bluuebunny/crossref_metadata_2025 huggingface dataset:
BRCA1 Phosphorylation Regulates Caspase-3 Activation in UV-Induced Apoptosis
Authors: Martin Sarah A. , Ouchi Toru
Published: December 2005

Apoptosis is implemented by death machinery that involves the caspase family of proteins, under the condition of a variety of stresses. Previous studies have shown that mouse embryonic stem cells deficient for caspase-3 are resistant to UV-induced apoptosis and that the active form of caspase-3 translocates to the nucleus. It has also been shown that the breast cancer tumor suppressor, BRCA1, is phosphorylated on Ser1423 and Ser1524 by the ataxia telangiectasia mutated–related kinase (ATR) after UV damage. Here, we show that activation of caspase-3 by UV is abrogated in BRCA1-mutated SNU251 and HCC1937 cells but was restored by reexpressing wild-type (wt) BRCA1, but not phosphorylation-deficient BRCA1Ser1423Ala/Ser1524Ala (BRCA1S1423/1524A). In SNU251 cells expressing BRCA1S1423/1524A, the inhibitory interaction between X-linked inhibitor of apoptosis protein (XIAP) and caspase-9 remains intact after UV, compared with cells expressing wt BRCA1. We determined that XIAP and BRCA1 interact and upon phosphorylation this complex is disrupted. Nuclear translocation of active caspase-3 is detected only when wt BRCA1 is reexpressed. Consistent with this, Rad21, a known substrate of caspase-3, is cleaved only when wt BRCA1 is expressed in vivo. These results propose a model that inhibition of BRCA1 phosphorylation leads to the abrogation of a specific form of apoptosis that is mediated by caspase-3.
Expression of the MutL Homologue hMLH3 in Human Cells and its Role in DNA Mismatch Repair
Authors: Cannavo Elda , Marra Giancarlo , Sabates-Bellver Jacob , Menigatti Mirco , Lipkin Steven M. , Fischer Franziska , Cejka Petr , Jiricny Josef
Published: December 2005

The human mismatch repair (MMR) proteins hMLH1 and hPMS2 function in MMR as a heterodimer. Cells lacking either protein have a strong mutator phenotype and display microsatellite instability, yet mutations in the hMLH1 gene account for ∼50% of hereditary nonpolyposis colon cancer families, whereas hPMS2 mutations are substantially less frequent and less penetrant. Similarly, in the mouse model, Mlh1−/− animals are highly cancer prone and present with gastrointestinal tumors at an early age, whereas Pms2−/− mice succumb to cancer much later in life and do not present with gastrointestinal tumors. This evidence suggested that MLH1 might functionally interact with another MutL homologue, which compensates, at least in part, for a deficiency in PMS2. Sterility of Mlh1−/−, Pms2−/−, and Mlh3−/− mice implicated the Mlh1/Pms2 and Mlh1/Mlh3 heterodimers in meiotic recombination. We now show that the hMLH1/hMLH3 heterodimer, hMutLγ, can also assist in the repair of base-base mismatches and single extrahelical nucleotides in vitro. Analysis of hMLH3 expression in colon cancer cell lines indicated that the protein levels vary substantially and independently of hMLH1. If hMLH3 participates in MMR in vivo, its partial redundancy with hPMS2, coupled with the fluctuating expression levels of hMLH3, may help explain the low penetrance of hPMS2 mutations in hereditary nonpolyposis colon cancer families.
Therapeutic Efficacy of Endostatin Exhibits a Biphasic Dose-Response Curve
Authors: Celik Ilhan , Sürücü Oguzkan , Dietz Carsten , Heymach John V. , Force Jeremy , Höschele Iris , Becker Christian M. , Folkman Judah , Kisker Oliver
Published: December 2005

We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.
High Frequency of Coexistent Mutations of PIK3CA and PTEN Genes in Endometrial Carcinoma
Authors: Oda Katsutoshi , Stokoe David , Taketani Yuji , McCormick Frank
Published: December 2005

