bluuebunny/crossref_metadata_2025 huggingface dataset:
Left Clouds Over Climate Change Policy
Authors: Hahnel Robin
Published: October 2011

Will there be an international climate treaty to follow Kyoto when it expires in 2012, and if so what will it look like? Many climate justice and anti-capitalist spokespersons denounce the Kyoto Protocol as a “pretend solution” and reject international carbon trading altogether. This article argues that, on the contrary, an international cap and trade treaty is the only way to avert climate change fairly before it is too late, and that the Kyoto Protocol is a framework that progressives should defend and fix rather than condemn and nix. After explaining why many climate justice and anti-capitalist criticisms of carbon trading are without merit and fail to appreciate how international carbon trading can favor lesser developed countries (LDCs), five changes to make a post-Kyoto cap and trade treaty more effective and fair are proposed, and common arguments against carbon trading are rebutted.

JEL codes: Q54, Q56, Q58
Mass–spring–damper modelling of the human body to study running and hopping – an overview
Authors: Nikooyan A A , Zadpoor A A
Published: October 2011

Several mass–spring–damper models have been developed to study the response of the human body to the collision with the ground during hopping, trotting, or running. The mass, spring, and damper elements represent the masses, stiffness properties, and damping properties of hard and soft tissues. The masses that models are composed of are connected to each other via springs and dampers. The present paper reviews the various types of mass–spring–damper models including one-body and multi-body models. The models are further categorized as being either passive or active. In passive models, the mechanical properties (stiffness and damping) of soft tissues remain constant regardless of the type of footwear, ground stiffness, etc. In active models, the mechanical properties adapt to external loads. The governing equations of motion of all models as well as their parameters are presented. The specific ways that the models take account of the shoe–ground interactions are discussed as well. The methods used for determination of different modelling parameters are briefly surveyed. The advantages and disadvantages of the different types of mass–spring–damper models are also discussed. The paper concludes with a brief discussion of possible future research trends in the area of mass–spring–damper modelling.
Comparison of Injuries Experienced by International Tourists Visiting Australia and Australian Residents
Authors: Mitchell Rebecca J. , Williamson Ann , Chung Amy Z. Q.
Published: October 2011

This article compares the epidemiological profile of injury-related hospitalized morbidity of international tourists in New South Wales (NSW) with the hospitalized injury profile of NSW residents. Injury-related hospitalizations were identified from the NSW Admitted Patients Data Collection during 1 July 2000 to 30 June 2009. Injuries were identified using a principal diagnosis code of injury (ie, ICD-10-AM range S00-T98) and the presence of an external cause code (ie, ICD-10-AM range V00-Y98). Overseas tourists were more likely to be hospitalized for an injury following air and water transport, near-drowning, and pedestrian-related injuries. Sport or leisure-related activities were the most common activity conducted at the time of the incident. International tourists are at a higher risk of experiencing injuries particularly following recreational pursuits, while as a pedestrian, in vehicle crashes for older age groups, as a result of interpersonal violence for young males, and following a poisoning or cut/pierce injury for young females. Prevention measures should be undertaken to limit the incidence of injury among international tourists, particularly during active recreational activities and while using the roadways.
Forecasting Hepatocellular Carcinoma Mortality in Taiwan Using an Age-Period-Cohort Model
Authors: Tzeng I-Shiang , Lee Wen-Chung
Published: October 2011

Hepatocellular carcinoma (HCC) is a common primary malignancy of the liver. Estimates of the future HCC burden are important for health planning. The authors applied an age-period-cohort (APC) model for a 15-year forecast of HCC mortality in Taiwan (based on mortality data between the years 1976 and 2005). It is found that for men, the mortality trend reverses itself in the period 2011-2015, from an increasing one to a slightly deceasing one. For women, the increasing trend reverses itself in the period 2001-2005. The age-adjusted HCC mortality for men and women in the most recent available years, 2006-2008, both fall in the range forecast by the APC model. Forecasting using the APC model can provide an advanced warning of trend reversals.
Brisk and Effective Fluency Instruction for Small Groups
Authors: Wilson Judith K.
Published: October 2011

Fluency is known as the bridge between phonics and comprehension. Teachers of reading provide high-quality instruction in phonics and decoding strategies, usually in a small-group format, but may be unsure how to insert fluency instruction into the small-group lesson. This article presents key concepts in fluency instruction and a description of steps teachers can follow to add brisk, brief, and effective fluency instruction to their small-group sessions.
The Social Ecological Model as a Framework for Determinants of 2009 H1N1 Influenza Vaccine Uptake in the United States
Authors: Kumar Supriya , Quinn Sandra Crouse , Kim Kevin H. , Musa Donald , Hilyard Karen M. , Freimuth Vicki S.
Published: October 2011

