bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo measurement of intrauterine pressure by telemetry: a new approach for studying parturition in mouse models
Authors: Pierce Stephanie L. , Kutschke William , Cabeza Rafael , England Sarah K.
Published: May 2010

Transgenic and knockout mouse models have proven useful in the study of genes necessary for parturition—including genes that affect the timing and/or progression of labor contractions. However, taking full advantage of these models will require a detailed characterization of the contractile patterns in the mouse uterus. Currently the best methodology for this has been measurement of isometric tension in isolated muscle strips in vitro. However, this methodology does not provide a real-time measure of changes in uterine pressure over the course of pregnancy. Recent advances have opened the possibility of using radiotelemetric devices to more accurately and comprehensively study intrauterine pressure in vivo. We tested the effectiveness of this technology in the mouse, in both wild-type (WT) mice and a mouse model of defective parturition (SK3 channel-overexpressing mice), after surgical implant of telemetry transmitters into the uterine horn. Continuous recordings from day 18 of pregnancy through delivery revealed that WT mice typically deliver during the 12-h dark cycle after 19.5 days postcoitum. In these mice, intrauterine pressure gradually increases during this cycle, to threefold greater than that measured during the 12-h cycle before delivery. SK3-overexpressing mice, by contrast, exhibited lower intrauterine pressure over the same period. These results are consistent with the outcome of previous in vitro studies, and they indicate that telemetry is an accurate method for measuring uterine contraction, and hence parturition, in mice. The use of this technology will lead to important novel insights into changes in intrauterine pressure during the course of pregnancy.
Multiscale Characterization of the PEPCK‐Cmus Mouse through 3D Cryoimaging
Authors: Roy Debashish , Gargesha Madhusudhana , Steyer Grant J. , Hakimi Parvin , Hanson Richard W. , Wilson David L.
Published: May 2010

We have developed, for the Case 3D Cryo‐imaging system, a specialized, multiscale visualization scheme which provides color‐rich volume rendering and multiplanar reformatting enabling one to visualize an entire mouse and zoom in to organ, tissue, and microscopic scales. With this system, we have anatomically characterized, in 3D, from whole animal to tissue level, a transgenic mouse and compared it with its control. The transgenic mouse overexpresses the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK‐C) in its skeletal muscle and is capable of greatly enhanced physical endurance and has a longer life‐span and reproductive life as compared to control animals. We semiautomatically analyzed selected organs such as kidney, heart, adrenal gland, spleen, and ovaries and found comparatively enlarged heart, much less visceral, subcutaneous, and pericardial adipose tissue, and higher tibia‐to‐femur ratio in the transgenic animal. Microscopically, individual skeletal muscle fibers, fine mesenteric blood vessels, and intestinal villi, among others, were clearly seen.
Vitiligo after Diphencyprone for Alopecia Areata
Authors: Pires Mario Cezar , Martins João Mauricio , Montealegre F. , Gatti Flávia Romero
Published: May 2010

The topical immunotherapy is used to treat alopecia areata and recalcitrant warts since the 1970s. Diphencyprone is a contact sensitizer used to treat dermatological conditions resulting from as altered immunological state, such as extensive alopecia areata, being partially effective and safe. Side effects include local eczema with blistering, regional lymphadenopathy and contact urticaria. Rare adverse effects include an erythema multiforme‐like reaction, hyperpigmenttion, hypopigmentation, and vitiligo. We report a 30‐year‐old, Brazilian male who developed vitiligo lesions following DPCP therapy for alopecia areata.
Iron Loading and Overloading due to Ineffective Erythropoiesis
Authors: Tanno Toshihiko , Miller Jeffery L.
Published: May 2010

Erythropoiesis describes the hematopoietic process of cell proliferation and differentiation that results in the production of mature circulating erythrocytes. Adult humans produce 200 billion erythrocytes daily, and approximately 1 billion iron molecules are incorporated into the hemoglobin contained within each erythrocyte. Thus, iron usage for the hemoglobin production is a primary regulator of plasma iron supply and demand. In many anemias, additional sources of iron from diet and tissue stores are needed to meet the erythroid demand. Among a subset of anemias that arise from ineffective erythropoiesis, iron absorption and accumulation in the tissues increases to levels that are in excess of erythropoiesis demand even in the absence of transfusion. The mechanisms responsible for iron overloading due to ineffective erythropoiesis are not fully understood. Based upon data that is currently available, it is proposed in this review that loading and overloading of iron can be regulated by distinct or combined mechanisms associated with erythropoiesis. The concept of erythroid regulation of iron is broadened to include both physiological and pathological hepcidin suppression in cases of ineffective erythropoiesis.
Optical Computing: A 60-Year Adventure
Authors: Ambs Pierre
Published: May 2010