The phosphatidylinositol 3′-kinase (PI3K) pathway is activated in many human cancers. In addition to inactivation of the PTEN tumor suppressor gene, mutations or amplifications of the catalytic subunit α of PI3K (PIK3CA) have been reported. However, the coexistence of mutations in these two genes seems exceedingly rare. As PTEN mutations occur at high frequency in endometrial carcinoma, we screened 66 primary endometrial carcinomas for mutations in the helical and catalytic domains of PIK3CA. We identified a total of 24 (36%) mutations in this gene and coexistence of PIK3CA/PTEN mutations at high frequency (26%). PIK3CA mutations were more common in tumors with PTEN mutations (17 of 37, 46%) compared with those without PTEN mutations (7 of 29, 24%). Array comparative genomic hybridization detected 3q24-qter amplification, which covers the PIK3CA gene (3q26.3), in one of nine tumors. Knocking down PTEN expression in the HEC-1B cell line, which possesses both K-Ras and PIK3CA mutations, further enhances phosphorylation of Akt (Ser473), indicating that double mutation of PIK3CA and PTEN has an additive effect on PI3K activation. Our data suggest that the PI3K pathway is extensively activated in endometrial carcinomas, and that combination of PIK3CA/PTEN alterations might play an important role in development of these tumors.
Tumor-Derived Interleukin-8 Stimulates Osteolysis Independent of the Receptor Activator of Nuclear Factor-κB Ligand Pathway
Authors: Bendre Manali S. , Margulies Aaron G. , Walser Brandon , Akel Nisreen S. , Bhattacharrya Sudeepa , Skinner Robert A. , Swain Frances , Ramani Vishnu , Mohammad Khalid S. , Wessner Lisa L. , Martinez Alfredo , Guise Theresa A. , Chirgwin John M. , Gaddy Dana , Suva Larry J.
Published: December 2005

Bone is a common site of cancer metastasis. Breast, prostate, and lung cancers show a predilection to metastasize to bone. Recently, we reported that the chemokine interleukin 8 (IL-8) stimulates both human osteoclast formation and bone resorption. IL-8 mRNA expression was surveyed in a panel of human breast cancer lines MDA-MET, MDA-MB-231, MDA-MB-435, MCF-7, T47D, and ZR-75, and the human lung adenocarcinoma cell line A549. IL-8 mRNA expression was higher in cell lines with higher osteolytic potential in vivo. Human osteoclast formation was increased by MDA-MET or A549 cell-conditioned medium, but not by MDA-MB-231. Pharmacologic doses of receptor activator of nuclear factor-κB (RANK)-Fc or osteoprotogerin had no effect on the pro-osteoclastogenic activity of the conditioned medium; however, osteoclast formation stimulated by conditioned medium was inhibited 60% by an IL-8-specific neutralizing antibody. The data support a model in which tumor cells cause osteolytic bone destruction independently of the RANK ligand (RANKL) pathway. Tumor-produced IL-8 is a major contributor to this process. The role of secreted IL-8 isoforms was examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, which detected distinct IL-8 isoforms secreted by MDA-MET and MDA-231 cells, suggesting different pro-osteoclastogenic activities of the two IL-8-derived peptides. These data indicate that (a) osteoclast formation induced by MDA-MET breast cancer cells and A549 adenocarcinoma cells is primarily mediated by IL-8, (b) cell-specific isoforms of IL-8 with distinct osteoclastogenic activities are produced by tumor cells, and (c) tumor cells that support osteoclast formation independent of RANKL secrete other pro-osteoclastogenic factors in addition to IL-8.
A Selective Tumor Microvasculature Thrombogen that Targets a Novel Receptor Complex in the Tumor Angiogenic Microenvironment
Authors: El-Sheikh Amr , Borgstrom Per , Bhattacharjee Gourab , Belting Mattias , Edgington Thomas S.
Published: December 2005

We have previously shown that part of the heparin-binding domain of the vascular endothelial growth factor (VEGF), designated HBDt, localizes very selectively to surfaces of the endothelial cells of i.t blood vessels. Here, we have coupled the HBDt to the extracellular domain of tissue factor (TFt), to locally initiate the thrombogenic cascade. In tumor-bearing mice, infusion of this HBDt.TFt results in rapid occlusive thrombosis selective only for tumor microvasculature with resultant infarctive destruction of tumors. We now show that infusion of an optimal combination of this HBDt.TFt and its requisite cofactor (factor VIIa) in tumor models results in significant tumor eradication. Binding studies and confocal microscopy indicate that the target for the HBDt.TFt seems to be a trimolecular complex of chondroitin C sulfate proteoglycan, neuropilin-1, and VEGF receptor-2, overexpressed together only in highly angiogenic sites of the tumor microenvironment. The HBDt.TFt was also colocalized with the trimolecular receptor complex in endothelial sprouts from tumor tissues, and its binding inhibited the growth of such sprouts. In vitro, we show that the HBDt structure has its highest affinity for chondroitin 6 sulfate. We show the potential of this HBDt.TFt as a candidate therapeutic and elucidate its target in vivo.
Tumor Inflammatory Angiogenesis and Its Chemoprevention
Authors: Albini Adriana , Tosetti Francesca , Benelli Roberto , Noonan Douglas M.
Published: December 2005

