bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic profiles in primordial germ cells: Global modulation and fine tuning of the epigenome for acquisition of totipotency
Authors: Mochizuki Kentaro , Matsui Yasuhisa
Published: July 2010

Germ cells, after fate determination as primordial germ cells (PGCs) in early embryos, undergo various unique changes in epigenetic status during their development, and these changes differ from the epigenetic changes occurring in any other somatic cells. For example, PGCs undergo demethylation of DNA and change histone modification states on a genome‐wide scale. Although the full physiological significance of these epigenetic alterations is still unclear, we can now discuss some of their mechanisms due to recent experimental evidence demonstrating the expression of candidate molecules involved in the processes of epigenetic change. On the other hand, DNA demethylation associated with PGC‐specific gene expression, reprogramming of imprinted genes and regulation of retrotransposons in PGCs differentially occur from the genome‐wide DNA demethylation. The tendency of epigenetic changes to appear on the whole genome, as well as more precise changes in the epigenetic status of particular parts of the genome, may play important roles in establishing the properties of PGCs required for acquiring totipotency.
Epigenetic performers in plants‡
Authors: Chen Ming , Lv Shaolei , Meng Yijun
Published: July 2010

Epigenetic research is at the forefront of plant biology and molecular genetics. Studies on higher plants underscore the significant role played by epigenetics in both plant development and stress response. Relatively recent advances in analytical methodology have allowed for a significant expansion of what is known about genome‐wide mapping of DNA methylation and histone modifications. In this review, we explore the different modification patterns in plant epigenetics, and the key factors involved in the epigenetic process, in order to illustrate various putative mechanisms. Experimental technology to exploit these modifications, and proposed focus areas for future plant epigenetic research, are also presented.
Divergence of CpG island promoters: A consequence or cause of evolution?
Authors: Sharif Jafar , Endo Takaho A. , Toyoda Tetsuro , Koseki Haruhiko
Published: July 2010

CpG islands (CGIs) are CG‐rich stretches in the genome that are concentrated near the transcription start sites (TSS) of genes. Genes that possess CGIs, such as the housekeeping genes, are often highly expressed in multiple tissues. Indeed, CGIs are enriched in approximately half of the promoters in humans and mice, suggesting an important role for CpG islands in mammalian transcriptional regulation. Interestingly, accumulation of CpG islands at TSS appears to be a vertebrate specific genomic feature, which implicates a link between CpG islands and evolution. However, it remains unclear whether the association of CGIs to gene promoters is a cause or consequence of evolution. In the present study, we have addressed this question by analyzing nine species including invertebrates, chordates and vertebrates, using bioinformatics based techniques. Our results indicate that CGIs arose at TSS as a “consequence” of warm‐blooded vertebrate evolution, presumably for efficient regulation of transcription in a larger genome. Furthermore, we reveal that CGIs could have functioned as a direct “cause” of evolution among the warm‐blooded vertebrates, such as contributing to the gain of placenta, which is a hallmark of eutherian mammals. Elucidation of the origin and functions of CpG islands and the process of their convergence into transcription start sites of genes will pave the way for a greater understanding of the roles for CGIs in gene expression, development and reprogramming of the genome.
Retrotransposon silencing by DNA methylation contributed to the evolution of placentation and genomic imprinting in mammals
Authors: Kaneko‐Ishino Tomoko , Ishino Fumitoshi
Published: July 2010

The evolution of two mammalian‐specific traits, viviparous reproduction with a placenta and genomic imprinting, have been addressed by multiple studies of two retrotransposon derived, mammalian‐specific genes. These gene targeting experiments in mice, together with recent comparative genomic analyses among three mammalian groups, suggest that extremely rare events; namely exaptations from retrotransposons, made crucial contributions to the establishment and diversification of mammals via placental formation. We propose that nearly neutral evolution, as well as Darwinian evolution (natural selection), plays an important role in the exaptation process. Comparative genomic analysis of various imprinted regions has also revealed that an imprinting control element essential for parent‐of‐origin specific monoallelic expression of imprinted genes emerged in each of the imprinted regions, possibly by the insertion of exogenous DNAs, such as retrotransposons. In both cases, DNA methylation in germ cells must have been of critical importance to repress the exogenous DNAs inserted into the genomes of mammalian ancestors. We propose that the ability of germ line DNA methylation enabled the emergence of certain mammalian‐specific features during the course of evolution.
DOES A PATENT ACCESSORY PANCREATIC DUCT PREVENT ACUTE PANCREATITIS?
Authors: Tabata Taku , Kamisawa Terumi , Takuma Kensuke , Anjiki Hajime , Fujiwara Junko , Egashira Hideto , Koizumi Koichi , Egawa Naoto
Published: July 2010

Background and Aim:  The role of the accessory pancreatic duct (APD) in pancreatic pathophysiology has been unclear. We previously examined the patency of the APD in 291 control cases who had a normal pancreatogram in the head of the pancreas by dye‐injection endoscopic retrograde pancreatography (ERP). APD patency was 43% and was closely related with the shape of the terminal portion of the APD. The present study aimed to clarify the clinical implications of a patent APD.

Methods:  Based on the underlying data, the patency rate of the APD was estimated from the terminal shape of the APD on ERP in 167 patients with acute pancreatitis.

