bluuebunny/crossref_metadata_2025 huggingface dataset:
School-Based Drug Prevention Among At-Risk Adolescents: Effects of ALERT Plus
Authors: Longshore Douglas , Ellickson Phyllis L. , McCaffrey Daniel F. , Clair Patricia A. St.
Published: June 2007

In a recent randomized field trial, Ellickson et al. found the Project ALERT drug prevention curriculum curbed alcohol misuse and tobacco and marijuana use among eighth-grade adolescents. This article reports effects among ninth-grade at-risk adolescents. Comparisons between at-risk girls in ALERT Plus schools (basic curriculum extended to ninth grade with five booster lessons) and at-risk girls in control schools showed the program curbed weekly alcohol and marijuana use, at-risk drinking, alcohol use resulting in negative consequences, and attitudinal and perceptual factors conducive to drug use. Program-induced changes in perceived social influences, one's ability to resist those influences, and beliefs about the consequences of drug use mediated the ALERT Plus effects on drug use. No significant effects emerged for at-risk boys or at-risk adolescents in schools where the basic ALERT curriculum (covering seventh and eighth grades only) was delivered. Possible reasons for gender differences and implications for prevention programming are discussed.
Inside a maximum-security juvenile training school
Authors: Inderbitzin Michelle
Published: June 2007

The focus of this article is on attempts within a juvenile correctional facility to `normalize' adolescent inmates and to deflate or redirect their goals and aspirations. Many young offenders have been socialized to fully embrace the `American Dream'. For the teenage boys in this study, the American Dream was about the attainment of wealth and masculine prestige. Lacking legitimate opportunities to attain wealth through conforming means, most turned to criminal enterprises, leading to their incarceration. In this article, I argue that juvenile correctional facilities are one of the last bastions of the `old penology' and one latent task of such institutions is to level the aspirations of young inmates so that they will face fewer anomic conditions when released back into the community. Drawing on ethnographic research of a cottage for violent offenders at one state's maximum-security juvenile training school, I demonstrate how cottage staff members play a central role in modeling conforming behaviors, strategies and attitudes for their institutional `sons', encouraging the boys to `aim low' and adopt aspirations and goals more in line with the opportunities available to them in the community.
The emergence of sentencing hearings
Authors: Horovitz Anat
Published: June 2007

The aim of this essay is to contribute to the understanding of the neglected topic of sentencing hearings, by describing the historical circumstances that led to the emergence of distinct sentencing hearings within the criminal trial. The novel account offered in this essay suggests that sentencing hearings evolved as a partially unintended result of the massive changes in the adversarial trial that took place during the second part of the 18th century. As a result of these changes, sentencing hearings began to emerge at the end of the 18th century. These findings stand in contradiction to various suggestions made in American case-law and law review articles, which linked the development of sentencing hearings to the rise of the rehabilitation model at the end of the 19th century.
The enemy on the border
Authors: Krasmann Susanne
Published: June 2007

So-called enemy penology is the invention of a German professor of criminal law. In a Foucauldian perspective, however, it turns out not to be a singular phenomenon. Instead it is a programme asserting itself as a strategy for solving contemporary security problems; it also assumes its place among developments that should be seen in the national as well as in the international area of criminal justice and security policy. These developments provoke a transformation of the constitutional state, challenging its hitherto valid principles and rearranging the relation between violence and right. This transformation occurs surreptitiously, since the security strategies promoting it do not appear violent, but, instead, preventive. They are based on a demarcation making certain distinctions — like those between a threatening enemy and a population that has to be protected — possible and appear unambiguous. Enemy penology is exemplary of prevailing tendencies in security policies, going all the way to Guantánamo. In the following, these will be read in a Foucauldian perspective as a renaissance of sovereign power in the name of population management.
Confused because exposed
Authors: Auyero Javier , Swistun Debora
Published: June 2007

Based on long-term collaborative ethnographic fieldwork in a shantytown called Flammable (real name) located in Argentina, this article examines residents' perceptions of their highly polluted surroundings. Using a case study to explore the relationship between objective space and subjective representations (habitat and habitus), the article a) describes the widespread confusion that dominates shantytown dwellers' views of contamination, and b) argues that this confusion translates into self-doubts, division, stigma, and a continual waiting time. The article ends with an empirically grounded speculation regarding the sources of toxic uncertainty.
Learning through the breach
Authors: Jacobs-Huey Lanita
Published: June 2007

