bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial neural networks applied to mineral potential mapping for copper‐gold mineralizations in the Carajás Mineral Province, Brazil
Authors: Leite Emilson Pereira , De Souza Filho Carlos Roberto
Published: January 2009

Motivated by recent successful results of artificial neural network modelling in a variety of problems related to the geosciences, we have applied a radial basis functional link net to a regional‐scale mapping of the potential for Cu‐Au mineralizations in the Carajás Mineral Province, northern Brazil. To derive the input feature vectors, we have used geological and both radiometric and magnetic geophysical data. Ak‐fold cross‐validation method was employed in order to tune the parameters of the network and to select the best radial basis functional link net model amongst several others. Subsets of the available data set were used for training and validation and the estimated overall accuracy of the selected model is 91.7%. The plotting of a cumulative area versus favourability curve allowed us to define favourability zones of occurrences of Cu‐Au mineralizations and to assess the efficiency and the predictive power of the model. A binary map showing high and low favourability sectors was produced for the study area as an end product that can be used to guide and support more detailed exploration efforts. Our results show that 4.18% of the study area has an extremely high potential to contain Cu‐Au mineralizations, especially those of iron‐oxide Cu‐Au type, which are related to volcanic rocks and hydrothermal alteration.
Chronic mustard toxicity on the testis: a historical cohort study two decades after exposure
Authors: Amirzargar Mohammad Ali , Yavangi Mahnaz , Rahnavardi Mohammad , Jafari Mohammad , Mohseni Mohammadjavad
Published: January 2009

We aimed to assess the long‐term toxic effects of sulphur mustard (SM) on the testis and male fertility two decades after exposure. A historical cohort study was conducted in 2005. Sixty‐four SM‐exposed and 64 matched SM‐unexposed casualties of the Iraq–Iran conflict were enrolled. Fecundity status, semen indices, hormonal assay results and testis histopathology were evaluated. Male factor infertility was diagnosed in 23 and 5% of married exposed and unexposed casualties, respectively (p < 0.01). All semen indices declined over the 15 years since 1990 among the exposed group. Furthermore, all indices with the exception of sperm motility were significantly lower in the exposed than in unexposed men. The follicle‐stimulating hormone level was higher in the infertile than in fertile exposed men (p < 0.001). Testis histopathology of the azoospermic men showed complete absence of spermatogenesis with only Sertoli cells in the seminiferous tubules. SM can be gonadotoxic and its chronic toxicity may be permanent. Germ cells are probably the most susceptible gonadal cells to SM.
Acquired cryptorchidism is frequent in infancy and childhood
Authors: Wohlfahrt‐Veje Christine , Boisen Kirsten A. , Boas Malene , Damgaard Ida N. , Kai Claudia M. , Schmidt Ida M. , Chellakooty Marla , Suomi Anne‐Maarit , Toppari Jorma , Skakkebæk Niels E. , Main Katharina M.
Published: January 2009

Accurate prevalence data for acquired cryptorchidism are currently sparse and systematic prospective studies have not yet been reported. Our aim was to determine the prevalence of testicular ascent in childhood. In a prospective longitudinal population‐based child cohort from Copenhagen, Denmark (1997–2007), testicular position was examined according to a standardised protocol in a total of 1072 boys, at birth (n = 1051), at 3 months (n = 983), 18 months (n = 888), 36 months (n = 790) and again once between 4½ and 10 years of age (n = 509). Ascensus testis was defined as ascent of the testis into a cryptorchid position after normal scrotal position at birth. A congenital cryptorchid testis with spontaneous postnatal descent followed by recurrence of cryptorchidism was named recurrent cryptorchidism. Ascensus testis occurred in 0.2%, 0.6% and 0.6% of boys at 3, 18 and 36 months of age respectively. When including recurrent cryptorchidism the prevalence was 0.2%, 1.2% and 0.8% respectively. Ascensus testis accounts for 58% of all cases of cryptorchidism (congenital and acquired) at 18 months, 71% at 36 months and thereafter 69%. Ascensus testis accounts for more than half of cryptorchid testes seen in childhood and occurs in both previously scrotal and cryptorchid testes. We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age.
Divergent selection and heterogeneous genomic divergence
Authors: NOSIL PATRIK , FUNK DANIEL J. , ORTIZ‐BARRIENTOS DANIEL
Published: January 2009

