bluuebunny/crossref_metadata_2025 huggingface dataset:
IL28B genetic polymorphism testing in the era of direct acting antivirals therapy for chronic hepatitis C: ten years too late?
Authors: Jensen Donald M. , Pol Stanislas
Published: December 2011

An association between variations at the IL28B gene locus and HCV clearance (spontaneous recovery or sustained virological response under pegylated interferon (PEG‐IFN) and ribavirin (RBV) has been extensively described. In genotype 1‐infected patients, the new direct antiviral agents (DAA) including the two approved protease inhibitors boceprevir and telaprevir, in association with the PEG‐IFN/RBV combination is the new standard of care making it necessary to redefine the interest of the IL28B genotype in the decision to treat and how to treat genotype 1‐infected patients. In treatment‐naïve patients, IL28B status can certainly identify those with a high probability of achieving SVR with response guided therapy and probably in whom the duration of treatment can be markedly reduced. In experienced patients, the impact of IL28B genotypes is limited and cancelled by early viral kinetics. However, the decision to initiate or withhold therapy remains a clinical one. In summary, although it was a major milestone in the treatment of patients with PEG‐IFN/RBV, IL28B polymorphism testing entered the clinical arena almost 10 years too late.
Response‐guided and ‐unguided treatment of chronic hepatitis C
Authors: Reddy K. Rajender , Lin Frederick , Zoulim Fabien
Published: December 2011

Over time, HCV therapy with pegylated interferon and ribavirin has evolved from a fixed duration strategy to one of response guided therapy and this has enabled us to optimize treatment duration. With the evolution of protease inhibitor based therapy, the paradigm of response guided therapy has further helped in decreasing treatment duration in greater number of patients and which then translates into shorter duration of adverse events. However, several population groups have done better with extended duration therapy as opposed to response guided therapy despite early viral clearance. These include the Black population, and those with cirrhosis, decreased interferon sensitivity, and unfavorable IL28B genotypes. The proper identification of those who might benefit from extended duration HCV therapy will undoubtedly lead to optimal care and outcomes.
Hepatitis C virus treatment pre‐ and post‐liver transplantation
Authors: Roche Bruno , Samuel Didier
Published: December 2011

Liver disease caused by the hepatitis C virus is the main indication for liver transplantation in Western countries. However, HCV re‐infection post‐transplantation is constant and recent data confirm that it significantly impairs patient and graft survival. Chronic HCV infection develops in 75–90% of patients, and 5–30% ultimately progress to cirrhosis within 5 years. Because of the impact of HCV recurrence on graft and patient survival, several treatment strategies have been evaluated. Antiviral therapy could be administered before transplantation to suppress viral replication and reduce the risk of recurrence. However, this approach is applicable in around 50% of patients and tolerance is poor, particularly in patients with decompensated cirrhosis. Pre‐emptive therapy in the early post‐transplant period is limited by the high rate of side effects. Frequently, antiviral therapy is initiated when HCV recurs to obtain viral eradication and/or reduce disease progression. Treatment of established graft lesions with Pegylated Interferon (PEG‐IFN) and Ribavirin (RBV) combination therapy results in a sustained virological response (SVR) in around 30% of patients. The new classes of potent and direct antiviral agents (DAA) will certainly improve the results of pre‐ and post‐transplant antiviral therapy. However, at the present time, no data are available on the use of these drugs in patients with decompensated cirrhosis or post‐transplant hepatitis.
Treatment of patients with genotype 3 chronic hepatitis C‐ current and future therapies
Authors: Sarin Shiv K. , Kumar Chandan K. N.
Published: December 2011

Genotype 3 is a common type of HCV infection, and standard therapy using pegylated interferon (PEG‐IFN) and ribavirin (RBV) is quite effective in these patients. While a short course of 16 weeks may result in comparable end of therapy responses, relapse rates are often high. A 24‐week course is therefore preferable, and is expected to result in sustained virological response (SVR) rates of more than 70%. The 24‐week course is especially recommended in the presence of steatosis (often associated with Genotype 3 infection), fibrosis stage two or more, high BMI and high viral load. In patients who do not achieve a rapid viral response (RVR) with combination therapy, an extended course up to 48 weeks should be considered. While not as definite as for genotype 1 patients, the presence of the CC variant of IL28b could help in the initial prognosis and the need for additional treatment, if an RVR is not achieved. The role of directly acting antiviral agents (DAA) has not been fully evaluated in treatment naïve, non‐responders and relapsers in genotype 3 patients. Initial results with the cyclophilin inhibitor Debio‐025 are quite encouraging. There is an urgent need for large clinical trials using DAA and host modulators in patients with G3 infection.
Triple combination treatment for chronic hepatitis C with Protease Inhibitors, pegylated interferon and ribavirin: ‘Lead‐in or no lead‐in’?
Authors: Foster Graham R. , Serfaty Lawrence D.
Published: December 2011

