bluuebunny/crossref_metadata_2025 huggingface dataset:
Spain's Transition to New Risks: A Farewell to ‘Superwomen’
Authors: Moreno Luis
Published: March 2005

Mediterranean welfare states, of which Spain is a major example, have traditionally relied on family support and in particular on the unwaged work of women to provide child and elder care and to support members who have a weak labour market position. During the 1980s and 1990s, social spending has increased and the regional system has played an important role in driving reform and welfare state expansion. However, greater labour market flexibility and demands on women to work have placed even more stress on the family system.
Diadochus of Photice
Authors: Plested Marcus
Published: March 2005

The work of Diadochus of Photice emerges as a profound synthesis of the Evagrian and (especially) Macarian legacies. Diadochus indubitably draws on Macarius for some of the key elements of his teaching, not least his anti-Messalian critique. Like Mark, he also ‘corrects’ Macarius on a number of key points, e.g. the coexistence of sin and grace in the intellect of the baptized – something Diadochus held to risk implying the deficiency of baptismal grace.
The Asceticon of Abba Isaiah
Authors: Plested Marcus
Published: March 2005

The Asceticon of Abba Isaiah is an intriguing work in that it contains works of Macarius in both the Greek and Syriac manuscript traditions. The Isaian material proper also contains clear signs of Macarian influence, although these are rarely very profound and tend to be located in a second redactional layer.
Introduction
Authors: Gavrilyuk Paul L.
Published: March 2005

Many modern theologians advocate the claim that God suffers and are convinced that divine impassibility is untenable on philosophical, exegetical, and broadly religious grounds. As a result, the scholars often interpret the patristic notion of divine apatheia as a Greek philosophical axiom the acceptance of which led to a distortion of the biblical image of the (allegedly) suffering God. This dominant interpretation is flawed. The problems with the unrestricted divine passibility are equally serious. Passibility and impassibility are correlative concepts, both of which must have their place in any sound account of divine agency. The introduction also provides a summary of the book.
1 The Case Against the Theory of Theology's Fall into Hellenistic Philosophy
Authors: Gavrilyuk Paul L.
Published: March 2005

The standard modern approach to the patristic idea of the divine (im)passibility is to draw a sharp distinction between the unemotional and uninvolved God of the Greek philosophers and the passionate God of the Bible. The allegedly biblical vision of an emotional and suffering God is then taken as a norm by which the whole development of patristic theology is judged. The verdict is that on the whole, patristic theology was a departure from this vision. The author argues that this approach, the attraction of its simplicity notwithstanding, is fundamentally flawed and misleading both with regard to the opinions of the philosophers and with regard to the biblical material.
3 Docetism Resisted: Christ's Suffering is Real
Authors: Gavrilyuk Paul L.
Published: March 2005

The christological hymns and creedal statements of the first three centuries are characterized by a tension between Christ’s divine status and his subjection to human suffering. The Docetic attempt to remove this tension was systematically opposed by the church. The reality of Christ’s suffering was especially emphasized in theological reflections upon the experience of martyrdom.
The Structure of Social Provision
Authors: Castles Francis G.
Published: March 2005

Seeks to use disaggregated measures of social expenditure derived from the OECD Social Expenditure Database (SOCX) to measure the extent of recent change in the structure of social provision and to identify types and trajectories of welfare state development. The account shows that change in welfare spending priorities in OECD countries has been much more modest than is commonly thought. It also demonstrates that disaggregated expenditure measures can be used to generate a typology of provision that closely mirrors Esping–Andersen’s three regimes model, but in a way that permits more precise measurement of regime change over time.
Population Ageing and the Public Purse
Authors: Castles Francis G.
Published: March 2005

Examines the supposed threat to the future trajectory of social spending posed by population ageing. An initial focus is on the contrast between the sense of crisis characterizing popular and governmental accounts with the more measured analysis of demographers and economists. Later sections examine a variety of welfare state programmes for the old and show that expenditure trajectories are only marginallyinfluenced by demographic considerations, but that what really influences expenditure outcomes is the differential generosity of pension provision in different families of nations. Differential generosity is also shown to be a further factor influencing aggregate patterns of social expenditure.
Demonstratives, Pure Indexicals, and Essential Indexicals
Authors: Corazza Eros
Published: March 2005

Concentrates on indexical reference and discusses the distinction between pure indexicals and essential indexicals. It is shown how indexical thoughts are perspectival. In focusing ‘now’ and ‘here’, the view that these indexicals may have different meanings is explained away.
A Church in Peril
Authors: Lennan Richard
Published: March 2005

Between the end of the nineteenth century and the end of the twentieth century, the Roman Catholic Church experienced not only a significant decline in its standing in Western societies, but also a loss of cohesion among its members; this chapter explores both developments. A particular focus is on how the church's response to ‘modernity’, which emerged in the wake of the Enlightenment, affected life within the communion of faith, especially the settled worldview that had developed after the Council of Trent (1545–63). The second half of the chapter examines the impact of the Second Vatican Council (1962–65), especially the upheaval that has accompanied the reception of that council. The goal of the chapter is to establish why the present‐day life of the church can validly be described as a state of ‘peril’.
This Church
Authors: Lennan Richard
Published: March 2005