Results:  In patients with acute pancreatitis, stick‐type APD, spindle‐type APD, and cudgel‐type APD, which showed a high patency, were rare, and branch‐type APD and halfway‐type or no APD, which showed quite low patency, were frequent in acute pancreatitis patients. Accordingly, the estimated patency of the APD in acute pancreatitis patients was only 21%. There was no significant relationship between the estimated APD patency and etiology or severity of acute pancreatitis.

Conclusions:  The terminal shapes of the APD with low patency were frequent in acute pancreatitis patients, and estimated APD patency was only 21% in acute pancreatitis. A patent APD may function as a second drainage system to reduce the pressure in the main pancreatic duct and prevent acute pancreatitis.
TOLERABILITY AND USEFULNESS OF MERCAPTOPURINE IN AZATHIOPRINE‐INTOLERANT JAPANESE PATIENTS WITH ULCERATIVE COLITIS
Authors: Kuriyama Motoaki , Kato Jun , Suzuki Hideyuki , Akita Mitsuhiro , Hiraoka Sakiko , Okada Hiroyuki , Yamamoto Kazuhide
Published: July 2010

Background and Aim:  Azathioprine (AZA) and mercaptopurine (6‐MP) are established as effective therapeutic drugs for the induction and maintenance of remission in patients with ulcerative colitis (UC). However, AZA is often intolerable due to adverse effects. Evidence regarding the approach of switching from AZA to 6‐MP in patients of Asian ethnicity is lacking. We assessed the tolerability and usefulness of 6‐MP in Japanese UC patients who had shown intolerance to AZA.

Methods:  One‐hundred and ten UC patients who had been treated with AZA and/or 6‐MP from January 1985 to October 2008 were examined retrospectively.

Results:  Among 110 patients, 107 were treated first with AZA; only three were treated first with 6‐MP. Thirty‐five (33%) of the 107 patients were intolerant of AZA, with adverse effects including myelosuppression (8/35, 23%), hepatotoxicity (8/35, 23%), and abdominal symptoms (6/35, 17%). Among 35 AZA‐intolerant patients, 23 were switched to 6‐MP treatment. The cumulative probability of colectomy was significantly higher in patients not treated with 6‐MP than in patients treated with 6‐MP (log–rank test, P = 0.0002). Among the 26 patients (23 AZA‐intolerant and three AZA‐untreated) treated with 6‐MP, 22 (85%) could tolerate the therapy. Adverse effects due to 6‐MP were abdominal symptoms (2/4), myelosuppression (1/4), and rash (1/4). The median initial dose of 6‐MP was 20 mg/day, and the median final dose was 30 mg/day.

Conclusions:  6‐MP was tolerated in 83% of AZA‐intolerant patients, and it was effective for maintenance therapy of UC patients. 6‐MP treatment should be considered in AZA‐intolerant patients.
Survival responses to oxidative stress and aging
Authors: Miura Yuri , Endo Tamao
Published: July 2010

Oxidative stress is recognized as an important environmental factor in aging; however, because reactive oxygen species (ROS) and related free radicals are normally produced both intra‐ and extracellularly, air‐living organisms cannot avoid the risk of oxidative stress. Consequently, these organisms have evolved various anti‐oxidant systems to prevent ROS, scavenge free radicals, repair damaged components and adaptive responses. This review will focus on the repair and adaptive response to oxidative stress, and summarize the changes of these systems as a result aging and their relationship to premature aging. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S1–S9.
Cervical endometriosis: Case series and review of literature
Authors: Wong Felix Wu Shun , Lim Chi Eung Danforn , Karia Sonal , Santos Leonardo
Published: July 2010

Cervical endometriosis is uncommon and usually an incidental or retrospective finding on histopathology reports. It can be asymptomatic or present with a diverse range of persistent symptoms and even life‐threatening hemorrhage. The condition can be managed expectantly in asymptomatic patients, however persistent symptoms may warrant surgery. We encountered four cases of histologically proven cervical endometriosis at our tertiary hospital in New South Wales, Australia. All our patients had different symptoms, presentations and indications for their surgery leading to their diagnosis. This review is to report these cases followed by discussion with a review of the literature.
Combination chemotherapy for Hodgkin's lymphoma during pregnancy: Favorable outcome for mother and child
Authors: Sagan Dariusz , Semczuk Andrzej , Lampka Elżbieta
Published: July 2010

The incidence of malignant neoplasms in pregnant women is rising dramatically. The management of such cases poses unusual medical and ethical challenges, particularly in hematological malignancies, when potentially teratogenic chemotherapy is indicated. We report a case of stage IIA nodular sclerosis Hodgkin's lymphoma (HL), diagnosed in a 24‐year‐old woman at 18 weeks of gestation. Individualized combination chemotherapy according to etoposide‐vinblastine‐doxorubicin (EVA) regimen was administered, resulting in effective local control of the disease and improvement in the patient's general condition. At the 36th week of pregnancy, the patient delivered a healthy female infant by elective cesarian section. Four weeks later, bleomycin‐dacarbazine‐doxorubicin‐vinblastine (ABVD) chemotherapy was commenced, which provided complete remission after five cycles. Individualized chemotherapy for HL according to EVA regimen during the second and third trimesters of pregnancy, with early cesarian delivery, followed by ABVD regimen, provided a positive outcome both for the mother and her child. This strategy may be considered as an alternative for the treatment of HL in pregnancy, and deserves further clinical assessment.
Levonorgestrel‐intrauterine system effects on hemostasis and menstrual blood loss in women seeking contraception
Authors: Koh Stephen C. L. , Singh Kuldip
Published: July 2010

Aim:  The purpose of the study is to determine the effects of levonorgestrel use on hemostasis, and menstrual blood loss over 24 months in a cohort of women seeking contraception.