Direct acting antiviral agents for the management of chronic hepatitis C infection have recently been licensed. These new protease inhibitors are combined with pegylated interferon and ribavirin and markedly increase the proportion of patients who respond to antiviral therapy. The protease inhibitors may be used with a ‘lead‐in’ phase of pegylated interferon and ribavirin and the value of this approach has been much debated with those supporting ‘lead in’ citing the advantages of assessing the early response to therapy before commencing the direct acting antiviral agent. Those opposed to the ‘lead‐in’ phase cite the complexity of the regime and the lack of robust evidence showing an improvement in clinical outcome in those treated in this fashion.
Hepatitis C virus‐human immunodeficiency virus coinfection
Authors: Sulkowski Mark S.
Published: December 2011

As a result of shared modes of transmission, chronic hepatitis C infection is common in HIV‐infected patients, particularly among those who have used injection drugs as well as men who have sex with men (MSMs). In the era of effective antiretroviral therapy, HCV infection has emerged as a major cause of morbidity and mortality worldwide. Over the last decade, treatment with peginterferon (PEG‐IFN) plus ribavirin (RBV) has been recommended for coinfected patients who are at the greatest risk for liver disease; however, the effectiveness of HCV treatment in this population has been disappointing. Challenges to the use of HCV NS3/4A protease inhibitors, telaprevir and boceprevir, patients with HIV/HCV coinfection include the potential for interactions between different drugs, addition of drug toxicities, and the need for therapy with PEG‐IFN. Despite these challenges, limited data indicate that telaprevir and boceprevir given in combination with PEG‐IFN/RBV increase the rate of viral suppression in coinfected patients with manageable toxicity and drug‐drug interaction profile. Accordingly, these agents may be recommended for HCV treatment in carefully selected HIV‐infected persons.
Triple therapy with telaprevir: results in hepatitis C virus‐genotype 1 infected relapsers and non‐responders
Authors: Forestier Nicole , Zeuzem Stefan
Published: December 2011

Treatment for chronic hepatitis C virus (HCV) infection has evolved considerably in the last few years. Combination therapy with pegylated interferon (PEG‐IFN)‐α plus ribavirin (RBV) has been the standard of care (SoC) treatment in the past few years. Several viral and host factors have been associated with treatment failure, including age, male gender, ethnicity, genotype, IL28B genotype, steatosis, obesity and insulin resistance. Several studies have also shown that in patients who fail treatment, several interferon‐stimulated genes are upregulated before treatment. Recently, the NS3/4A protease inhibitors telaprevir and boceprevir have been approved and are considered the new SoC therapy in combination with PEG‐IFN‐α/RBV in HCV genotype 1 treatment‐naïve patients, as well as in previously treated patients, with significant improvements in SVR rates. The REALIZE phase III trial with telaprevir in previously treated patients showed SVR rates of 83–88% in prior relapsers, 54–58% in prior partial responders and, 29–33% in prior non‐responders.
Phase equilibrium constraints on a deep crustal metamorphic field gradient: metapelitic rocks from the Ivrea Zone (NW Italy)
Authors: REDLER C. , JOHNSON T. E. , WHITE R. W. , KUNZ B. E.
Published: December 2011