The existence of the church as the symbol of the Holy Spirit means that the external reality of the church, its historical manifestation, has theological significance. Concentrates on the specifics of the church's identity; in particular, it focusses on the role that tradition plays in the church and on the church's institutional structures. In exploring ‘tradition’, the chapter investigates how dependence on tradition relates to faith in Jesus Christ and to the role of the Spirit. As an example of the dynamics of tradition, the chapter analyses the status and interpretation of Scripture in the church. The sections on ‘authority’ highlight the relationship between authority and the communion in faith of the whole church and outline possibilities for a positive reception of authority.
The Centre, Downs, and New Labour
Authors: Hindmoor Andrew
Published: March 2005

The median voter theorem states that political parties will move to the electoral centre to maximise their vote. This theorem has been routinely linked to Downs and An Economic Theory of Democracy. It is argued that Downs’ determination to develop a theory to predict party behaviour has led him to develop a spatial framework in a misleading way. It is further argued that the electoral centre can be on the political right, left, or centre.
Innovation, New Labour, and the Construction of the Centre
Authors: Hindmoor Andrew
Published: March 2005

This chapter examines how New Labour sought to distinguish itself from Old Labour and the Conservatives by developing its policies as innovative. New Labour constructed its position at the political centre by arguing that its policies were radically different from those of Old Labour and the Conservatives. This spatial position that New Labour sought was one contested by others.
Leadership, New Labour, and the Construction of the Centre
Authors: Hindmoor Andrew
Published: March 2005

This chapter examines the frequent claim in newspapers that Blair is a ‘Presidential’ leader. It argues that in describing Blair as such, journalists were making a claim about the way New Labour and Blair govern. The ways the Conservatives sought to undermine the political threat posed by New Labour, the way Blair’s political and personal past were used to advance New Labour’s bid for office, and the way in which this image was fought over by the parties are discussed.
Perceptions of Mortality Risk: Implications for Annuities
Authors: Sondergeld Eric T. , Drinkwater Matthew
Published: March 2005

This chapter reviews research on how retirees and near-retirees view and manage mortality risks, and the implications for annuity buying behaviour. It is shown that the ownership of an annuity product is not synonymous with mortality risk transfer. People are becoming less protected over time from mortality risk, as evidenced by the decline in traditional pension plan coverage.
The European Court and Integration
Authors: Stone Sweet Alec
Published: March 2005

Provides an introduction to the book by explaining its origin, purpose, approach, and structure. The first section presents the generic question posed by the book: how is a particular mode of governance, the judicial mode, consolidated as a stable set of practices; it explains that the approach taken combines three strains of theory – theory on judicialization and governance, on the courts as commitment devices, and on the dynamics of judicial rulemaking and precedent. The second section, European Integration and the Legal System, indicates that the book expands on previous efforts to elaborate and test a theory of European integration, and shows that its primary focus is on the impact of adjudicating European Community law on the institutionalization of the European Union (EU), rather than on the impact of EU law on national legal systems. The third section, Determinants of Judicial Discretion in the EU, looks at the question of how the European Court has been able to have such an impact on the course of European integration and the work of the national courts. The fourth section, Precedent and the Path Dependence of Legal Institutions, focuses on why legal institutions tend to develop in path dependent ways; it begins by conceptualizing precedent, and then attempts to show how legal systems can develop in path dependent ways, and discusses how the book goes about analysing precedent in Europe. The last two sections look at the case selection and data used in the book and give a brief outline of its structure.
Constructing a Supranational Constitution
Authors: Stone Sweet Alec
Published: March 2005

The evolution of the European Community (EC) towards a supranational constitution is charted by combining three different perspectives. First, an examination is made of the major features of the integration process since 1959, which argues that the European market and polity developed symbiotically, as the activities of economic actors, organized interests, litigators and judges, and the EC's legislative and regulatory organs became linked, to create a self‐sustaining, dynamic system. Second, the ‘constitutionalization’ of the treaty system is investigated, and the activities of the European Court of Justice (ECJ) surveyed; among other things, constitutionalization secured property rights for transnational market actors, expanded the discretionary powers of national judges, and reduced the EC's intergovernmental character. Third, the relationship between the ECJ and the national courts is considered, focusing on how intra‐judicial conflict and cooperation have shaped the production of specific constitutional doctrines; through these ‘constitutional dialogues’, the supremacy of EC law was gradually achieved, rendering it judicially enforceable. Overall, the chapter situates the development of the European legal system within the overall process of European integration.
Conclusion
Authors: Stone Sweet Alec
Published: March 2005