Research on influenza vaccine uptake has focused largely on intrapersonal determinants (perceived risk, past vaccine acceptance, perceived vaccine safety) and on physician recommendation. The authors used a social ecological framework to examine influenza vaccine uptake during the 2009 H1N1 pandemic. Surveying an adult population ( n = 2,079) in January 2010 with significant oversamples of Blacks and Hispanics, this study found that 18.4% (95% confidence interval = 15.6-21.5) had gotten the 2009 H1N1 vaccine. Variables at each level of the social ecological model were significant predictors of uptake as well as of intent to get the vaccine. The intrapersonal level explained 53%, the interpersonal explained 47%, the institutional level explained 34%, and the policy and community levels each explained 8% of the variance associated with vaccine uptake. The levels together explained 65% of the variance, suggesting that interventions targeting multiple levels of the framework would be more effective than interventions aimed at a single level.
Socioeconomic status, labour market connection, and self-rated psychological health: The role of social capital and economic stress
Authors: Lindström Martin , Ali Sadiq M. , Rosvall Maria
Published: October 2011

Aims: To investigate the association between socioeconomic status, unemployment and self-rated psychological health, taking economic stress and horizontal trust into account. Design/setting/participants/measurements: The 2008 public health survey in Skåne is a cross-sectional postal questionnaire study with a 55% participation rate. A random sample was invited and 28,198 persons aged 18–80 participated. Logistic regression models were used to investigate associations between socioeconomic status by occupation (SES), labour market connection and self-rated psychological health (GHQ12). The multiple regression analyses included age, country of birth, education, economic stress and generalized (horizontal) trust. Results: 13.8% of the men and 18.2% of the women had poor psychological health. Poor psychological health was more common among the young, among those born abroad, among those with lower education, with economic stress, and low horizontal trust. There were no significant differences between the employed and self-employed groups. However, the people who had retired early, the unemployed and those on long-term sick leave had significantly higher odds ratios of poor psychological health than higher non-manual employees throughout the analyses. Conclusions: There were no differences in psychological health between non-manual employees in higher positions and other employed and self-employed SES groups among men or women. In contrast, the early retired, the unemployed and the category on long-term sick leave had significantly higher odds ratios of poor psychological health among both men and women throughout the multiple analyses. Both economic stress and trust affected this association (i.e., lowered the odds ratios of poor psychological health), but affected by economic stress to a somewhat higher extent.
Needs and care of older people living at home in Iceland
Authors: Sigurdardottir Sigurveig H. , Sundstrom Gerdt , Malmberg BO , Bravell Marie Ernsth
Published: October 2011

Background: The Icelandic old-age care system is universal and the official goal is to support older people live independently for as long as possible. The aim of this study is to analyse living conditions and use of formal and informal care of older people in Iceland. Methods: The results are based on the new study ICEOLD, a telephone survey which included questions on social network, health, activities of daily living, and received support from the community and/or from relatives, neighbours, and friends. Results: Almost half of the sample (47%) receives some kind of care, with 27% of them receiving only informal care, which is understood to mean that informal care is of great importance and families are the main providers of help. For hypothetical future long-term care, older people wish to be cared for in their homes, but those already in need of assistance prefer to be cared for in institutions. Discussion: Caring relatives are the main providers of support to older people in their homes and it is important to provide them with suitable formal support when the care responsibility increases. Conclusions: As the care system in Iceland is now under reconstruction, the important contribution of informal carers must be recognised and taken into account when planning the care of older people.
Immigrants across the U.S. Federal Laboratory: Explaining State-Level Innovation in Immigration Policy
Authors: Boushey Graeme , Luedtke Adam
Published: October 2011

The passage of a restrictive immigration law in Arizona in 2010 rekindled an old debate in the United States on immigration policy and the role of federalism. Despite periodic constitutional controversies, scholars of federalism and U.S. state politics have not adequately explained variation in state-level policy making on immigration. The authors explore pressures leading to state immigration policy innovation and adoption in the United States. The article evaluates factors leading to the introduction and adoption of two types of policies: those dictating the cultural and economic incorporation of immigrants and those attempting to control their flow and settlement. Factors such as fiscal federalism, ethnic contact, and ethnic threat generate incentives for states to pass such laws. The authors compiled a comprehensive data set of state immigration laws from the past decade to explain how factors commonly associated with national immigration policy development—economic conditions, rates of immigration, demographics, party control, and political institutions—influence state-level immigration policy activity.
Analyzing behavior signatures for terrorist attack forecasting
Authors: Reed Gregory S , Colley Wesley N , Aviles Steven M
Published: October 2011

In this paper we outline statistical methods used to analyze the behavior signatures that are hidden deep within data on terrorist attacks. These methods have the potential to allow military commanders to identify trends in attacks and to make informed decisions about how best to prevent future attacks. While this work focuses primarily on terrorist attacks that have occurred during Operation Iraqi Freedom, the methodology can be expanded and applied to a variety of areas. With the terrorists’ advantage of the element of surprise, analyzing their behavior may appear to be a very daunting task; however, it is demonstrated that even a collection of largely random data can often lead to insightful inferences. This paper provides a discussion of the project as a whole, the challenges faced in data collection and analysis, the methodology used, and the results and implications of the study.
Compliance of children in northern France with physical activity recommendations
Authors: Apété Geoffroy K , Zitouni Djamel , Hubert Hervé , Guinhouya Benjamin C
Published: October 2011

Aims: This study examined the compliance of French children with physical activity (PA) guidelines, using objective assessments of PA.