Levels of genetic differentiation between populations can be highly variable across the genome, with divergent selection contributing to such heterogeneous genomic divergence. For example, loci under divergent selection and those tightly physically linked to them may exhibit stronger differentiation than neutral regions with weak or no linkage to such loci. Divergent selection can also increase genome‐wide neutral differentiation by reducing gene flow (e.g. by causing ecological speciation), thus promoting divergence via the stochastic effects of genetic drift. These consequences of divergent selection are being reported in recently accumulating studies that identify: (i) ‘outlier loci’ with higher levels of divergence than expected under neutrality, and (ii) a positive association between the degree of adaptive phenotypic divergence and levels of molecular genetic differentiation across population pairs [‘isolation by adaptation’ (IBA)]. The latter pattern arises because as adaptive divergence increases, gene flow is reduced (thereby promoting drift) and genetic hitchhiking increased. Here, we review and integrate these previously disconnected concepts and literatures. We find that studies generally report 5–10% of loci to be outliers. These selected regions were often dispersed across the genome, commonly exhibited replicated divergence across different population pairs, and could sometimes be associated with specific ecological variables. IBA was not infrequently observed, even at neutral loci putatively unlinked to those under divergent selection. Overall, we conclude that divergent selection makes diverse contributions to heterogeneous genomic divergence. Nonetheless, the number, size, and distribution of genomic regions affected by selection varied substantially among studies, leading us to discuss the potential role of divergent selection in the growth of regions of differentiation (i.e. genomic islands of divergence), a topic in need of future investigation.
Activated T cells Inhibit NK Cell‐mediated Tumour Rejection
Authors: Wang X.‐J. , Hu J. , Yuan J. , Peng Y.‐M. , Gui L. , He W.‐F. , Tan J. , Luo G.‐X. , Wu J.
Published: January 2009

Previous studies have described the regulation of some T‐cell subsets toward natural killer (NK) cells. Naturally occurring CD4+CD25+ T regulatory cells can inhibit NK cell cytotoxicity, while activated interleukin‐2 (IL‐2) secreting T cells can stimulate NK cells. However, little is known about the impact of the integrity T‐cell population on the final outcome of NK cell cytotoxicity. We thus examined the possible role of activated T cells in affecting NK cell cytotoxicity by mixed lymphocyte co‐cultures in vitro and a B16 melanoma tumour model in vivo. In our study, activated T cells were found to be able to significantly inhibit NK cell cytotoxicity in vitro and blunt NK cell‐mediated tumour rejection in vivo. The inhibition of NK cell function is a cell–cell contact dependent way. Results suggest that activated T cells may play an important role in limiting NK cell functions, which might be very significant for the design of biotherapy against tumour or infection in future.
How to prescribe antihistamines for chronic idiopathic urticaria: desloratadine daily vs PRN and quality of life
Authors: Grob J.‐J. , Auquier P. , Dreyfus I. , Ortonne J.‐P.
Published: January 2009

Background:  Chronic idiopathic urticaria (CIU) impairs quality of life (QoL). Currently, no consensus exists regarding how second‐generation H1‐antihistamines (proven to control CIU symptoms) should be taken long‐term: as daily treatment or only when symptoms return (PRN). We sought to determine which regimen improves or better maintains QoL in CIU: desloratadine (DL) daily or PRN.

Methods:  Subjects with CIU initially responding to DL 5 mg/day for 4 weeks were randomized for an additional 8 weeks, to DL 5 mg/day (arm 1: ‘continuous’, n = 46) or to DL only on days when urticarial wheals were present (arm 2: “PRN”, n = 60). To ensure blinding, treatment was presented in both arms as a combination of daily treatment (arm 1: DL; arm 2: placebo), plus a “rescue” tablet (arm 1: placebo; arm 2: DL) to be taken only in case of symptoms. The main outcome measure was QoL assessed by the VQ‐Dermato, a validated French QoL instrument, and the Dermatology Life Quality Index (DLQI).

Results:  At 4 and 8 weeks after randomization, subjects taking continuous DL showed statistically significant improvements in VQ‐Dermato Global Index score (P = 0.001 and P = 0.016, respectively) and dimension scores for daily living activity, mood state, and social functioning vs subjects taking DL PRN. Improvement in DLQI score at Week 4 was also significantly greater with continuous DL (P = 0.001).

Conclusion:  Continuous daily therapy with DL 5 mg is a better regimen than PRN treatment to maintain or improve QoL in subjects with CIU.
Allelic distribution and the effect of haplotype combination for HLA type II loci in the celiac disease population of the Valencian community (Spain)
Authors: Donat E. , Planelles D. , Capilla‐Villanueva A. , Montoro J. A. , Palau F. , Ribes‐Koninckx C.
Published: January 2009

The association between human leukocyte antigen (HLA) class II antigens and celiac disease (CD) was analyzed in a Spanish population. No association with DRB1*04 and DQB1*0302 was noted. The main associated haplotype (70.8%) was DRB1*03–DQB1*0201–DQA1*0501(DR3–DQ2), followed by DRB1*07–DQB1*0202–DQA1*0201 (DR7–DQ2) haplotype, which is associated with DRB1*11–DQB1*0301–DQA1*0505 (DR11–DQ7). The combinations of DR3–DQ2 with DR7–DQ2, and DR7–DQ2 with DR11–DQ7, present a twofold risk compared with each haplotype in homozygosis. An independence test in DR3‐DQ2 haplotype found that association with CD was attributable to the whole haplotype, but for DR7‐DQ2 was secondary to DQB1/DQA1. There is no need of a double gene dosage to increase the risk. CD‐associated alleles typing demonstrates a very high negative predictive value to exclude CD in risk groups.
Ethnic variation of the HLA‐G*0105N allele in two Chinese populations
Authors: Lin A. , Li M. , Xu D.‐P. , Zhang W.‐G. , Yan W.‐H
Published: January 2009

