bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Economic Conditions and Identity Formation in Adulthood
Authors: Fadjukoff Päivi , Kokko Katja , Pulkkinen Lea
Published: December 2010

Identity formation in political and occupational domains was examined from young to middle adulthood based on an ongoing longitudinal study. In addition to the participants’ identity status (diffused, moratorium, foreclosed, achieved), we assessed their perceived importance of politics, future orientation, and career stability four times in adulthood, at ages 27, 36, 42, and 50. The number of participants varied between analyses, from 168 to 291. Changes in the economic situation in Finland from 1986 to 2009 provided a context for the study. Data collections at ages 36 (in 1995) and 50 (in 2009) took place during economic recessions, and at age 42 (in 2001) during an economic boom. The results were discussed from both age-graded and history-graded perspectives. Developmental trends in political and occupational identity were reversed across age and changes in the economic situation. Political identity was at its lowest level and occupational identity was at its highest level at age 42 during the economic boom. Political identity progressed at a time of economic recession at age 50, whereas occupational identity regressed. In women, identity changes were associated with personal career stability. The perceived importance of politics increased concurrently with political identity achievement. During the recession when they were age 50, women tended to worry about future financial problems, while men perceived their future depending decreasingly on themselves and increasingly on the world situation. The results indicate that macro-level economic conditions may have psychological implications on people’s conceptions of themselves that are worth considering in developmental studies.
When the “We” Impacts How “I” Feel About Myself
Authors: de la Sablonnière Roxane , Auger Émilie , Sadykova Nazgul , Taylor Donald M.
Published: December 2010

Dramatic social change leads to profound societal transformations in many countries around the world. The two recent revolutions in March 2005 and April 2010, and the ethnic conflict in June 2010 in Kyrgyzstan are vivid examples. The present research aims to understand people’s reactions to dramatic social change in terms of personal well-being. To further understand how people react psychologically to dramatic social change, the theoretical framework of our research is based on a dominant theory in social psychology: Collective relative deprivation theory. In the past, researchers have argued that collective relative deprivation is logically associated with collective outcomes, and thus is not likely to impact personal well-being (e.g., Walker & Mann, 1987 ). Others, however, have argued that feelings of collective relative deprivation do impact personal well-being (e.g., Zagefka & Brown, 2005 ). We postulate that these inconsistent results arise because past research has failed to consider multiple points of comparison over time to assess collective relative deprivation. Specifically, we theorize that multiple points of collective relative deprivation need to be taken into account, and in so doing, collective relative deprivation will, indeed, be related to personal well-being. We also explore the entire trajectory of collective relative deprivation (which represents how an individual perceives the evolution of his/her group’s history across time) to predict personal well-being. In the present study, we tested these theoretical propositions in the context of dramatic social change in Kyrgyzstan. Regressions, group-based trajectory modeling, and MANOVA confirm our hypotheses.
Leaving School Early – and Making It!
Authors: Schoon Ingrid , Duckworth Kathryn
Published: December 2010

Leaving school early is generally associated with relative poor adult outcomes, as indicated by relative low social status, reduced earnings, and poor mental health. Yet, not all young people leaving school early are failing to make it. Some are able to find continuous employment and achieve financial independence. Comparing the experiences of two British Birth cohorts born in 1958 and 1970, respectively, this study examines the trajectories of young people leaving school early, and identifies factors associated with a successful transition, that is achieving financial independence. The study comprises 11,219 individuals born in 1958 and 9,541 born in 1970 following their lives from childhood into adulthood. While the majority of young people born in 1958 left school at age 16 to enter the labor market, increasing numbers of young people born in 1970 are participating in further and higher education. In both cohorts those young people who left school early and who succeeded in reaching financial independence by age 34 showed higher school motivation than those who failed to make it. The findings highlight the importance of building up positive attitudes for learning among children and their parents, as these factors have long-term beneficial effects, even for those who are leaving school early. Moreover, the role of macro-economic circumstances has to be acknowledged for a better understanding of variation in transition experiences in times of social change.
Individuals Negotiating Demands of Social and Economic Change
Authors: Tomasik Martin J. , Silbereisen Rainer K. , Pinquart Martin
Published: December 2010

We investigated how individuals negotiated demands of social change in the domains of work and family life in terms of primary and secondary control strategies of goal engagement and disengagement. A sample of N = 2,153 adults from East and West Germany was interviewed on demands they experienced, related primary and secondary control strategies, occupational and relationship status, and primary and secondary appraisals of demands. Results show little specific variance in the control strategies between the domain of work and the domain of family and a general preference for goal engagement over goal disengagement in dealing with demands of social change. Participants outside the labor market and singles reported relatively less engagement and more disengagement strategies. More favorable primary and secondary appraisals were associated with more engagement and less disengagement whereas a higher load of demands of social change predicted all control strategies in a positive way.
Tephrosia purpurea Ameliorates N‐Diethylnitrosamine and Potassium Bromate‐Mediated Renal Oxidative Stress and Toxicity in Wistar Rats
Authors: Khan Naghma , Sharma Sonia , Alam Aftab , Saleem Mohammad , Sultana Sarwat
Published: December 2010