The conclusion addresses certain major features of the overall course of European integration in light of the book's priorities and findings, indicating that the book has pursued two main objectives: the first, to demonstrate that the course of European integration has been profoundly shaped by a system of adjudication managed by the European Court of Justice (ECJ); the second, to test a range of propositions about how the legal system operates, and to trace the effects of the ECJ's case law on policy outcomes, and on the policy‐relevant behaviour of nonjudicial actors. In some areas, including free movement of goods and sex equality, judges – not governments or legislatures or the Member States – have broadly determined the paths along which institutions evolved. Judicial supremacy partly inheres in the ECJ's status as trustee, partly in the dynamics of the constitutionalization process provoked by the ECJ in the mid‐1960s, and partly by the propagation and diffusion of specific techniques of judicial governance, such as those associated with precedent‐based balancing standards. Every chapter of the book presents evidence refuting claims that the ECJ and the national courts operate as relatively perfect ‘agents’ of the Member States or national governments, and shows that the activities of supranational organizations such as the ECJ routinely produce ‘unintended consequences, from the perspective of those who have designed and redesigned the EC. The author concludes that he does not see how theories that make predictions about how integration has proceeded from institutional design can be rescued.
Global Public Economics
Authors: Mirrlees James A.
Published: March 2005

This chapter, together with chs. 2 and 11, approaches the question of development funding in a theoretical way, rather than by examining individual proposals for sources. One purpose of the book is to bring to bear on this accumulated knowledge in the field of national public finance, and more generally public economics. Consequently, a discussion of global public finance/economics is presented here that considers the lessons from optimal tax design when applied at a global level. The different sections of the chapter look at: global taxation; taxation for aid; the possibility of an international agreement whereby income taxation is applied to nationals (rather than residents) and countries report people's income to their country of nationality (international allocation of tax bases); supranational taxation; subsidies and transfers; voluntary contributions and taxation; and development assistance expansion. An appendix considers the conditions for marginal tax rates to be independent of the revenue requirement.
Partial Reconstruction of Flavonoid and Isoflavonoid Biosynthesis in Yeast Using Soybean Type I and Type II Chalcone Isomerases
Authors: Ralston Lyle , Subramanian Senthil , Matsuno Michiyo , Yu Oliver
Published: March 2005

Flavonoids and isoflavonoids are major plant secondary metabolites that mediate diverse biological functions and exert significant ecological impacts. These compounds play important roles in many essential physiological processes. In addition, flavonoids and isoflavonoids have direct but complex effects on human health, ranging from reducing cholesterol levels and preventing certain cancers to improving women's health. In this study, we cloned and functionally characterized five soybean (Glycine max) chalcone isomerases (CHIs), key enzymes in the phenylpropanoid pathway that produces flavonoids and isoflavonoids. Gene expression and kinetics analysis suggest that the soybean type I CHI, which uses naringenin chalcone as substrate, is coordinately regulated with other flavonoid-specific genes, while the type II CHIs, which use a variety of chalcone substrates, are coordinately regulated with an isoflavonoid-specific gene and specifically activated by nodulation signals. Furthermore, we found that some of the newly identified soybean CHIs do not require the 4′-hydroxy moiety on the substrate for high enzyme activity. We then engineered yeast (Saccharomyces cerevisiae) to produce flavonoid and isoflavonoid compounds. When one of the type II CHIs was coexpressed with an isoflavone synthase, the enzyme catalyzing the first committed step of isoflavonoid biosynthesis, various chalcone substrates added to the culture media were converted to an assortment of isoflavanones and isoflavones. We also reconstructed the flavonoid pathway by coexpressing CHI with either flavanone 3β-hydroxylase or flavone synthase II. The in vivo reconstruction of the flavonoid and isoflavonoid pathways in yeast provides a unique platform to study enzyme interactions and metabolic flux.
A Model of Hygiene Practices and Consumption Patterns in the Consumer Phase
Authors: Christensen Bjarke B. , Rosenquist Hanne , Sommer Helle M. , Nielsen Niels L. , Fagt Sisse , Andersen Niels L. , Nørrung Birgit
Published: March 2005

A mathematical model is presented, which addresses individual hygiene practices during food preparation and consumption patterns in private homes. Further, the model links food preparers and consumers based on their relationship to household types. For different age and gender groups, the model estimates (i) the probability of ingesting a meal where precautions have not been taken to avoid the transfer of microorganisms from raw food to final meal (a risk meal), exemplified by the event that the cutting board was not washed during food preparation, and (ii) the probability of ingesting a risk meal in a private home, where chicken was the prepared food item (a chicken risk meal). Chicken was included in the model, as chickens are believed to be the major source of human exposure to the foodborne pathogen Campylobacter. Monte Carlo simulations showed that the probability of ingesting a risk meal was highest for young males (aged 18–29 years) and lowest for the elderly above 60 years of age. Children aged 0–4 years had a higher probability of ingesting a risk meal than children aged 5–17 years. This difference between age and gender groups was ascribed to the variations in the hygiene levels of food preparers. By including the probability of ingesting a chicken meal at home, simulations revealed that all age groups, except the group above 60 years of age, had approximately the same probability of ingesting a chicken risk meal, the probability of females being slightly higher than that of males. The simulated results show that the probability of ingesting a chicken risk meal at home does not only depend on the hygiene practices of the persons preparing the food, but also on the consumption patterns of consumers, and the relationship between people preparing and ingesting food. This finding supports the need of including information on consumer behavior and preparation hygiene in the consumer phase of exposure assessments.
Touch Noise Increases Vibrotactile Sensitivity in Old and Young
Authors: Wells Cari , Ward Lawrence M. , Chua R. , Inglis J. Timothy
Published: March 2005