Methods:  Data from 30 women (median age 36 years) were analyzed. Samplings at pre‐insertion, 1 and 3 months for blood and additional endometrial aspirates at 2 and 6 months were performed. Systemic determination for hemoglobin, hematocrit, computerized thromboelastography, tissue‐type plasminogen activator, urokinase‐like plasminogen activator and receptor, plasminogen activator inhibitor‐1/2, D‐dimer and von Willebrand Factor was performed. In endometrial extracts, tissue‐type plasminogen activator, urokinase‐like plasminogen activator and receptor and plasminogen activator inhibitor‐1/2 were assayed. The Menstrual Blood Loss Pictorial Chart Score for measurement of menstrual blood loss was carried out for 24 months.

Results:  There were no significant changes in systemic hemostasis within 3 months of device use. In the endometrium, there was a significant increase in tissue‐type plasminogen activator antigen, plasminogen activator inhibitor‐1/2 and urokinase‐like plasminogen activator receptor levels from pre‐insertion state, with the highest level seen by 6 months. Amenorrhea was seen in 20% of women by 6 months and 50% by 24 months.

Conclusions:  Enhanced expression of plasminogen activator inhibitor‐1/2 in the presence of increased urokinase‐like plasminogen activator receptor and tissue‐type plasminogen activator antigen was seen in the endometrium. The effects on hemostasis appear to be localized in the endometrium. Systemic hemostasis was not duly affected and menstrual blood loss was reduced. No women in the study had a pregnancy or expulsion of the levonorgestrel‐intrauterine system device in the 24 months of the study period.
High prevalence of diabetes mellitus in patients with liver cirrhosis
Authors: Wlazlo N. , Beijers H. J. B. H. , Schoon E. J. , Sauerwein H. P. , Stehouwer C. D. A. , Bravenboer B.
Published: July 2010

Diabet. Med. 27, 1308–1311 (2010)

Aims  The reported prevalence of Type 2 diabetes mellitus in patients with liver cirrhosis is five times higher than in the general population. However, these data were never adjusted for classical risk factors for Type 2 diabetes. We therefore investigated the association between cirrhosis and Type 2 diabetes and adjusted for known risk factors for Type 2 diabetes.

Methods  We reviewed medical files for presence of Type 2 diabetes and potential confounders in 94 patients with cirrhosis (cases) and compared these with a control group of 107 patients with non‐ulcer dyspepsia. Multiple logistic regression analysis was used to adjust for potential confounders.

Results  The aetiology of our cirrhosis population was alcohol (59%), viral hepatitis (10%), biliary cirrhosis (3%) or cryptogenic (28%). Prevalence of Type 2 diabetes was significantly higher in patients with cirrhosis than in control subjects: 35/94 (37%) vs. 7/107 (7%) (OR 8.5, 95% CI 3.5–20.2, P < 0.001). After adjustment for age, sex, family history of Type 2 diabetes, alcohol use and BMI, cirrhosis remained significantly associated with Type 2 diabetes (OR 13.6, 95% CI 4.3–42.9, P < 0.001). Most cases of Type 2 diabetes were already diagnosed before diagnosis of cirrhosis (21/35, 60%) or were incidentally found together with cirrhosis (5/35, 14%).

Conclusions  Liver cirrhosis had a strong, independent association with Type 2 diabetes. Classical risk factors such as family history and BMI could not explain the high Type 2 diabetes prevalence in cirrhosis. Therefore, a liver‐derived factor might aggravate glucose intolerance and cause Type 2 diabetes in cirrhosis. In addition, Type 2 diabetes might also cause cirrhosis through liver steatosis and fibrosis.
Alcohol drinking, the metabolic syndrome and diabetes in a population with high mean alcohol consumption
Authors: Clerc O. , Nanchen D. , Cornuz J. , Marques‐Vidal P. , Gmel G. , Daeppen J.‐B. , Paccaud F. , Mooser V. , Waeber G. , Vollenweider P. , Rodondi N.
Published: July 2010

Diabet. Med. 27, 1241–1249 (2010)

Aims  To investigate the relationship of alcohol consumption with the metabolic syndrome and diabetes in a population‐based study with high mean alcohol consumption. Few data exist on these conditions in high‐risk drinkers.

Methods  In 6172 adults aged 35–75 years, alcohol consumption was categorized as 0, 1–6, 7–13, 14–20, 21–27, 28–34 and ≥ 35 drinks/week or as non‐drinkers (0), low‐risk (1–13), medium‐to‐high‐risk (14–34) and very‐high‐risk (≥ 35) drinkers. Alcohol consumption was objectively confirmed by biochemical tests. In multivariate analysis, we assessed the relationship of alcohol consumption with adjusted prevalence of the metabolic syndrome, diabetes and insulin resistance, determined with the homeostasis model assessment of insulin resistance (HOMA‐IR).