Abstract: In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide‐induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T. purpurea against N‐diethylnitrosamine‐initiated and potassium bromate‐mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N‐diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose‐6‐phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione‐S‐transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N‐diethylnitrosamine‐initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate‐induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose‐dependently. Our data indicate that T. purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N‐diethylnitrosamine and KBrO3.
Na+ and K+ Dependence of Morphological Changes of Cultured Rat Cortical Astrocytes
Authors: Abe Kazuho , Saito Hiroshi
Published: December 2010

Abstract: Cultured astrocytes display flattened, polygonal morphology in the absence of stimuli, and change into process‐bearing stellate cells in response to specific stimuli. In the present study, we investigated possible role of Na+, K+ and Ca2+ in this morphological change of cultured rat cortical astrocytes. Astrocyte stellation induced by dibutyryl cyclic AMP (1 mM), phorbol ester (100 nM) or amyloid β peptide (20 μM) was partly suppressed by replacing NaCl with choline chloride or LiCl in the extracellular medium or by adding KCl, and was completely abolished by replacing NaCl with KCl. Furthermore, the astrocyte stellation was blocked by the specific Na+‐K+ pump inhibitor ouabain. However, it was not significantly affected by removing CaCl2 from the extracellular medium nor by adding the voltage‐dependent Ca2+ channel blocker nicardipine. These results suggest that Na+ and K+, but not Ca2+, electrochemical gradients across the plasma membrane are necessary for morphological changes of astrocytes. In addition, amyloid β25–35‐induced stellation was most susceptible to changing Na+ and K+ concentrations or ouabain, while phorbol ester‐induced stellation was least sensitive, demonstrating that the Na+ and K+ dependence differs among stimuli.
The Haemodynamic Effects of Losartan after Right Ventricle Infarct in Young Pigs
Authors: Spalding Michael , Ala‐Kokko Tero , Kiviluoma Kai , Ruskoaho Heikki , Alahuhta Seppo
Published: December 2010

Abstract: The effect of an intravenous bolus injection of the type 1 angiotensin II receptor antagonist, losartan on haemodynamics after right heart infarct was studied in an experimental setting. Right heart infarct was induced in twelve young swine and losartan was given in a bolus intravenous dose one hr later to five animals, while seven animals served as controls. Haemodynamics were then followed for one hr at 15 min. intervals. Losartan was subsequently shown to decrease central venous pressure and wedge pressure, while cardiac output, left ventricle stroke work and stroke volume all showed improvement. Compared to the control animals, pulmonary vascular resistance, systemic vascular resistance and systemic pressures were unaffected by the drug, as was heart rate. The use of losartan shortly after right heart infarct reduced both right and left heart preload as well as inducing an improvement in cardiac performance. At the same time, systemic pressures and heart rate were maintained. We conclude that an inhibition of angiotensin II action may be a benefit in the treatment of right heart failure symptoms during the first hours after right heart infarct.
Fingerprints of order and disorder on the high-frequency dynamics of liquids
Authors: Giordano Valentina M. , Monaco Giulio
Published: December 2010

It is largely accepted that liquids are characterized by a short-range order usually corresponding to that of the solid phase at the same density. It is less clear to what extent dynamic properties of liquids and crystals can be compared. In particular, high-frequency collective excitations reminiscent of phonons in solids exist as well in liquids. They are however traditionally discussed in terms of relaxation processes characteristic of the liquid phase. We report here on a quantitative comparison of the collective excitations in liquid and polycrystalline sodium. We show that liquid sodium exhibits acoustic excitations of both longitudinal and transverse polarization at frequencies strictly related to those of the corresponding crystal. The only relevant difference between the liquid and the polycrystal appears in the broadening of the excitations: An additional disorder-induced contribution comes into play in the case of the liquid, which we show to be related to the distribution of local structures around the average one. These results establish a direct connection between structural and dynamic properties of liquids, with short-range order and overall structural disorder leaving very specific fingerprints.
Discovery of a CXCR4 agonist pepducin that mobilizes bone marrow hematopoietic cells
Authors: Tchernychev Boris , Ren Yong , Sachdev Pallavi , Janz Jay M. , Haggis Lynn , O'Shea Adam , McBride Ed , Looby Richard , Deng Qing , McMurry Thomas , Kazmi Manija A. , Sakmar Thomas P. , Hunt Stephen , Carlson Kenneth E.
Published: December 2010