Stochastic resonance (SR) occurs when the detection of a subthreshold signal is aided by the presence of random energy fluctuations in the signal modality, commonly called noise. SR is counterintuitive because such noise usually worsens performance. Nonetheless, SR has been demonstrated both theoretically and experimentally in human sensory systems. Using a psychophysically sophisticated paradigm, we show that SR aids the detection of vibrating touch stimuli presented to the foot soles of both healthy elderly people with elevated vibrotactile thresholds and healthy young people with normal vibrotactile thresholds. The results also suggest that it is possible to know a priori the amount of noise needed for optimal SR effects given the degree to which the signal is subthreshold. Thus, SR may be practical as a rehabilitative aid for individuals with elevated sensory thresholds.
Cardiovascular pharmacogenomics
Authors: Johnson Julie A. , Cavallari Larisa H.
Published: March 2005

There is large interpatient variability in the response to drugs, including cardiovascular drugs. Thus, while some patients achieve the desired therapeutic response from their drug therapy, others do not. There is also a subset of patients who will experience adverse effects, which can range from bothersome to life threatening. Research in recent years has provided compelling evidence that in many cases, genetics contributes importantly to this variable drug response. Thus, pharmacogenomics is a field focused on unravelling the genetic determinants of variable drug response. Examples from the literature of genetic associations with drug efficacy and toxicity are described to provide insight into the field, including the roles of genetic variability in drug‐metabolizing enzymes and drug targets. There is also a detailed discussion of the experimental approaches used in cardiovascular pharmacogenomics. Current research is largely focused on a limited candidate gene approach, which allows for description of significant genetic associations with variable response, but often does not explain the genetic basis of variable drug response enough to be useful clinically. As such, there is a move towards genome‐wide approaches, and the various technologies available to obtain genomic data are discussed. Cardiovascular pharmacogenomics has the potential for leading to improvements in the use of cardiovascular drug therapy, through selection of the most appropriate drug therapy in an individual based on their genetic information. It will probably be a decade or more before genetic information is widely used in drug therapy decisions, but it seems clear that important findings in the area will continue to expand and the experimental approaches will continue to evolve.
Impact of occupational stress and other psychosocial factors on musculoskeletal pain among Chinese offshore oil installation workers
Authors: Chen W Q , Yu I T-S , Wong T W
Published: March 2005

Aims:To explore the relation between psychosocial factors and musculoskeletal pain in Chinese offshore oil installation workers.

Methods:Half of all offshore workers (being a representative sample) in a Chinese oil company were invited to complete a self-administered questionnaire providing information on sociodemographic characteristics, occupational stressors, type A behaviour, social support, coping style, health related behaviour, past injuries, and musculoskeletal pain. Factor analysis was used to identify the sources of occupational stress and the domains of type A behaviour and coping style. Logistic regression analyses were used to study the relations between psychosocial factors and musculoskeletal pain in each body region.

Results:The prevalence of musculoskeletal pain over the previous 12 months varied between 7.5% for elbow pain and 32% for low back pain; 56% workers had at least one complaint. Significant associations were found between various psychosocial factors and musculoskeletal pain in different body regions after adjusting for potential confounding factors. Occupational stressors, in particular stress from safety, physical environment, and ergonomics, were important predictors of musculoskeletal pain, as was coping by eating behaviour.

Conclusions:These observations supported the widely accepted biopsychosocial model of musculoskeletal disorders and suggested that in future studies of work related musculoskeletal disorders, psychosocial factors must be given due consideration.
Computer based safety training: an investigation of methods
Authors: Wallen E S , Mulloy K B
Published: March 2005

Background:Computer based methods are increasingly being used for training workers, although our understanding of how to structure this training has not kept pace with the changing abilities of computers. Information on a computer can be presented in many different ways and the style of presentation can greatly affect learning outcomes and the effectiveness of the learning intervention. Many questions about how adults learn from different types of presentations and which methods best support learning remain unanswered.

Aims:To determine if computer based methods, which have been shown to be effective on younger students, can also be an effective method for older workers in occupational health and safety training.

Methods:Three versions of a computer based respirator training module were developed and presented to manufacturing workers: one consisting of text only; one with text, pictures, and animation; and one with narration, pictures, and animation. After instruction, participants were given two tests: a multiple choice test measuring low level, rote learning; and a transfer test measuring higher level learning.

Results:Participants receiving the concurrent narration with pictures and animation scored significantly higher on the transfer test than did workers receiving the other two types of instruction. There were no significant differences between groups on the multiple choice test.