Unlike high polymorphic classical human leukocyte antigen (HLA) class I molecules, the genetic polymorphism of HLA‐G is very limited. However, the prevalence of HLA‐G alleles among different ethnic populations varied dramatically. The HLA‐G null allele (HLA‐G*0105N) is defined by a cytosine deletion (ΔC) at position 1597 in exon 3, which disrupts the reading frame and alters the expression of HLA‐G proteins. The HLA‐G*0105N allelic frequency was investigated in previous studies and possible roles were addressed. In the current study, a total of 310 Chinese Han and 260 Chinese She ethnic minority population had been genotyped for the G*0105N polymorphism. Marked difference was observed that the G*0105N allelic frequency in Chinese Han was 1.61%, while no copy of the null allele was observed in the Chinese She minority population (Pc = 0.0073). Data also revealed that no homozygote of HLA‐G*0105N allele exists in this Chinese Han population. Furthermore, significant difference was found for the frequencies of HLA‐G*0105N both in Chinese Han and in Chinese She populations when compared with other ethnic populations. Taken together, our results indicated that ethnic variation of the HLA‐G*0105N polymorphism among different ethnic populations is possibly the result of evolution. However, the advantages of the selection of this allele are necessary to be further investigated.
Identification of a novel HLA‐A allele, A*3120
Authors: Chang Y. , Pascual C. J. , Alonzo P. , Chamizo A.
Published: January 2009

A novel human leukocyte antigen (HLA)‐A allele, HLA‐A*3120, was first identified in a National Marrow Donor Program (NMDP) donor. The A*3120 allele resulted from a single nucleotide substitution (T to G) at codon 92 of exon 3 of A*310102. The substitution caused an amino acid change (serine to alanine). This novel allele was also seen in two other unrelated NMDP donors.
Eight novel MHC class I alleles identified in Chinese‐origin rhesus macaques
Authors: Ouyang D.‐Y. , Xu L.‐H. , Shi H.‐J. , Zheng Y.‐T. , He X.‐H.
Published: January 2009

We report here the identification of four Mamu‐A1 and four Mamu‐B novel alleles of Chinese‐origin rhesus macaques.
The profile of renal function over time in a cohort of pediatric heart transplant recipients
Authors: Bharat Winston , Manlhiot Cedric , McCrindle Brian W. , Pollock‐BarZiv Stacey , Dipchand Anne I.
Published: January 2009

Abstract: To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post‐transplantation, gender, and average calcineurin‐inhibitor dose for the first two months post‐transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth – 17.8). Median first GFR at 0.7 yr (0.1–4.1) post‐transplant was normal (94 mL/kg/1.73 m2). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post‐transplant. Females had better renal function early post‐transplant (GFR 105 mL/min/1.73 m2) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post‐transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 ± 26 mL/kg/1.73 m2. Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.
New‐onset post‐transplantation food allergy in children – Is it attributable only to the immunosuppressive protocol?
Authors: Levy Yael , Davidovits Miriam , Cleper Roxana , Shapiro Rivka
Published: January 2009

Abstract:  New‐onset post‐transplantation food allergy has been described mainly after liver transplantation, and its pathogenesis was attributed to the immunomodulatory effects of tacrolimus therapy. The aim of the present study was to evaluate the association of food allergy with solid organ transplantation in our center. The medical records of children who underwent kidney transplantation and children who underwent liver or liver and kidney transplantation from 1986 to 2005 were reviewed. A total of 189 children (124 after kidney transplantation, 65 after liver or liver and kidney transplantation) received tacrolimus as part of the immunosuppressive regimen. New‐onset post‐transplantation food allergy was documented in four of them: two with liver transplants and two with combined kidney and liver transplants. The absence of new‐onset food allergy in the children with isolated kidney transplants is compatible with other reports in the literature. This study supports the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is a main contributor to food allergy in this patient population.
Study of coagulation function in thawed apheresis plasma for photochemical treatment by amotosalen and UVA
Authors: De Valensart N. , Rapaille A. , Goossenaerts E. , Sondag‐Thull D. , Deneys V.
Published: January 2009

Background and Objectives  Photochemical treatment (PCT) based on amotosalen and ultraviolet A light (UVA) demonstrated a wide range of pathogen inactivation. However, coagulation proteins are affected by this treatment. The aim of this study was to evaluate the coagulation parameters in apheresis plasma units after thawing and processing by PCT.

Materials and Methods  Thirty apheresis plasma units were rapidly frozen at ≤ –30°C after collection. Plasma units were thawed after 7 days for PCT with amotosalen and UVA light. Treated apheresis units were refrozen and stored at ≤ –30°C for 1 month. Samples were collected for each plasma units at several times of process. Coagulation times (prothrombin time, activated partial thromboplastin time), coagulation factors (fibrinogen, Factor [F] II, FV, FVII, FVIII, FIX, FX, FXI), prothrombin fragments 1 and 2, antithrombotic proteins (protein C, protein S, antithrombin) and total protein content were measured. Functionality of ADAMTS‐13 was also tested.