The G protein-coupled receptor (GPCR), chemokine CXC-type receptor 4 (CXCR4), and its ligand, CXCL12, mediate the retention of polymorphonuclear neutrophils (PMNs) and hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Agents that disrupt CXCL12-mediated chemoattraction of CXCR4-expressing cells mobilize PMNs and HSPCs into the peripheral circulation and are therapeutically useful for HSPC collection before autologous bone marrow transplantation (ABMT). Our aim was to develop unique CXCR4-targeted therapeutics using lipopeptide GPCR modulators called pepducins. A pepducin is a synthetic molecule composed of a peptide derived from the amino acid sequence of one of the intracellular (IC) loops of a target GPCR coupled to a lipid tether. We prepared and screened a small CXCR4-targeted pepducin library and identified several pepducins with in vitro agonist activity, including ATI-2341, whose peptide sequence derives from the first IC loop. ATI-2341 induced CXCR4- and G protein-dependent signaling, receptor internalization, and chemotaxis in CXCR4-expressing cells. It also induced dose-dependent peritoneal recruitment of PMNs when administered i.p. to mice. However, when administered systemically by i.v. bolus, ATI-2341 acted as a functional antagonist and dose-dependently mediated release of PMNs from the bone marrow of both mice and cynomolgus monkeys. ATI-2341–mediated release of granulocyte/macrophage progenitor cells from the bone marrow was confirmed by colony-forming assays. We conclude that ATI-2341 is a potent and efficacious mobilizer of bone marrow PMNs and HSPCs and could represent a previously undescribed therapeutic approach for the recruitment of HSPCs before ABMT.
Toward an automatic method for extracting cancer- and other disease-related point mutations from the biomedical literature
Authors: Doughty Emily , Kertesz-Farkas Attila , Bodenreider Olivier , Thompson Gary , Adadey Asa , Peterson Thomas , Kann Maricel G.
Published: December 2010

Motivation: A major goal of biomedical research in personalized medicine is to find relationships between mutations and their corresponding disease phenotypes. However, most of the disease-related mutational data are currently buried in the biomedical literature in textual form and lack the necessary structure to allow easy retrieval and visualization. We introduce a high-throughput computational method for the identification of relevant disease mutations in PubMed abstracts applied to prostate (PCa) and breast cancer (BCa) mutations.

Results: We developed the extractor of mutations (EMU) tool to identify mutations and their associated genes. We benchmarked EMU against MutationFinder—a tool to extract point mutations from text. Our results show that both methods achieve comparable performance on two manually curated datasets. We also benchmarked EMU's performance for extracting the complete mutational information and phenotype. Remarkably, we show that one of the steps in our approach, a filter based on sequence analysis, increases the precision for that task from 0.34 to 0.59 (PCa) and from 0.39 to 0.61 (BCa). We also show that this high-throughput approach can be extended to other diseases.

Discussion: Our method improves the current status of disease-mutation databases by significantly increasing the number of annotated mutations. We found 51 and 128 mutations manually verified to be related to PCa and Bca, respectively, that are not currently annotated for these cancer types in the OMIM or Swiss-Prot databases. EMU's retrieval performance represents a 2-fold improvement in the number of annotated mutations for PCa and BCa. We further show that our method can benefit from full-text analysis once there is an increase in Open Access availability of full-text articles.

Availability: Freely available at: http://bioinf.umbc.edu/EMU/ftp.

Contact:  mkann@umbc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
W-ChIPeaks: a comprehensive web application tool for processing ChIP-chip and ChIP-seq data
Authors: Lan Xun , Bonneville Russell , Apostolos Jeff , Wu Wangcheng , Jin Victor X
Published: December 2010

Summary: ChIP-based technology is becoming the leading technology to globally profile thousands of transcription factors and elucidate the transcriptional regulation mechanisms in living cells. It has evolved rapidly in recent years, from hybridization with spotted or tiling microarray (ChIP-chip), to pair-end tag sequencing (ChIP-PET), to current massively parallel sequencing (ChIP-seq). Although there are many tools available for identifying binding sites (peaks) for ChIP-chip and ChIP-seq, few of them are available as easy-accessible online web tools for processing both ChIP-chip and ChIP-seq data for the ChIP-based user community. As such, we have developed a comprehensive web application tool for processing ChIP-chip and ChIP-seq data. Our web tool W-ChIPeaks employed a probe-based (or bin-based) enrichment threshold to define peaks and applied statistical methods to control false discovery rate for identified peaks. The web tool includes two different web interfaces: PELT for ChIP-chip, BELT for ChIP-seq, where both were tested on previously published experimental data. The novel features of our tool include a comprehensive output for identified peaks with GFF, BED, bedGraph and .wig formats, annotated genes to which these peaks are related, a graphical interpretation and visualization of the results via a user-friendly web interface.

Availability:  http://motif.bmi.ohio-state.edu/W-ChIPeaks/.