The importance of angiogenesis for the growth of tumors is widely recognized. Drugs that successfully target the endothelium, such as antivascular endothelial growth factor antibodies, are beginning to have an effect on the life expectancy of cancer patients. However, the endothelial cell is not the only possible target for antiangiogenic therapy or prevention of vascularization (angioprevention). It is evident from the literature that native immune cells recruited into tumors in turn stimulate the endothelium and are responsible for an indirect pathway of tumor vascularization. Inflammation-dependent angiogenesis seems to be a central force in tumor growth and expansion, a concept supported by the observation that the use of “classic” anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs, leads to angiogenesis inhibition. The mechanisms of inflammatory angiogenesis provide new approaches to target, cure, or even better, prevent tumor angiogenesis by treatment with synthetic or natural agents with anti-inflammatory properties. We propose chemoprevention of inflammatory angiogenesis as a way of checking the cancer before it progresses.
Education and Youth Integration into European Labour Markets
Authors: Müller Walter
Published: December 2005

Education is a crucial determinant of people’s life chances, and it particularly affects the integration of youth into labour markets. The article shows how different kinds and levels of education shape the access of young people to jobs of varying advantage and the smoothness of the transition from school to work. It elaborates the common patterns in the relationship between education and early career labour market outcomes and investigates - especially for EU member countries - how varying institutional arrangements in the educational systems and in the regulation of labour markets lead to varying integration outcomes.
Mass Media and the Linguistic Marketplace
Authors: Popp Richard K.
Published: December 2005

This article applies theories of the political economy of language to examine howlinguistic acts in media are used to create distinction by tapping into ideas about the functions of language in society. From this standpoint, language ideology serves as a mode of leverage for media institutions. A discourse analysis investigates press coverage of two texts that have used language in conspicuousways. Nickelodeon's Dora the Explorer purportedly introduces children to bilingualism. This bilingualism serves as capital, converted into notions of educational merit and cosmopolitanism, that distinguishes Dora from other children's programs. Mel Gibson's use of ancient languages in The Passion of the Christacts as capital for notions of historical authenticity and mysticism that helped counter the film's critics.
Supporting both learning and research in a UK post-1992 university library
Authors: Wakeham Maurice , Garfield Diana
Published: December 2005

Nationally, there has been debate on the role of research within higher education and increased interest in the teaching/research nexus. A team of Academic Liaison Librarians at Anglia Polytechnic University was awarded funding to investigate the extent to which learning resources overlap with research resources, whether researcher/teachers encourage their students to use the resources they use themselves and how far electronic resources have affected the relationship between learning and research materials. Semistructured interviews were carried out with 21 academics who are both teachers and researchers. They proved to be committed to using research in their teaching. Students were encouraged to engage with research through the recommendation of resources, seminar discussion, and researchers’ own work for reading and illustrating methodologies. Respondents claimed to be making significant use of the APU library website, online databases and journals. The majority of them were also recommending the same resources to their students. Convenience, speed and variety of information sources were quoted as some of the advantages of the new e-environment. A loss of a relationship with librarians and with the physical library was cited as an example of negative effects of the electronic resource environment.
Editorial : LIS and the Creation of a European Educational Space
Authors: Audunson Ragnar
Published: December 2005

The Bologna process aims to create a transparent European educational space. Educational programmes in LIS throughout Europe are structured according to different models and traditions, for example, LIS as an academic discipline - information science - similar to economics, sociology or history, versus a profession-oriented perspective, or models where a PhD builds upon a Masters degree which again builds upon a BA, versus a model where an MA builds upon a BA in another subject. LIS as an academic field draws on computer science and mathematics, linguistics, the social sciences, the humanities. Different programmes make different choices from which the debate on the core of LIS stems to a large extent. This situation creates challenges to LIS in relation to its adaptation to the Bologna process. Accreditation and certification are important topics. The article recommends a process approach instead of a bureaucratic and rule-oriented one. The Copenhagen workshop on European curriculum development in LIS, which took place on the 11th and 12th of August this year, is seen as important in such a gradual process towards transparency. Europeanising national evaluations and accreditations by building up a pool of European LIS experts that national accreditation bodies can utilise when programmes are to be evaluated, is also seen as important.
The public opinion climate for gene technologies in Canada and the United States: competing voices, contrasting frames
Authors: Priest Susanna Hornig
Published: December 2005

This exploratory study of Canadian and US public opinion about gene technologies is based primarily on survey data collected by the Government of Canada, with media data from a widely available commercial database (LexisNexis) used in an illustrative case study of the apparent resonance between the climate of opinion and media frames in different regions of the two countries. The study uses regression modeling, factor analysis and cluster analysis to characterize the structure of the opinion data, concluding that observed opinion differences might be understood in terms of the greater number of individuals in the United States who belong to an identifiable opinion group that believes these technologies are benign and must be developed (termed, for convenience, “true believers”), as well as a somewhat greater number in Canada who belong to a group believing that ordinary people should be able to decide based on ethical considerations (“ethical populists”). However, the most common group in each country is made up of people who believe risks or costs and benefits should be weighed in developing policy, and that this should be done by experts (“utilitarians”). This group and two other cluster groups identified in the analysis (“moral authoritarians” and “democratic pragmatists”) exist in roughly equivalent proportions in both countries, with some regional variation evident within each. While these observations represent descriptive findings only, they nevertheless underscore the complexity of the opinion climate and problematize the development of consensus policy. Preliminary analysis of news coverage of selected gene technologies revealed both similarities and differences in patterns of news discourse between Canada and the US. A sample of stem cell coverage for February 2004, following the American Association for the Advancement of Science meeting in Seattle (during which the announcement of new Korean research on human cloning was made), was used as a case study for a pilot media analysis.
Moral presentation of genetics-based narratives for public understanding of genetic science and its implications
Authors: Nisker Jeff , Daar Abdallah S.
Published: December 2005