In this article, I analyze a series of breaches (Garfinkel, 1967) observed during an 18-month ethnographic study of an African American cosmetology school in South Carolina. Students, clients, teachers (and this author) committed endless verbal and nonverbal mistakes during everyday hair care encounters. They also employed an array of cultural and professional communicative strategies to resolve them. Their candid deliberations over what went wrong or was supposed to happen in client-stylist and stylist-stylist negotiations provide critical insights into the role of language in marking hair care expertise. Their evaluations also underscore the importance of speaker intentionality and accountability, as well as the virtues of forgiveness, within African American women's hair care practices. Moreover, their breach assessments clarify what is at stake in terms of professionalism and clientdom for African American stylists, their predominantly Black female clientele, and a vulnerable constituency of cosmetology students when mistakes are made at the level of language and representation.
Imagining the `iron cage'
Authors: Nugent Paul D. , Abolafia Mitchel Y.
Published: June 2007

In this article we argue that the rhetorical power of critical ethnography cannot be fully explained by current concepts in rhetorical studies. Although rhetorical studies acknowledge the role played by sympathy and imagination, they have not recognized the extent to which organizational ethnographers elicit the identification of readers with characters through the depiction of `hidden emotions.' Hidden emotions are those that are subjectively experienced but not publicly expressed. They tend to be depicted in situations in which characters are faced with evaluative judgment or the potential for such judgment. Rhetorical data from four widely-read critical ethnographies were analyzed using this framework. The analysis revealed strong patterns in the ways the ethnographers portray characters experiencing hidden emotions in controlling institutional contexts. It is through this strategy that the authors are able to succeed in their narrative aims to elaborate Max Weber's `iron cage.'
Constructing (Film) Art: Bourdieu's Field Model in a Comparative Context
Authors: Heise Tatiana , Tudor Andrew
Published: June 2007

In this paper we seek to apply Bourdieu’s approach to consecration, legitimacy and autonomization in the fields of art to the struggle to legitimize film as art.We examine the efficacy of Bourdieu’s theory in relation to the early ‘film-as-art’ campaign as it received institutional expression in the profoundly different economic, social and cultural circumstances of Brazil and Britain in the 1920s and 1930s. After tracing the broad history of film art movements in each case,we employ Bourdieu’s concepts of heteronomy/autonomy and degree of consecration as the principal axes in mapping the fields of film art in Britain and Brazil.We then compare the conditions of possibility for failure or success in institutionally establishing film as art in the two cases, and conclude with an evaluation of the utility of Bourdieu’s model when applied to film art in such diverse social, cultural and political circumstances.
Accomplishing Journalism: Towards a Revived Sociology of a Media Occupation
Authors: Dickinson Roger
Published: June 2007

This article sets out a case for a revived sociology of media work. It suggests that a certain sociological approach, neglected for some time, offers the promise of (a) providing a more rounded sociological account of journalistic practice that (b) will help us better understand what journalists do and how and why they do it, (c) will ultimately help us better understand the process of news production and message creation, and (d) may have wider applicability for the study of occupations in the realm of cultural production.The article argues that there is still much to be gained from sociologically informed empirical enquiry into the work of journalists. The examples of journalists’ mistakes and the ways journalists regulate and control each others’ work are used to illustrate the case. This involves an analytical framework built on the concept of journalism as an occupational accomplishment.
Why Salem Made Sense: Culture, Gender, and the Puritan Persecution of Witchcraft
Authors: Reed Isaac
Published: June 2007

Sociological explanations of the Salem witch trials, and of witch-hunts in the West more generally, have focused on economic transition, political instability, and the functional aspects of witchcraft belief. A more interpretive approach to the explanation of Salem is proposed: an analysis of the intersection of the gendered symbolization of witchcraft in colonial Massachusetts and the larger tensions within Puritan culture at the close of the 17th century. A broad theoretical implication of this interpretive shift is also proposed: that a cultural-sociological approach to witch-hunting as symbolic action can bring together feminist theorizations of witch-hunting as an exercise in patriarchal power with the social history of the broad, structural causes of witchhunting in pre-modern Europe and New England.
From the Narrative of the Blitz to the Rhetoric of Vulnerability
Authors: Furedi Frank
Published: June 2007

Through comparing the cultural representations of the floods of the 1950s with those of the year 2000, this article explores the changing conceptualizations of adversity in Britain.The focus of this study is the shift from a narrative of resilience in the 1950s to a narrative of vulnerability in the early 21st century.This shift is paralleled by a reorientation of cultural scripts from an emphasis on community solidarity to individual distress. This article contends that both the representations of how a community copes with a disaster, and people’s lived experiences of disasters, were influenced by this shift.Through exploring the evolution of the cultural narrative of adversity, its changing meaning is discussed.
Apoptosis is a natural stimulus of IL6R shedding and contributes to the proinflammatory trans-signaling function of neutrophils
Authors: Chalaris Athena , Rabe Björn , Paliga Krzysztof , Lange Hans , Laskay Tamas , Fielding Ceri A. , Jones Simon A. , Rose-John Stefan , Scheller Jürgen
Published: June 2007