Contact:  victor.jin@osumc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Both Plant and Bacterial Nitrate Reductases Contribute to Nitric Oxide Production in Medicago truncatula Nitrogen-Fixing Nodules
Authors: Horchani Faouzi , Prévot Marianne , Boscari Alexandre , Evangelisti Edouard , Meilhoc Eliane , Bruand Claude , Raymond Philippe , Boncompagni Eric , Aschi-Smiti Samira , Puppo Alain , Brouquisse Renaud
Published: December 2010

Nitric oxide (NO) is a signaling and defense molecule of major importance in living organisms. In the model legume Medicago truncatula, NO production has been detected in the nitrogen fixation zone of the nodule, but the systems responsible for its synthesis are yet unknown and its role in symbiosis is far from being elucidated. In this work, using pharmacological and genetic approaches, we explored the enzymatic source of NO production in M. truncatula-Sinorhizobium meliloti nodules under normoxic and hypoxic conditions. When transferred from normoxia to hypoxia, nodule NO production was rapidly increased, indicating that NO production capacity is present in functioning nodules and may be promptly up-regulated in response to decreased oxygen availability. Contrary to roots and leaves, nodule NO production was stimulated by nitrate and nitrite and inhibited by tungstate, a nitrate reductase inhibitor. Nodules obtained with either plant nitrate reductase RNA interference double knockdown (MtNR1/2) or bacterial nitrate reductase-deficient (napA) and nitrite reductase-deficient (nirK) mutants, or both, exhibited reduced nitrate or nitrite reductase activities and NO production levels. Moreover, NO production in nodules was found to be inhibited by electron transfer chain inhibitors, and nodule energy state (ATP-ADP ratio) was significantly reduced when nodules were incubated in the presence of tungstate. Our data indicate that both plant and bacterial nitrate reductase and electron transfer chains are involved in NO synthesis. We propose the existence of a nitrate-NO respiration process in nodules that could play a role in the maintenance of the energy status required for nitrogen fixation under oxygen-limiting conditions.
Cellular responses to chlorin‐based photosensitizer DH‐II‐24 under darkness in human gastric adenocarcinoma AGS cells
Authors: Lim Young‐Cheol , Yoo Je‐Ok , Kang Seong‐Sik , Kim Young‐Myeong , Ha Kwon‐Soo
Published: December 2010

We investigated cellular responses to chlorin‐based photosensitizer DH‐II‐24 under darkness in human gastric adenocarcinoma AGS cells. Cells were loaded with 0.5–10 μg/mL DH‐II‐24 for 12 h, and intracellular reactive oxygen species (ROS) and intracellular Ca2+levels,in situtissue transglutaminase (tTGase) activity, cell viability, cell morphology and cell cycle were examined. DH‐II‐24 treatment had no effect on intracellular ROS production or cell morphology, and did not induce cell detachment at any concentrations tested. In addition, cell viability and cell cycle progression were not altered by the photosensitizer. However, DH‐II‐24 treatment elevated the basal level of intracellular Ca2+in a dose‐dependent manner and inhibited tTGase activity without affecting tTGase expression levels. Furthermore, DH‐II‐24 inhibited lysophosphatidic acid‐induced activation of tTGase in a dose‐dependent manner. In contrast, photodynamic therapy (PDT) with 1 μg/mL DH‐II‐24 significantly elevated intracellular ROS andin situtTGase activity in parallel with a rapid and large increase in intracellular Ca2+levels. DH‐II‐24‐mediated PDT decreased cell viability and induced cell detachment. These results demonstrate that DH‐II‐24 treatment alone under darkness induced different cellular responses to DH‐II‐24‐mediated PDT. (Cancer Sci2011; 102: 549–556)
Anti‐platelet therapy: glycoprotein IIb‐IIIa antagonists
Authors: Schneider David J.
Published: December 2010

Glycoprotein (GP) IIb‐IIIa antagonists inhibit the aggregation of activated platelets. Three agents are approved for clinical use. In this review, the characteristics of each agent, their pharmacodynamic profile, results in pivotal clinical trials and the associated clinical implications are discussed. GP IIb‐IIIa antagonists have greatest benefit when used as adjunctive therapy during percutaneous coronary intervention (PCI) when the patient has intra‐coronary thrombosis. These agents appear to provide greatest benefit when used in combination with heparin. The clinical niche for parenteral GP IIb‐IIIa antagonists is evolving. The rapid onset and offset of GP IIb‐IIIa antagonists plus dosing designed to inhibit extensively platelet aggregation differentiates them from oral agents. The contemporary niche appears to include patients in transition, such as individuals requiring emergent PCI before oral agents are fully active and for unstable patients requiring transport to PCI centres, particularly in patients likely to have intracoronary thrombus. Subsequent studies should evaluate the optimal duration of therapy with GP IIb‐IIIa antagonists.
A comparison of the natural history and outcome of treatment for Asian and non‐Asian hepatitis C‐infected patients
Authors: Lawson A. ,   on behalf of the Trent Hepatitis C Study Group
Published: December 2010