The metamorphic rocks of the Ivrea Zone in NW Italy preserve a deep crustal metamorphic field gradient. Application of quantitative phase equilibria methods to metapelitic rocks provides new constraints on the P–T conditions recorded in Val Strona di Omegna, Val Sesia and Val Strona di Postua. In Val Strona di Omegna, the metapelitic rocks show a structural and mineralogical change from mica‐schists with the common assemblage bi–mu–sill–pl–q–ilm ± liq at the lowest grades, through metatexitic migmatites (g–sill–bi–ksp–pl–q–ilm–liq) at intermediate grades, to complex diatexitic migmatites (g–sill–ru–bi–ksp–pl–q–ilm–liq) at the highest grades. Partial melting in the metapelitic rocks is consistent with melting via the breakdown of first muscovite then biotite. The metamorphic field gradient in Val Strona di Omegna is constrained to range from conditions of ∼3.5–6.5 kbar at ≈650 °C to ∼10–12 kbar at >900 °C. The peak P–T estimates, particularly for granulite facies conditions, are significantly higher than those of most earlier studies. In Val Sesia and Val Strona di Postua, cordierite‐bearing rocks record the effects of contact metamorphism associated with the intrusion of a large mafic body (the Mafic Complex). The contact metamorphism occurred at lower pressures than the regional metamorphic peak and overprints the regional metamorphic assemblages. These relationships are consistent with the intrusion of the Mafic Complex having post dated the regional metamorphism and are inconsistent with a model of magmatic underplating as the cause of granulite facies metamorphism in the region.
Phonological Specificity in 12‐ and 17‐Month‐Old French‐Speaking Infants
Authors: Zesiger Pascal , Lozeron Elise Dupuis , Lévy Arik , Frauenfelder Ulrich H.
Published: December 2011

The literature reports some contradictory results on the degree of phonological specificity of infants’ early lexical representations in the Romance language, French, and Germanic languages. It is not clear whether these discrepancies are because of differences in method, in language characteristics, or in participants’ age. In this study, we examined whether 12‐ and 17‐month‐old French‐speaking infants are able to distinguish well‐pronounced from mispronounced words (one or two features of their initial consonant). To this end, 46 infants participated in a preferential looking experiment in which they were presented with pairs of pictures together with a spoken word well pronounced or mispronounced. The results show that both 12‐ and 17‐month‐old infants look longer at the pictures corresponding to well‐pronounced words than to mispronounced words, but show no difference between the two mispronunciation types. These results suggest that, as early as 12 months, French‐speaking infants, like those exposed to Germanic languages, already possess detailed phonological representations of familiar words.
Shortcuts in Complex Engineering Systems: A Principal‐Agent Approach to Risk Management
Authors: Garber Russ , Paté‐Cornell Elisabeth
Published: December 2011

In this article, we examine the effects of shortcuts in the development of engineered systems through a principal‐agent model. We find that occurrences of illicit shortcuts are closely related to the incentive structure and to the level of effort that the agent is willing to expend from the beginning of the project to remain on schedule. Using a probabilistic risk analysis to determine the risks of system failure from these shortcuts, we show how a principal can choose optimal settings (payments, penalties, and inspections) that can deter an agent from cutting corners and maximize the principal's value through increased agent effort. We analyze the problem for an agent with limited liability. We consider first the case where he is risk neutral; we then include the case where he is risk averse.
Why Income Inequality Indexes Do Not Apply to Health Risks
Authors: Cox Louis Anthony (Tony)
Published: December 2011

Several recent papers have sought to apply inequality measures from economics, such as the Atkinson Index (AI) for inequality of income distributions, to compare the risk inequality of different mortality risk distributions in an effort to help promote efficiency and environmental justice in pollution‐reducing interventions. Closer analysis suggests that such applications are neither logically coherent nor necessarily ethically desirable. Risk inequality comparisons should be based on axioms that apply to probabilistic risks, and should consider the multidimensional and time‐varying nature of individual and community risks in order to increase efficiency and justice over time and generations. In light of the limitations of the AI applied to mortality risk distributions, it has not been demonstrated to have ethical or practical value in helping policymakers to identify air pollution management interventions that reduce (or minimize) risk and risk inequity.
Discriminating geographic origins of migratory waders at stopover sites: insights from stable isotope analysis of toenails
Authors: Catry Teresa , Martins Ricardo C. , Granadeiro José P.
Published: December 2011