Conclusions:Narration with pictures and text may be a more effective method for training workers about respirator safety than other popular methods of computer based training. Further study is needed to determine the conditions for the effective use of this technology.
Long-term tetrachlorethene degradation sustained by endogenous cell decay
Authors: Sleep Brent E , Brown Andrea J , Lollar Barbara Sherwood
Published: March 2005

The role of endogenous decay in the reductive dechlorination of tetrachlorethene (PCE) was studied in a sand column containing an anaerobic microbial consortium that included Dehalococcoides ethenogenes. The column consortium had continuously transformed PCE to vinyl chloride (<5%) and ethene (>95%) with the addition of ethanol and yeast extract for a 3 year period. The column was operated for a further period of 1 year with the addition of 60 µM PCE only. In the absence of external electron donors, PCE dechlorination in the column initially slowed but continued at a relatively constant rate for 1 year. The conversion to vinyl chloride (VC) and ethene (ETH) was significantly reduced with cis-dichloroethylene (cis-DCE) becoming the major (90%) end product of dechlorination. Microcosm studies, with no external electron donor added, indicated that reductive dechlorination was sustained by reducing equivalents derived from endogenous decay products. Measures of cellular adenosine triphosphate (ATP) along the length of the column indicated that even after 1 year of only PCE addition, an active biological community was sustained. Key words: tetrachloroethene (PCE), ethanol, anaerobic biodegradation, endogenous decay, column study.
Ozone-enhanced electroflocculation in municipal wastewater treatment
Authors: Nielson Kai , Smith Daniel W
Published: March 2005

The use of electrochemical principles for the treatment of wastewaters has received increased attention in recent years. This paper examines one such technology termed the ElectroflocPLUS wastewater treatment system developed by Applied Oxidation Technologies Inc. of Ladysmith, British Columbia. The study investigated the ability of the system to treat municipal wastewater. The results of an extensive experimental program showed that the technology was effective in the reduction of certain water quality parameters, including total suspended solids (TSS) and total phosphorus (TP), and the unit was capable of meeting regulatory guidelines for these parameters. The removals of chemical oxygen demand (COD) and 5-d biochemical oxygen demand (BOD5) were inadequate, as the test unit was unable to treat the wastewater adequately to meet regulatory guidelines. Other points were also examined, including the ElectroflocPLUS treatment systems energy requirements. The results showed energy consumption to be quite high relative to competing technologies. Key words: electroflocculation, electrocoagulation, municipal wastewater treatment, ozone, microorganism reduction, coagulation, flotation.
Skeletal muscle reperfusion injury is enhanced in extracellular superoxide dismutase knockout mouse
Authors: Park Jong Woong , Qi Wen-Ning , Cai Yongting , Zelko Igor , Liu John Q. , Chen Long-En , Urbaniak James R. , Folz Rodney J.
Published: March 2005

This study investigates the role of extracellular SOD (EC-SOD), the major extracellular antioxidant enzyme, in skeletal muscle ischemia and reperfusion (I/R) injury. Pedicled cremaster muscle flaps from homozygous EC-SOD knockout (EC-SOD−/−) and wild-type (WT) mice were subjected to 4.5-h ischemia and 90-min reperfusion followed by functional and molecular analyses. Our results revealed that EC-SOD−/−mice showed significantly profound I/R injury compared with WT littermates. In particular, there was a delayed and incomplete recovery of arterial spasm and blood flow during reperfusion, and more severe acute inflammatory reaction and muscle damage were noted in EC-SOD−/−mice. After 90-min reperfusion, intracellular SOD [copper- and zinc-containing SOD (CuZn-SOD) and manganese-containing (Mn-SOD)] mRNA levels decreased similarly in both groups. EC-SOD mRNA levels increased in WT mice, whereas EC-SOD mRNA was undetectable, as expected, in EC-SOD−/−mice. In both groups of animals, CuZn-SOD protein levels decreased and Mn-SOD protein levels remained unchanged. EC-SOD protein levels decreased in WT mice. Histological analysis showed diffuse edema and inflammation around muscle fibers, which was more pronounced in EC-SOD−/−mice. In conclusion, our data suggest that EC-SOD plays an important role in the protection from skeletal muscle I/R injury caused by excessive generation of reactive oxygen species.
Sources of Variability of Evapotranspiration in California
Authors: Hidalgo Hugo G. , Cayan Daniel R. , Dettinger Michael D.
Published: March 2005

The variability (1990–2002) of potential evapotranspiration estimates (ETo) and related meteorological variables from a set of stations from the California Irrigation Management System (CIMIS) is studied. Data from the National Climatic Data Center (NCDC) and from the Department of Energy from 1950 to 2001 were used to validate the results. The objective is to determine the characteristics of climatological ETo and to identify factors controlling its variability (including associated atmospheric circulations). Daily ETo anomalies are strongly correlated with net radiation (Rn) anomalies, relative humidity (RH), and cloud cover, and less with average daily temperature (Tavg). The highest intraseasonal variability of ETo daily anomalies occurs during the spring, mainly caused by anomalies below the high ETo seasonal values during cloudy days. A characteristic circulation pattern is associated with anomalies of ETo and its driving meteorological inputs, Rn, RH, and Tavg, at daily to seasonal time scales. This circulation pattern is dominated by 700-hPa geopotential height (Z700) anomalies over a region off the west coast of North America, approximately between 32° and 44° latitude, referred to as the California Pressure Anomaly (CPA). High cloudiness and lower than normal ETo are associated with the low-height (pressure) phase of the CPA pattern. Higher than normal ETo anomalies are associated with clear skies maintained through anomalously high Z700 anomalies offshore of the North American coast. Spring CPA, cloudiness, maximum temperature (Tmax), pan evaporation (Epan), and ETo conditions have not trended significantly or consistently during the second half of the twentieth century in California. Because it is not known how cloud cover and humidity will respond to climate change, the response of ETo in California to increased greenhouse-gas concentrations is essentially unknown; however, to retain the levels of ETo in the current climate, a decline of Rn by about 6% would be required to compensate for a warming of +3°C.
Population Pharmacokinetics of Efalizumab (Humanized Monoclonal Anti‐CD11a Antibody) Following Long‐Term Subcutaneous Weekly Dosing in Psoriasis Subjects
Authors: Sun Yu‐Nien , Lu Jian‐Feng , Joshi Amita , Compton Peter , Kwon Paul , Bruno Rene A.
Published: March 2005