Results  Seventy‐three per cent of participants consumed alcohol, 16% were medium‐to‐high‐risk drinkers and 2% very‐high‐risk drinkers. In multivariate analysis, the prevalence of the metabolic syndrome, diabetes and mean HOMA‐IR decreased with low‐risk drinking and increased with high‐risk drinking. Adjusted prevalence of the metabolic syndrome was 24% in non‐drinkers, 19% in low‐risk (P < 0.001 vs. non‐drinkers), 20% in medium‐to‐high‐risk and 29% in very‐high‐risk drinkers (P = 0.005 vs. low‐risk). Adjusted prevalence of diabetes was 6.0% in non‐drinkers, 3.6% in low‐risk (P < 0.001 vs. non‐drinkers), 3.8% in medium‐to‐high‐risk and 6.7% in very‐high‐risk drinkers (P = 0.046 vs. low‐risk). Adjusted HOMA‐IR was 2.47 in non‐drinkers, 2.14 in low‐risk (P < 0.001 vs. non‐drinkers), 2.27 in medium‐to‐high‐risk and 2.53 in very‐high‐risk drinkers (P = 0.04 vs. low‐risk). These relationships did not differ according to beverage types.

Conclusions  Alcohol has a U‐shaped relationship with the metabolic syndrome, diabetes and HOMA‐IR, without differences between beverage types.
Gleaner, fisher, trader, processor: understanding gendered employment in fisheries and aquaculture
Authors: Weeratunge Nireka , Snyder Katherine A , Sze Choo Poh
Published: July 2010

Most research on gender difference or inequities in capture fisheries and aquaculture in Africa and the Asia‐Pacific focuses on the gender division of labour. Emerging research on globalization, market changes, poverty and trends in gendered employment within this sector reveals the need to move beyond this narrow perspective. If gleaning and post‐harvesting activities were enumerated, the fisheries and aquaculture sector might well turn out to be female sphere. A livelihoods approach better enables an understanding of how employment in this sector is embedded in other social, cultural, economic, political and ecological structures and processes that shape gender inequities and how these might be reduced. We focus on four thematic areas – markets and migration, capabilities and well‐being, networks and identities, governance and rights – as analytical entry points. These also provide a framework to identify research gaps and generate a comparative understanding of the impact of development processes and socioecological changes, including issues of climate change, adaptation and resilience, on gendered employment. Without an adequate analysis of gender, fisheries management and development policies may have negative effects on people’s livelihoods, well‐being and the environment they depend on, or fail altogether to achieve intended outcomes.
Role of low‐glycemic index diet in management of childhood obesity
Authors: Kong A. P. S. , Chan R. S. M. , Nelson E. A. S. , Chan J. C. N.
Published: July 2010

Conventional dietary recommendation for obesity management is a low‐fat energy‐restricted diet, which however, only have modest and non‐sustained effects on weight reduction. Alternative dietary interventions, including low‐glycemic index (GI) diet, have been proposed.

Glycemic index is a measure of blood glucose excursion per unit of carbohydrate. Foods with high GI are rapidly digested, absorbed and transformed into glucose. These processes cause accelerated and transient surges in blood glucose and insulin, earlier return of hunger sensation and excessive caloric intake. Conversely, low‐GI diet decreases blood glucose and insulin excursion, promotes greater fat oxidation, decreases lipogenesis and increases satiety. Modern food‐processing technology has produced many food products with high GI which may contribute to the burgeoning epidemic of obesity especially in children/adolescents.

Epidemiological and clinical trials suggest a role for low‐GI diet in the management of childhood obesity and associated cardio‐metabolic risks although results are not always consistent. In this article, we shall review the physiological basis and current evidence for and against low‐GI diet in obesity management, with particular focus in children and adolescents.
Communicating stereotype‐relevant information: How readily can people individuate?
Authors: Yeung Victoria Wai Lan , Kashima Yoshihisa
Published: July 2010

It is often suggested that people automatically form an impression of a target by using stereotypes. However, people can flexibly deploy different types of individuating processes, depending on the communicative context. We showed that people can individuate targets from their social category by communicating stereotype‐inconsistent information (person–group individuation) when they are required to reproduce information about the targets and people can individuate targets from other individuals by communicating information that is distinctive about the targets (person–person individuation) when required to identify the targets. The participants' performance is unrelated to information memorability (Experiment 1) and is not affected by time pressure (Experiment 2). Humans' adaptive capacity for individuation is discussed.
Voting Power and Shareholder Activism: A Study of Swedish Shareholder Meetings
Authors: Poulsen Thomas , Strand Therese , Thomsen Steen
Published: July 2010

Manuscript Type: Empirical

Research Question/Issue: This paper analyses the impact of voting power on shareholder activism using unique data on activism at Swedish shareholder meetings. We hypothesize that there is a positive relationship between shareholder activism and a measure of the largest shareholder's sensitivity to increased participation by small shareholders.

Research Findings/Insights: We find that firms' amenability to small shareholder influence leads to more proposals by the nomination committee, but fewer proposals by other shareholders and fewer proposals voted against. We interpret this as evidence that the shareholder elected nomination committees effectively channel shareholder concerns and preempt other kinds of activism. In addition, we find more shareholder activity in large firms and less activity in leveraged firms.

Theoretical/Academic Implications: This paper offers a new voting power approach to the study of shareholder activism. We show the empirical implications of this approach, but also the importance of local institutions such as nomination committees in shaping the nature of shareholder activism.