Results  After thawing, coagulation times were slightly increased and a decrease of FV, FVIII and protein C activity was found. The mean recovery for all proteins, except one, ranged from 81% to 97% of the baseline activity in plasma units after thawing and PCT. FVIII was more affected with a mean recovery of 69 ± 8%. ADAMTS‐13 function was also preserved after the whole process. The effect of an additional 1‐month frozen storage on coagulation parameters was minimum.

Conclusion  Coagulation protein levels after thawing and processing of plasma by PCT with amotosalen and UVA were preserved well in the physiological ranges.
HEART DISEASE AND SOCIAL INEQUALITY: ETHICAL ISSUES IN THE AETIOLOGY, PREVENTION AND TREATMENT OF HEART DISEASE
Authors: BODDINGTON PAULA
Published: January 2009

Heart disease is a complex condition that is a leading cause of death worldwide. It is often seen as a disease of affluence, yet is strongly associated with a gradient in socio‐economic status. Its highly complex causality means that many different facets of social and economic life are implicated in its aetiology, including factors such as workplace hierarchy and agricultural policy, together with other well‐known factors such as what passes for individual ‘lifestyle’. The very untangling of causes for heart disease thus inevitably raises social, moral and political issues. These include the proper role of the individual and of larger social forces in its aetiology, prevention and treatment. The construction of risk factors for heart disease likewise is enmeshed with questions of distributive justice in the responsible targeting of those at risk for heart disease, a debate which has received much overt attention in the medical literature, but less attention within the ethical literature. Strategies for addressing a condition of such complex causality can be highly diverse, from pharmaceutical to social interventions, and value issues attach to the choice and presentation of such strategies. For example, prevention strategies may raise complex issues of responsibility and of judgements of what it is to ‘live well’. Further ethical debate on this highly political disease would be welcome.
JUSTICE, STIGMA, AND THE NEW EPIDEMIOLOGY OF HEALTH DISPARITIES
Authors: COURTWRIGHT ANDREW M.
Published: January 2009

Recent research in epidemiology has identified a number of factors beyond access to medical care that contribute to health disparities. Among the so‐called socioeconomic determinants of health are income, education, and the distribution of social capital. One factor that has been overlooked in this discussion is the effect that stigmatization can have on health. In this paper, I identify two ways that social stigma can create health disparities: directly by impacting health‐care seeking behaviour and indirectly through the internalization of negative interpersonal judgments. I then argue that social arrangements that foster self‐respect can reduce the impact of stigmatization on health disparities. I conclude by showing how John Rawls' conception of justice can be used to address the intersection of stigma, health, and self‐respect, in contrast to critics of his position, who have seen him as excessively focused on the allocation of material goods.
HEALTH AS FREEDOM: ADDRESSING SOCIAL DETERMINANTS OF GLOBAL HEALTH INEQUITIES THROUGH THE HUMAN RIGHT TO DEVELOPMENT
Authors: FOX ASHLEY M. , MEIER BENJAMIN MASON
Published: January 2009

In spite of vast global improvements in living standards, health, and well‐being, the persistence of absolute poverty and its attendant maladies remains an unsettling fact of life for billions around the world and constitutes the primary cause for the failure of developing states to improve the health of their peoples. While economic development in developing countries is necessary to provide for underlying determinants of health – most prominently, poverty reduction and the building of comprehensive primary health systems – inequalities in power within the international economic order and the spread of neoliberal development policy limit the ability of developing states to develop economically and realize public goods for health. With neoliberal development policies impacting entire societies, the collective right to development, as compared with an individual rights‐based approach to development, offers a framework by which to restructure this system to realize social determinants of health. The right to development, working through a vector of rights, can address social determinants of health, obligating states and the international community to support public health systems while reducing inequities in health through poverty‐reducing economic growth. At an international level, where the ability of states to develop economically and to realize public goods through public health systems is constrained by international financial institutions, the implementation of the right to development enables a restructuring of international institutions and foreign‐aid programs, allowing states to enter development debates with a right to cooperation from other states, not simply a cry for charity.
Pre‐adolescents’ Peer‐relational Schemas and Social Goals across Relational Contexts
Authors: Salmivalli Christina , Peets Kätlin
Published: January 2009

Current theorists stress the context‐specificity of social behaviors and social cognitions. Although researchers have started to investigate the relationship as one context that might influence social cognitions, relatively little is known about the influence of relational context on the social goals endorsed by children and adolescents. The current study tested the hypothesis that pre‐adolescents’ goals would vary between individuals as well as across relational contexts, and examined factors that might explain such variation. Participants (N = 102, 11–12 years) filled in questionnaires regarding their social goals and self‐ and peer‐perceptions when around each same‐sex classmate. Both goals and perceptions displayed significant variation between individuals, as well as between different relationship contexts. The goals pre‐adolescents pursued in different relationships were partly explained by varying perceptions of self and of the relationship partner in each relational context, as well as by the affective nature of the relationship. After accounting for the relationship‐specific variation, few associations were significant at the individual level. The results highlight the importance of studying contextual variance in social goals and social cognitions in general.
Are the Competent the Morally Good? Perspective Taking and Moral Motivation of Children Involved in Bullying
Authors: Gasser Luciano , Keller Monika
Published: January 2009