In this study we test the potential of stable isotope analysis to reveal wintering origins of waders mixing at stopover sites, using the dunlin Calidris alpina as a case study. We determined stable carbon (δ13C) and nitrogen (δ15N) isotope signatures of toenails of dunlins captured during winter at reference sites along the East‐Atlantic Flyway, from Mauritania to the United Kingdom. Afterwards, during spring migration, dunlins were sampled at the Tagus estuary, Portugal, and assigned to their wintering grounds according to their stable isotope signatures. Toenails from wintering dunlins at different sites had significantly different δ13C and δ15N signatures, despite some overlap in isotopic carbon ratios of birds from Morocco, Portugal and the UK. Among birds sampled during migration in Portugal, we found a clear bimodal pattern in δ13C values, corresponding to passage migrants from Mauritania (enriched δ13C values) and wintering birds from the Tagus estuary (depleted δ13C values). The first passage migrants from Mauritania appeared at the Tagus estuary by the end of March, with peak numbers during late April and early May. Our study provides evidence that isotopic signatures of toenails can play a determinant role in tracing the wintering origins of migrant dunlins at their stopover areas. Toenails, instead of feathers, can be the powerful and innovating tissue to sample in wader studies, allowing to bridge the gap in the field of migratory connectivity between sites used in different phases of the life cycle of waders.
Parental infanticide in birds through early eviction from the nest: rare or under‐reported?
Authors: Moreno Juan
Published: December 2011

Avian parental infanticide is apparently a rare phenomenon judging from the scant reports in the literature. However, unexplained cases of single nestling disappearance or of apparent fall from the nest are rather common and are routinely attributed to parental eviction of dead nestlings, single chick predation or dislodging of nestlings through errors by nestlings or parents. During long‐term studies of pied flycatchers Ficedula hypoleuca in central Spain 29 cases of eviction from the nest cup of mostly hatchlings or small, heterothermic nestlings were recorded, leading invariably and quickly to death. Parental errors and failed attempts to predate single chicks are unlikely in these cases. Although the incidence of recorded evictions was mostly below 5% of nests, it reached higher levels in years and populations where reproductive success was low. Some cases were preceded by prior egg eviction. In these studies, there were unexplained disappearances affecting 3.7% of eggs laid which amounted to 20% of all losses. During studies of three other passerine cavity nesting species, similar cases were observed. The rarity of reports of parentally evicted nestlings is apparently based on the difficulty of directly observing parents evicting live nestlings but may also be due to observer bias as ejections of dead nestlings, erroneous dislodgings or single‐chick predation events are also rarely observed but are normally given as reasons for single‐chick losses. Field researchers should attempt to determine the real causes of partial brood loss before assuming that parsimony excludes parental infanticide through eviction.
Chromobacterium violaceum infections in 13 non‐human primates
Authors: Liu David X. , Didier Peter J. , Plauche Gail B.
Published: December 2011

Background  Recently, an Indian‐origin macaque was found dead and Chromobacterium violaceum was isolated from the skin wound, and hepatic and pulmonary abscesses.

Methods  By searching the database, a total of thirteen cases of C. violaceum infection in pigtail macaques (n = 8), rhesus macaques (n = 4), and one baboon were identified from 2001 to 2010 at Tulane National Primate Research Center. Medical records were reviewed for breed, sex, age, clinical findings, treatment, outcome, bacteriology, and gross and histological findings.

Results  Seven pigtail macaques and one Indian‐origin rhesus macaque died of chromobacterial septicemia. All chromobacterial septicemic pigtail macaques were adult with higher incidence in female. Hepatic abscess and thrombosis were typical findings along with pulmonary abscess and thrombosis, renal venous thromboembolism, and necrosuppurative pleuritis, peritonitis, splenitis, myocarditis, pericarditis, and meningoencephalitis. Skin wound, uterine infection, and oral and respiratory exposure were considered the points of entry for these animals.

Conclusions  This represents the first report of chromobacteriosis in pigtail, rhesus macaque, and baboon. Our experience suggests that chromobacterial infections may be more common in non‐human primates than previously recognized.
Advantages and disadvantages of interference‐competitive ability and resource‐use efficiency when invading established communities
Authors: Hart Simon P. , Marshall Dustin J.
Published: December 2011

Invaders into established communities must overcome low resource availability. To establish, invaders must either appropriate resources from existing individuals through interference competition or efficiently use the small amount of resource that remains. Although both strategies may be important, they are rarely considered together and, in particular, resource‐use efficiency is often ignored in systems dominated by interference competition. To identify the traits that confer invasion success, we experimentally invaded resource patches in established communities with multiple species from two functional groups that differ in interference competitive ability and resource‐use efficiency. In contrast to previous assessments, we show that resource‐use efficiency can facilitate invasion in systems dominated by interference competition. Furthermore, large resource requirements can be a liability when establishing because interference competition is inherently costly and so cannot fully compensate for limitations in the primary resource. However, we also show that there is a tradeoff in performance among functional groups between small and large resource gaps. Our results suggest we modify the way we view and manage species invasion in systems dominated by interference competition.
Population dynamics in a guild of four Mediterranean ungulates: density‐dependence, environmental effects and inter‐specific interactions
Authors: Imperio S. , Focardi S. , Santini G. , Provenzale A.
Published: December 2011