Interleukin 6 (IL6) trans-signaling has emerged as a prominent regulator of immune responses during both innate and acquired immunity. Regulation of IL6 trans-signaling is reliant upon the release of soluble IL6 receptor (sIL6R), which binds IL6 to create an agonistic IL6/sIL6R complex capable of activating cell types that would not normally respond to IL6 itself. Here we show that intrinsic and extrinsic apoptotic stimulation by DNA damage, cytokine deprivation, and Fas stimulation promotes shedding of sIL6R. Apoptosis-induced shedding of the IL6R was caspase dependent but PKC independent, with inhibition of ADAM17 preventing IL6R shedding. Such insight is relevant to the control of acute inflammation, where transition from the initial neutrophil infiltration to a more sustained population of mononuclear cells is essential for the resolution of the inflammatory process. This transitional event is governed by IL6 trans-signaling. This study demonstrates that IL6R is shed from apoptotic human neutrophils. In vivo studies in a murine inflammation model showed that neutrophil depletion resulted in reduced local sIL6R levels and a concomitant decrease in mononuclear cells, suggesting that apoptosis-induced IL6R shedding from neutrophils promotes IL6 trans-signaling and regulates the attraction of monocytic cells involved in the clearance of apoptotic neutrophils.
Polymorphisms and functional activity in superoxide dismutase and catalase genes in smokers with COPD
Authors: Mak J. C. W. , Ho S. P. , Yu W. C. , Choo K. L. , Chu C. M. , Yew W. W. , Lam W. K. , Chan-Yeung M.
Published: June 2007

Increased oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study investigated the risk of COPD and the substitution of alanine 16 with valine (Ala16Val) polymorphism of manganese-superoxide dismutase (Mn-SOD) and the cytosine to thymidine transition of nucleotide -262 (-262C>T) polymorphism of the catalase gene, and the activity of erythrocyte SOD and catalase.

The subjects were stable COPD patient ever smokers (n = 165) and healthy controls, matched for age and cigarette consumption. Genotyping of Mn-SOD at Ala16Val and the catalase gene at -262C>T was performed, and the functional activity of SOD and catalase in erythrocytes determined.

There were no significant differences in the distribution of the different genotypes or allele frequencies between patients and controls for both the Mn-SOD and catalase genes. Among healthy controls or COPD patients, no differences were observed in erythrocyte SOD and catalase activity, irrespective of genotype. Significantly higher erythrocyte catalase activity was found in COPD patients than in healthy controls. The T/T catalase genotype and Ala/Ala Mn-SOD genotype were uncommon in the present Chinese population.

The increase in erythrocyte catalase activity in Chinese patients with chronic obstructive pulmonary disease probably indicates dysfunction of the oxidant/antioxidant defence system, but it is unclear whether this increase is compensatory or a pathogenic factor.
A 10-year prospective surveillance ofMycobacterium tuberculosisdrug resistance in France 1995–2004
Authors: Khuê P. M. , Truffot-Pernot C. , Texier-Maugein J. , Jarlier V. , Robert J.
Published: June 2007

Drug resistance surveillance and trend monitoring resistance rates bring some insights into tuberculosis (TB) control. The current study reports the characteristics of TB and drug resistance during a 10-yr prospective surveillance of culture-positive TB in France.

Data for the current study was collected from 1995–2004viaa sentinel network of laboratories from university hospitals that complied with the international recommendations for the surveillance of drug resistance. Susceptibility test results were performed in each individual laboratory.

Data on 13,283 patients were collected during the 10-yr period, 49% of whom had been born in France, 10% were HIV co-infected and 8% had previously been treated. As expected, previously treated and HIV co-infected patients were more likely to harbour resistant strains, especially rifampicin (RMP)-resistant strains. Among new patients, the mean resistance rate to at least one drug was 8.8%, and there was an upward trend in resistance to isoniazid and RMP (0.8–1%) related to the increase in the proportion of patients who had been born outside of France (38–53%). Among previously treated patients, the mean resistance rate to one drug was 20.6% and there was no significant time trend in resistance rates.

The sentinel network provided valuable data on trends regarding the characteristics of tuberculosis and on drug resistance rates and reinforced the interest of analysing data by country of birth and history of treatment.
Early discharge of patients with pulmonary embolism: a two-phase observational study
Authors: Davies C. W. H. , Wimperis J. , Green E. S. , Pendry K. , Killen J. , Mehdi I. , Tiplady C. , Kesteven P. , Rose P. , Oldfield W.
Published: June 2007

The aim of the present study was to assess whether patients with pulmonary embolism (PE) could be managed as outpatients after early discharge from hospital using low molecular weight heparin instead of remaining as in-patients until effective oral anticoagulation was achieved.

Phase 1 of the study identified criteria for the safe discharge of selected patients; phase 2 treated a cohort of low-risk patients with PE as outpatients with tinzaparin using existing deep venous thrombosis services.