The present study tested the hypothesis of the cognitively competent but morally insensitive bully. On the basis of teacher and peer ratings, 212 young elementary school children were selected and categorized as bullies, bully–victims, victims, and prosocial children. Children's perspective‐taking skills were assessed using theory‐of‐mind tasks, and moral motivation was assessed with a task about moral emotion attributions after moral rule transgressions. Analyses at the group level revealed that only bully–victims, but not bullies, were characterized by a deficit in perspective taking, while both aggressive groups showed a deficit in moral motivation. Analyses at the individual level, however, revealed that bullies were a more heterogeneous group, including children with an asymmetry between perspective taking and moral motivation, as well as children scoring consistently low or high on both measures. The findings highlight the importance of distinguishing between (1) strategic social–cognitive and moral competencies and (2) different subgroups of bullies.
Relations of Parent–Youth Interactive Exchanges to Adolescent Socioemotional Development
Authors: Hutt Rachel L. , Wang Qi , Evans Gary W.
Published: January 2009

This study examined the relations of parent–youth agreement and disagreement during a joint problem‐solving task and multi‐methodological indices of socioemotional outcomes in adolescents (mean age = 13). One hundred and sixty‐seven parents and their adolescent children participated. Each parent–youth pair played the interactive game ‘Jenga’, and their interactions were analyzed for frequency of elaborations (agreement during three or more conversational turns) and negotiations (disagreement during three or more conversational turns). Elaborations during parent–youth interactions were related to less negative classroom behavior, better self‐regulation, and more task persistence in youth. Findings are discussed in light of the importance of parent–youth interaction and youth autonomy in adolescent socioemotional development.
A MINOR MATTER? THE FRANCISCAN THESIS AND PHILOSOPHICAL THEOLOGY1
Authors: DILLARD PETER S.
Published: January 2009

The Franciscan thesis maintains that the primary motive of the Incarnation is to glorify the triune God in the person of Jesus Christ: though Christ atones for human sins, his coming isn't relative to our need for redemption but rather has an absolute primacy. The Franciscan thesis is sometimes associated with the counterfactual claim that Christ would have come even if humans hadn't sinned. In recent work on the Franciscan thesis, an attempt is made to prove the counterfactual claim on the basis of a purely logical argument drawn from the writings of Bl. John Duns Scotus. After showing that this proof fails, I construct an axiological argument for the Franciscan thesis that disentangles it from unsubstantiated counterfactual claims while respecting the subtle interplay between natural and revealed theology. I then provide a metaphysical interpretation of the axiological argument that builds upon Scotist notions. Seen through this interpretive lens, Scotus's logical argument can be understood not as attempting to prove a counterfactual claim but as articulating Scotus's vision of what is required of any created order that is radically contingent on God's will yet perfectly glorifies its Creator. Thus understood, the Franciscan thesis challenges a powerful and influential picture in philosophical theology.
Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies
Authors: Hanes Jozef , Zilka Norbert , Bartkova Miriam , Caletkova Miroslava , Dobrota Dusan , Novak Michal
Published: January 2009

Human brain encompasses six tau isoforms, containing either three (3R) or four (4R) repeat domains, all of which participate in the pathogenesis of human tauopathies. To investigate the role of tau protein in the disease, transgenic rat models have been created. However, unlike humans, it has been suggested that rat brain expresses only three 4R tau isoforms. Because of the significance of the number of tau isoforms for faithful reproducibility of neurofibrillary pathology in transgenic rat models, we reopened this issue. Surprisingly, our results showed that adult rat brain contains six tau isoforms like humans. Protein expression of 4R tau isoforms was ninefold higher than 3R isoforms. Furthermore, the protein levels of tau isoforms with none, one or two N‐terminal inserts were 30%, 35%, and 35% of total tau, respectively. Moreover, amount and ratio of tau isoforms were developmentally regulated. The levels of 4R tau isoforms progressively increased from early postnatal period until adulthood, whereas the expression of 3R tau isoforms reached maximum at P10 and then gradually declined. Our results show that rat brain encompasses full tau proteome similar to humans. These findings support the use of rat as an animal model in human tauopathies research.
The development of a model for the investigation of stresses in the cement layer underlying a tibial plateau
Authors: Little E. G. , Daly G. , Dawson M. , Kelly P.
Published: January 2009

Tibial component loosening is a major problem associated with knee prostheses. Tensile stresses in the brittle cement immediately below the tibial plateau are likely to influence loosening. To establish the stresses at selected sites in the cement layer, a large model of a tibial plateau, underlying cement and bone was constructed and three dimensional strain rosettes were embedded into it. The mechanical properties of the model materials were evaluated and compared with properties of an actual knee. The construction of the model is described and different methods for embedding the three dimensional strain rosettes into the cement are evaluated.
F 15845 inhibits persistent sodium current in the heart and prevents angina in animal models
Authors: Vacher B , Pignier C , Létienne R , Verscheure Y , Le Grand B
Published: January 2009

Background and purpose:  Activation of the persistent sodium current in ischaemic myocardium results in calcium overload which is toxic for the cardiomyocyte. Thus, the activity of 3‐(R)‐[3‐(2‐methoxyphenylthio‐2‐(S)‐methylpropyl]amino‐3,4‐dihydro‐2H‐1,5 benzoxathiepine bromhydrate (F 15845), a new selective persistent sodium current blocker, in protecting against the effects of cardiac ischaemia was examined, in both in vitro and in vivo models.