Practitioner/Policy Implications: Politicians and companies that desire active shareholders could improve the amenability of firms to shareholder influence by ownership transparency, shareholder committees, contacts with shareholder associations and other vehicles for collective action.
The Spatial Mobility of the ‘Creative Class’: A European Perspective
Authors: MARTIN‐BRELOT HELENE , GROSSETTI MICHEL , ECKERT DENIS , GRITSAI OLGA , KOVÁCS ZOLTÁN
Published: July 2010

The main aim of this article is to test Richard Florida's hypothesis regarding the spatial mobility of the ‘creative class’ and the role of soft factors in their decisions concerning their place of residence. Empirical data from 11 European cities suggest that the European ‘creative class’ is not as mobile as Florida suggests. Cultural and institutional constraints contribute to lower mobility rates in Europe. In the article the role of ‘personal trajectories’, completely disregarded until now, is highlighted. On the basis of empirical research data, the role of soft location factors in the decisions of creative workers does not seem to be as relevant as has been implied by Florida and others. These factors play only a marginal role in attracting members of the creative class to a city. On the other hand, they do indeed play an important role in retaining them once they have relocated. This provides some support for policies aimed at bringing about the type of conditions characteristic of creative cities.

L'article met à l'épreuve l'hypothèse de Richard Florida concernant la mobilité spatiale de la ‘classe créative’ et le rôle des facteurs intangibles (soft factors) dans le choix du lieu de résidence de ses membres. Des données empiriques collectées dans onze grandes villes d'Europe indiquent que la classe créative européenne n'est pas aussi mobile que Florida le suggère. Des contraintes culturelles et institutionnelles contribuent notamment à y abaisser les taux de mobilité. L'article souligne l'importance des ‘trajectoires personnelles’ jusqu'à présent totalement négligées. D'après les données de l'étude empirique, les facteurs d'implantation intangibles qui entrent dans les décisions des travailleurs créatifs ne sont apparemment pas aussi importants que ce que Florida et d'autres ont donnéà entendre. Ces facteurs ne jouent qu'un rôle marginal pour attirer les membres de la classe créative vers une ville. En revanche, ils présentent effectivement un grand intérêt dans la mesure où ils aident à les retenir une fois sur place. Cet aspect vient appuyer les politiques qui cherchent à réunir les conditions caractéristiques des villes créatives.
An INSIG2 Polymorphism Affects Glucose Homeostasis in Sardinian Obese Children and Adolescents
Authors: Zavattari Patrizia , Loche Alberto , Civolani Patrizia , Pilia Sabrina , Moi Loredana , Casini Maria Rosaria , Minerba Luigi , Loche Sandro
Published: July 2010

Allelic variants of a single nucleotide polymorphism (SNP), rs7566605, located approximately 10 kb upstream of the INSIG2 gene have been found in association with body weight and with other clinical features related to obesity in some populations but not in others. Our objective was to test the association of this SNP in obese children and adolescents from the genetically isolated population of Sardinia. We tested the association of rs7566605 with body mass index (BMI) and with serum glucose and insulin concentrations and a surrogate measure of insulin resistance (HOMA‐IR) in a cohort of 747 Sardinian obese children and adolescents. A case control analysis was performed using 548 ethnically‐matched healthy controls. Allelic frequencies of the SNP were similar between patients and controls. Mean glucose and insulin concentration and mean HOMA‐IR values were significantly higher in patients carrying the CC genotype than in the CG and GG carriers. In the patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), allele C was significantly more frequent than in controls. Although INSIG2 polymorphisms do not consistently associate with BMI, the observation of an association with glucose concentration would support a role for this gene in the metabolic complications of obesity.
Power of Genetic Association Studies with Fixed and Random Genotype Frequencies
Authors: Kozlitina Julia , Xing Chao , Pertsemlidis Alexander , Schucany William R.
Published: July 2010

When estimating the power of genetic association studies, the allele and genotype frequencies are often assumed to be known, and the numbers of individuals with each genotype are set equal to their expectations under Hardy‐Weinberg equilibrium. In fact, both allele and genotype frequencies are unknown and thus random. It has previously been suggested that ignoring uncertainty in these parameters could lead to inflated power expectations. To overcome the problem, one can average power estimates over the distributions of unknown frequencies. We investigate the power‐averaging method and find that, despite the intuitive appeal, it may not improve accuracy in practice, while significantly increasing computational time. For a fixed allele frequency, we show that the amount of overestimation diminishes rapidly with sample size and is completely negligible for N > 200. For an unknown frequency, the result of averaging depends on the genetic model, and may not always provide a more conservative estimate of power. We explore the effect of uncertainty in the factors that determine statistical power of association studies and propose a more economical approach to the power analysis.
Access to computerised analysis of intrapartum cardiotocographs improves clinicians’ prediction of newborn umbilical artery blood pH
Authors: Costa A , Santos C , Ayres‐de‐Campos D , Costa C , Bernardes J
Published: July 2010

Please cite this paper as: Costa A, Santos C, DAyres‐, de‐Campos, Costa C, Bernardes J. Access to computerised analysis of intrapartum cardiotocographs improves clinicians’ prediction of newborn umbilical artery blood pH. BJOG 2010;117:1288–1293.

Objective  To evaluate the impact of access to computerised cardiotocograph (CTG) analysis on reproducibility and accuracy of clinicians’ predictions of umbilical artery blood pH (UAB pH) and 5‐minute Apgar score.