The increasing number of sequenced genes that can be used to develop tests for inherited conditions has stimulated an increasing number of genetics-based narratives by journalists, novelists, playwrights, filmmakers, and health-care educators. Genetics-based narratives are to be welcomed if the public is to understand genetic science and its implications on persons, families, and communities. However, a number of important ethical issues insist caution in their research and presentation. Just as the requirements for informed consent to undergo genetic testing exceed the requirements for informed consent to undergo other types of medical testing because of the inherent complex relationships (such as between parent and child, gene carrier and other family members, gene carrier and ethnic community) and because of concerns regarding privacy and insurance discrimination, the requirements for informed consent to present a genetics-based narrative must exceed the requirements for informed consent to present other medical narratives. We recommend that a transmedia, multidisciplinary, international conference should be convened to develop guidelines for the moral presentation of genetics-based narratives, whose deliberations should be informed by the protections provided for narrative research participants, the requirements of consent for genetic testing (which include a counseling process involving all appropriate family members), and a professional obligation to do no harm to the persons and families whose genetics-based stories we present.
Local steps in an international career: a Danish-style consensus conference in Austria
Authors: Seifert Franz
Published: December 2005

The article gives an account of the first Austrian nationwide Danish-style consensus conference, held in the summer of 2003, treating policy issues related to genetic data. Consensus conferences are currently widely discussed for their promise to democratize fields of technological decision-making which are both crucial to the fate of modern society and inaccessible to public involvement. Instead of evaluating the “democratic efficiency” of the deliberative exercise, the essay will contextualize the event in local, as well as international developments comprising discursive, institutional and political elements. Rather than offering definitive claims about the normative significance of the rapidly diffusing deliberative technique, the discussion of a local experience with it will arrive at ambivalent conclusions.
Societal deliberation on genetically modified maize in southern Africa: the debateness and publicness of the Zambian national consultation on genetically modified maize food aid in 2002
Authors: Mwale Pascal Newbourne
Published: December 2005

In the 2001/2002 farming season, southern Africa faced acute hunger. According to UN WFP/FAO statistics, about 14 million people were on the verge of death by starvation in the region. In Zambia alone, the UN WFP/FAO estimated that about 3 million people were threatened with serious food shortages, and they would need about 630 000 metric tons of food. The UN WFP offered genetically modified (GM) maize grain, procured from the US, to various countries in the region, including Zambia. A significant debate emerged around the question of US-produced GM maize grain in the region. This regional debate around the question of GM maize was most probably aroused by the issues raised by the Zambian case. The form of this debate and the issues driving its dynamics, are interesting both in themselves and also because they reveal something about the form by which public biotechnological debate, or public controversy on biotechnology, takes in public domains. This paper is an experimental intellectual exercise, an attempt at a conceptual analysis of “public debate” as a derivative, but quintessential, concept within what is broadly conceived of as public understanding of science. Thus, this conceptual analysis is an attempt at a prolegomena for, i.e. a preparatory conceptual approach to, our understanding better what public debate on science is and how it works in practice.
Business Growth and Development Trajectories in Lagging and Remote Areas of Southern Europe
Authors: Skuras Dimitris , Meccheri Nicolas , Moreira Manuel Belo , Rosell Jordi , Stathopoulou Sophia
Published: December 2005

The resurgence of many lagging, mountainous or peripheral areas of the European Union may be attributed to the significant regional exports by firms located there. A survey in four mountainous areas of Southern Europe revealed that nearly one-third of surveyed businesses spanning the whole range of economic activities and industries sell more than 50 percent of their value of production outside the geographical boundaries of the local area. Strategic entrepreneurship creates two broad sets of ‘windows of entrepreneurial-locational opportunity’ and firms from different industries of the manufacturing sector together with firms from the services or the hospitality industries may utilize the same common stock of resources and develop the same conventions irrespective of the industry they operate in.