Population fluctuations in ungulates are driven by both intrinsic and extrinsic factors. Available information, however, mainly refers to arctic, temperate and African ungulate populations, while the dynamics of Mediterranean species, exposed to a milder climate, is known to a much lesser extent. Here we studied the population dynamics of four wild ungulate species in the Castelporziano Preserve near Rome, Italy, as obtained from detailed bag counts from hunting drives during the period 1878–1986: the Italian roe deer Capreolus capreolus italicus, the Maremma wild boar Sus scrofa majori (both endemic to Italy), the native red deer Cervus elaphus, and the alien fallow deer Dama dama. We also considered the effects of the presence of another alien ungulate, the nilgai Boselaphus tragocamelus.

This ungulate community experienced an accidental ‘removal experiment’ when, during World War II, red deer and nilgai were exterminated. This event and the length of the time series allowed us to test two main hypotheses: 1) that the complexity level of the ungulate community affects the strength of intra‐ and inter‐specific competition; and 2) that in Mediterranean environments intra‐ and inter‐specific interactions are stronger than climate forcing. Statistical methods ranged from state‐space‐modelling, GLM analysis and structural equation models.

The results indicated that direct intra‐specific density dependence played a relevant role for all species, and was stronger after the removal. A complex pattern of species interactions was however revealed; fallow deer had a negative effect on roe deer population, while roe deer had an apparent positive effect on red deer and wild boar, possibly mediated by environmental factors. Nilgai appeared to facilitate all deer species. The results of the analysis also confirmed that at present climate appears to play a minor role with respect to density dependence; however, the increasing aridity of the Mediterranean area could change this picture in coming decades.
A perspective on match/mismatch of phenology in community contexts
Authors: Nakazawa Takefumi , Doi Hideyuki
Published: December 2011

Climate change has significant impacts on phenology of various organisms in a species‐specific manner. Facing this problem, the match/mismatch hypothesis that phenological (a)synchrony with resource availability strongly influences recruitment success of a consumer population has recently received much attention. In this article, we discuss extending the conventional pairwise concept and demonstrate a community module‐based approach as an initial step for exploring community consequences of species‐specific phenological shifts caused by climate change. Our multispecies match/mismatch perspective leads to the prediction that phenological (a)synchrony among interacting species critically affects not only population recruitment of species but also key dynamical features of ecological communities such as trophic cascades, competitive hierarchies, and species coexistence. Explicit identification and consideration of species relationships is therefore desirable for a better understanding of seasonal community dynamics and thus community consequences of climate change‐induced phenological shifts.
Effect of PUVA therapy on melanocytes and keratinocytes in non‐segmental vitiligo: histopathological, immuno‐histochemical and ultrastructural study
Authors: Anbar Tag S. , El‐Sawy Ashraf E. , Attia Sameh K. , Barakat Manal T. , Moftah Noha H. , El‐Ammawy Tarek S. , Abdel‐Rahman Amal T. , El‐Tonsy Mohamed H.
Published: December 2011

Background and Aims

Psoralen ultraviolet A (PUVA) is an important modality in treating vitiligo. Its effect on melanocytes and keratinocytes is not sufficiently studied. In this work, we investigated 30 cases of non‐segmental vitiligo regarding the changes of melanocytes and keratinocytes in both vitiliginous and nearby areas before and after PUVA therapy.

Methods

Three skin biopsies were obtained from each patient from the vitiliginous, marginal and perilesional areas before and after 12 months of PUVA. Biopsies were examined histologically using haematoxylin and eosin, Masson–Fontana stains and 3,4‐dihydroxyphenylalanine (DOPA) reaction and histochemically using human melanoma black‐45 (HMB‐45) antibody while ultrastructural examination was performed on six patients. Control biopsies were taken from five healthy volunteers.

Results

In 10% of pretreated biopsies from the centre of vitiligo lesions, scanty melanocytes were detected histologically and ultrastructurally, while they did not stain with DOPA or HMB‐45 antibody suggesting that these melanocytes were inactive. Moreover, degenerative changes were detected by electron microscopy in both melanocytes and keratinocytes in all areas. After PUVA therapy, obvious improvement of the histopathological changes occurred with significant increase in active melanocytes. The degeneration of melanocytes and keratinocytes was also reduced at the ultrastructural level.