In phase 1, 127 (56.4%) of 225 patients were considered unsuitable for outpatient management. Reasons included: admission for another medical reason; additional monitoring or requirement for oxygen; bleeding disorders; previous PE/further PE while on warfarin; co-existing major deep venous thrombosis; likelihood of poor compliance; significant immobility; and pregnancy. In phase 2, 157 patients with PE received outpatient anticoagulation therapy. There were no deaths, bleeding or recurrent thromboembolic events during acute treatment with low molecular weight heparin. The median (range) length of hospital stay was 1.0 (1–4) day, with a median saving of 5.0 (1–42) bed-days per patient.

Patients were highly satisfied with outpatient management; 144 (96.6%) indicated that they would prefer treatment as outpatients for a subsequent pulmonary embolism. Early discharge and outpatient management of pulmonary embolism appears safe and acceptable in selected low-risk patients, and can be implemented using existing outpatient deep venous thrombosis services.
Use of tunnelled catheters for malignant pleural effusions in patients fit for pleurodesis
Authors: Tremblay A. , Mason C. , Michaud G.
Published: June 2007

The aim of the present study was to examine the effectiveness of tunnelled pleural catheters (TPC) in patients with malignant pleural effusions who would otherwise be candidates for pleurodesis.

Patients were selected from a previously reported database of 250 TPC insertions. The study group was selected based on lung re-expansion and survival as a surrogate maker of eligibility for pleurodesis procedure, as defined by survival of ≥90 days and lung re-expansion ≥80% post-drainage on a standard chest radiograph 2 weeks post TPC placement.

There were 109 procedures in 97 patients that met the entry criteria. Spontaneous pleurodesis (SP) was achieved following 70% of procedures and correlated with symptom control. The mean time to SP was 90 days. There was no need for a repeat procedure in 87% of cases overall and in 92% of patients experiencing SP. There were few complications and no procedure-related deaths.

Tunnelled pleural catheters are an effective way of controlling malignant pleural effusions when used as first-line treatment in patients who appear to be candidates for pleurodesis procedures.
Evaluation of sample size effect on the identification of haplotype blocks
Authors: Osabe Dai , Tanahashi Toshihito , Nomura Kyoko , Shinohara Shuichi , Nakamura Naoto , Yoshikawa Toshikazu , Shiota Hiroshi , Keshavarz Parvaneh , Yamaguchi Yuka , Kunika Kiyoshi , Moritani Maki , Inoue Hiroshi , Itakura Mitsuo
Published: June 2007

Background

Genome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation.

Results

A region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with θ value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times.

Conclusion

These analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research.
The Entamoeba histolytica genome: primary structure and expression of proteolytic enzymes
Authors: Tillack Manuela , Biller Laura , Irmer Henriette , Freitas Michelle , Gomes Maria A , Tannich Egbert , Bruchhaus Iris
Published: June 2007

Background

A number of studies have shown that peptidases and in particular cysteine peptidases constitute major pathogenicity factors in Entamoeba histolytica. Recent studies have suggested that a considerable number of genes coding for proteolytic enzymes are present within the E. histolytica genome and questions remain about the mode of expression of the various molecules.

Results

By homology search within the recently published amoeba genome, we identified a total of 86 E. histolytica genes coding for putative peptidases, including 46 recently described peptidase genes. In total these comprise (i) 50 cysteine peptidases of different families but most of which belong to the C1 papain superfamily, (ii) 22 different metallo peptidases from at least 11 different families, (iii) 10 serine peptidases belonging to 3 different families, and (iv) 4 aspartic peptidases of only one family. Using an oligonucleotide microarray, peptidase gene expression patterns of 7 different E. histolytica isolates as well as of heat stressed cells were analysed. A total of 21 out of 79 amoeba peptidase genes analysed were found to be significantly expressed under standard axenic culture conditions whereas the remaining are not expressed or at very low levels only. In heat-stressed cells the expression of 2 and 3 peptidase genes, respectively, were either decreased or increased. Only minor differences were observed between the various isolates investigated, despite the fact that these isolates were originated from asymptomatic individuals or from patients with various forms of amoebic diseases.

Conclusion

Entamoeba histolytica possesses a large number of genes coding for proteolytic enzymes. Under standard culture conditions or upon heat-stress only a relatively small number of these genes is significantly expressed and only very few variations become apparent between various clinical E. histolytica isolates, calling into question the importance of these enzymes in E. histolytica pathogenicity. Further studies are required to define the precise role of most of the proteolytic enzyme for amoeba cell biology but in particular for E. histolytica virulence.
A global view of Staphylococcus aureus whole genome expression upon internalization in human epithelial cells
Authors: Garzoni Christian , Francois Patrice , Huyghe Antoine , Couzinet Sabine , Tapparel Caroline , Charbonnier Yvan , Renzoni Adriana , Lucchini Sacha , Lew Daniel P , Vaudaux Pierre , Kelley William L , Schrenzel Jacques
Published: June 2007

Background

Staphylococcus aureus, a leading cause of chronic or acute infections, is traditionally considered an extracellular pathogen despite repeated reports of S. aureus internalization by a variety of non-myeloid cells in vitro. This property potentially contributes to bacterial persistence, protection from antibiotics and evasion of immune defenses. Mechanisms contributing to internalization have been partly elucidated, but bacterial processes triggered intracellularly are largely unknown.