As such, local clusters should not be defined in terms of industries and/or sectors but in terms of common strategic entrepreneurial actions that can mix industries under common opportunities (entrepreneurship) and advantages (strategies). These firms are the mountain gazelles as they present very high growth rates and serve as paradigms and a source for innovative thought by other local entrepreneurs.
Bridal Diaspora
Authors: Rosario Teresita C. Del
Published: December 2005

In the electronic age the increase in Internet-mediated marriages constitute a new phenomenon among Filipinas who navigate the Web in search of (mostly) American spouses. This article discusses the notion of the ‘cultural logic of desire’ (Constable 2003) as the basis for Filipinas’ preference for American male spouses. This logic has been fashioned out of a specific historical relationship between the United States and the Philippines in which American cultural superiority and American benevolence provide the filters for Filipino women's marital preferences. This logic underlies these migration choices. The United States as the proverbial ‘land of milk and honey’ constitutes migrants’ first preference as a destination, and marriage as the most efficient route by which to realise migrants’ aspirations.
Marriage, Money and Gender
Authors: Sheel Ranjana
Published: December 2005

Based on fieldwork in Vancouver, British Columbia, this study examines the complex interplay of money, marriage and gender that impacts significantly upon women's status in society. In doing so, it has worked outward from its central focus to develop a general interpretation of the linkages between the vicissitudes of the immigration process, the construction of notions of culture and identity, and marriage practices and gender relations.
Vulnerable Brides and Transnational Ghar Damads
Authors: Charsley Katharine
Published: December 2005

Based on research in Pakistan and the English city of Bristol, this article examines the increasingly common practice of transnational marriages between British-born Pakistanis and Pakistani nationals, in which the latter normally migrate to join their spouses in the UK. Informants and the literature stress the risks faced by women in marriage, and these may be heightened by the increased distance between migrant brides’ natal and marital homes in transnational marriages. The challenges faced by migrant husbands in the culturally unusual position of moving to join their wives have, however, received far less attention. These are examined in terms of cultural models of marriage and migration, asymmetry in expectations of marital ‘adjustment’ and compromise, masculinity and the position of the uxorilocally resident son-in-law (ghar damad). It is suggested that this approach, which recognises the relational character of gender, has much to contribute to the understanding of the dynamics of transnational marriages, including insights on marriages that have ended with the husband's violence or desertion.
The Impact of a Caregiver Health Education Program on Health Care Costs
Authors: Toseland Ronald W. , Smith Tamara L.
Published: December 2005

Objectives: This study examined health care cost outcomes resulting from a health education program (HEP), a social work intervention for spouse caregivers of frail older adults. Method: One-hundred five spouses were recruited and randomly assigned to HEP or usual care (UC). Health care utilization and cost data were collected from the HMO's management information system for both the spouse caregivers and care recipients in quarterly increments for a 30-month period. Results: The results indicate that HEP was cost-effective. Caregivers and care recipients who participated in HEP had significantly lower overall health care costs and significantly lower outpatient costs than those who participated in usual care. Conclusions: By 2 years, total cost savings for caregivers and care recipients who participated in HEP was $309,461.14. HEP is a cost-effective intervention for caregivers and care recipients receiving medical care from a staff-model HMO.
Long-Term Effects of Outpatient Geriatric Evaluation and Management on Health Care Utilization, Cost, and Survival
Authors: Engelhardt Joseph B. , Toseland Ronald W. , Gao Jian , Banks Steven
Published: December 2005

Purpose: The long-term effectiveness and efficiency of an outpatient geriatric evaluation and management (GEM) program was compared to usual primary care (UPC). Design and Method: A randomized controlled group design was used. Health care utilization, cost of care, and survival were assessed during a 48-month period among a sample of 160 male veterans age 55 and over who were above-average users of outpatient services. Results: The results indicate that GEM patients incurred significantly lower overall health care costs than UPC patients by 24 months and that cost savings plateaued during the 24- to 48-month period. Cost savings were due primarily to fewer hospital days of care. No significant differences were found in survival. Implications: Results of this follow-up study suggest that outpatient GEMoffers a specialized health delivery option for frail older persons that may reduce costs over the long term without having a negative impact on survival rates.
Choosing Outcome Measures in Systematic Reviews: Critical Challenges
Authors: Mullen Edward J.
Published: December 2005

There are a number of challenges facing those who set out to conduct systematic reviews of intervention effects in the social sciences. These challenges include formulation of a review problem, gathering data about relevant studies and outcomes, analyzing that data, and interpreting the results. The first challenge, formulating a workable review problem, includes three subchallenges: delimiting interventions, specifying the intervention targets including problems and populations, and choosing outcome measures. This article examines the challenge of how to choose outcome measures.
Housing First Services for People Who Are Homeless With Co-Occurring Serious Mental Illness and Substance Abuse
Authors: Padgett Deborah K. , Gulcur Leyla , Tsemberis Sam
Published: December 2005