Optical computing is a very interesting 60-year old field of research. This paper gives a brief historical review of the life of optical computing from the early days until today. Optical computing
generated a lot of enthusiasm in the sixties with major breakthroughs opening a large number of
perspectives. The period between 1980 and 2000 could be called the golden age with numerous new
technologies and innovating optical processors designed and constructed for real applications.
Today the field of optical computing is not ready to die, it has evolved and its results benefit to new
research topics such as nanooptics, biophotonics, or communication systems.
Which Metabolic Pathways Generate and Characterize the Flux Space? A Comparison among Elementary Modes, Extreme Pathways and Minimal Generators
Authors: Llaneras Francisco , Picó Jesús
Published: May 2010

Important efforts are being done to systematically identify the relevant pathways in a metabolic network. Unsurprisingly, there is not a unique set of network-based pathways to be tagged as relevant, and at least four related concepts have been proposed: extreme currents, elementary modes, extreme pathways, and minimal generators. Basically, there are two properties that these sets of pathways can hold: they can generate the flux space—if every feasible flux distribution can be represented as a nonnegative combination of flux through them—or they can comprise all the nondecomposable pathways in the network. The four concepts fulfill the first property, but only the elementary modes fulfill the second one. This subtle difference has been a source of errors and misunderstandings. This paper attempts to clarify the intricate relationship between the network-based pathways performing a comparison among them.
POT‐Based Estimation of the Renewal Function of Interoccurrence Times of Heavy‐Tailed Risks
Authors: Necir Abdelhakim , Rassoul Abdelaziz , Meraghni Djamel
Published: May 2010

Making use of the peaks over threshold (POT) estimation method,
we propose a semiparametric estimator for the renewal function of
interoccurrence times of heavy‐tailed insurance claims with infinite
variance. We prove that the proposed estimator is consistent and
asymptotically normal, and we carry out a simulation study to compare its finite‐sample behavior with respect to the nonparametric one.
Our results provide actuaries with confidence bounds for the renewal
function of dangerous risks.
Approaches towards Individualized Immune Intervention
Authors: Giese Thomas , Sommerer Claudia , Zeier Martin , Meuer Stefan
Published: May 2010

Long-term immunosuppression causes a significantly increased risk for the development of malignancies in transplanted patients. A link between immunosuppression and incidence of cancer is well documented and involves the effect of immunosuppression on antitumor surveillance and antiviral adaptive immune responses. Using a recently described pharmacodynamic assay, a strong correlation between the incidence of malignancies and the individual degree of immunosuppression after cyclosporin A treatment in patients with kidney transplants was observed. The availability of a quantitative and quick laboratory test for the assessment of the individual functional activity of immunocompetent cells crucial for transplant rejection, defense against viral infection and tumor surveillance, along with the ability to adjust doses of immunosuppressive agents such that patients are largely protected against malignant disease and/or viral infection while maintaining a stable allograft function, represents an enormous breakthrough in transplantation medicine and advances our attempts to individualize treatment in transplanted patients.
Pathology of Immune-Mediated Liver Injury
Authors: Dienes Hans-Peter , Drebber Uta
Published: May 2010

The liver is a special lymphoid organ with its own defense mechanism and it is prone to chronic viral and autoimmune diseases. All constituent liver cells are involved in immune mechanisms against foreign toxins and infectious agents: hepatocytes, Kupffer cells, endothelial cells, hepatic stellate cells and liver resident lymphocytes such as natural killer, natural killer T and dendritic cells. The first line of defense is held up by the innate immune system where the adaptive immune response is more antigen-specific, but needs a longer time to build up. Even in drug injury of the liver, the innate immune system is involved. There is activation of natural killer and natural killer T cells, and liver cell damage is induced mainly by the Fas and FasL pathways. In viral hepatitis, the mechanism of liver injury is mainly immune-mediated since almost none of the hepatitis viruses have turned out to be cytopathic by themselves. Cytotoxic T lymphocytes with CD8 epitopes are the most important effector cell population. The immune defense may be downregulated by regulatory T cell lymphocytes, PD1/PDL-positive lymphocytes or suppressor dendritic cells. In Epstein-Barr virus infection, liver cell injury does not seem to be due to direct antigen-specific CTLs, but the injury is assumingly induced by a bystander reaction from activated lymphocytes in the sinusoids. Autoimmune hepatitis is a paradigm of immune-mediated liver injury and has a special, but not pathognomonic, histopathology. The main effector lymphocytes belong to the CD8 population, which are antigen-specific; however, the mechanisms seem to be suppressed by regulatory T cells.
Mouse Models for Experimental Autoimmune Hepatitis: Limits and Chances
Authors: Hardtke-Wolenski Matthias , Jaeckel Elmar
Published: May 2010