Summary.  Ethnicity is an important host variable, but its impact on disease progression and response to therapy in Hepatitis C infection is unclear. Here we compare the natural history and outcome of therapy in White and Asian (Indian subcontinent) Hepatitis C infected patients. A total of 2123 White and 120 Asian HCV infected patients were identified within the Trent HCV study. Response to therapy was assessed in 224 White and 46 Asian patients with genotype 3 infection who received Pegylated Interferon and Ribavirin. Asian patients were more likely to be older, female, infected with genotype 3 and to consume no alcohol. At time of first biopsy, fibrosis stage was significantly higher in Asian patients than in Whites (3.0 ± 2.3 vs 1.8 ± 2.0, P < 0.001), as were necro‐inflammation and steatosis scores. However, in those patients where duration of infection could be estimated, fibrosis progression was similar for both groups (0.25 ± 0.31 vs 0.16 ± 0.54 Ishak points/year, P = 0.068). 78.3% of Asian and 67.9% of White genotype 3 patients had a sustained virological response following Pegylated Interferon and Ribavirin. Cirrhosis and increased levels of GGT, but not ethnicity were associated with a reduction in the likelihood of a sustained virological response on multivariate analysis. Asian patients with Hepatitis C are more likely to be female, less likely to give a history of risk factors, present to medical services at an older age, and have more severe liver disease at diagnosis, but disease progression and response to treatment are similar to White patients.
Tracking Changes of Lymphocyte Subsets and Pre‐inflammatory Mediators in Full‐term Neonates with Suspected or Documented Infection
Authors: Hotoura E. , Giapros V. , Kostoula A. , Spirou P. , Andronikou S.
Published: December 2010

Investigation was made of changes in immune system parameters during the course of neonatal infection. The study population consisted of 95 full‐term neonates matched for chronological age and sex, divided into three groups: suspected infection (n = 20), sepsis (n = 25), infection‐free control subjects (n = 50). Serial measurements were made of the cytokines interleukin‐6 (IL‐6), interleukin‐1b (IL‐1b) and tumour necrosis factor‐α (TNF‐α), lymphocyte subsets [CD3+, CD4+, CD8+, natural killer (NK) cells and B cells], the immunoglobulins (Ig) (IgG, IgM and IgA), C‐reactive protein (CRP), and the total blood count, before, 2 days after initiation of treatment and after stopping treatment (time periods first, second and third, respectively). IL6, TNF‐α, IL1‐b and CRP were higher at the first time period in the sepsis group, and IL6 and TNF‐α continued to be higher in this group at the second period. IL‐6 and TNF‐α were precise sepsis predictors with sensitivity and specificity of 0.92, 0.98 and 0.91, 0.92, respectively. NK cells, B cells, CD3+, CD4+, CD8+ were higher in the sepsis and suspected infection groups, but the ratios CD3+/CD4+, CD3+/CD8+, CD4+/CD8+ showed no difference from the controls. IgG was lower and IgM higher in the sepsis group. In the control subjects CD3+, CD4+, CD8+ lymphocytes increased with increasing age. It is concluded that IL‐6 and TNF are good diagnostic markers of sepsis in full‐term neonates. Lymphocyte subsets were affected by both the clinical condition and the chronological age. NK and B cells may be elevated in suspected and documented sepsis, and further studies are needed to determine their clinical significance.
The Human NADPH Oxidase: Primary and Secondary Defects Impairing the Respiratory Burst Function and the Microbicidal Ability of Phagocytes
Authors: de Oliveira‐Junior E. B. , Bustamante J. , Newburger P. E. , Condino‐Neto A.
Published: December 2010

Phagocytes, such as granulocytes and monocytes/macrophages, contain a membrane‐associated NADPH oxidase that produces superoxide leading to other reactive oxygen species with microbicidal, tumoricidal and inflammatory activities. Primary defects in oxidase activity in chronic granulomatous disease (CGD) lead to severe, life‐threatening infections that demonstrate the importance of the oxygen‐dependent microbicidal system in host defence. Other immunological disturbances may secondarily affect the NADPH oxidase system, impair the microbicidal activity of phagocytes and predispose the host to recurrent infections. This article reviews the primary defects of the human NADPH oxidase leading to classical CGD, and more recently discovered immunological defects secondarily affecting phagocyte respiratory burst function and resulting in primary immunodeficiencies with varied phenotypes, including susceptibilities to pyogenic or mycobacterial infections.
Antiretroviral Therapy‐Induced Dominant Interleukin‐2 HIV‐1 Gag CD4+ T Cell Response: Evidence of Functional Recovery of HIV‐1‐Specific CD4+ T Cells
Authors: Tsalimalma K. , Kordossis T. , Choremi‐Papadopoulou E.
Published: December 2010