Methods: The study involved 252 children aged 9.9 ± 0.9 years, with mean height and weight of 1.39 ± 0.08 m and 35.8 ± 8.8 kg, respectively. Their usual PA was evaluated during a week using an Actigraph accelerometer.

Results: The time spent in a moderate-to-vigorous PA (MVPA) ranged from 142 ± 44 min.d-1 to 25 ± 18 min/day according to the cut-offs used. Boys were significantly more active than girls ( p ≤ .001). Overweight/obese children spent significantly less time in MVPA as determined with cut-off points at 3200 cpm (-26%) or 3600 cpm (-35%) ( p < .01). Between 5% (8% of boys vs 1% of girls, p < .0001) and 9% (14% of boys vs 3% of girls, p < .0001) of children probably met the PA guidelines. No relationships were found with socioeconomic status.

Conclusions: This high proportion of insufficiently active children (> 90%), together with the relatively high proportion of overweight children in this area, advocates a more aggressive PA promotion project, which should target all children whatever their social origins.
Agomelatine in unipolar depression in clinical practice: a retrospective chart review
Authors: Langan Julie , Shajahan Polash , Martin Daniel , Carleton Rebecca
Published: October 2011

Agomelatine (Valdoxan), a synthetic melatonergic receptor agonist at the MT1 and MT2 receptors, was first used in the management of sleep disorder. Its 5HT2C receptor antagonistic properties support its antidepressant potential. It is currently licensed in the UK, Europe and USA for the treatment of major depressive disorder. Although the randomized controlled evidence base for its use is growing, there are no retrospective, naturalistic studies available. We aimed to determine the tolerability and clinical effectiveness of agomelatine in unipolar depression. We also examined whether being refractory to treatment altered clinical outcome. Forty-eight patient records were examined. Twenty-five percent were treatment refractory: Clinical Global Impression (CGI) Severity score at the start of treatment was 3.81 compared with 3.38 at the end of treatment. Fifty-four percent improved at least minimally; only 12.5% were much or very much improved. Treatment-refractory patients had a poorer outcome with higher discontinuation rates and lower CGI Improvement ( p = 0.0205). Treatment-refractory patients also had a higher CGI Severity score at the end of treatment than at treatment commencement (3.92 versus 3.75), although this was not statistically significant.
TACI deficiency impairs sustained Blimp-1 expression in B cells decreasing long-lived plasma cells in the bone marrow
Authors: Tsuji Shoichiro , Cortesão Catarina , Bram Richard J. , Platt Jeffrey L. , Cascalho Marilia
Published: October 2011

Deficiencies in transmembrane activator and CAML interactor (TACI) result in common variable immune deficiency, a syndrome marked by recurrent infections with encapsulated microorganisms, impaired production of antibodies, and lymphoproliferation. How TACI promotes antibody production and inhibits lymphoproliferation is not understood. To answer this question, we studied the generation of immunity to protein antigens in both TACI-deficient and TACI-proficient mice. We show that TACI promotes sustained Blimp-1 expression by B cells responding to antigen, which in turn limits B-cell clonal expansion and facilitates differentiation of long-lived antibody-secreting cells. Short-term IgG secretion occurs independently of TACI as DNA double-strand breaks associated with isotype class switching induce Blimp-1 transiently, independently of TACI. Our results showing that TACI induces and maintains Blimp-1 provide, for the first time, a unified molecular and cellular mechanism explaining the primary features of common variable immune deficiency, exquisite vulnerability to infection with encapsulated organisms, lymphoproliferation, and hypogammaglobulinemia.
Antitumor activity and long-term fate of chimeric antigen receptor–positive T cells in patients with neuroblastoma
Authors: Louis Chrystal U. , Savoldo Barbara , Dotti Gianpietro , Pule Martin , Yvon Eric , Myers G. Doug , Rossig Claudia , Russell Heidi V. , Diouf Oumar , Liu Enli , Liu Hao , Wu Meng-Fen , Gee Adrian P. , Mei Zhuyong , Rooney Cliona M. , Heslop Helen E. , Brenner Malcolm K.
Published: October 2011

We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4+ cells and central memory cells (CD45RO+CD62L+) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at www.clinialtrials.gov as #NCT00085930.
Lung glutathione adaptive responses to cigarette smoke exposure
Authors: Gould Neal S , Min Elysia , Gauthier Steve , Martin Richard J , Day Brian J
Published: October 2011

Background

Smoking tobacco is a leading cause of chronic obstructive pulmonary disease (COPD), but although the majority of COPD cases can be directly related to smoking, only a quarter of smokers actually develop the disease. A potential reason for the disparity between smoking and COPD may involve an individual's ability to mount a protective adaptive response to cigarette smoke (CS). Glutathione (GSH) is highly concentrated in the lung epithelial lining fluid (ELF) and protects against many inhaled oxidants. The changes in GSH that occur with CS are not well investigated; therefore the GSH adaptive response that occurs with a commonly utilized CS exposure was examined in mice.