The difficulty in studying human autoimmune hepatitis (AIH) is usually the late time-point of diagnosis which is followed by long-standing immunosuppression and the fact that human immune responses can usually only be studied in peripheral blood. Therefore, animal models with defined onset of AIH and, ideally, a positive impact of standard therapeutic interventions are key to understanding the disease and its pathophysiology, and providing a platform for new therapy options or better prevention. For over a century, the lack of a reliable model with a chronic immune response against hepatocytes has been a key problem in AIH research. Initial attempts to break tolerance against liver tissue resulted in mild and transient hepatitis. Many transgenic models demonstrated different aspects of liver-specific immune regulation. The fate of liver-specific T cells is under intense research and many mechanisms have demonstrated ignorance, anergy, deletion or TCR downregulation. Furthermore, these studies defined a role of professional antigen-presenting cells and especially of liver sinusoidal cells. Other models have shown the mechanism of T cell activation in liver and the interaction of adaptive and innate immune cells. Most recently, some approaches have been made to establish models of chronic AIH resembling human disease. These attempts might open new research chances to study AIH onset and its pathophysiology, and they might result in new options for therapy and prevention research.
Tolerance Induction in Response to Liver Inflammation
Authors: Erhardt Annette , Tiegs Gisa
Published: May 2010

Background/Aims: The liver plays an important role in immunological tolerance due to its anatomical location, as it links the gastrointestinal tract and the systemic venous circulation. Therefore, immune reactions against dietary or bacterial antigens from the gut have to be avoided. However, immune responses resulting in elimination of harmful hepatotrophic pathogens have to be induced. We investigated mechanisms of tolerance induction in response to liver inflammation in a murine model of immune-mediated liver injury. Methods: Liver damage was induced by injection of the plant lectin concanavalin A (ConA). Cytokine levels were measured in plasma and liver tissue. The frequencies of intrahepatic and splenic cell subsets were measured by FACS analyses. Results: ConA hepatitis was mediated by activation of CD4+ T cells, NKT cells and Kupffer cells releasing IFN-γ and TNF-α. Tolerance developed towards ConA rechallenge within 8 days, lasted for several weeks and was characterized by significantly reduced plasma transaminase activities, decreased Th1/Th17 responses and an increased IL-10 release, the latter being produced by CD4+CD25+FoxP3+ regulatory T cells and Kupffer cells. Moreover, regulatory T cells from ConA-tolerant mice displayed a higher immunosuppressive potential in vitro and in vivo compared to those from non-tolerant animals. Interestingly, ConA hepatitis was aggravated in CCR5–/– and CXCR3–/– mice. Conclusion: These results suggest that ConA tolerance is mediated by induced IL10+ regulatory T cells, probably trafficking into the liver depending on the IFN-γ-inducible chemokine receptors CCR5 and CXCR3.
Occult Hepatitis B Virus Infection: Detection and Significance
Authors: Gerlich Wolfram H. , Bremer Corinna , Saniewski Mona , Schüttler Christian G. , Wend Ulrike C. , Willems Wulf R. , Glebe Dieter
Published: May 2010

The Taormina Consensus Conference defined ‘occult hepatitis B virus (HBV) infection’ (OBI) as the ‘presence of HBV DNA in the liver of individuals testing HBsAg-negative with currently available assays’. Most occult is the so-called ‘window period’ after exposure before HBV DNA appears in the blood. We identified two blood donors whose donations tested HBsAg- and HBV DNA-negative, but transmitted HBV. Both subsequently developed HBsAg and acute hepatitis. However, such cases are not considered as true OBI. A true transient OBI remains HBsAg-negative during the entire course. One case of acute OBI showed a peak viremia of 15,000 IU/ml HBV DNA and sub-borderline HBsAg, suggesting a ratio of virions to subviral particles of 1:10, whereas ‘normal’ cases show at peak viremia a ratio of 1:3,000. Blood donors with OBI may transmit HBV. We studied 5 blood donors with OBI and 55 of their recipients. In 22 recipients, transmission was probable, but they remained healthy. However, in 3 recipients, who were immunosuppressed at the time of transfusion, fatal fulminant hepatitis B developed. The majority of anti-HBc-positive healthy individuals have HBV DNA in the liver which may start replication under severe immunosuppression. Nine such cases are described here. OBI or reactivated HBV infections often lead to selection of HBsAg escape mutations as we could show in 11 of 14 cases. Infection of vaccinated individuals favors development of OBI as we observed in 6 blood donors. HB vaccination may solve the problem of overt HBV infection but may favor OBI.
Innate and Adaptive Immune Responses in Hepatitis B Virus Infection
Authors: Das Abhishek , Maini Mala K.
Published: May 2010