Prolonged antiretroviral treatment (ART) significantly changes the cytokine secretion capacities of HIV‐1‐specific T cells. However, it is unclear whether these changes result from decreased viremia or they correspond to true functional recovery of viral‐specific immune response. To study this issue, we analysed the quantitative and qualitative differences of HIV‐1‐specific and polyclonal CD4+ and CD8+ T cells between 26 naive and 52 treated individuals. HIV‐1 Gag and staphylococcal enterotoxin B (SEB)‐reactive T cells were determined by flowcytometric intracellular secretion of IFN‐γ or/and ΙL‐2. ART resulted in increase of single IL‐2 and decrease of single IFN‐γ‐secreting HIV‐1 CD4+ T cells, while both cytokines secreting HIV‐1 CD4+ T cells were presented in comparable frequencies in both groups. Viral loads correlated negatively with single IL‐2 and positively with single IFN‐γ‐secreting HIV‐1 CD4+ cells. Single IL‐2 HIV‐1 CD4+ T cells correlated positively with both cytokines secreting polyclonal CD8+ T cells. By qualitative analysis, a dominant IL‐2 HIV‐1 CD4+ T cell response (>70% single IL‐2) was identified only in ART suppressed patients, who also generated increased dual specific polyclonal CD8+ T cells. Polyfunctional HIV‐1 CD4+ T cell responses were detected even in naive individuals with high viremia. In conclusion, the presence of dominant IL‐2 HIV‐1 CD4+ T cell response, associated with increased CD8+ T cells capable to produce IL‐2, indicates that the recovery of HIV‐1‐specific CD4+ T cell functionality under ART is a feasible goal. Furthermore, polyfunctional HIV‐1 CD4+ T cell responses seem not to be directly involved in viral replication control.
Surveillance of community antimicrobial use in resource‐constrained settings – experience from five pilot projects
Authors: Holloway Kathleen , Mathai Elisabeth , Gray Andy ,   on behalf of the Community‐Based Surveillance of Antimicrobial Use and Resistance in Resource‐Constrained Settings Project Group
Published: December 2010

Objective  To investigate the feasibility of surveillance of antimicrobial use in the community in resource‐constrained settings. Overuse and misuse of antimicrobial medicines is contributing to the development of resistance. The WHO Global Strategy for Containment of Antimicrobial Resistance recommends surveillance of use at all levels of the health sector but this is not done in most low and middle income countries.

Methods  Pilot projects were established in three sites in India (Delhi, Mumbai and Vellore) and 2 in South Africa (Brits and Durban). Antimicrobial use data were collected monthly from both public and private facilities. Each pilot site sought to document 30 patient encounters where antimicrobials were provided from 7 to 30 facilities per month. Antimicrobial use was expressed as the percentage of patients receiving a specific antimicrobial and as the number of defined daily doses of each specific antibiotic per 100 patients attending the facility per month.

Results  In all sites, there was extensive use of antimicrobials, with older agents being used more in the public sector and newer agents in the private sector. Although methodological differences limit the comparability of data, use appeared to be higher in India than in South Africa. Expressing antimicrobial use as the percentage of patients receiving a specific antimicrobial was more easily computed. Defined daily dose measure was useful in demonstrating differences in dosing and duration.

Conclusion  All pilot sites provided data on antimicrobial use but also raised several issues related to methodology and logistics of long‐term surveillance in community settings under resource constraints. Use measured as percentage of prescriptions is easier and more reliable in these settings.
Fine‐tuned coupling between human parahippocampal ripples and sleep spindles
Authors: Clemens Zsófia , Mölle Matthias , Erőss Loránd , Jakus Rita , Rásonyi György , Halász Péter , Born Jan
Published: December 2010

Sleep‐associated memory consolidation is thought to rely on coordinated information transfer between the hippocampus and neocortex brought about during slow wave sleep (SWS) by distinct local field potential oscillations. Specifically, findings in animals have led to the concept that ripples originating from hippocampus combine with spindles to provide a fine‐tuned temporal frame for a persistent transfer of memory‐related information to the neocortex. The present study focused on characterizing the temporal relationship between parahippocampal ripple activity (80–140 Hz) and spindles recorded from frontal, parietal and parahippocampal cortices in 12 epilepsy patients implanted with parahippocampal foramen ovale electrodes. Overall, parietal and parahippocampal spindles showed closer relationships to parahippocampal ripple activity than frontal spindles, with the latter following parietal and parahippocampal spindles at a variable delay of up to 0.5 s. On a timescale of seconds, ripple activity showed a continuous increase before the peak of parietal and parahippocampal spindles, and decreased thereafter. At a fine timescale of milliseconds, parahippocampal ripple activity was tightly phase‐locked to the troughs of these spindles. The demonstration of spindle phase‐locked ripple activity in humans is consistent with the idea of a temporally fine‐tuned hippocampus‐to‐neocortex transfer of information taking place during SWS.
SMALL‐AREA ESTIMATION OF POVERTY: THE AID INDUSTRY STANDARD AND ITS ALTERNATIVES
Authors: Haslett S. J. , Jones G.
Published: December 2010