Methods

Mice were exposed to CS for 5 h after which they were rested in filtered air for up to 16 h. GSH levels were measured in the ELF, bronchoalveolar lavage cells, plasma, and tissues. GSH synthesis was assessed by measuring γ-glutamylcysteine ligase (GCL) activity in lung and liver tissue.

Results

GSH levels in the ELF, plasma, and liver were decreased by as much as 50% during the 5 h CS exposure period whereas the lung GSH levels were unchanged. Next, the time course of rebound in GSH levels after the CS exposure was examined. CS exposure initially decreased ELF GSH levels by 50% but within 2 h GSH levels rebound to about 3 times basal levels and peaked at 16 h with a 6-fold increase and over repeat exposures were maintained at a 3-fold elevation for up to 2 months. Similar changes were observed in tissue GCL activity which is the rate limiting step in GSH synthesis. Furthermore, elevation in ELF GSH levels was not arbitrary since the CS induced GSH adaptive response after a 3d exposure period prevented GSH levels from dropping below basal levels.

Conclusions

CS exposures evoke a powerful GSH adaptive response in the lung and systemically. These data suggests there may be a sensor that sets the ELF GSH adaptive response to prevent GSH levels from dipping below basal levels. Factors that disrupt GSH adaptive responses may contribute to the pathophysiology of COPD.
Genomic and proteomic analyses of Mycobacterium bovis BCG Mexico 1931 reveal a diverse immunogenic repertoire against tuberculosis infection
Authors: Orduña Patricia , Cevallos Miguel A , de León Samuel Ponce , Arvizu Adriana , Hernández-González Ismael L , Mendoza-Hernández Guillermo , López-Vidal Yolanda
Published: October 2011

Background

Studies of Mycobacterium bovis BCG strains used in different countries and vaccination programs show clear variations in the genomes and immune protective properties of BCG strains. The aim of this study was to characterise the genomic and immune proteomic profile of the BCG 1931 strain used in Mexico.

Results

BCG Mexico 1931 has a circular chromosome of 4,350,386 bp with a G+C content and numbers of genes and pseudogenes similar to those of BCG Tokyo and BCG Pasteur. BCG Mexico 1931 lacks R egion of D ifference 1 (RD1), RD2 and N-RD18 and one copy of IS6110, indicating that BCG Mexico 1931 belongs to DU2 group IV within the BCG vaccine genealogy. In addition, this strain contains three new RDs, which are 53 (RDMex01), 655 (RDMex02) and 2,847 bp (REDMex03) long, and 55 single-nucleotide polymorphisms representing non-synonymous mutations compared to BCG Pasteur and BCG Tokyo. In a comparative proteomic analysis, the BCG Mexico 1931, Danish, Phipps and Tokyo strains showed 812, 794, 791 and 701 protein spots, respectively. The same analysis showed that BCG Mexico 1931 shares 62% of its protein spots with the BCG Danish strain, 61% with the BCG Phipps strain and only 48% with the BCG Tokyo strain. Thirty-nine reactive spots were detected in BCG Mexico 1931 using sera from subjects with active tuberculosis infections and positive tuberculin skin tests.

Conclusions

BCG Mexico 1931 has a smaller genome than the BCG Pasteur and BCG Tokyo strains. Two specific deletions in BCG Mexico 1931 are described (RDMex02 and RDMex03). The loss of RDMex02 (fadD23) is associated with enhanced macrophage binding and RDMex03 contains genes that may be involved in regulatory pathways. We also describe new antigenic proteins for the first time.
Hybrid methods for accretive variational inequalities involving pseudocontractions in Banach spaces
Authors: Wang Yaqin , Chen Rudong
Published: October 2011

We use strongly pseudocontractions to regularize a class of accretive variational inequalities in Banach spaces, where the accretive operators are complements of pseudocontractions and the solutions are sought in the set of fixed points of another pseudocontraction. In this paper, we consider an implicit scheme that can be used to find a solution of a class of accretive variational inequalities.

Our results improve and generalize some recent results of Yao et al. (Fixed Point Theory Appl, doi:10.1155/2011/180534, 2011) and Lu et al. (Nonlinear Anal, 71(3-4), 1032-1041, 2009).

2000 Mathematics subject classification 47H05; 47H09; 65J15
Toll-like receptors in cerebral ischemic inflammatory injury
Authors: Wang Yan-Chun , Lin Sen , Yang Qing-Wu
Published: October 2011

Cerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the innate immune system, particularly in regard to the signaling mechanisms of Toll-like receptors (TLRs), whose primary role is the initial activation of immune cell responses. So far, few studies have examined the role of TLRs in cerebral ischemia. However, work with experimental models of ischemia suggests that TLRs are involved in the enhancement of cell damage following ischemia, and their absence is associated with lower infarct volumes. It may be possible that therapeutic targets could be designed to modulate activities of the innate immune system that would attenuate cerebral brain damage. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Interpreting the molecular mechanism of ischemic tolerance will open investigative avenues into the treatment of cerebral ischemia. In this review, we discuss the critical role of TLRs in mediating cerebral ischemic injury. We also summarize evidence demonstrating that cerebral preconditioning downregulates pro-inflammatory TLR signaling, thus reducing the inflammation that exacerbates ischemic brain injury.
Changes in met perceived need for mental healthcare in Australia from 1997 to 2007
Authors: Meadows Graham N. , Bobevski Irene
Published: October 2011

Background

The Australian National Survey of Mental Health and Wellbeing conducted in 1997 and 2007 allows for exploration of changes in perceptions of mental healthcare. Major demographic, economic and health-behaviour changes have unfolded in Australia during this time. Governments also have increased spending on mental health services and been active in mental healthcare policy-making and implementation.