There is urgent need for novel immunotherapeutic strategies which, combined with current anti-viral therapy, may facilitate viral control and remove the need for long-term suppressive therapy in patients who have chronic hepatitis B virus (HBV) infection. To achieve this, it is critical to better understand mechanisms of innate and adaptive immune dysfunction and pathways of liver pathology. Here, we summarise recent advances pertaining to early immune events during acute HBV infection in an unusual cohort of patients sampled in the pre-clinical phase, and describe mechanisms of CD8 T cell attrition that apply to patients with chronic HBV infection. Furthermore, we describe a novel pathway of hepatocyte death mediated by innate natural killer (NK) cells. These pathways together provide novel pathogenic mechanisms for impaired viral control and liver damage during chronic HBV infection.
Hepatitis D: Clinical Features and Therapy
Authors: Rizzetto Mario
Published: May 2010

Surveys in the 1980s showed that the hepatitis D virus (HDV) is endemic worldwide, though with prevalences and patterns of infection varying in different areas. Medical scrutiny confirmed that chronic hepatitis D usually runs a severe and progressive course, the prototype patient having HBsAg in blood, elevated ALT, a liver biopsy exhibiting aggressive hepatitis and markers of HDV (but no marker of HBV replication in serum). Although the circulation of HDV has declined significantly following the control of HBV achieved over the last 20 years, depriving HDV of the HBV network necessary to propagate its infection, there is still a consistent reservoir of the virus in Europe, sustained by two different pools of HDV-infected patients: the residual ageing domestic pool that survived the brunt of the hepatitis D epidemic in the 1970s and 1980s and the population of young patients with recent HDV infections migrating to Europe. Therapy of hepatitis D remains an unsolved business. The therapy available today is not different from the limited interferon treatment attempted more than 20 years ago. The problem is formidable as HDV has no enzymatic protein to be targeted by conventional antiviral therapy. A potential target of therapy is offered by the process of hepatitis D virion assembly.
Environmental and Genetic Determinants of Fatty Liver in Humans
Authors: Kantartzis Konstantinos , Schick Fritz , Häring Hans-Ulrich , Stefan Norbert
Published: May 2010

Non-alcoholic fatty liver represents one of the most prevalent conditions affecting about one third of the general population in the Western world, and its prevalence is continuously increasing parallel to the epidemics of obesity. Non-alcoholic fatty liver is a strong predictor of non-alcoholic steatohepatitis, but also of cirrhosis, end-stage liver disease and hepatocellular carcinoma. In recent years, non-alcoholic fatty liver (in addition to overall and visceral obesity) has emerged as a risk factor for insulin resistance, hypertension, dyslipidemia, cardiovascular events and type 2 diabetes. This review summarizes the information currently available about the mechanisms involved in liver fat accumulation (e.g. hepatic lipid supply, de novo lipogenesis, lipid oxidation and the packaging and secretion of triglycerides in the form of very-low-density lipoproteins). New aspects concerning mechanisms potentially leading to a ‘dissociation’ of fatty liver and insulin resistance are also discussed. Understanding the pathogenesis of fatty liver and its complications, including the identification of new factors secreted from the liver under excess fat accumulation that are involved in the regulation of metabolism (‘hepatokines’), is crucial in order to develop and implement efficient prevention and treatment strategies.
Metabolic Factors and Non-Alcoholic Fatty Liver Disease as Co-Factors in Other Liver Diseases
Authors: Powell Elizabeth E. , Jonsson Julie R. , Clouston Andrew D.
Published: May 2010

Over the last few years, the paradigm in hepatology has changed from focusing on a single liver disease to considering concurrent diseases, in particular obesity and related metabolic factors. Obesity has reached epidemic proportions globally and is associated with insulin resistance, steatosis and a low-grade systemic inflammatory state. These metabolic factors have a synergistic role in the natural history and treatment outcomes related to chronic liver disease. This is characterized best in chronic hepatitis C where steatosis and insulin resistance are caused by viral and metabolic effects. Non-alcoholic fatty liver disease and related metabolic abnormalities also exacerbate other diseases, such as alcoholic liver disease and haemochromatosis. In addition, there is growing evidence linking obesity and type 2 diabetes with hepatocellular carcinoma in subjects with chronic viral hepatitis. The pathogenesis of co-morbid disease may be related to increased oxidative stress, inflammatory injury and cell death, along with altered hepatocyte regeneration and repair. Hyperinsulinaemia and other metabolic factors may also have a direct role in the progression of liver injury. Data indicate that weight reduction improves steatosis and inflammation in patients with chronic hepatitis C. This has important clinical and therapeutic implications and suggests that obesity should be actively addressed in the management of patients with other chronic liver diseases.
Pathology and Biopsy Assessment of Non-Alcoholic Fatty Liver Disease
Authors: Straub Beate Katharina , Schirmacher Peter
Published: May 2010