Design  Prospective evaluation of pre‐recorded cases.

Setting  A tertiary‐care university hospital.

Population  From databases of intrapartum CTGs acquired in singleton term pregnancies, 204 tracings with low signal loss and short time interval to delivery were consecutively selected.

Methods  Tracings were randomly assigned to computer analysis by the Omniview‐SisPorto 3.5® system (study group n = 104) or to no analysis (control group n = 100). Three experienced clinicians evaluated all tracing printouts independently and were asked to predict the newborns’ UAB pH and 5‐minute Apgar scores from them.

Main outcome measures  Interobserver agreement (measured by the intraclass correlation coefficient [ICC]) and accuracy in prediction of neonatal outcomes with 95% CI.

Results  Agreement on prediction of UAB pH was significantly higher in the study group (ICC = 0.70; 95% CI 0.61–0.77) than in the control group (ICC = 0.43; 95% CI 0.21–0.60), and a trend towards better agreement was also seen in estimation of 5‐minute Apgar scores (ICC = 0.55; 95% CI 0.38–0.68 versus ICC = 0.43; 95% CI 0.25–0.57). Observers predicted UAB pH values correctly within a 0.10 margin in 70% of cases in the study group (95% CI 0.61–0.79) versus 46% in the control group (95% CI 0.35–0.56). They predicted 5‐minute Apgar scores within a margin of one in 81% of cases in the study group (95% CI 0.73–0.88) and in 70% of cases in the control group (95% CI 0.61–0.79).

Conclusions  Prediction of UAB pH is more reproducible and accurate when clinicians have access to computerised analysis of CTGs.
BIODIVERSITY RESEARCH: Current distribution and predicted geographic expansion of the Rufous‐backed Robin in Mexico: a fading endemism?
Authors: Martínez‐Morales Miguel Angel , Zuria Iriana , Chapa‐Vargas Leonardo , MacGregor‐Fors Ian , Ortega‐Álvarez Rubén , Romero‐Águila Edgar , Carbó Pilar
Published: July 2010

Aim The Rufous‐backed RobinTurdus rufopalliatusis a bird endemic to the Pacific slope of Mexico. The species recently established populations in several localities in the Mexican Central Highlands. Based on available data, we modelled the range expansion of the Rufous‐backed Robin in Mexico to understand the pattern, mechanisms and ecological and biogeographic implications of its expansion.

Location Mexico.

Methods We assessed the species’ presence and habitat requirements at two spatial scales. At the site level, we evaluated the relationship between land use and species presence in an urban environment. At the country level, we generated a niche model. We then produced a dispersion model through the interpolation of points generated from information derived from the niche model, the location of records within and outside its native distribution range, the species’ natural history, habitat requirements and its estimated dispersion rate (4.2 km year−1).

Results The dispersion model predicted that the species will significantly increase its distribution range in Mexico in the coming decades. Its expansion would occur by a stepping‐stone colonization of suitable habitat in areas of native vegetation and human settlements. The model predicted that the species should arrive on the Gulf slope of Mexico before 2025.

Main conclusions Mechanisms that could explain the species’ success in establishing viable populations outside its native distribution include its dispersion ability, competitive release, the urban heat island phenomenon and the trade of wild birds. The geographic range expansion of the Rufous‐backed Robin will probably create new interactions with other species, particularly with close taxonomic and ecological relatives. The increase in the distribution range of the Rufous‐backed Robin has resulted from direct and indirect human‐induced dispersion; therefore, it cannot be considered a fading endemism. In part of its expanded range (to date the Mexican Central Highlands), it should be considered an invasive alien species.
Use of the GTPγS ([35S]GTPγS and Eu‐GTPγS) binding assay for analysis of ligand potency and efficacy at G protein‐coupled receptors
Authors: Strange Philip G.
Published: July 2010

In this review I consider assays for G protein‐coupled receptor (GPCR) activity based on the binding of labelled analogues of GTPγS ([35S]GTPγS or Eu‐GTPγS) to G proteins in tissues (GTPγS binding assays). Such assays provide convenient measures of GPCR activity close to the receptor in the signalling cascade. In order to set up a GTPγS binding assay, the requirements of the assay must be considered. These are tissue source, GTPγS analogue, G protein, GDP, Mg2+/Na+ions, saponin, incubation time. The assay, once optimized, can be used to generate concentration/response curves for GPCRs signalling via Gi/oproteins (or to other G proteins with a modified assay) and actions of agonists, inverse agonists and antagonists may, in principle, be assessed. For agonists and inverse agonists, data for the maximal agonist effect, the concentration of ligand giving a half‐maximal response and the Hill coefficient may be derived. For antagonists, data for the equilibrium dissociation constant can be obtained. The mechanistic basis of the assay is considered. Although the assay can be used to profile ligands, under the conditions it is used, it may not be measuring the same event that determines GPCR action in cells.