Aims

To compare rates of meeting of perceived need for mental healthcare between these two surveys dealing with adjustable sources of error.

Method

Combined data-sets from 1997 and 2007 were analysed to provide weighted population estimates. Selection, indirect standardisation to a common reference population and multinomial logistic regression were employed, addressing bias and confounding.

Results

Between 1997 and 2007 perceived need for information, counselling and skills training among people who consulted a general practitioner, psychiatrist, or psychologist for mental health reasons has increased. Within these service users, increases in perceived responses from services are evident among people who have perceived needs for information provision and counselling.

Conclusions

Policy and service changes are among possible causal explanations. Generally, trends are in the direction that policy changes were intended to achieve, giving some encouragement that these initiatives have had some effect. Reduced unmet perceived need suggests improved access to some interventions. However, the proportion of service responses to perceived need seen as sufficient is generally unchanged. This suggests the adequacy of treatments offered, as perceived by the Australian public, may not have improved and that a continued focus on quality of care is important for the future.
BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development
Authors: Shu Bing , Zhang Ming , Xie Rong , Wang Meina , Jin Hongting , Hou Wei , Tang Dezhi , Harris Stephen E. , Mishina Yuji , O'Keefe Regis J. , Hilton Matthew J. , Wang Yongjun , Chen Di
Published: October 2011

The BMP signaling pathway has a crucial role in chondrocyte proliferation and maturation during endochondral bone development. To investigate the specific function of the Bmp2 and Bmp4 genes in growth plate chondrocytes during cartilage development, we generated chondrocyte-specific Bmp2 and Bmp4 conditional knockout (cKO) mice and Bmp2,Bmp4 double knockout (dKO) mice. We found that deletion of Bmp2 and Bmp4 genes or the Bmp2 gene alone results in a severe chondrodysplasia phenotype, whereas deletion of the Bmp4 gene alone produces a minor cartilage phenotype. Both dKO and Bmp2 cKO mice exhibit severe disorganization of chondrocytes within the growth plate region and display profound defects in chondrocyte proliferation, differentiation and apoptosis. To understand the mechanism by which BMP2 regulates these processes, we explored the specific relationship between BMP2 and Runx2, a key regulator of chondrocyte differentiation. We found that BMP2 induces Runx2 expression at both the transcriptional and post-transcriptional levels. BMP2 enhances Runx2 protein levels through inhibition of CDK4 and subsequent prevention of Runx2 ubiquitylation and proteasomal degradation. Our studies provide novel insights into the genetic control and molecular mechanism of BMP signaling during cartilage development.
Apaf1 plays a pro-survival role by regulating centrosome morphology and function
Authors: Ferraro Elisabetta , Pesaresi Maria Grazia , De Zio Daniela , Cencioni Maria Teresa , Gortat Anne , Cozzolino Mauro , Berghella Libera , Salvatore Anna Maria , Oettinghaus Bjorn , Scorrano Luca , Pérez-Payà Enrique , Cecconi Francesco
Published: October 2011

The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway. Here we show that Apaf1 plays a role in regulating centrosome maturation. By analyzing Apaf1-depleted cells, we have found that Apaf1 loss induces centrosome defects that impair centrosomal microtubule nucleation and cytoskeleton organization. This, in turn, affects several cellular processes such as mitotic spindle formation, cell migration and mitochondrial network regulation. As a consequence, Apaf1-depleted cells are more fragile and have a lower threshold to stress than wild-type cells. In fact, we found that they exhibit low Bcl-2 and Bcl-XL expression and, under apoptotic treatment, rapidly release cytochrome c. We also show that Apaf1 acts by regulating the recruitment of HCA66, with which it interacts, to the centrosome. This function of Apaf1 is carried out during the cell life and is not related to its apoptotic role. Therefore, Apaf1 might also be considered a pro-survival molecule, whose absence impairs cell performance and causes a higher responsiveness to stressful conditions.
Pulsatile patterns of pituitary hormone gene expression change during development
Authors: Featherstone Karen , Harper Claire V. , McNamara Anne , Semprini Sabrina , Spiller David G. , McNeilly Judith , McNeilly Alan S. , Mullins John J. , White Michael R. H. , Davis Julian R. E.
Published: October 2011