Conclusion

Vitiligo affects both melanocytes and keratinocytes causing degenerative changes. These changes were present in both the leucodermic and the apparently normal perilesional skin. PUVA increases the number of active epidermal melanocytes in the three tested areas and recovers the melanocyte and keratinocyte degeneration.
Acquired perforating dermatosis successfully treated with photodynamic therapy
Authors: Sezer Engin , Erkek Emel
Published: December 2011

Acquired perforating dermatosis is a rare perforating skin disorder characterized by intensely pruritic papules or nodules with central adherent plugs mainly observed on the lower extremities and transepidermal elimination of collagen bundles. Treatment of acquired perforating dermatosis is a matter of debate and conventional treatment options including topical and systemic retinoids, topical corticosteroids and keratolytics, ultraviolet B phototherapy, psoralen plus ultraviolet A (PUVA), allopurinol and cryosurgery show mixed results. Herein, we describe a 60‐year‐old woman with a diagnosis of acquired perforating dermatosis secondary to diabetes mellitus in whom we achieved excellent results with photodynamic treatment. As far as we are aware, this is the first case report of photodynamic treatment for acquired perforating dermatosis.
Electrical Conductivity as a Proxy for Groundwater Density in Coastal Aquifers
Authors: Post V. E. A.
Published: December 2011

Groundwater density is an important parameter in the interpretation of flow patterns. This paper investigates the relationship between electrical conductivity (EC) and groundwater density in coastal aquifers and evaluates the suitability of the UNESCO 1980 equation of state, developed for the world's oceans, for determining the density of groundwater based on its EC. To achieve this aim, a dataset of groundwater samples from four different types of coastal aquifers was collected. It is found that the density of a sample can be estimated to a good approximation on the basis of its EC using the UNESCO 1980 equation of state. Deviations from the equation of state were found to be due to the changes in EC and the density caused by geochemical reactions, such as the dissolution of carbonates, degradation of organic carbon, cation exchange, and sulfate loss. Owing to these deviations, the UNESCO 1980 equation of state may underestimate the density by up to 1.5 kg/m3. The effect of this uncertainty on the correction terms applied to the hydraulic head required for a proper interpretation of groundwater flow patterns and rates is quantified. It was found that the fresh water head may be wrong by centimeters to a few decimeters. From this it is concluded that, unless the purpose of a groundwater investigation requires great accuracy, the equation of state provides an efficient and inexpensive way to estimate density from EC.
A knockout mouse resource for the biomedical research community
Authors: Lloyd K. C. Kent
Published: December 2011

The Knockout Mouse Project (KOMP) Repository archives and distributes vectors, embryonic stem cell clones, frozen germplasm, and live mutant mice for 8,500 knockout genes. Here, we describe the creation and functions of the KOMP Repository.
The blessings and curses of C57BL/6 substrains in mouse genetic studies
Authors: Bryant Camron D.
Published: December 2011

Phenotypic and genetic differences among C57BL/6 substrains are accumulating. Investigators must address these differences to improve the quality of their studies.
Human stem cell‐derived cardiomyocytes for pharmacological and toxicological modeling
Authors: Harding Sian E.
Published: December 2011

Cardiomyocytes derived from human pluripotent stem cells have advantages for modeling in terms of phenotype, longevity in culture, ease of transfection, and high‐throughput capability.
Minimizing strain influences in a genetically modified mouse phenotyping platform
Authors: Hayward Michael D. , Buiakova Olesia , Grass David S.
Published: December 2011

Our approach has been to power studies to allow for detection of at least modest changes from a wild‐type littermate control, include assays with overlapping physiological systems to provide cross‐functional interpretive value, and to employ challenge assays.
Imaging of endocrine gene expression in a humanized transgenic rat
Authors: Davis Julian R.E.
Published: December 2011

Reporter gene imaging has revealed cyclical patterns of gene expression in living cells. Transgenic animal studies show that these patterns are modified by tissue architecture.
Animal models got you puzzled?: think pig
Authors: Walters Eric M. , Agca Yuksel , Ganjam Venkataseshu , Evans Tim
Published: December 2011