Experimental approach:  Electrophysiological studies using patch‐clamp and conventional microlelectrode techniques, isolated perfused hearts and models of angina in anaesthetized animals were used to assess the protection afforded by F 15845 against ischaemia‐induced changes.

Key results:  F 15845 reduced the persistent sodium current activated by veratridine (IC50 1.58 × 10−6 mol·L−1). F 15845 blocked voltage‐gated human cardiac sodium channels in a novel, voltage‐dependent manner, selectively affecting steady‐state inactivation. F 15845 did not affect action potential shape and basal function of guinea pig isolated perfused hearts but did reduce ischaemia‐induced diastolic contracture in this model (IC50 0.64 × 10−6 mol·L−1). In rabbits, F 15845 given i.v. (ED50 0.05 mg·kg−1) or orally (ED50 0.13 mg·kg−1) dose‐dependently and powerfully inhibited regional myocardial ischaemia‐induced ST segment elevation in the absence of haemodynamic effects, implying direct cardiac activity. In dogs, F 15845 dose‐dependently inhibited epicardial ST segment changes (70 ± 8% at 0.63 mg·kg−1) in an experimental angina model of demand ischaemia, again without haemodynamic effects, confirming a direct anti‐anginal activity.

Conclusions and implications:  F 15845 is a selective, potent blocker of the persistent sodium current, generated by the human Nav1.5 channel isoforms, and prevents cardiac angina in animal models.
Persistent (current) in the face of adversity … A new class of cardiac anti‐ischaemic compounds on the horizon?
Authors: Saint David A
Published: January 2009

Although a persistent component of the sodium current (INaP) was described in cardiac tissue about three decades ago, its physiological role and potential as a therapeutic target was not immediately apparent. Subsequent demonstrations that INaP is enhanced by hypoxia and ischaemia, and that Na+ influx via INaP may contribute to cellular damage, diastolic dysfunction and arrhythmias during ischaemia and reperfusion, raised interest in INaP as a target for anti‐ischaemic drugs. Several agents have now been developed to clinical stages, which have INaP block as either their main action, or as a useful co‐effect. In this issue of the British Journal of Pharmacology, Vacher et al. report the anti‐ischaemic actions of F15845, which appears to exhibit the most selective block of INaP yet described. Its efficacy in animal models of angina raises the prospect of new, specific, INaP blockers that may represent a largely unexploited opportunity for a new class of anti‐ischaemic compounds.
Marginal formations of the last Kara and Barents ice sheets in northern European Russia
Authors: ASTAKHOV VALERY I. , SVENDSEN JOHN INGE , MATIOUCHKOV ALEXEI , MANGERUD JAN , MASLENIKOVA OLGA , TVERANGRE JAN
Published: January 2009

Glacial landforms in northern Russia, from the Timan Ridge in the west to the east of the Urals, have been mapped by aerial photographs and satellite images supported by field observations. An east‐west trending belt of fresh hummock‐and‐lake glaciokarst landscapes has been traced to the north of 67°N. The southern boundary of these landscapes is called the Markhida Line, which is interpreted as a nearly synchronous limit of the last ice sheet that affected this region. The hummocky landscapes are subdivided into three types according to the stage of postglacial modification: Markhida, Harbei and Halmer. The Halmer landscape on the Uralian piedmont in the east is the freshest, whereas the westernmost Markhida landscape is more eroded. The west‐ east gradient in morphology is considered to be a result of the time‐transgressive melting of stagnant glacier ice and of the underlying permafrost. The pattern of ice‐pushed ridges and other directional features reflects a dominant ice flow direction from the Kara Sea shelf. Traces of ice movement from the central Barents Sea are only discernible in the Pechora River left bank area west of 50°E. In the Polar Urals the horseshoe‐shaped end moraines at altitudes of up to 560 m a.s.l. reflect ice movement up‐valley from the Kara Ice Sheet, indicating the absence of a contemporaneous ice dome in the mountains. The Markhida moraines, superimposed onto the Eemian strata, represent the maximum ice sheet extent in the western part of the Pechora Basin during the Weichselian. The Markhida Line truncates the huge arcs of the Laya‐Adzva and Rogovaya ice‐pushed ridges protruding to the south. The latter moraines therefore reflect an older ice advance, probably also of Weichselian age. Still farther south, fluvially dissected morainic plateaus without lakes are of pre‐Eemian age, because they plunge northwards under marine Eemian sediments. Shorelines of the large ice‐dammed Lake Komi, identified between 90 and 110 m a.s.l. in the areas south of the Markhida Line, are radiocarbon dated to be older than 45 ka. The shorelines, incised into the Laya‐Adzva moraines, morphologically interfinger with the Markhida moraines, indicating that the last ice advance onto the Russian mainland reached the Markhida Line during the Middle or Early Weichselian, before 45 ka ago.
Postglacial emergence and Late Quaternary glaciation on northern Novaya Zemlya, Arctic Russia
Authors: FORMAN STEVEN L. , LUBINSKI DAVID J. , ZEEBERG JACOBUS J. , POLYAK LEONID , MILLER GIFFORD H. , MATISHOV GENNADY , TARASOV GENNADY
Published: January 2009