Results

We have developed an in vitro model using human lung epithelial cells that shows intracellular bacterial persistence for up to 2 weeks. Using an original approach we successfully collected and amplified low amounts of bacterial RNA recovered from infected eukaryotic cells. Transcriptomic analysis using an oligoarray covering the whole S. aureus genome was performed at two post-internalization times and compared to gene expression of non-internalized bacteria. No signs of cellular death were observed after prolonged internalization of Staphylococcus aureus 6850 in epithelial cells. Following internalization, extensive alterations of bacterial gene expression were observed. Whereas major metabolic pathways including cell division, nutrient transport and regulatory processes were drastically down-regulated, numerous genes involved in iron scavenging and virulence were up-regulated. This initial adaptation was followed by a transcriptional increase in several metabolic functions. However, expression of several toxin genes known to affect host cell integrity appeared strictly limited.

Conclusion

These molecular insights correlated with phenotypic observations and demonstrated that S. aureus modulates gene expression at early times post infection to promote survival. Staphylococcus aureus appears adapted to intracellular survival in non-phagocytic cells.
Functional distribution of Ca2+-coupled P2 purinergic receptors among adrenergic and noradrenergic bovine adrenal chromaffin cells
Authors: Tomé Ângelo R , Castro Enrique , Santos Rosa M , Rosário Luís M
Published: June 2007

Background

Adrenal chromaffin cells mediate acute responses to stress through the release of epinephrine. Chromaffin cell function is regulated by several receptors, present both in adrenergic (AD) and noradrenergic (NA) cells. Extracellular ATP exerts excitatory and inhibitory actions on chromaffin cells via ionotropic (P2X) and metabotropic (P2Y) receptors. We have taken advantage of the actions of the purinergic agonists ATP and UTP on cytosolic free Ca2+concentration ([Ca2+]i) to determine whether P2X and P2Y receptors might be asymmetrically distributed among AD and NA chromaffin cells.

Results

The [Ca2+]iand the [Na+]iwere recorded from immunolabeled bovine chromaffin cells by single-cell fluorescence imaging. Among the ATP-sensitive cells ~40% did not yield [Ca2+]iresponses to ATP in the absence of extracellular Ca2+(Ca2+o), indicating that they expressed P2X receptors and did not express Ca2+- mobilizing P2Y receptors; the remainder expressed Ca2+-mobilizing P2Y receptors. Relative to AD-cells approximately twice as many NA-cells expressed P2X receptors while not expressing Ca2+- mobilizing P2Y receptors, as indicated by the proportion of cells lacking [Ca2+]iresponses and exhibiting [Na+]iresponses to ATP in the absence and presence of Ca2+o, respectively. The density of P2X receptors in NA-cells appeared to be 30–50% larger, as suggested by comparing the average size of the [Na+]iand [Ca2+]iresponses to ATP. Conversely, approximately twice as many AD-cells expressed Ca2+-mobilizing P2Y receptors, and they appeared to exhibit a higher (~20%) receptor density. UTP raised the [Ca2+]iin a fraction of the cells and did not raise the [Na+]iin any of the cells tested, confirming its specificity as a P2Y agonist. The cell density of UTP-sensitive P2Y receptors did not appear to vary among AD- and NA-cells.

Conclusion

Although neither of the major purinoceptor types can be ascribed to a particular cell phenotype, P2X and Ca2+-mobilizing P2Y receptors are preferentially located to noradrenergic and adrenergic chromaffin cells, respectively. ATP might, in addition to an UTP-sensitive P2Y receptor, activate an UTP-insensitive P2Y receptor subtype. A model for a short-loop feedback interaction is presented whereby locally released ATP acts upon P2Y receptors in adrenergic cells, inhibiting Ca2+influx and contributing to terminate evoked epinephrine secretion.
Polymorphisms cMyc-N11S and p27-V109G and breast cancer risk and prognosis
Authors: Figueiredo Jane C , Knight Julia A , Cho Stewart , Savas Sevtap , Onay U Venus , Briollais Laurent , Goodwin Pamela J , McLaughlin John R , Andrulis Irene L , Ozcelik Hilmi
Published: June 2007

Background

cMyc and p27 are key genes implicated in carcinogenesis. Whether polymorphisms in these genes affect breast cancer risk or prognosis is still unclear. In this study, we focus on a rare non-synonymous polymorphism in cMyc (N11S) and a common polymorphism in p27 (V109G) and determine their role in risk and prognosis using data collected from the Ontario Breast Cancer Family Registry.