The literature on homeless adults with severe mental illness is generally silent on a critical issue surrounding service delivery—the contrast between housing first and treatment first program philosophies. This study draws on data from a longitudinal experiment contrasting a housing first program (which offers immediate permanent housing without requiring treatment compliance or abstinence) and treatment first (standard care) programs for 225 adults who were homeless with mental illness in New York City. After 48 months, results showed no significant group differences in alcohol and drug use. Treatment first participants were significantly more likely to use treatment services. These findings, in combination with previous reports of much higher rates of housing stability in the housing first group, show that “dual diagnosed” adults can remain stably housed without increasing their substance use. Thus, housing first programs favoring immediate housing and consumer choice deserve consideration as a viable alternative to standard care.
An Emerging Framework for Including Different Types of Evidence in Systematic Reviews for Public Policy
Authors: Oliver Sandy , Harden Angela , Rees Rebecca , Shepherd Jonathan , Brunton Ginny , Garcia Jo , Oakley Ann
Published: December 2005

Evidence-informed policy and practice call on research addressing a broad range of research questions: evaluating the need for, and development, implementation, acceptability and effectiveness of interventions. Synthesizing this evidence requires methods that integrate the findings from diverse study designs. This article reports the development of a new model of research synthesis for this purpose. On completion of a series of substantive reviews, methodological reflections addressed: the interrelationship between review questions, relevant theory and values within the review process; methodological similarities and differences with more conventional reviews of effectiveness; the added value in terms of conclusions and specific recommendations; and the relevance to public policy.
Medical sociology and the biological body: where are we now and where do we go from here?
Authors: Williams Simon J.
Published: December 2005

In this article I pose the question, ‘where is the biological body in medical sociology today?’ The first part of the article provides a selective corporeal balance sheet of where we are now in medical sociology, with particular reference to social constructionist and phenomenological approaches and their respective stances or takes on the (biological) body. The subsequent section considers where we might profitably be going in the future in terms of bringing the biological body (back) in, and the broader issues this raises for the sociological enterprise as a whole. Various problems associated with this evolving project and merits of other recent approaches, such as the sociology of translation, are considered. The article concludes with some further thoughts and reflections on these matters, including a revisiting of relations between the sociology of the body and medical sociology in the light of these debates.
A preliminary investigation into factors influencing limiting long-standing illness among UK university graduates: a retrospective cohort study
Authors: Markham Wolfgang A. , Aveyard Paul , Bullock Alison , Thomas Hywel
Published: December 2005

Two competing hypotheses underpinned an investigation into limiting long-standing illness (LLI) among UK graduates. Hypothesis 1 proposed childhood social class (CSC) influences LLI independently of educational attainment and adult income. Hypothesis 2 proposed typical middle-class graduates would have lower LLI prevalence than typical and atypical working-class and atypical middle-class graduates. Working/ middleclass refers to childhood circumstances. Atypical/typical refers to full-time employment duration before attending university. Graduates (1985; N= 5093 and 1990; N= 8147) were followed up in 1996. Logistic regression was used to examine LLI in 1996 by CSC only and CSC, atypical graduate status and their interaction, adjusting for age and adult income. Hypothesis 1 was not confirmed. Hypothesis 2 was partially confirmed. Typical middle-class graduates had a lower LLI prevalence than typical working-class and atypical middle-class graduates. These results support the idea that opportunities for good human functioning are culturally determined and affect health.
High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis
Authors: De Tommaso Adriana MA , Andrade Paula D , Costa Sandra CB , Escanhoela Cecília AF , Hessel Gabriel
Published: December 2005

Background

Biliary atresia (BA) is the most severe hepatic disorder in newborns and its etiopathogenesis remains unknown. Viral involvement has been proposed, including the human cytomegalovirus (HCMV). The aims of the study were to use the polymerase chain reaction (PCR) to screen the liver tissue of infants with extrahepatic cholestasis for HCMV and to correlate the results with serological antibodies against HCMV and histological findings.

Methods

A retrospective study in a tertiary care setting included 35 patients (31 BA, 1 BA associated with a choledochal cyst, 2 congenital stenosis of the distal common bile duct and 1 hepatic cyst). HCMV serology was determined by ELISA. Liver and porta hepatis were examined histologically. Liver samples from infants and a control group were screened for HCMV DNA.

Results

Twelve patients had HCMV negative serology, 9 were positive for IgG antibodies and 14 were positive for IgG and IgM. Nine liver and seven porta hepatis samples were positive for HCMV DNA but none of the control group were positive (general frequency of positivity was 34.3% – 12/35). There was no correlation between HCMV positivity by PCR and the histological findings. The accuracy of serology for detecting HCMV antibodies was low.