Recent observations on postglacial emergence and past glacier extent for one of the least accessible areas in the Arctic, northern Novaya Zemlya are here united. The postglacial marine limit formed 5 to 6 ka is registered on the east and west coasts of the north island at 10 ± 1 and 18 ± 2 m aht, respectively. This modest and late isostatic response along with deglacial ages of >9.2 ka on adjacent marine cores from the northern Barents Sea indicate either early (>13 ka) deglaciation or modest ice sheet loading (<1500 m thick ice sheet) of Novaya Zemlya. Older and higher (up to 50 m aht) raised beaches were identified beneath a discontinuous glacial drift. Shells from the drift and underlying sublittoral sediments yield minimum limiting 14C ages of 26 to 30 ka on an earlier deglacial event(s). The only moraines identified are within 4 km of present glacier margins and reflect at least three neoglacial advances in the past 2.4 ka.
Isolation basin stratigraphy and Holocene relative sea‐level change at the Norwegian—Russian border north of Nikel, northwest Russia
Authors: CORNER GEOFFREY D. , YEVZEROV VLADIMIR Y. , KOLKA VASILI V. , MØLLER JAKOB J.
Published: January 2009

The marine‐lacustrine transition (isolation contact) in sediment cores from eight lake basins situated 13.5–72 m a.s.l., in the Norwegian‐Russian border area north of Nikel, northwest Russia, was identified based on lithological and diatom analysis, radiocarbon dated, and used to construct a relative sea‐level (RSL) curve for the Holocene. All the lakes except one (interpreted as having an unconformable slumped transition) show a regressive I‐II‐III (marine‐transitional‐lacustrine) facies succession, indicating a postglacial history of continuous emergence. The RSL curve shows rapid emergence between 10 000 and 8000 BP, very slow emergence between 7000 and 5000 BP, increased rate of emergence between 4500 and 4000 BP, and a moderate rate of emergence after 3500 BP. The low rate of emergence around 6000 BP correlates with the Tapes transgression of more coastal regions, but corresponding sea level, at 25–26 ma. present s.l., lies 5–10 m lower than the elevation predicted based on existing isobase maps for the region. The discrepancy suggests a need for further work in order to more rigorously define and map the Tapes transgression and associated shoreline complex in the northern Fennoscandian‐Kola region.
Lithological and biochemical properties in sediments of Lama Lake as indicators for the late Pleistocene and Holocene ecosystem development of the southern Taymyr Peninsula, Central Siberia
Authors: HARWART STEFANIE , HAGEDORN BIRGIT , MELLES MARTIN , WAND ULRICH
Published: January 2009

In order to evaluate the sensitivity of aquatic and terrestrial ecosystems to climatic changes, lithological (sediment structure and color, grain size, physical properties) and biochemical (TOC, TOC/TN, δ13C of TOC and carbonates) investigations were carried out on an 11.12 m‐long sediment core from Lama Lake (Central Siberia, Putorana Plateau). According to the pollen data, the sequence represents the termination of the Pleistocene, and the entire Holocene. It is composed of highly terrigenous and stratified clays and silts. Sediment structure, grain‐size distribution, carbonate contents and physical properties of the sediment indicate that glaciers were present in the catchment area of Lama Lake during the period Oldest Dryas to AllerØd. For the same time period, δ13C values of TOC give indications of a perennial ice cover. Since the AllerØd, organic matter accumulation has increased, caused by an increasing input of land vegetation and aquatic primary production as revealed by relations TOC contents, TOC/TN ratios and δ13C values of TOC. During the Holocene climatic optimum, in late Preboreal and Boreal times, biogenic primary production in Lama Lake reached its maximum and the vegetation in the catchment area changed from grassy tundra to a dense forest. From the Atlantic period to the present, small variations in δ13C values of TOC and TOC contents are probably related to the location of Lama Lake on the border between grass and wooded steppe, leading to responses of environmental conditions to even small changes in climate.
Soil and Fertilizer Amendments and Edge Effects on the Floral Succession of Pulverized Fuel Ash
Authors: Shaw Peter
Published: January 2009