Methods

Risk factor data was collected at baseline on a large group of women (cases = 1,115 and population-based controls = 710) and clinical data (including treatment and follow-up) were collected prospectively by periodic review of medical records for a subset of cases (N = 967) for nearly a decade. A centralized pathology review was conducted. Unconditional logistic regression was used to determine the association of polymorphisms with breast cancer risk and the Cox proportional hazards model was used to determine their association with survival.

Results

Our results suggest that while cMyc-N11S can be considered a putatively functional polymorphism located in the N-terminal domain, it is not associated with risk, tumor characteristics or survival. The p27-G109 allele was associated with a modest protective effect in adjusted analyses and higher T stage. We found no evidence to suggest that p27-V109G alone or in combination with cMyc-N11S was associated with survival. Age at onset and first-degree family history of breast or ovarian cancer did not significantly modify the association of these polymorphisms with breast cancer risk.

Conclusion

Further work is recommended to understand the potential functional role of these specific non-synonymous amino acid changes and a larger, more comprehensive investigation of genetic variation in these genes (e.g., using a tagSNP approach) in combination with other relevant genes is needed as well as consideration for treatment effects when assessing their potential role in prognosis.
Crystal structure of Saccharomyces cerevisiae 6-phosphogluconate dehydrogenase Gnd1
Authors: He Weiwei , Wang Yi , Liu Wei , Zhou Cong-Zhao
Published: June 2007

Background

As the third enzyme of the pentose phosphate pathway, 6-phosphogluconate dehydrogenase (6PGDH) is the main generator of cellular NADPH. Both thioredoxin reductase and glutathione reductase require NADPH as the electron donor to reduce oxidized thioredoxin or glutathione (GSSG). Since thioredoxin and GSH are important antioxidants, it is not surprising that 6PGDH plays a critical role in protecting cells from oxidative stress. Furthermore the activity of 6PGDH is associated with several human disorders including cancer and Alzheimer's disease. The 3D structural investigation would be very valuable in designing small molecules that target this enzyme for potential therapeutic applications.

Results

The crystal structure of 6-phosphogluconate dehydrogenase (6PGDH/Gnd1) from Saccharomyces cerevisiae has been determined at 2.37 Å resolution by molecular replacement. The overall structure of Gnd1 is a homodimer with three domains for each monomer, a Rossmann fold NADP+ binding domain, an all-α helical domain contributing the majority to hydrophobic interaction between the two subunits and a small C-terminal domain penetrating the other subunit. In addition, two citrate molecules occupied the 6PG binding pocket of each monomer. The intact Gnd1 had a Km of 50 ± 9 μM for 6-phosphogluconate and of 35 ± 6 μM for NADP+ at pH 7.5. But the truncated mutants without the C-terminal 35, 39 or 53 residues of Gnd1 completely lost their 6PGDH activity, despite remaining the homodimer in solution.

Conclusion

The overall tertiary structure of Gnd1 is similar to those of 6PGDH from other species. The substrate and coenzyme binding sites are well conserved, either from the primary sequence alignment, or from the 3D structural superposition. Enzymatic activity assays suggest a sequential mechanism of catalysis, which is in agreement with previous studies. The C-terminal domain of Gnd1 functions as a hook to further tighten the dimer, but it is not necessary for the dimerization. This domain also works as a lid on the substrate binding pocket to control the binding of substrate and the release of product, so it is indispensable for the 6PGDH activity. Moreover, the co-crystallized citrate molecules, which mimic the binding mode of the substrate 6-phosphogluconate, provided us a novel strategy to design the 6PDGH inhibitors.
Why, and how, mixed methods research is undertaken in health services research in England: a mixed methods study
Authors: O'Cathain Alicia , Murphy Elizabeth , Nicholl Jon
Published: June 2007

Background

Recently, there has been a surge of international interest in combining qualitative and quantitative methods in a single study – often called mixed methods research. It is timely to consider why and how mixed methods research is used in health services research (HSR).

Methods

Documentary analysis of proposals and reports of 75 mixed methods studies funded by a research commissioner of HSR in England between 1994 and 2004. Face-to-face semi-structured interviews with 20 researchers sampled from these studies.

Results

18% (119/647) of HSR studies were classified as mixed methods research. In the documentation, comprehensiveness was the main driver for using mixed methods research, with researchers wanting to address a wider range of questions than quantitative methods alone would allow. Interviewees elaborated on this, identifying the need for qualitative research to engage with the complexity of health, health care interventions, and the environment in which studies took place. Motivations for adopting a mixed methods approach were not always based on the intrinsic value of mixed methods research for addressing the research question; they could be strategic, for example, to obtain funding. Mixed methods research was used in the context of evaluation, including randomised and non-randomised designs; survey and fieldwork exploratory studies; and instrument development. Studies drew on a limited number of methods – particularly surveys and individual interviews – but used methods in a wide range of roles.