Conclusion

These results indicate an elevated frequency of HCMV in pediatric patients with extrahepatic neonatal cholestasis. They also show the low accuracy of serological tests for detecting active HCMV infection and the lack of correlation between HCMV positivity by PCR and the histopathological changes.
Correlates of health and healthcare performance: applying the Canadian health indicators framework at the provincial-territorial level
Authors: Arah OA , Westert GP
Published: December 2005

Background

Since, at the health system level, there is little research into the possible interrelationships among the various indicators of health, healthcare performance, non-medical determinants of health, and community and health system characteristics, we conducted this study to explore such interrelationships using the Canadian Health Indicators Framework.

Methods

We conducted univariate correlational analyses with health and healthcare performance as outcomes using recent Canadian data and the ten Canadian provinces and three territories as units of the analyses. For health, 6 indicators were included. Sixteen healthcare performance indicators, 12 non-medical determinants of health and 16 indicators of community and health system characteristics were also included as independent variables for the analysis. A set of decision rules was applied to guide the choice of what was considered actual and preferred performance associations.

Results

Health (28%) correlates more frequently with non-medical determinants than healthcare does (12%), in the preferred direction. Better health is only correlated with better healthcare performance in 13% of the cases in the preferred direction. Better health (24%) is also more frequently correlated with community and health system characteristics than healthcare is (13%), in the preferred direction.

Conclusion

Canadian health performance is a function of multiple factors, the most frequent of which may be the non-medical determinants of health and the community characteristics as against healthcare performance. The contribution of healthcare to health may be limited only to relatively small groups which stand to benefit from effective healthcare, but its overall effect may be diluted in summary measures of population health. Interpreting multidimensional, multi-indicator performance data in their proper context may be more complex than hitherto believed.
Cell biology as the basis of a better understanding of cancer
Authors: Wheatley Denys N
Published: December 2005

Clinicians will argue that cancer can only really receive the treatment that is needed through thorough understanding of medicine. However, even empirical approaches to therapy result in experimental analysis of the agencies involved on test cells, usually in culture. From the obverse perspective, cell biologists will argue that until we fully understand cell cycle regulation, tumour management will be too imprecise to make the best advances. A forum is needed whereby the fundamental studies on cells prior to, during and after transformation in vitro can be freely reported (open access) and discussed. The action of anticancer agents and cancer preventative substances can more easily be studied in vitro before the often excessive complexity of making similar studies in experimental and human cancers is tackled. Cancer Cell International is committed to providing such a forum. Ironically within a few months of launching this open access journal, Elsevier had much the same idea, and there one has to pay for the privilege of downloading vital papers in this biomedical field.
A low-carbohydrate, ketogenic diet to treat type 2 diabetes
Authors: Yancy William S , Foy Marjorie , Chalecki Allison M , Vernon Mary C , Westman Eric C
Published: December 2005

Background

The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes.

Methods

From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A1c.

Results

Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0 ± 7.9 years and BMI was 42.2 ± 5.8 kg/m2. Hemoglobin A1c decreased by 16% from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A1c. Fasting serum triglyceride decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly.

Conclusion

The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.
Auditory processing in individuals with auditory neuropathy
Authors: Kumar Ajith U , Jayaram M
Published: December 2005

Background

Auditory neuropathy is a disorder characterized by no or severely impaired auditory brainstem responses in presence of normal otoacoustic emissions and/or cochlear microphonics. Speech perception abilities in these individuals are disproportionate to their hearing sensitivity and reported to be dependent on cortical evoked potentials and temporal processing abilities. The disproportionate loss of auditory percept in presence of normal cochlear function is suggestive of impairment of auditory neural synchrony.

Methods

We studied the auditory evoked potentials and psychophysical abilities in 14 adults with auditory neuropathy to characterize their perceptual capabilities. Psychophysical tests included measurement of open set speech identification scores, just noticeable difference for transition duration of syllable /da/ and temporal modulation transfer function. Auditory evoked potentials measures were, recording of P1/N1, P2/N2 complex and mismatch negativity (MMN).

Results

Results revealed a significant correlation between temporal processing deficits and speech perception abilities. In majority of individuals with auditory neuropathy P1/N1, P2/N2 complex and mismatch negativity could be elicited with normal amplitude and latency. None of the measured evoked potential parameters correlated with the speech perception scores. Many of the subjects with auditory neuropathy showed normal MMN even though they could not discriminate the stimulus contrast behaviorally.