The population pharmacokinetics of efalizumab was characterized in patients with moderate to severe plaque psoriasis. The study included 1088 subjects who received 1 or 2 mg/kg/wk subcutaneous efalizumab for 12 weeks from a phase I (64 subjects) and 3 phase III studies with day 42 and/or day 84 trough levels (1024 patients). Due to the limitation of the data, a 1‐compartment model with first‐order absorption and elimination was used to fit the data. The population means for V/F, Ka, and CL/F were 9.13 L, 0.191 day−1, and 1.29 L/d, respectively, for a typical subject receiving a 1‐mg/kg dose. Interindividual variability in CL/F was 48.2%. Body weight has the largest influence on CL/F. Other covariates (obesity, baseline lymphocyte counts, Psoriasis Area and Severity Index score, and age) had only modest effects. Subjects in the 2‐mg/kg dose group had a 24.0% lower CL/F, consistent with nonlinear pharmacokinetics of efalizumab. The results of this analysis support the current body weight‐adjusted dosing strategy.
FTY720 Pharmacokinetics in Mild to Moderate Hepatic Impairment
Authors: Kovarik J. M. , Schmouder R. L. , Serra D. , Wang Y. , Wiegand H. , Dilzer S. C. , Lasseter K. C.
Published: March 2005

The influence of mild and moderate hepatic impairment on FTY720 pharmacokinetics was assessed. The authors enrolled 32 subjects consisting of 8 with mild and 8 with moderate hepatic impairment based on Child‐Pugh criteria and 16 demographically matched control subjects. A single 1‐mg oral dose of FTY720 was administered under fasting conditions. Blood, plasma, and urine samples were obtained over a 14‐day period for measurement of FTY720 and metabolite concentrations and protein binding. Total blood lymphocyte counts and heart rate were serially monitored to assess pharmacologic responses to FTY720. Peak FTY720 blood concentrations were similar across groups. Oral clearance (CL/F) was reduced 10% in mild hepatic impairment (P = .493) and 31% in moderate hepatic impairment (P = .034). There were no significant differences in blood exposure to the hexanoic or butanoic acid metabolites among groups. The effect of FTY720 on blood lymphocytes was similar across groups, with a mean decrease of 44% from the predose value. Likewise, the effect of FTY720 on supine heart rate was similar across groups, with a mean 13% decrease from the predose rate occurring 2 to 4 hours postdose and recovering within 1 to 2 days. Although hepatic impairment elicited changes in the disposition of FTY720, the magnitude of these changes suggests that the FTY720 dose does not need to be adjusted in mild or moderate hepatic‐impaired patients.
Review of UCN‐01 Development: A Lesson in the Importance of Clinical Pharmacology
Authors: Fuse Eiichi , Kuwabara Takashi , Sparreboom Alex , Sausville Edward A. , Figg William D.
Published: March 2005

UCN‐01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmacologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimination half‐life was unusually long (>200 hours). The unbound fraction in human plasma was also much smaller than that in dogs, rats and mice, as was the binding of UCN‐01 to human alpha‐1 acid glycoprotein much stronger than that to human serum albumin or human γ‐globulin. The association constants for alpha‐1 acid glycoprotein and human plasma were approximately 8 × 108 (mol/L)−1, indicating extremely high affinity. In this review article, the authors discuss the pharmacologic features of UCN‐01 across species and provide a perspective on how this information could be applied prospectively to the future development of this agent.
Periodontal Diseases and the Risk of Preterm Birth and Low Birth Weight: A Meta‐Analysis
Authors: Khader Yousef S. , Ta'ani Quteish
Published: March 2005

Background: This meta‐analysis of periodontal disease in relation to the risk of preterm birth/low birth weight (PTB/ LBW) is based on two case‐control studies and three prospective cohort studies that met prestated inclusion criteria.

Methods: Information on the designs of the studies, characteristics of the study population, exposure and outcome measures, control for confounders, and risk estimates were abstracted independently by two investigators using a standard protocol.

Results: Pregnant women with periodontal disease had an overall adjusted risk of preterm birth that was 4.28 (95% confidence interval [CI], 2.62 to 6.99; P <0.005) times that risk for healthy subjects. The overall adjusted odds ratio of preterm low birth weight was 5.28 (95% CI, 2.21 to 12.62; P <0.005), while the overall adjusted odds ratio of a delivery of either PTB or LBW was 2.30 (95% CI, 1.21 to 4.38; P <0.005).