Conclusion

Mixed methods research is common in HSR in the UK. Its use is driven by pragmatism rather than principle, motivated by the perceived deficit of quantitative methods alone to address the complexity of research in health care, as well as other more strategic gains. Methods are combined in a range of contexts, yet the emerging methodological contributions from HSR to the field of mixed methods research are currently limited to the single context of combining qualitative methods and randomised controlled trials. Health services researchers could further contribute to the development of mixed methods research in the contexts of instrument development, survey and fieldwork, and non-randomised evaluations.
Postoperative outcome of caesarean sections and other major emergency obstetric surgery by clinical officers and medical officers in Malawi
Authors: Chilopora Garvey , Pereira Caetano , Kamwendo Francis , Chimbiri Agnes , Malunga Eddie , Bergström Staffan
Published: June 2007

Background

Clinical officers perform much of major emergency surgery in Malawi, in the absence of medical officers. The aim of this study was to validate the advantages and disadvantages of delegation of major obstetric surgery to non-doctors.

Methods

During a three month period, data from 2131 consecutive obstetric surgeries in 38 district hospitals in Malawi were collected prospectively. The interventions included caesarean sections alone and those that were combined with other interventions such as subtotal and total hysterectomy repair of uterine rupture and tubal ligation. All these surgeries were conducted either by clinical officers or by medical officers.

Results

During the study period, clinical officers performed 90% of all straight caesarean sections, 70% of those combined with subtotal hysterectomy, 60% of those combined with total hysterectomy and 89% of those combined with repair of uterine rupture. A comparable profile of patients was operated on by clinical officers and medical officers, respectively. Postoperative outcomes were almost identical in the two groups in terms of maternal general condition – both immediately and 24 hours postoperatively – and regarding occurrence of pyrexia, wound infection, wound dehiscence, need for re-operation, neonatal outcome or maternal death.

Conclusion

Clinical officers perform the bulk of emergency obstetric operations at district hospitals in Malawi. The postoperative outcomes of their procedures are comparable to those of medical officers. Clinical officers constitute a crucial component of the health care team in Malawi for saving maternal and neonatal lives given the scarcity of physicians.
Differential vascular dysfunction in response to diets of differing macronutrient composition: a phenomenonological study
Authors: Fatani Sameer , Pickavance Lucy C , Sadler Claire J , Harrold Joanne A , Cassidy Roslyn , Wilding John PH , Naderali Ebrahim K
Published: June 2007

Background

Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats.

Methods

Male Wistar rats (n = 6/group) were fed diets providing varying percentages of energy from fat and carbohydrate (CHO). For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO), chow supplemented with chocolate biscuit (30% fat; 56% CHO) or a high-fat diet (45% fat; 35% CHO). Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA).

Results

Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; p < 0.01) and elevated concentrations of TGs and NEFAs (+41% and +17%; both p < 0.05). High-fat-fed animals showed an increase only in NEFAs (+38%; p < 0.01). Arterial vasoconstriction in response to NA and KCl increased only in biscuit-fed rats (both p < 0.01), while vasorelaxation in response to CCh and SNP, but not histamine, was attenuated in both groups (both p < 0.01). Furthermore, whereas the effect of the high-fat diet was most pronounced in endothelium-dependent vasorelaxation, the biscuit diet had the greater effect on endothelium-independent vasorelaxation.

Conclusion

Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.
Celsius: a community resource for Affymetrix microarray data
Authors: Day Allen , Carlson Marc RJ , Dong Jun , O'Connor Brian D , Nelson Stanley F
Published: June 2007

Celsius is a data warehousing system to aggregate Affymetrix CEL files and associated metadata. It provides mechanisms for importing, storing, querying, and exporting large volumes of primary and pre-processed microarray data. Celsius contains ten billion assay measurements and affiliated metadata. It is the largest publicly available source of Affymetrix microarray data, and through sheer volume it allows a sophisticated, broad view of transcription that has not previously been possible.
LongSAGE profiling of nine human embryonic stem cell lines
Authors: Hirst Martin , Delaney Allen , Rogers Sean A , Schnerch Angelique , Persaud Deryck R , O'Connor Michael D , Zeng Thomas , Moksa Michelle , Fichter Keith , Mah Diana , Go Anne , Morin Ryan D , Baross Agnes , Zhao Yongjun , Khattra Jaswinder , Prabhu Anna-Liisa , Pandoh Pawan , McDonald Helen , Asano Jennifer , Dhalla Noreen , Ma Kevin , Lee Stephanie , Ally Adrian , Chahal Neil , Menzies Stephanie , Siddiqui Asim , Holt Robert , Jones Steven , Gerhard Daniela S , Thomson James A , Eaves Connie J , Marra Marco A
Published: June 2007