Small‐area estimation of poverty‐related variables is an increasingly important analytical tool in targeting the delivery of food and other aid in developing countries. We compare two methods for the estimation of small‐area means and proportions, namely empirical Bayes and composite estimation, with what has become the international standard method of Elbers, Lanjouw & Lanjouw (2003). In addition to differences among the sets of estimates and associated estimated standard errors, we discuss data requirements, design and model selection issues and computational complexity. The Elbers, Lanjouw and Lanjouw (ELL) method is found to produce broadly similar estimates but to have much smaller estimated standard errors than the other methods. The question of whether these standard error estimates are downwardly biased is discussed. Although the question cannot yet be answered in full, as a precautionary measure it is strongly recommended that the ELL model be modified to include a small‐area‐level error component in addition to the cluster‐level and household‐level errors it currently contains. This recommendation is particularly important because the allocation of billions of dollars of aid funding is being determined and monitored via ELL. Under current aid distribution mechanisms, any downward bias in estimates of standard error may lead to allocations that are suboptimal because distinctions are made between estimated poverty levels at the small‐area level that are not significantly different statistically.
THE MATHEMATICS OF TIME IN HISTORY1
Authors: BONNEUIL NOËL
Published: December 2010

The themes of connectedness and continuity, which are also mathematical properties, have run like a red thread through the last fifty years of History and Theory, notably in the theory of the narration of action in history. In this essay I review various answers to the question of the driving force that motivates action and that propels a sequence, continuous or discontinuous. These answers underpin narrative strategies intended to solve the problem of human agency and thereby to provide the basis for historical narratives. I argue that both continuous and discontinuous conceptions of history have to do with the restrictive concept of trajectory. Most of our familiar concepts such as trajectory, equilibrium, optimum, probability, and sensitivity to initial conditions are taken from mathematics and physics, but how well adapted are they to dealing with the time of actors, whose actions are intermingled with uncertainty? I shall present alternative concepts of dynamics, ones that no longer lead toward just one particular future or that reflect a single past. On this basis I suggest reorganizing our view of historical time along the principles of maintenance, acquisition, and victory. Historical sources trace back not to one story or one process that is plausible or that appeals to common sense, but to a whole family of processes. From the past, we can obtain sets of constraints that circumscribe sets of stories rather than a single scenario. I shall then propose a topology of the time of action based on my alternative conception of dynamics, a topology made of what I call viability kernels, capture basins, and victory domains.
WHERE DO WE GO FROM HERE? JUBILEE REPORT ON HISTORY AND THEORY
Authors: TUCKER AVIEZER
Published: December 2010

Progress in understanding, clarifying, forming, and devising methods for analyzing, eliminating, or resolving the problems of the philosophies of history and historiography requires integration with other branches of philosophy such as metaphysics, epistemology, the philosophy of science, the philosophy of mind, and ethics. Conversely, mainstream philosophical theories would benefit from confronting the problems of the philosophies of history and historiography. Solving the problems of the philosophies of historiography and history requires considering historiography as continuous with philosophy.

This approach is exemplified by examining metaphysical issues in the philosophy of history—historical contingency, necessity, determination, causation, over‐determination, and under‐determination—as well as investigating the epistemology of testimony for its relevance to the epistemology of our knowledge of the past.

Inference from multiple testimonies is a particular case of a general model of inference, one in which scientists infer a common cause from multiple sources of evidence that preserve similar information about their common causes. The historical sciences—history, phylogeny, evolutionary biology, comparative historical linguistics, and cosmology—all infer common causes or origins. The theoretical sciences are not interested in any particular token event, but in types of events, whereas, in contrast, the historical sciences attempt to infer common‐cause tokens.

The main reasons for the absence of decisive progress in the philosophy of historiography along the promising directions the article outlines are external: random, adverse institutional and market conditions that block the professionalization of the field.
WHEN THE MONOGRAPH IS NO LONGER THE MEDIUM: HISTORICAL NARRATIVE IN THE ONLINE AGE1
Authors: RIGNEY ANN
Published: December 2010

Over the last fifty years there has been much discussion about the value of narrative in the production of historical knowledge whereby it is generally assumed that “narrative” is a given and that the only thing at issue is its epistemological value. This article critically examines this assumption. It shows how conceptions of “narrative” have mutated in response to changes in cultural practice and, as importantly, how they have been implicitly modeled on the particular medium envisaged for telling stories: the stand‐alone monograph. The belief that history's natural form is a book written by an individual historian has thus informed most discussions of narrative in the twentieth century, meaning that the primacy of language, the autonomy of the author, and the finished, self‐contained character of the work have been taken for granted. The “naturalness” of the stand‐alone monograph can no longer be taken as a given, however, in the new media ecologies. Digitization and the internet offer new technologies for producing and disseminating historical knowledge and, in the process, present both opportunities and challenges to professional historians. Beyond their practical implications, the digital media also provide a new theoretical model for viewing historical narrative in terms of its social production by multiple agents across different platforms, and this changes our understanding both of past and of future practices.
What is society? Social thought and the arts of government
Authors: Dean Mitchell
Published: December 2010