LINKED ARTICLESThis article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visithttp://dx.doi.org/10.1111/bph.2010.161.issue‐6
Intracorporeal Partial Artificial Hearts: Initial Results in Ten Patients
Authors: Norman John C.
Published: July 2010

We have initiated clinical trials with an intracorporeal (abdominal) partial artificial heart during the past year. Ten pre‐terminal, post‐cardiotomy patients have been studied in strict compliance with institutional and federal protocols, including prior informed consent*† We have learned that emergency implantation and subsequent elective removal of the device is feasible. Its hemodynamic effectiveness over a wide range of left ventricular dysfunctions has been demonstrated. Substantial, reproducible, electrocardiographic, hemodynamic and angiographic evidence has been accumulated to support our hypothesis that the human left ventricle can recover from profound depression during prolonged ALVAD support and that an adherent, biocompatible, bioderived pseudo‐neointima develops on the textured surface of the pump within 24 hours following implantation. The device is six to ten times more effective than IABP pumping in man and has maintained systemic perfusion during clinical asystole and ventricular fibrillation. Although there have been no long‐term survivors, in two instances ventricular recovery was sufficient to allow removal of the device six to seven days after implantation. The ultimate causes of death were right ventricular failure and/or extracardiac multiple organ failure. The current limiting factors are overcoming varying degrees of institutional and/or physician reluctance in utilization of the device and earlier deployment prior to the onset of 1) hemorrhagic diatheses which preclude optimal postimplantation anticoagulation regimens (A.S.A., Persantin & Coumadin); 2) right heart failure which closely follows left heart failure; and 3) multiple organ failure which accompanies prolonged cardiopulmonary bypass and is exacerbated by overzealous pharmacologic support. The early results are encouraging; continued, cautious clinical trials seem indicated.
Engineering Aspects of ECMO Technology
Authors: Drinker Philip A. , Lehr John L.
Published: July 2010

The primary areas of extracorporeal membrane oxygenation (ECMO) technology with engineering components are: biomaterials, oxygenator design, ECMO physiology and total system design. The evolution of ECMO has been largely empirical, with many innovations introduced directly from clinical experience and observation. Major advances are needed in both materials and oxygenator design if current hematologic hazards are to be reduced. Optimization of ECMO systems has not been attempted in any systematic way because the basic physiology is not well enough understood to define the rationales for optimum control and management strategies. Once these strategies have been developed and tested, currently available automation technology can be applied to make the ECMO system simpler and safer for clinical use.
High Flux Hemofiltration
Authors: Bosch Juan P. , Geronemus Robert , Glabman Sheldon , Lysaght Michael , Kahn Thomas , von Albertini Beat
Published: July 2010

Experiments were performed using a new hollow fiber hemofilter. Ultrafiltration rates and whole blood urea clearances were measured in post‐dilution hemofiltration. High ultrafiltration rates were obtained with the new hemofilter. No adverse effects were detected despite filtration fractions above 45%. These experiments suggest that it is possible in post‐dilution hemofiltration to obtain small solute clearances comparable to those of hemodialysis without apparent deleterious effects.
Preparative Isolation of Middle Molecular Weight Fractions from the Hemofiltrate of Patients with Chronic Uremia
Authors: Brunner H. , Mann H. , Essers U. , Schultheis R. , Byrne T. , Heintz R.
Published: July 2010

Fractions in the molecular weight range of the so‐called middle molecules (500 ‐ 3000 daltons) were isolated on a preparative scale from hemofiltrate of patients. Hemofiltration was performed with an RP‐6 dialyzer using a predilution technique. The hemofiltrate was concentrated and desalinated by reverse osmosis with membranes with a nominal cut‐off of 500 daltons. The retentate was freeze‐dried, redissolved in volatile buffer and fractionated on Sephadex G‐15 macrocolumns. The middle molecule molecular weight range in the elution profiles (detected at 206 and 280 nm simultaneously) was marked with peptides. Isolated fractions in the middle molecule molecular weight range showed strong inhibitory activity upon 3H‐thymidine incorporation into rat bone‐marrow cells in vitro. The described combination of hemofiltration, reverse osmosis and gel chromatography is suggested as a useful approach to the isolation of these ninhydrin‐positive substances which, according to their proved heterogeneity, are to be subfractionated by further procedures.
Digoxin Removal from an Anephric Patient by Hemoperfusion over XAD‐4
Authors: Gibson Thomas P. , Nelson Howard A. , Ivanovich Peter
Published: July 2010

Removal of digoxin by hemoperfusion over Amberlite XAD‐4 was determined in a functionally anephric patient. During four hours of hemoperfusion, 50.45 μg of digoxin were removed by the column and serum digoxin concentrations decreased by 0.2 ng/ml after the post‐hemoperfusion reequilibration was complete.
Evolution of the Solenoid‐Actuated Left Ventricular Assist System: Integration with a Pusher‐Plate Pump for Intra‐Abdominal Implantation in the Calf
Authors: Portner Peer M. , Oyer Philip E. , Miller Phillip J. , Jassawalla Jal S. , Ream Allen K. , Corbin Steven D. , Skytte Kurt W.
Published: July 2010

The performance of an implantable left ventricular assist system (LVAS) utilizing a pulsed solenoid energy converter and a pusher‐plate blood pump has been characterized in vitro and in vivo. A microprocessor‐based electronic control system makes the LVAS completely self‐regulating over the range of operating conditions and provides considerable flexibility in various assist modalities.

Over forty thousand hours of in vitro and in vivo operating experience has been accumulated with current systems, and significant progress has been achieved in system durability and reliability. A new toggle latch has provided nearly a year of failure‐free operation on the bench, without measurable wear. Energy converter efficiencies of 50% have been demonstrated.