Important questions in biology have emerged recently concerning the timing of transcription in living cells. Studies on clonal cell lines have shown that transcription is often pulsatile and stochastic, with implications for cellular differentiation. Currently, information regarding transcriptional activity at cellular resolution within a physiological context remains limited. To investigate single-cell transcriptional activity in real-time in living tissue we used bioluminescence imaging of pituitary tissue from transgenic rats in which luciferase gene expression is driven by a pituitary hormone gene promoter. We studied fetal and neonatal pituitary tissue to assess whether dynamic patterns of transcription change during tissue development. We show that gene expression in single cells is highly pulsatile at the time endocrine cells first appear but becomes stabilised as the tissue develops in early neonatal life. This stabilised transcription pattern might depend upon tissue architecture or paracrine signalling, as isolated cells, generated from enzymatic dispersion of the tissue, display pulsatile luminescence. Nascent cells in embryonic tissue also showed coordinated transcription activity over short distances further indicating that cellular context is important for transcription activity. Overall, our data show that cells alter their patterns of gene expression according to their context and developmental stage, with important implications for cellular differentiation.
Time-resolved MR angiography of the calf arteries using a phased array cardiac coil: comparison of visibility with standard three-step bolus chase MR angiography
Authors: Eshed Iris , Rimon Uri , Novikov Ilia , Goitein Orly , Konen Eli
Published: October 2011

Background

Standard bolus chase MR angiography (MRA) is increasingly replacing digital subtraction angiography (DSA) in the diagnostic evaluation of peripheral vascular disease. However, a major limitation of bolus chase MRA is the relatively poor visibility of the calf arteries.

Purpose

To evaluate the feasibility of visualizing the calf arteries and the visibility quality of an 8-channel cardiac phased array coil using time-resolved imaging of contrast kinetics (TRICKS) MRA compared with standard bolus chase MRA on a 1.5 Tesla MRI scanner.

Material and Methods

MRA findings of 59 sequential patients (mean age 57.8 years, range 14-83 years; 41 men) were retrospectively evaluated. All examinations included preliminary TRICKS for the lower leg using a surface 8-channel cardiac coil, followed by a 3-step MRA of the abdominal aorta, thigh, and lower leg using a body coil. Images yielded by both methods were separately evaluated by consensus of two radiologists unaware of the patients’ clinical data. Visibility of the calf arteries (popliteal, tibialis anterior, tibialis posterior, tibioperoneal trunk, and peroneal) for both sides was subjectively classified as ‘diagnostic’ or ‘non-diagnostic’. Descriptive statistics for image diagnostic quality were assessed.

Results

A total of 575 calf arterial segments were evaluated. Visibility of all calf arteries was significantly better with TRICKS than with the standard bolus chase MRA ( P < 0.001). The improvement of calf artery visibility with TRICKS was more pronounced in patients with peripheral vascular disease compared to those with arteritis, vascular malformation and popliteal entrapment syndrome.

Conclusion

Using a cardiac coil for MRA of the lower extremities resulted in visibility comparable to that of a dedicated leg coil, with diagnostic superiority for the TRICKS method compared to the standard bolus chase method.
Corporate Governance, Debt, and Investment Policy During the Great Depression
Authors: Graham John R. , Hazarika Sonali , Narasimhan Krishnamoorthy
Published: October 2011

We study a period of severe disequilibrium to investigate whether board characteristics are related to corporate investment, debt usage, and firm value. During the 1930–1938 Depression era, when the corporate sector was shocked by an unprecedented downturn, we document a relation between board characteristics and firm performance that varies in economically sensible ways: Complex firms (that would benefit more from board advice) exhibit a positive relation between board size and firm value, and simple firms exhibit a negative relation between board size and firm value. Moreover, simple firms with large boards do not downsize adequately in response to the severe economic contraction: they invest more (or shrink less) and use more debt during the 1930s. We document similar effects for the number of outside directors on the board. Finally, we also find that companies with properly aligned governance structures are more likely to replace the company president following poor performance.

This paper was accepted by Wei Xiong, finance.
Routing to Manage Resolution and Waiting Time in Call Centers with Heterogeneous Servers
Authors: Mehrotra Vijay , Ross Kevin , Ryder Geoff , Zhou Yong-Pin
Published: October 2011

In many call centers, agents are trained to handle all arriving calls but exhibit very different performance for the same call type, where we define performance by both the average call handling time and the call resolution probability. In this paper, we explore strategies for determining which calls should be handled by which agents, where these assignments are dynamically determined based on the specific attributes of the agents and/or the current state of the system. We test several routing strategies using data obtained from a medium-sized financial service firm's customer service call centers and present empirical performance results. These results allow us to characterize overall performance in terms of customer waiting time and overall resolution rate, identifying an efficient frontier of routing rules for this contact center.
Theoretical prediction of drug-receptor interactions
Authors: Frecer Vladimir
Published: October 2011

The crucial event in the pharmacological action of drugs is the interaction between a drug molecule and its receptor. Molecular recognition and binding affinity of a drug is driven by a flexible steric fit and a molecular field match between two complementary molecular surfaces of the receptor and the approaching ligand. Rational drug design methods, which attempt to predict the free energy change resulting from ligand binding, rely on a detailed knowledge of the physical forces that govern the drug−receptor interactions in several populated configurations of the intermolecular complex. The overall strength of the interaction is determined by the fine balance between the forces contributed by the individual chemical function groups of the two entities and the physiological medium. This paper recounts some basic information about the description of molecular structures and highlights the methods and approximations commonly used to calculate the binding affinity of a drug to its receptor.
Gene dose effect of NAT2 variants on the pharmacokinetics of isoniazid and acetylisoniazid in healthy Chinese subjects
Authors: Bing Chen , Xiaomeia Cao , Jinhenga Li
Published: October 2011

Background: The aim of this study was to elucidate the gene dose effect of NAT2 and the effect on the pharmacokinetics of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) in Chinese subjects.