Conclusions: Our findings indicate that periodontal diseases in the pregnant mother significantly increase the risk of subsequent preterm birth or low birth weight. While it remains important to promote good oral hygiene during routine prenatal visits, there is no convincing evidence, on the basis of existing casecontrol and prospective studies, that treatment of periodontal disease will reduce the risk of preterm birth. Consequently, large randomized, placebo‐controlled, masked clinical trials are required. J Periodontol 2005;76:161‐165.
Quantitative Measures of Aggressive Periodontitis Show Substantial Heritability and Consistency With Traditional Diagnoses
Authors: Diehl Scott R. , Wu Tianxia , Michalowicz Bryan S. , Brooks Carol N. , Califano Joseph V. , Burmeister John A. , Schenkein Harvey A.
Published: March 2005

Background: Aggressive periodontitis (AgP) research nearly always classifies subjects into traditional discrete categories of localized or generalized, based upon degree of attachment loss (AL) and types of affected teeth. Since AL is continuous and quantitative, however, useful information is lost. We developed quantitative measures of AgP, compared these to traditional methods, and estimated heritabilities in families.

Methods: We examined 237 healthy, 169 localized AgP, and 204 generalized AgP subjects. We used the site of maximum AL of each tooth to calculate means for each subject for different groups of teeth. We also applied principal components analysis (PCA) to condense variation among 28 teeth into three orthogonal (uncorrelated) variables. We used discriminant function analysis (DFA) to evaluate how well the quantitative measures match with traditional classifications. Quantitative trait heritabilities were estimated by variance components.

Results: PCA clustered first molars, incisors, and the other teeth into three groups. DFA showed that quantitative measures classified subjects consistent with traditional methods (87% to 94% agreement). Heritabilities ranged from 13.7% (P = 0.10) to 30.0% (P = 0.008) for quantitative measures, with highest values obtained for first molars. A combination of the principal component variables most heavily weighted on first molars and incisors gave the best model of disease susceptibility, with good separation of healthy versus diseased subjects, independent of disease extent or severity.

Conclusions: Quantitative measures may provide improved precision and power for many kinds of periodontal research. Our finding of significant heritability supports their use in gene mapping studies of AgP susceptibility. J Periodontol 2005;76:279‐288.
Congenital diaphragmatic hernia in WAGR syndrome
Authors: Scott D.A. , Cooper M.L. , Stankiewicz P. , Patel A. , Potocki L. , Cheung S.W.
Published: March 2005

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is a contiguous gene deletion syndrome involving the Wilms tumor 1 gene (WT1), the paired box gene 6 (PAX6), and possibly other genes on chromosome 11p13. WT1 is required for normal formation of the genitourinary system and the high incidence of Wilms tumor and genitourinary anomalies found in patients with WAGR are attributed to haploinsufficiency of this gene. It has been hypothesized that WT1 also plays an important role in the development of the diaphragm. During mammalian embryonic development, WT1 is expressed in the pleural and abdominal mesothelium that forms part of the diaphragm. Furthermore, mice that are homozygous for a deletion in the mouse homolog of WT1 have diaphragmatic hernias. Case reports describing congenital diaphragmatic hernias in infants with Denys–Drash and Frasier syndromes, both of which can be caused by mutations in WT1, provide additional support for this hypothesis. We report an infant with aniridia, bilateral cryptorchidism, vesicoureteral reflux, and a right‐sided Morgagni‐type diaphragmatic hernia. G‐banded chromosome analysis revealed a deletion of 11p12‐p15.1. Breakpoint regions were refined by fluorescence in situ hybridization (FISH) and deletion of the WAGR critical region, including WT1, was confirmed. A review of the medical literature identified a second patient with a deletion of 11p13, a left‐sided Bochdalek‐type diaphragmatic hernia, and anomalies that suggest a diagnosis of WAGR including bilateral microphthalmia, a small penis, bilateral cryptorchidism, and a hypoplastic scrotum. These cases demonstrate that congenital diaphragmatic hernia can be associated with WAGR syndrome and suggest that deletions of WT1 may predispose individuals to develop congenital diaphragmatic hernia. © 2005 Wiley‐Liss, Inc.
A provisionally unique syndrome of macrosomia, bone overgrowth, macrocephaly, and tall stature
Authors: Sadeghi‐Nejad Ab , Karlin Lawrence I.
Published: March 2005

We report a young man with intrauterine macrosomia, macrocephaly, and bony abnormalities. Excessive growth continued throughout infancy and childhood. Bone age was advanced. He developed contractures of the large joints and was confined to a wheelchair. Extensive laboratory studies, repeated on multiple occasions were all normal. Intellectually, he was normal. His near final height was 234 cm. The constellation of findings in this patient is at variance with previously described syndromes of tall stature. We postulate that excessive size and bone overgrowth in this young man is caused by a receptor/post‐receptor abnormality involving a growth on/off mechanism at the cellular level. © 2005 Wiley‐Liss, Inc.
Variability in food‐processing behavior among white‐faced capuchins (Cebus capucinus) in Santa Rosa National Park, Costa Rica
Authors: O'Malley Robert C. , Fedigan Linda
Published: March 2005