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters.
Non-Alcoholic Steatohepatitis Pathogenesis: Role of Repair in Regulating the Disease Progression
Authors: Jung Youngmi , Diehl Anna Mae
Published: May 2010

Background: Increased hepatocyte apoptosis distinguishes non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver disease (NAFLD). Therefore, we postulated that outcomes of NASH depended upon whether or not hepatic regenerative responses could keep pace with the increased rate of hepatocyte death. Methods: To investigate mechanisms that the liver deploys to compensate for increased hepatocyte apoptosis, we studied a transgenic mouse model in which hepatocyte vulnerability to apoptosis was increased due to disruption of NF-ĸB survival signaling. Results: We learned that hepatocyte death is coupled to the expansion of cell types that are involved in liver repair, including progenitors and myofibroblasts, and discovered that the outgrowth of these cell types occurs, at least in part, because dying hepatocytes produce Hedgehog morphogens that enhance the growth of progenitor and myofibroblast populations. The clinical significance of this discovery is supported by evidence that the degree of Hedgehog pathway activation also parallels the severity of liver fibrosis in patients with NASH, a disease in which hepatocyte apoptotic activity has been strongly linked to fibrosis progression. Conclusion: The data generated by studying a mouse model of chronic hepatocyte apoptosis, as well as NASH, a common human liver disease that is characterized by increased rates of hepatocyte apoptosis, are very similar. Both strongly support the concept that repair responses play an important role in controlling the outcomes of NASH.
Molecular Mechanisms of Hepatic Fibrosis in Non-Alcoholic Steatohepatitis
Authors: Rombouts Krista , Marra Fabio
Published: May 2010

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. The more severe form of this condition, non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Fibrosis and cirrhosis are the final outcomes of all chronic liver diseases; however, some morphological and biological differences distinguish fibrosis due to NASH from the forms secondary to other causes of liver damage. Fibrosis due to NASH develops primarily in the pericentral areas, surrounding groups of hepatocytes and thickening the space of Disse. This pericellular fibrosis eventually forms septa isolating regenerating nodules. The main cell type responsible for extracellular matrix deposition is represented by hepatic stellate cells that undergo activation in conditions of liver injury enabling them to participate in the liver wound healing process. Although the profibrogenic mechanisms operating in NASH are partly in common with those observed in other chronic liver diseases, the altered pattern of circulating adipokines, oxidative stress generation and the hormonal profile associated with the metabolic syndrome might have a specific role for the induction of fibrogenesis in this condition. In this paper, we review recent developments regarding the basic mechanisms of NASH and the involvement of hepatic stellate cells in this disease.
PTEN in Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis and Cancer
Authors: Peyrou Marion , Bourgoin Lucie , Foti Michelangelo
Published: May 2010

The tumor suppressor PTEN is a protein/phosphoinositide phosphatase regulating the PI3K/Akt signaling pathway and is mutated or deleted in a variety of human cancers, including hepatocellular carcinoma (HCC). Accumulating evidence indicates that alterations of PTEN expression and activity in hepatocytes are common and recurrent molecular events associated with liver disorders of various etiologies including obesity, the metabolic syndrome, hepatitis B virus/hepatitis C virus infection and abusive alcohol consumption. Genetic and molecular studies, particularly in the context of non-alcoholic fatty liver disease (NAFLD), support a critical role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis and fibrosis. PTEN mutations/deletion or low PTEN expression are also associated with diverse liver malignancies, suggesting a critical role for PTEN in hepatic cancers. This review provides an overview of the current knowledge on pathological dysregulations of PTEN expression/activity in the liver with obesity and the metabolic syndrome, and the role of this enzyme in the development of non-alcoholic fatty liver disease and hepatocellular carcinoma.
Insulin Resistance and Response to Antiviral Therapy in Chronic Hepatitis C: Mechanisms and Management
Authors: del Campo José A. , López Reyes Aparcero , Romero-Gómez Manuel
Published: May 2010

Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C.
Glycosylated Hemoglobin Is a Predictor of Major Adverse Cardiac Events after Drug-Eluting Stent Implantation in Patients with Diabetes Mellitus
Authors: Ueda Hiroyasu , Mitsusada Nobuhiro , Harimoto Kuniyasu , Miyawaki Masami , Yasuga Yuji , Hiraoka Hisatoyo
Published: May 2010

