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very‐low‐birthweight preterm children (41 males, 37 females; mean gestational age 27.6wks, SD 2.5; mean birthweight 1021g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049;p=0.025) and right posterior limb of the internal capsule (PLIC;p=0.003;p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2;p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001;p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371,p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.
Cognition and adaptive skills in myotonic dystrophy type 1: a study of 55 individuals with congenital and childhood forms
Authors: EKSTRÖM ANNE‐BERIT , HAKENÄS‐PLATE LOUISE , TULINIUS MÁR , WENTZ ELISABET
Published: April 2009

Aims  To investigate cognitive abilities and adaptive skills in children and adolescents with myotonic dystrophy type 1 (DM1) and correlate the findings to the cytosine‐thymine‐guanine (CTG) repeat expansion size.

Method  Cognitive level was assessed in 55 children and adolescents with DM1 (31 males, 24 females; mean age 12y 1mo, SD 5y 1mo; range 2y 7mo–21y 5mo) divided into the following categories: severe congenital DM1 (n=19), mild congenital DM1 (n=18), and childhood DM1 (n=18). The Griffiths Mental Developmental Scale, the Wechsler Scales, and the Vineland Adaptive Behavior Scales (VABS) for adaptive skills were used for this purpose.

Results  Learning disability was found in 95% of the severe congenital group, 83% of the mild congenital group, and 89% of the childhood DM1 group. The more severe the form of DM1, the lower the full‐scale IQ (FSIQ; rs=0.28, p=0.044). The individuals with severe congenital and childhood DM1 had a significantly higher verbal IQ than performance IQ (severe congenital: mean difference 5.7, SD 5.7, p=0.008; childhood DM1: mean difference 9.8, SD 18.0, p=0.038). CTG repeat expansion correlated negatively with FSIQ (rs=−0.63, p<0.006). Almost all participants showed poor results on the VABS. There was a positive relationship between cognitive level and adaptive skills in the mild congenital (rs=0.95, p<0.01) and childhood DM1 groups (rs=0.92, p<0.01).

Interpretation  Children and adolescents with DM1 exhibit significant cognitive and adaptive problems.
In vivo muscle architecture and size of the rectus femoris and vastus lateralis in children and adolescents with cerebral palsy
Authors: MOREAU NOELLE G , TEEFEY SHARLENE A , DAMIANO DIANE L
Published: April 2009

Aim  Our aim was to investigate muscle architecture and size of the rectus femoris (RF) and vastus lateralis (VL) in children and adolescents with cerebral palsy (CP) compared with age‐matched typically developing participants.

Method  Muscle architecture and size were measured with ultrasound imaging in 18 participants with spastic CP (9 females, 9 males; age range 7.5–19y; mean age 12y [SD 3y 2mo]) within Gross Motor Function Classification System levels I (n=4), II (n=2), III (n=9), and IV (n=3) and 12 typically developing participants (10 females, 2 males; age range 7–20y; mean age 12y 4mo [SD 3y 11mo]). Exclusion criteria were orthopedic surgery or neurosurgery within 6 months before testing or botulinum toxin injections to the quadriceps within 3 months before testing.

Results  RF cross‐sectional area was significantly lower (48%), RF and VL muscle thickness 30% lower, RF fascicle length 27% lower, and VL fascicle angle 3° less in participants with CP compared to the typically developing participants (p<0.05). Intraclass correlation coefficients were ≥0.93 (CP) and ≥ 0.88 (typical development), indicating excellent reliability.

Interpretation  These results provide the first evidence of altered muscle architecture and size of the RF and VL in CP, similar to patterns observed with disuse and aging. These alterations may play a significant role in the decreased capacity for force generation as well as decreased shortening velocity and range of motion over which the quadriceps can act.