To facilitate discovery of novel human embryonic stem cell (ESC) transcripts, we generated 2.5 million LongSAGE tags from 9 human ESC lines. Analysis of this data revealed that ESCs express proportionately more RNA binding proteins compared with terminally differentiated cells, and identified novel ESC transcripts, at least one of which may represent a marker of the pluripotent state.
Neurokinin-1 receptor antagonist treatment protects mice against lung injury in polymicrobial sepsis
Authors: Hegde Akhil , Zhang Huili , Moochhala Shabbir M , Bhatia Madhav
Published: June 2007

Earlier work from our laboratory has suggested a role for the neuropeptide substance P (SP) in inducing lung injury in sepsis. In that study, mice lacking the preprotachykinin-A gene, which encodes for SP, were protected against lung injury in sepsis. To further substantiate the role of SP in sepsis and to study its mchanism, we have evaluated the effect of SR140333, a SP receptor antagonist, on lung injury in sepsis, which was induced in male Swiss mice by cecal ligation and puncture (CLP). Sham-operated animals received the same surgical procedure, except CLP. Vehicle or SR140333 (1 mg/kg, s.c.) was administered to CLP mice 30 min before or 1 h after the CLP. Eight hours after surgery, lung tissue was collected and analyzed for myeloperoxidase (MPO) activity, chemokines, cytokines, and adhesion molecules. The CLP procedure alone caused a significant increase in the lung levels of MIP-2, MCP-1, IL-1β, IL-6, ICAM-1, E- and P-selectin, and MPO activity when compared with sham-operated mice. SR140333 injected 30 min before or 1 h after CLP significantly attenuated the increased lung MPO activity and levels of MIP-2, MCP-1, IL-1β, IL-6, ICAM-1, and E- and P-selectin compared with CLP-operated mice injected with the vehicle. Histological evaluation of the lung sections further supported the beneficial effect of SR140333 on lung inflammation. Therefore, SP receptor antagonism can be a potential therapeutic target in polymicrobial sepsis, and this effect is brought about via reduction in leukocyte recruitment.
The Elder Patient with Suspected Acute Coronary Syndromes in the Emergency Department
Authors: Han Jin H. , Lindsell Christopher J. , Hornung Richard W. , Lewis Timothy , Storrow Alan B. , Hoekstra James W. , Hollander Judd E. , Miller Chadwick D. , Peacock W. Frank , Pollack Charles V. , Gibler W. Brian
Published: June 2007

ObjectivesTo describe the evaluation and outcomes of elder patients with suspected acute coronary syndromes (ACS) presenting to the emergency department (ED).

MethodsThis was a post hoc analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i∗trACS) registry, which had 17,713 ED visits for suspected ACS. First visits from the United States with nonmissing patient demographics, 12‐lead electrocardiogram results, and clinical history were included in the analysis. Those who used cocaine or amphetamines or left the ED against medical advice were excluded. Elder was defined as age 75 years or older. ACS was defined by 30‐day revascularization, Diagnosis‐related Group codes, or death within 30 days with positive cardiac biomarkers at index hospitalization. Multivariable logistic regression analyses were performed to determine the association between being elder and 1) 30‐day all‐cause mortality, 2) ACS, 3) diagnostic tests ordered, and 4) disposition. Multivariable logistic regression was also performed to determine which clinical variables were associated with ACS in elder and nonelder patients.

ResultsA total of 10,126 patients with suspected ACS presenting to the ED were analyzed. For patients presenting to the ED, being elder was independently associated with ACS and all‐cause 30‐day mortality, with adjusted odds ratios of 1.8 (95% confidence interval [CI] = 1.5 to 2.2) and 2.6 (95% CI = 1.6 to 4.3), respectively. Elder patients were more likely to be admitted to the hospital (adjusted odds ratio, 2.2; 95% CI = 1.8 to 2.6), but there were no differences in the rates of cardiac catheterization and noninvasive stress cardiac imaging. Different clinical variables were associated with ACS in elder and nonelder patients. Chest pain as chief complaint, typical chest pain, and previous history of coronary artery disease were significantly associated with ACS in nonelder patients but were not associated with ACS in elder patients. Male gender and left arm pain were associated with ACS in both elder and nonelder patients.

ConclusionsElder patients who present to the ED with suspected ACS represent a population at high risk for ACS and 30‐day mortality. Elders are more likely to be admitted to the hospital, but despite an increased risk for adverse events, they have similar odds of receiving a diagnostic test, such as stress cardiac imaging or cardiac catheterization, compared with nonelder patients. Different clinical variables are associated with ACS, and clinical prediction rules utilizing presenting symptoms should consider the effect modification of age.