Objectives: Diabetes mellitus is associated with the risk of restenosis and mortality after coronary stenting, but the relation between glycosylated hemoglobin (hemoglobin A1c) and prognosis has not yet been fully elucidated in patients with diabetes mellitus. The purpose of this study was to evaluate whether hemoglobin A1c is associated with a risk of major adverse cardiac events (MACE) after successful drug-eluting stent (DES) implantation in patients with diabetes mellitus. Methods: In a retrospective study with a prospective follow-up, 206 patients with diabetes mellitus undergoing successful DES implantation were enrolled in this study. Hemoglobin A1c levels were measured within 1 month before coronary stenting. Results: During a period of 4,811 person-months, we confirmed 40 cases of MACE. Higher hemoglobin A1c levels increased the incidence of MACE. Based on multivariate analysis, hemoglobin A1c was a significant predictor of MACE. The multiple-adjusted hazard ratio for a 1% increase in hemoglobin A1c levels was 1.40 (95% CI: 1.13–1.74, p = 0.002) for MACE after adjustment for age, gender, ejection fraction, chronic renal failure on hemodialysis, and statins. Conclusions: Hemoglobin A1c is associated with an increased risk of MACE after successful DES implantation in patients with diabetes mellitus.
Acute Kidney Injury and Cardiovascular Outcomes in Acute Severe Hypertension
Authors: Szczech Lynda A. , Granger Christopher B. , Dasta Joseph F. , Amin Alpesh , Peacock W. Frank , McCullough Peter A. , Devlin John W. , Weir Matthew R. , Katz Jason N. , Anderson Frederick A. , Wyman Allison , Varon Joseph
Published: May 2010

Background—

Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate ≥25% from baseline) and outcome in patients hospitalized with acute severe hypertension.

Methods and Results—

The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as ≥1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (
P
<0.0001), non–ST-elevation myocardial infarction (
P
=0.003), and AKI (
P
<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (
P
≤0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (
P
=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05;
P
=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (
P
<0.0001), male gender (
P
=0.016), white versus black race (
P
=0.003), and worse baseline kidney function (
P
=0.003).

Conclusions—

Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.
Seeing God ‘in a riddle’ or ‘face to face’: An Analysis of 1 Corinthians 13.12
Authors: Hollander Harm W.
Published: May 2010

In his praise of the attitude of loving one another in 1 Cor. 13 Paul argues that ‘now we see in a mirror and in a riddle’ but at the eschaton we will see ‘face to face’ (v. 12). The implied object of ‘seeing’ is God. By introducing the image of a mirror Paul uses a well-known Hellenistic metaphor to describe the indirect, partial and incomplete nature of man’s knowledge of God. The expressions ‘in a riddle’ and ‘face to face’ are taken from Old Testament descriptions of Moses’ unique communication with God found in Num. 12.8 and Deut. 34.10.
Control of interval parameter overhead cranes via Monte Carlo simulation
Authors: Omar F. , Harib K.H. , Moustafa Kamal A.F.
Published: May 2010

Variations in system parameters because of changing operating conditions could result in deteriorated system performance. To ensure robustness, modelling of such systems requires uncertain parameters to be dealt with as interval quantities. An overhead crane is a type of system that has inherent variation in some of its parameters. These parameters include cable length, trolley mass and payload. Hence, the interval parameter concept plays an important role in the control of overhead cranes. This paper considers the control problem of an overhead crane system with interval parameters. The paper presents a new technique based on Monte Carlo simulation to select properly optimal controller parameters. The objective of the control is to minimize the overshoot of the swing angle response throughout the crane travel regardless of the variations of the cable length. The cable length is assumed known within lower and upper bounds. The presented results show the usefulness of the Monte Carlo simulation approach as applied to the control problem of overhead cranes. A scaled-down crane model has been built and used to validate the results of the numerical simulation.
The End of Liberal Finance? The Changing Paradigm of Global Financial Governance
Authors: Nesvetailova Anastasia , Palan Ronen
Published: May 2010

Has the global credit crunch shifted the foundations of global financial architecture away from the philosophy of ‘neoliberalism’? In this article, we argue that the neoliberal project is most probably dead and buried, despite the apparent commitment, which we detail in this article, to the spirit of neoliberal thinking in economic thought. By analysing three constitutive elements of neoliberalism (its public, private and regulatory components) before and after the credit crunch, we reveal important geopolitical shifts which are likely to prevent a return to ‘business as usual’ in the world of finance. We find that the defining trend among these changes is the global rise of the Eurozone. Specifically, we argue that the ideal, Anglo-Saxon model of neoliberalism was viable because it was heavily subsidised from around the world. Accordingly, the key to the future of Anglo-Saxon neoliberalism lies with the willingness of European, East Asian and Middle Eastern creditors to continue extending their financial support to the Anglo-Saxon model of finance. We believe that they are unlikely to do so in the future. Spurred by the magnitude of the credit crunch, the rise of Europe is progressively weakening each of the three dimensions of Anglo-Saxon neoliberalism we identify in this article.
Antecedents of Medical Workplace Violence in South China
Authors: Wenzhi Cai  , Ling Deng  , Meng Liu  , Min Yu
Published: May 2010