Conclusion

Conclusions drawn from the study are

1. Individuals with auditory neuropathy have severely affected temporal processing.

2. The presence of MMN may not be directly linked to presence of behavioral discrimination and to speech perception capabilities at least in adults with auditory neuropathy.
Polarized subsets of human T-helper cells induce distinct patterns of chemokine production by normal and systemic sclerosis dermal fibroblasts
Authors: Chizzolini Carlo , Parel Yann , Scheja Agneta , Dayer Jean-Michel
Published: December 2005

The role of fibroblasts in inflammatory processes and their cross-talk with T cells is increasingly being recognized. Our aim was to explore the capacity of dermal fibroblasts to produce inflammatory chemokines potentially involved in fibrosis occurring in response to contact with polarized human T cells. Our findings indicate that the program of chemokine production by fibroblasts is differentially regulated depending on the T-helper (Th) cell subset used to activate them. Thus, Th1 and Th2 cells preferentially induced production of IFN-γ inducible protein (IP)-10 and IL-8, respectively, whereas monocyte chemoattractant protein (MCP)-1 was equally induced by both subsets at mRNA and protein levels. Neutralization experiments indicated that membrane-associated tumour necrosis factor-α and IL-1 played a major role in the induction of IL-8 and MCP-1 by Th1 and Th2 cells, whereas membrane-associated IFN-γ (present only in Th1 cells) was responsible, at least in part, for the lower IL-8 and higher IP-10 production induced by Th1 cells. The contributions of tumour necrosis factor-α, IL-1 and IFN-α were confirmed when fibroblasts were cultured separated in a semipermeable membrane from living T cells activated by CD3 cross-linking. We observed further differences when we explored signal transduction pathway usage in fibroblasts. Pharmacological inhibition of c-Jun N-terminal kinase and nuclear factor-κB resulted in inhibition of IL-8 mRNA transcription induced by Th1 cells but not that by Th2 cells, whereas inhibition of MEK/ERK (mitogen-activated protein kinase of extracellular signal-regulated kinase/extracellular signal-regulated kinase) and nuclear factor-κB resulted in inhibition of MCP-1 mRNA induced by Th2 but not by Th1 cells. Finally, no distinct differences in chemokine production were observed when the responses to T cell contact or to prototypic Th1 and Th2 cytokines were examined in systemic sclerosis versus normal fibroblasts. These findings indicate that fibroblasts have the potential to participate in shaping the inflammatory response through the activation of flexible programs of chemokine production that depend on the Th subset eliciting their response.
Uncovering the Richness of the Stimulus: Structure Dependence and Indirect Statistical Evidence
Authors: Reali Florencia , Christiansen Morten H.
Published: December 2005

The poverty of stimulus argument is one of the most controversial arguments in the study of language acquisition. Here we follow previous approaches challenging the assumption of impoverished primary linguistic data, focusing on the specific problem of auxiliary (AUX) fronting in complex polar interrogatives. We develop a series of corpus analyses of child‐directed speech showing that there is indirect statistical information useful for correct auxiliary fronting in polar interrogatives and that such information is sufficient for distinguishing between grammatical and ungrammatical generalizations, even in the absence of direct evidence. We further show that there are simple learning devices, such as neural networks, capable of exploiting such statistical cues, producing a bias toward correct AUX questions when compared to their ungrammatical counterparts. The results suggest that the basic assumptions of the poverty of stimulus argument may need to be reappraised.
Distinguishing Between Causes and Enabling Conditions—Through Mental Models or Linguistic Cues?
Authors: Kuhnmünch Gregory , Beller Sieghard
Published: December 2005

The mental model theory of naive causal understanding and reasoning (Goldvarg & Johnson‐Laird, 2001, Cognitive Science, 25, 565–610) claims that people distinguish between causes and enabling conditions on the basis of sets of models that represent possible causal situations. In the tasks used to test this hypothesis, however, the proposed set of models was confounded with linguistic cues that frame which event to assume as given (the enabling condition) and which to consider as responsible for the effect under this assumption (the cause). By disentangling these two factors, we were able to show that when identifying causes and enabling conditions in these tasks, people rely strongly on the linguistic cues but not on the proposed set of models and that this set of models does not even reflect people's typical interpretation of the tasks. We propose an alternative explanation that integrates syntactic and causal considerations.
p38 MAPK is essential for secondary axis specification and patterning in sea urchin embryos
Authors: Bradham Cynthia A. , McClay David R.
Published: December 2005

Most eggs in the animal kingdom establish a primary, animal-vegetal axis maternally, and specify the remaining two axes during development. In sea urchin embryos, the expression of Nodal on the oral (ventral) side of the embryo is the first known molecular determinant of the oral-aboral axis (the embryonic dorsoventral axis), and is crucial for specification of the oral territory. We show that p38 MAPK acts upstream of Nodal and is required for Nodal expression in the oral territory. p38 is uniformly activated early in development, but, for a short interval at late blastula stage, is asymmetrically inactivated in future aboral nuclei. Experiments show that this transient asymmetry of p38 activation corresponds temporally to both oral specification and the onset of oral Nodal expression. Uniform inhibition of p38 prevents Nodal expression and axis specification, resulting in aboralized embryos. Nodal and its target Gsc each rescue oral-aboral specification and patterning when expressed asymmetrically in p38-inhibited embryos. Thus, our results indicate that p38 is required for oral specification through its promotion of Nodal expression in the oral territory.