Following conservative politicians, neoliberal philosophers and radical critics, different strands of social science, including those using Foucault's governmentality approach, joined the questioning of the salience of ‘society’ and ideas of ‘the social’ over the last decades. When the social reappeared, it was often in the moral domains of community and civil society. This argument re‐evaluates the contribution of Foucauldian histories, or ‘genealogies’, of the social to these fundamental questions. Drawing upon them, it attends to their arguments concerning the place of social thought on the modernepistemein relation to economics, the emergence of the idea of ‘society’ with the modern arts of government of the state, and the formation of the ‘social question’. The argument here allows that preconditions of formation of ‘society’ lie in the legal and political techniques of the territorial sovereign state. However, the literature under investigation indicates the implicit normativity of an idea of ‘society’ as a ‘problematic unity’ and the enduring necessity of a social domain in a law‐governed state with a relatively independent economic sphere. This discussion thus seeks to contribute to the wider revaluation and redeployment of these terms in today's context.
The double helix of cultural assimilationism and neo‐liberalism: citizenship in contemporary governmentality
Authors: Schinkel Willem , Van Houdt Friso
Published: December 2010

In this article the recent transformations of citizenship in the Netherlands are analysed in relation to a developing form of governmentality. We regard citizenship as a state regulated technique of in‐ and exclusion and a crucial instrument in the management of populations. Taking the Dutch contexts of immigration and integration as our case, we argue that cultural assimilationism and neo‐liberalism appear in a double helix: they combine to form a new governmental strategy we callneo‐liberal communitarianism. Neo‐liberal communitarianism is the underlying rationale of a population management that operates both in an individualizing (citizenship as individual participation and responsibility) and a de‐individualizing way (‘community’ at various aggregate and localized levels as frame of ‘integration’). It thus combines a communitarian care of a Dutch culturally grounded national community – conceived astraditionally‘enlightened’ and ‘liberal’– with a neo‐liberal emphasis on the individual's responsibility to achieve membership of that community. ‘Community’ is thereby selectively seen as mobilized and present (when immigrant integration is concerned) or as latently present and still in need of mobilization (when indigenous Dutch are concerned). Concomitantly, arepressive responsibilizationand afacilitative responsibilizationare aimed at these two governmentally differentiated populations.
Reflexivity over and above convention: the new orthodoxy in the sociology of personal life, formerly sociology of the family
Authors: Gilding Michael
Published: December 2010

There is a new orthodoxy in the field that was once understood as the sociology of the family, and is increasingly understood as the sociology of ‘personal life’, ‘intimacy’, ‘relationships’ and ‘families’. The orthodoxy highlights the open‐endedness of intimate relations at the expense of the family as an institution; that is, reflexivity over and above convention. This article argues that the new orthodoxy not only overstates reflexivity at the expense of convention, but abdicates understanding to frameworks grounded in biologistic and economistic understandings of human behaviour. The article makes its point through attention to three areas of research at odds with the new orthodoxy: paternity uncertainty, inheritance and family business. It then proposes that conceptualization of the family as an institutional regime gives due weight to the reflexive reconfiguration of family relationships and practices on the one hand, and their institutional embeddedness on the other.
Differentiating among penal states
Authors: Lacey Nicola
Published: December 2010

This review article assesses Loïc Wacquant's contribution to debates on penality, focusing on his most recent book,Punishing the Poor: The Neoliberal Government of Social Insecurity(Wacquant 2009), while setting its argument in the context of his earlierPrisons of Poverty(1999). In particular, it draws on both historical and comparative methods to question whether Wacquant's conception of ‘the penal state’ is adequately differentiated for the purposes of building the explanatory account he proposes; about whether ‘neo‐liberalism’ has, materially, the global influence which he ascribes to it; and about whether, therefore, the process of penal Americanization which he asserts in his recent writings is credible.
Educational ties, social capital and the translocal (re)production of MBA alumni networks
Authors: HALL SARAH
Published: December 2010

Research on elite, transnational networks has identified social and cultural capital associated with particular academic credentials as being an important element in network formation. How and why such networks are reproduced after graduation, however, has received less attention. In response, in this article I combine work on social capital and personal networks to explore the reproduction of MBA alumni networks in London's financial services district that were created in leading business schools in the USA and UK. My analysis documents the ways in which business schools and individual alumni combine forms of virtual and corporeal co‐presence to reproduce translocal educational ties. I then argue that the motivation for sustaining these educational ties lies in the potential to convert the social and cultural capital of MBA alumni networks into different types of value ranging from enhanced career progression to increased alumni donations. In doing so, I develop debates on the intersections between social capital, academic credentials and the reproduction of elite networks.
Aggregation Decomposition and Aggregation Guidelines for a Class of Minimax and Covering Location Models
Authors: Francis Richard L. , Lowe Timothy J. , Tamir Arte , Emir‐Farinas Hulya
Published: December 2010

Facility location problems often involve movement between facilities to be located and customers/demand points, with distances between the two being important. For problems with many customers, demand point aggregation may be needed to obtain a computationally tractable model. Aggregation causes error, which should be kept small. We consider a class of minimax location models for which the aggregation may be viewed as a second‐order location problem, and use error bounds as aggregation error measures. We provide easily computed approximate “square root” formulas to assist in the aggregation process. The formulas establish that the law of diminishing returns applies when doing aggregation. Our approach can also facilitate aggregation decomposition for location problems involving multiple “separate” communities.