It has been noted that workplace violence most frequently occurs in hospitals. The purpose of this study was to explore antecedents of workplace violence in south China. The authors conducted face-to-face, in-depth, semistructured interviews with 30 hospital staff who had experienced at least one incident of workplace violence from patients during the past 12 months at three general hospitals in south China. The interviews were tape-recorded, then transcribed, and analyzed. The authors’ analyses identified five major antecedents of workplace violence. First, 93.0% of medical workplace violence was related to insufficient communication between hospital staff and patients. Second, inadequate medical service quality was found to be a factor in 56.7% of the incidences. Third, unsatisfactory treatment outcome was reported in 60.0%. Fourth, heavy workload accounted for 43.3%. Fifth, patient frustration due to high medical expenses was reported in 40.0% of cases. The authors recommended a reengineering of hospital service delivery to create a more supportive and safer working environment for prevention of workplace violence.
Measuring Welfare Gains from Better Quality Infrastructure
Authors: Klytchnikova Irina , Lokshin Michael
Published: May 2010

Projects and reforms targeting infrastructure services can affect consumer welfare through changes in the price, coverage, or quality of the services provided. The benefits of improved service quality—while significant—are often overlooked because they are difficult to quantify. This article reviews methods of evaluating the welfare implications of changes in the quality of infrastructure services within the broader theoretical perspective of welfare measurement. The study outlines the theoretical assumptions and data requirements involved, illustrating each method with examples that highlight common methodological features and differences. The article also presents the theoretical underpinnings and potential applications of a new approach to analysing the effects of interruptions in the supply of infrastructure services on household welfare.
High Prevalence of B-RAF Mutation in Papillary Carcinoma of the Thyroid in North-East Italy
Authors: Girlando Salvatore , Cuorvo Lucia Veronica , Bonzanini Mariella , Morelli Luca , Amadori Pierluigi , Dalla Palma Paolo , Barbareschi Mattia
Published: May 2010

B-RAF V600E mutation is frequently observed in several tumors, including papillary thyroid carcinomas (PTCs), where it is considered of potential diagnostic and prognostic value. The reported prevalence of B-RAF mutation in PTCs in different Italian populations varies from 14% to 69%. The authors investigate the prevalence and utility of the B-RAF V600E mutation in a series of 91 fine needle aspiration biopsies (FNABs) of the thyroid and in 60 histologically proven PTCs in a well-defined north Italian population. In their series, the B-RAF mutation was detected in 43 (72%) PTCs and was more frequent in classic (34 out of 44, 77%) versus variant follicular PTCs (PTCVF; 9 out of 16, 56%). In all, 41 (46%) FNABs showed B-RAF mutation and corresponded to histologically proven PTCs (33 classic type and 8 PTCVF), which had been cytologically classified as malignant (28 cases), atypical/suspicious (10), inadequate (1), and benign (2). B-RAF mutations were never seen in non-PTC/ PTCVF FNAB cases, implying a 100% positive predictive value.These data demonstrate a high prevalence of B-RAF mutations in the present study population, underscoring the possibility of strong regional differences in B-RAF mutation prevalence in PTCs and further confirming its high diagnostic value on FNAB.
Adolescent Sexual Offenders: The Relationship Between Typology and Recidivism
Authors: Chi Meng Chu  , Thomas Stuart D. M.
Published: May 2010

Adolescent sexual offending represents an ongoing social, judicial, clinical, and policy issue for services. The current study investigated the characteristics, criminal versatility, and rates of recidivism of a cohort of 156 male adolescent sexual offenders who were referred for psychological assessments by the courts between 1996 and 2007 in Singapore. Analyses revealed that specialists (sex-only offenders; n = 71, Mfollow-up = 56.99 months, SDfollow-up = 31.33) and generalists (criminally versatile offenders; n = 77, Mfollow-up = 67.83 months, SDfollow-up = 36.55) differed with respect to offense characteristics (e.g., sexually assaulting familial victims) and recidivistic outcomes. Although both groups sexually reoffended at roughly the same rate (14.3% vs. 9.9%), consistent with their typology, significantly more of the generalists reoffended violently (18.2% vs. 1.4%), sexually and/or violently (27.3% vs. 11.3%), nonviolently (37.7% vs. 16.9%), and engaged in any further criminal behaviors (45.5% vs. 23.9%) during follow-up. Adjusting for total number of offenses and age at first sexual offense, Cox regression analyses showed that generalists were significantly more likely than specialists to reoffend violently (hazard ratio = 9.31; 95% confidence interval = 1.15-76.39). The differences between generalists and specialists suggest a valid typological distinction with a higher risk trajectory for the generalists. These findings therefore have important clinical implications for assessment, management, and intervention planning for adolescent sexual offenders.
Social exclusion and inclusion of young immigrants
Authors: Fangen Katrine
Published: May 2010