In vivo evaluation has been highlighted by an animal experiment still in progress after nearly four months of fault‐free, continuous synchronous pumping.
Removal of Endogenous Middle Molecules by Hemoperfusion
Authors: Asaba Hiroyuki , Bergstrom Jonas , Fürst Peter , Gunnarsson Bo , Neuhauser Monica , OulGst Raymond , Yahieltt Veronique
Published: July 2010

In four regular dialysis patients, the removal of uremic middle molecules was studied during a threehour hemoperfusion using a column containing 300 gm of activated carbon encapsulated with cellulose.

Middle molecules in plasma were determined by high‐speed gel filtration followed by gradient elution chromatography. Different adsorption characteristics were shown for the four middle molecule fractions measured. The initial clearances for middle molecule fractions were about 120 ml/min; clearances were 20–50 ml/min after two hours, and less than 25 ml/min, with release of some middle molecule fractions from the column, after three hours. The findings suggest that saturation of the column occurs after two to three hours of perfusion.

Thus, prolongation of the perfusion time beyond two hours appears to be of little benefit. The reduction of middle molecules in plasma by a three‐hour hemoperfusion was, in magnitude, similar to that obtained by three‐hour dialysis with a large surface area dialyzer or high‐flux membrane.
Multi‐Chambered Dialyzers and Their Efficiencies
Authors: Lee Kyu H. , Taylor John A.
Published: July 2010

The performance of a dialyzer at a given test condition is strongly affected by its design and flow patterns as well as other factors such as membrane permeability, membrane area and liquid‐side resistances.

Mathematical solutions that describe multichambered dialyzers in both countercurrent and cocurrent dialysis modes are given. In limiting cases, as the number of chambers approaches infinity, these solutions yield a simple equation which is essentially the solution to a cross‐flow dialyzer in which blood is unmixed and dialysate fluid is mixed. Currently, it is a rather tedious process to obtain a theoretical dialysance value for a cross‐flow dialyzer even though many such dialyzers are widely used. In reality, a dialyzer cannot achieve its theoretical performance level because actual flow patterns and flow distributions are not ideal. The effect of non‐ideality as a percentage of channeling of dialysate fluid was accounted for in the performance calculations of various types of dialyzers. The ideal single‐chambered dialyzer in the countercurrent mode has the highest theoretical performance. Its performance, however, decreases rapidly as the degree of the non‐ideality increases, while multi‐chambered dialyzers are relatively insensitive to deviation from the ideal condition.
Evaluation of the Impact of Ultrafiltration on Dialyzer Clearance
Authors: Weryński Andrzej
Published: July 2010

The influence of ultrafiltration on dialyzer clearance is analyzed. As the starting point for the analysis, the known theoretical and experimental expressions for clearance are utilized. The results obtained theoretically are verified with experimental data.

ultrafiltration, dialyzer clearance, diffusive clearance, transmittance coefficient
Liver Support Systems: A 1978 Perspective
Authors: Kulbe Klaus D.
Published: July 2010

The present status of support systems and devices for the injured liver is reviewed with emphasis on both long‐term and short‐term substitution. Longterm replacement can only be possible by the grafting or transplantation of a human and/or other primate liver. Most artificial systems may be applied for short‐term biological and technical substitution, e.g., by hemodialysis/hemoperfusion through adsorbents and resins. More sophisticated devices for detoxification of blood or cell‐free plasma in acute liver failure should combine the catalytic specificity of immobilized microsomal enzymes with the adsorptive capacity of activated charcoal, resins and affinity gels.
Regeneration of Dialysate
Authors: van Doorn Albert W. J.
Published: July 2010

Large amounts (250 liters) of dialysate fluid are needed for dialysis of patients with chronic kidney diseases. A reduction of these amounts is obtainable by regeneration. With the Redy® system, in which urea is decomposed by the enzyme urease, only 5.5 liters of dialysate is used. Other systems depending solely on sorption of urea still need excessive amounts of sorbents and no alternative, in the form of stable chemical binding, is available. If, therefore, further reduction of dialysate volume is desired, the problem of urea removal must be solved.
Prediction of Solute Transport During Peritoneal Dialysis
Authors: Hirszel Przemyslaw , Lasrich Mark , Maher J. Michael , Maher John F.
Published: July 2010

Solute transport, predominantly diffusion, across the peritoneum correlates inversely with molecular weight. Provided that the solute is water soluble, not protein bound, not of unusual density, not ionized, does not have a large hydration shell, and is transported from plasma to dialysate, the peritoneal clearance is predictable over the molecular weight range from 60 to 11, 000 daltons. Transport rates that deviate from the predicted can be explained by known physical properties of particular solutes.
Continuous Blood Pressure Monitoring During Hernodialysis
Authors: Agishi Tetsuzo , Kaneko Iwakazu , Kumagai Eiji , Ota Kazuo
Published: July 2010

As the number of patients suffering from circulatory problems increases, continuous blood pressure monitoring during hemodialysis is desirable. Monitoring of the fistulated venous pressure was proven to be a satisfactory substitute for that of the systemic arterial pressure, after fistulated venous pressure had been ascertained to correlate strictly with systemic arterial pressure.

Utilization of a double‐lumened cannula, one lumen for blood outflow and another for monitoring of fistulated venous pressure, was established and showed clinical applicability. This principle is considered to be useful not only for blood pressure monitoring, but also for activation of a dialysis machine control system.