Plots of fresh pulverized fuel ash (PFA, an industrial waste) were inoculated with soils from existing PFA sites and fertilizers in a factorial design, then left unmanaged for 12 years during which time the floral development and soil chemistry were monitored annually. For the first 3 years, the site supported a sparse mix of chenopods (including the scarceChenopodium glaucum) and halophytes. As salinity declined, ruderals, legumes, and grasses plus the fire‐site mossFunaria hygrometricacolonized, followed byFestuca arundinaceagrassland (NVC community MG12) andHippophae rhamnoidesscrub.Dactylorhiza incarnata(orchidacea) appeared after 7 years, but only in plots that had received soil from existing orchid colonies. Four years later, a larger second generation ofDactylorhizaappeared, but only in the central zone of the site where vegetation was thinnest. By year 12, the site was dominated by coarse grasses and scrub, with early successional species persisting only in the sparsely vegetated center, where nitrate levels were lowest. This edge effect is interpreted as centripetal encroachment, a process of potentially wider concern for the conservation of low‐fertility habitat patches. Overall, seed bank inoculation seems to have introduced few but desirable species (D. incarnata,Pyrola rotundifolia, some halophytes, and annuals), whereas initial application of organic fertilizer had long‐lasting (≥10 years) effects on cover and soil composition.
Using Structured Decision Making to Help Implement a Precautionary Approach to Endangered Species Management
Authors: Gregory Robin , Long Graham
Published: January 2009

Endangered species protection is a significant risk management concern throughout North America. An extensive conceptual literature emphasizes the role to be played by precautionary approaches. Risk managers, typically working in concert with concerned stakeholders, frequently cite the concept as key to their efforts to prevent extinctions. Little has been done, however, to evaluate the multidimensional impacts of precautionary frameworks or to assist in the examination of competing precautionary risk management options as part of an applied risk management decision framework. In this article we describe how decision‐aiding techniques can assist in the creation and analysis of alternative precautionary strategies, using the example of a multistakeholder committee charged with protection of endangered Cultus Lake salmon on the Canadian west coast. Although managers were required to adopt a precautionary approach, little attention had been given to how quantitative analyses could be used to help define the concept or to how a precautionary approach might be implemented in the face of difficult economic, social, and biological tradeoffs. We briefly review key steps in a structured decision‐making (SDM) process and discuss how this approach was implemented to help bound the management problem, define objectives and performance measures, develop management alternatives, and evaluate their consequences. We highlight the role of strategy tables, employed to help participants identify, alternative management options. We close by noting areas of agreement and disagreement among participants and discuss the implications of decision‐focused processes for other precautionary resource management efforts.
Regulatory Models and the Environment: Practice, Pitfalls, and Prospects
Authors: Holmes K. John , Graham Judith A. , McKone Thomas , Whipple Chris
Published: January 2009

Computational models support environmental regulatory activities by providing the regulator an ability to evaluate available knowledge, assess alternative regulations, and provide a framework to assess compliance. But all models face inherent uncertainties because human and natural systems are always more complex and heterogeneous than can be captured in a model. Here, we provide a summary discussion of the activities, findings, and recommendations of the National Research Council's Committee on Regulatory Environmental Models, a committee funded by the U.S. Environmental Protection Agency to provide guidance on the use of computational models in the regulatory process. Modeling is a difficult enterprise even outside the potentially adversarial regulatory environment. The demands grow when the regulatory requirements for accountability, transparency, public accessibility, and technical rigor are added to the challenges. Moreover, models cannot be validated (declared true) but instead should be evaluated with regard to their suitability as tools to address a specific question. The committee concluded that these characteristics make evaluation of a regulatory model more complex than simply comparing measurement data with model results. The evaluation also must balance the need for a model to be accurate with the need for a model to be reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs requires model evaluation to be applied over the “life cycle” of a regulatory model with an approach that includes different forms of peer review, uncertainty analysis, and extrapolation methods than those for nonregulatory models.
An Integrated Methodology for Assessment and Selection of the Project Risk Response Actions
Authors: Seyedhoseini Seyed Mohammad , Noori Siamak , Hatefi Mohammad Ali
Published: January 2009

In a systematic process of project risk management, after risk assessment is implemented, the risk analysts encounter the phase of assessment and selection of the project risk response actions (RA). As indicated by many researchers, there are less systematic and well‐developed solutions in the area of risk response assessment and selection. The present article introduces a methodology including a modeling approach with the objective of selecting a set of RA that minimizes the undesirable deviation from achieving the project scope. The developed objective function comprises the three key success criteria of a project, namely, time, quality, and cost. Our model integrates overall project management into the project risk response planning (P2RP). Furthermore, the proposed model stresses on an equivalent importance for both “risk” and “response.” We believe that applying the proposed model helps the project risk analyst in most effective and efficient manner dealing with his or her complicated RA selection problems. The application of the proposed model was implemented in projects in the construction industry in which it showed tremendous time, cost, and quality improvements.
Parallel Solution‐Based Synthesis Approach for Search of Lanthanoid‐Activated Ca2SnO4 Phosphor Materials
Authors: Suzuki Yoshihito , Kakihana Masato
Published: January 2009

In the search for new fluorescent materials among lanthanoid‐activated Ca2SnO4 compounds, a parallel solution‐based synthesis approach was applied and a new blue‐emission Ca2SnO4:Ce phosphor was discovered; its emission intensity reaches 80% of the intensity of one of the best commercial Y3Al5O12:Ce3+ phosphors. Among 14 lanthanoid‐activated materials, three categories could be distinguished with respect to the effect of the dopant ion on the excitation and emission properties of the phosphor. In addition, potential phosphors in the A–Sn–O (A=Mg, Ca, Sr, and Ba) systems were investigated and Ca2SnO4 was found to be the most suitable host compound for the lanthanoid‐activated phosphors.