Social exclusion is a term which was introduced in the social sciences in the early 1990s in order to extend the focus beyond poverty by focusing on the relation between the individual and the society. During later years, it has been common to speak of a new social exclusion perspective, which is better fit to analyze the more heterogeneous, multicultural and complex society (Body-Gendrot, 2002). In this article, I will focus on the social exclusion in different arenas, thus underlining the multi-dimensional aspect of social exclusion. The underlying question is: ‘What is it that contributes to social exclusion of young adult immigrants in different social settings?’ and ‘How do young adult immigrants with different backgrounds experience social exclusion in different social arenas?’ I will distinguish between educational exclusion, labour market exclusion, spatial exclusion, relational exclusion and finally, socio-political exclusion. The combination of information from macro-oriented quantitative research and its focus on structural explanations and micro-oriented qualitative research and its focus on agency together make a holistic picture of social exclusion which underlines its dynamic, complex and multi-dimensional character.
The democratic common sense
Authors: Arensmeier Cecilia
Published: May 2010

This article highlights ordinary young citizens’ understanding of democracy. In a system based on rule of the people, it is surprising how little attention scholars have paid to common-sense views of democracy. The article is based on focus group interviews with young Swedes. Their views of democracy are analyzed in the context of democratic theory. The results show that there is massive support among the youths for the democratic idea, that they see elite democracy as a self-evident form of democracy and that they consider democracy to be a problematic good, emphasizing their doubts about human capacity, limited ruling opportunities and problems around inequality and risky principles. References to research on Swedish education show that the conceptualizations in several respects reflect how democracy and citizenship are framed in Swedish schools. It is suggested that the results of the study can influence both the form and content of civic education.
Constructions of Pregnant and Postnatal Embodiment across Three Generations
Authors: Nicolson Paula , Fox Rebekah , Heffernan Kristin
Published: May 2010

The academic study of the ‘body’ has come to occupy the foreground over the past two decades and the differential influences of physical and social worlds particularly upon body management practices have become fundamental to the 21st-century ‘project’ of the body. In this article we explore three generations of women’s accounts of living in/with a pregnant and postnatal body which is now both visible and ‘public’ as women ‘leave’ the home for work. However this now takes place in the context of public surveillance (and self-surveillance) particularly about food/eating, ‘health’ and ‘beauty’.
In VitroCalcification of Immature Bovine Articular Cartilage
Authors: Hwang Jennifer , Kyubwa Espoir M. , Bae Won C. , Bugbee William D. , Masuda Koichi , Sah Robert L.
Published: May 2010

Introduction:

The zone of calcified cartilage (ZCC) anchors articular cartilage (AC) to subchondral bone through a layer of intermediate stiffness. The regulation and functional consequences of cartilage calcification may vary with depth from the articular surface. The hypothesis of this study was that the in vitro calcification of immature AC occurs selectively in the deep region and is associated with a local increase in stiffness.

Methods:

AC and growth plate cartilage (GPC) from calves were incubated in DMEM, 1% fetal bovine serum, 100 µg/mL ascorbate, and ±10 mM β-glycerophosphate (βGP) for up to 3 weeks. To assess the time course and effects of cell viability and βGP, full-depth strips of AC and GPC were analyzed by histology, indentation, and45Ca++uptake. To assess the effect of tissue zone, disks harvested from surface and deep zone AC and from reserve and hypertrophic zone of GPC were incubated independently and analyzed by compression and for45Ca++uptake and biochemical components.

Results:

The deep ~20% of immature AC calcified within 3 weeks, with calcification dependent on cell viability and βGP. Mineral was deposited continuously around cells in AC but only between cell columns in GPC. The deep zone of AC exhibited a compressive modulus of 0.53 MPa after βGP-induced calcification, ~4-fold stiffer than AC incubated without βGP.

Conclusions:

Cartilage explants exhibit inherent zone-specific calcification processes, resulting in an increase in stiffness associated with cartilage calcification. Such properties may be useful for engineering a biomimetic ZCC tissue to integrate cartilaginous tissue to bone, thereby forming a mechanically functional osteochondral unit.