Methods: A total of 24 healthy Chinese subjects, consisting of eight homozygous wild types (wt/wt), eight heterozygous mutants (m/wt) and eight homozygous mutants (m/m) for NAT2, were enrolled in the study. The blood samples (0–14 h) of the subjects were taken after oral administration of a single dose (300 mg) of INH. Concentrations of INH and AcINH in plasma were measured by a reversed-phase HPLC method.

Results: The ratio of AcINH and INH (RA/I) 3 h post-dose of wt/wt, m/wt and m/m groups were 3.22±1.34, 1.35±0.20 and 0.22±0.06, respectively (p<0.01). The area under concentration-time curve (AUC) values of three groups were 10.35±2.12, 16.34±3.05, 42.24±8.51 mg/h/L for INH and 42.19±8.80, 38.05±5.32, 19.78±3.72 mg/h/L for AcINH, res­pectively (p<0.01). There was a good linear relationship between pharmacokinetic parameters and the number of active NAT2 genes.

Conclusions: The results suggest that there is a conspicuous gene dose effect in the pharmacokinetics of INH and AcINH. This finding may be valuable in the personalized therapy of tuberculosis with INH.
Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen
Authors: Cousins Darren , Topping Kate , Lee Vincent , Sweeney John , Lawton Mark
Published: October 2011

A HIV positive patient who received a cadaveric renal transplantation developed tacrolimus toxicity as manifest by renal failure and decreased consciousness. This was due to atazanavir and ritonavir therapy for her HIV inhibiting the CYP3A4 hepatic enzyme resulting in accumulation of tacrolimus. Her HIV treatment was switched to raltegravir which is metabolized by UGT1A1 which does not affect tacrolimus. Tacrolimus was then reintroduced, and follow-up at 1 year demonstrated successful immunosuppression and undetectable HIV viral loads.
Increased circulating levels of FGF23: an adaptive response in primary hyperparathyroidism?
Authors: Witteveen Janneke E , van Lierop Antoon H , Papapoulos Socrates E , Hamdy Neveen A T
Published: October 2011

Introduction

Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are major players in the bone–parathyroid–kidney axis controlling phosphate homeostasis. In patients with primary hyperparathyroidism (PHPT), data on the relationship between PTH and FGF23 are scarce and not always concordant.

Objective

The aim of our study was to evaluate the relationship between PTH and FGF23 in patients with PHPT and in euparathyroid patients cured after successful parathyroidectomy (PTx).

Patients and methods

Twenty-one patients with PHPT and 24 patients in long-term cure after successful PTx (EuPTH) were studied. All patients underwent biochemical evaluation of renal function, parathyroid status, vitamin D status, bone turnover markers, and serum intact FGF23 levels.

Results

Mean serum FGF23 concentration was significantly higher in PHPT than in EuPTH patients (50.8±6.1 vs 33.1±2.6 pg/ml,P=0.01). FGF23 levels significantly correlated with PTH levels (r=0.361,P=0.02), also after correction for 1,25(OH)2D levels (r=0.419,P=0.01). FGF23 levels showed a significant negative correlation with 1,25(OH)2D, which was more pronounced in PHPT than in EuPTH patients (r=−0.674,P=0.001, vsr=−0.509,P=0.01).

Conclusion

Our findings suggest that in PHPT, FGF23 levels are increased independent of 1,25(OH)2D levels. The more pronounced negative relationship between FGF23 and 1,25(OH)2D in the presence of high circulating PTH levels suggests that the increase in FGF23 levels may be an adaptive mechanism to counteract the PTH-induced increase in 1,25(OH)2D levels, although not completely overriding it.
Low residual proliferation after short-term letrozole therapy is an early predictive marker of response in high proliferative ER-positive breast cancer
Authors: Bedard Philippe L , Singhal Sandeep K , Ignatiadis Michail , Bradbury Ian , Haibe-Kains Benjamin , Desmedt Christine , Loi Sherene , Evans Dean B , Michiels Stefan , Dixon J Michael , Miller William R , Piccart Martine J , Sotiriou Christos
Published: October 2011