Observed patterns of variability in the food‐processing behavior of white‐faced capuchins (Cebus capucinus) across populations may reflect foraging traditions. However, there has been relatively little attention given to intrapopulation variability in food processing among groups and age/sex classes, making recent cross‐population comparisons difficult to interpret. In this paper, we provide data on patterns of object use in foraging that we observed at Santa Rosa National Park, Costa Rica, for comparison with published data from a neighboring research site, Palo Verde National Park. We also describe the techniques used to process two food items consumed by Cebus capucinus at Santa Rosa, and discuss the factors that may underlie observed variability. We conducted a 6‐month study on two groups of capuchins in 2001, and collected data on general activity and feeding patterns, rates and forms of object use, and distinctive processing techniques employed for two specific foods (Sloanea terniflora and Luehea candida). Rates of object‐use behavior at Santa Rosa were considerably higher than those reported for Palo Verde and showed significant variation between groups and age/sex classes, as did patterns of Sloanea and Luehea processing. Observed differences in feeding rates between groups may reflect food availability or relative profitability, whereas variation between age/sex classes seems to reflect differences in the physical capabilities, foraging strategies, and the relative experience of mature and immature animals. Further research is needed to identify how a social context may influence the acquisition of food‐processing techniques in juveniles and the development of foraging traditions in social groups. Am J Phys Anthropol 128:63–73, 2005. © 2005 Wiley‐Liss, Inc.
The impact of preoperative serum C‐reactive protein on the prognosis of patients with hepatocellular carcinoma
Authors: Hashimoto Koji , Ikeda Yasuharu , Korenaga Daisuke , Tanoue Kazuo , Hamatake Motoharu , Kawasaki Katsumi , Yamaoka Terutoshi , Iwatani Yasue , Akazawa Kohei , Takenaka Kenji
Published: March 2005

BACKGROUND

The authors evaluated the significance of the preoperative serum C‐reactive protein (CRP) level as a prognostic indicator in patients with hepatocellular carcinoma (HCC).

METHODS

One hundred forty‐one patients who underwent curative resection for HCC were reviewed retrospectively. Clinicopathologic variables were compared between patients with serum CRP levels ≥ 1.0 mg/dL (n = 22 patients; the CRP‐positive group) and patients with serum CRP levels < 1.0 mg/dL (n = 119 patients; the CRP‐negative group). Univariate and multivariate analyses were conducted to identify factors that affected survival and disease recurrence.

RESULTS

There was a significant correlation between the preoperative serum CRP level and tumor size. Invasion to the portal vein in the CRP‐positive group was significantly more frequent than that in the CRP‐negative group. Even after they underwent curative resection, 75.3% of patients in the CRP‐positive group experienced recurrence within 1 year. The overall survival and recurrence‐free survival rates in the CRP‐positive group were significantly lower compared with the rates in the CRP‐negative group. On multivariate analysis, the preoperative serum CRP level was selected as one of the unfavorable indicators regarding survival and recurrence. When CRP levels, albumin levels, and platelet counts that were available before surgery were scored as a combined index, the total score demonstrated a good stratification value for survival after hepatic resection.

CONCLUSIONS

The current results showed that the preoperative serum CRP level is an independent and significant indicator predictive of poor prognosis and early recurrence in patients with HCC. The new CRP‐based scoring system offers reliable information for predicting survival. Cancer 2005. © 2005 American Cancer Society.
Development and validation of algorithms for measuring G‐protein coupled receptor activation in cells using the LSC‐based imaging cytometer platform
Authors: Ozawa Kazuo , Hudson Christine C. , Wille Kirsten R. , Karaki Sachiko , Oakley Robert H.
Published: March 2005

Background

A cell‐based assay system (Transfluor) has been developed for measurement of G‐protein coupled receptor (GPCR) activity by using cells transfected to express a fusion protein of arrestin plus green fluorescent protein (GFP) and the target GPCR. Upon agonist stimulation, the arrestin‐GFP translocates to and binds the activated GPCR at the plasma membrane. The receptor/arrestin‐GFP complexes then localize in clathrin‐coated pits and/or intracellular vesicles. This redistribution of arrestin‐GFP into condensed fluorescent spots is useful for visually monitoring the active status of GPCRs and its quantitation is possible with certain types of digital image analysis systems.

Methods

We designed two lines of image processing algorithms to carry out quantitative measurement of the arrestin‐GFP movement on an inverted version of laser scanning cytometry (iCyte) as an imaging platform. We used a cell line expressing arrestin‐GFP and the wild‐type β2‐adrenergic receptor or a modified version of this receptor with enhanced affinity for arrestin. Each cell line was challenged with various concentrations of agonist.

Results

A dose‐dependent signal was measured and half‐maximal effective concentration values were obtained that agreed well with results determined by other methods previously reported.

Conclusions

The results indicate that the combination of Transfluor, iCyte, and our algorithms is suitable for robust and pharmacologically relevant GPCR ligand exploration. © 2005 Wiley‐Liss, Inc.