The gene expression grade index (GGI) is a 97-gene algorithm that measures proliferation and divides intermediate histological grade tumors into two distinct groups. We investigated the association between early changes in GGI and clinical response to neoadjuvant letrozole and compared this to Ki67 values. The paired gene expression data at the beginning and after 10–14 days of neoadjuvant letrozole treatment were available for 52 post-menopausal patients with estrogen receptor (ER)-positive breast cancer. Baseline values and changes in GGI, Ki67, and RNA expression modules representing oncogenic signaling pathways were compared to sonographic tumor volume changes after 3 months of treatment in the subsets of patients defined by high and low baseline GGI. The clinical response was observed in 80% genomic low-grade (24/30) and 59% genomic high-grade (13/22) tumors (P=0.10). Low residual proliferation after 10–14 days of neoadjuvant letrozole therapy, measured by either GGI or Ki67, was associated with sonographic response in genomic high-grade (GGI, P=0.003; Ki67, P=0.017) but not genomic low-grade (GGI, P=0.25; Ki67, P=1.0) tumors. The analysis of expression modules suggested that sonographic response to letrozole in genomic high-grade tumors was associated with an early reduction in IGF1 signaling (unadjusted P=0.018). The major conclusion of this study is that the early assessment of proliferation after short-term endocrine therapy may be useful to evaluate endocrine responsiveness, particularly in genomic high-grade ER-positive breast cancer.
Promoção da saúde em ambientes hospitalares
Authors: Silva Maria Adelane Monteiro da , Pinheiro Ana Karina Bezerra , Souza Ângela Maria Alves e , Moreira Andréa Carvalho Araújo
Published: October 2011

Apresentam-se reflexões acerca da prática da promoção da saúde em instituições hospitalares, abordando os aspectos que permeiam o ambiente hospitalar e dificultam a implementação de estratégias para a promoção da saúde nesses serviços. Discute-se o hospital como lugar estratégico para novas práticas, ressaltando-se ações realizadas nesse espaço, que podem contribuir para efetivação da promoção da saúde dos clientes. Acredita-se que a promoção da saúde tanto seja possível quanto necessária em ambientes hospitalares; e que as ações desenvolvidas nesse sentido podem conduzir o indivíduo e sua família na busca de uma melhor qualidade de vida.
Terceirização: a integração acabou?
Authors: Rezende Wilson
Published: October 2011

As mudanças significativas em termos de lógica do processo produtivo, as novas tecnologias e as alterações nas condições de competitividade abriram espaço para que a terceirização fosse alçada à condição de solucionadora de quase todas as questões estratégicas das empresas. A terceirização apresenta-se como uma possibilidade infinitamente mais adequada para uma série de situações enfrentadas pelas empresas, mas não pode ser tratada como um novo dogma, visto que estes, tanto os velhos como os novos, não conseguem mais dar respostas satisfatórias à efetiva prática empresarial moderna. O artigo pretende fazer uma análise conceitual dos principais fatores vinculados à integração e à terceirização - analisando os fatores propulsores, os restritivos, as condições alavancadoras - e um levantamento das empresas sediadas no Brasil que, nos últimos anos, fizeram uso dessas estratégias.
Alianças estratégicas - internacionais: formaçao e estruturação em indústrias manufatureiras
Authors: Arruda Maria Cecília Coutinho de , Arruda Marcelo Leme de
Published: October 2011

A estratégia de negócios internacionais de indústrias latino-americanas e a forma como se conduzem suas parcerias com indústrias estrangeiras foram analisadas com o objetivo de conhecer melhor aspectos como: 1. implementação de uma estratégia internacional bem-sucedida; 2. forma como as empresas conduzem suas relações com empresas de outros países; 3. determinação dos fatores de sucesso dessas alianças de negócios internacionais. A pesquisa integrou um estudo multinacional, desenvolvido com o patrocínio de algumas das mais importantes universidades do Canadá, Estados Unidos, Brasil, Chile e México, e empresas destes três últimos países. Os resultados serão apresentados em dois artigos, sendo o primeiro voltado para a formação e estruturação das alianças estratégicas e o segundo, para desempenho e estratégias de marketing internacional das parcerias.
Desevolvimento de uma estratégia de manufatura em um ambiente turbulento
Authors: Gonçalves Ernesto Lima
Published: October 2011

A proposta da nova estrutura organizacional do hospital baseia-se em estruturas funcionais, geográficas ou de produto sob forma de gerência. Os gerentes, encarregados de decisões em suas áreas específicas, compõem o Conselho Técnico-Administrativo no qual as decisões gerais serão tomadas por consenso, formando uma estrutura empresarial participativa.
A lei e o corpo
Authors: Chauvenett Antoinette
Published: October 2011

Partindo do conceito do arbitrário cultural, onde se relativiza a categoria de enfermidade e se evidencia a inserção desta no campo da significação, o ensaio discute a problemática da autonomia do organismo e da saúde como constituinte da lei, para estabelecer então as relações entre as categorias de causalidade, desvio e ordem jurídica, que se desdobra na discussão entre corpo e história.
A medicina social e a questão feminina
Authors: Nunes Silvia Alexim
Published: October 2011

Este trabalho pretende analisar o tipo de saber sobre a mulher produzido pela medicina a partir da constituição de uma medicina social, no século XIX, no Rio de Janeiro. Podemos observar a constituição de um discurso sobre o sexo feminino que, calcando-sena noção de degeneração psíquica, vai tratá-lo como possuidor de uma base degenerada, podendo portanto sucumbir às mais terríveis ameaças. Esse tipo de discurso que descreve a mulher como um ser doentio, capaz de fazer mal a si e a toda sociedade, viabiliza a tentativa de tomá-la cada vez mais incapaz de gerir sua própria vida, tratando como patológico qualquer comportamento que não corresponda ao modelo de esposa e mãe.