Swine are an excellent large animal model for human health and disease because their size and physiology are similar to humans, in particular, with respect to the skin, heart, gastrointestinal tract, and kidneys. In addition, the pig has many emerging technologies that will only enhance the development of the pig as the nonrodent biomedical model of choice.
The (α‐4) Photoconjugates of 5‐Methylcytosine, 1,5‐Dimethylcytosine, 1‐Methylthymine and Thymidine
Authors: Shetlar Martin D. , Chung Janet
Published: December 2011

The pyrimidine nucleobases contained in DNA undergo a variety of photoinduced reactions in which two moieties become joined to form a product (e.g. formation of cyclobutane dimers and [6‐4] adducts). Herein, we describe a new type of photoconjugation reaction that has been shown to occur for 5‐methylcytosine (5‐MeC), 1,5‐dimethylcytosine (1,5‐diMeC), 1‐methylthymine and thymidine; in this reaction the 5‐methyl group of one nucleobase (or nucleoside) becomes attached to the 4‐position of the second moiety. For example, 5‐MeC forms α‐4′‐(5′‐methylpyrimidin‐2′‐one)‐5‐methylcytosine. The various (α‐4) conjugates are produced upon irradiation of the parent compound in frozen aqueous solution at −78.5°C. The UV spectra of these compounds display a characteristic “double humped” profile, similar to that expected from overlaying the spectrum of parent nucleobase with that of a 2′‐pyrimidone moiety. Preliminary results suggest that thymine and 5‐methyl‐2′‐deoxycytidine (5‐MedCyd) form analogous photoproducts. A variety of other previously unreported photoproducts are described as well for the 5‐MeC, 1,5‐diMeC and 5‐MedCyd systems.
Mixed phenotype acute leukemia of T/myeloid type with a prominent cellular heterogeneity and unique karyotypic aberration 45,XY, dic(11;17)
Authors: COLOVIC M. , COLOVIC N. , JANKOVIC G. , KRAGULJAC KURTOVIC N. , VIDOVIC A. , DJORDJEVIC V. , BOGDANOVIC A.
Published: December 2011

Introduction.  A 26‐yr‐old male patient with mixed phenotype acute leukemia of T/myeloid type with prominent leukemic cell heterogeneity, and the presence of a so far unreported karyotype aberration in this type of acute leukemia 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) is presented.

Methods.  Flow immunocytometry was performed by direct multicolor immunofluorescent technique on bone marrow aspirates. Cytogenetic analyses were performed using G‐banding method by direct preparation of unstimulated bone marrow cells and following 24 hours of culture in RPMI 1540 culture medium with 25% fetal calf serum at 37°C

Results.  The flow immunocytometry of bone marrow nucleated cells revealed the existance of three distinct blast cell populations with overlapping immunophenotypes. Predominant blast cell population had an early myeloid phenotype and aberrant expression of CD7 antigen (HLA‐DR+, CD34+, anti‐MPO+, CD117+, CD33+, CD13+, CD7+low, cyCD3−, TdT−). The other two blast cell populations, smaller in cell diameter and less sizable in cell proportion, both shared the T‐lymphoid features. The patient was treated with ADE protocol (etoposide, cytarabine and doxorubicine). A complete remission was achieved and lasted 5 months.

Conclusion.  A case of MPAL with complex biological features, 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) karyotype and an aggressive, therapy‐resistant clinical course, is presented.
Bivalirudin Inhibits Periprocedural Platelet Function and Tissue Factor Expression of Human Smooth Muscle Cells
Authors: Pepke Wojciech , Eisenreich Andreas , Jaster Markus , Ayral Yunus , Bobbert Peter , Mayer Alexander , Schultheiss Heinz‐Peter , Rauch Ursula
Published: December 2011

Aim: A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined. Methods: Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real‐time PCR and Western blotting. The thrombogenicity of platelet‐derived microparticles and SMC was assessed via a TF activity assay. Results: Bivalirudin significantly diminished the agonist‐induced platelet reactivity post‐PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor‐activating peptide (TRAP)‐induced thrombospondin expression post‐PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P‐selectin expression of unstimulated and ADP‐induced platelets post‐PCI. Moreover, bivalirudin inhibited the thrombin‐, but not FVIIa‐ or FVIIa/FX‐induced TF expression and pro‐coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet‐derived microparticles postinduction with TRAP or ADP. Conclusions: Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin‐induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.
Effect of Tight Blood Glucose Control Versus Conventional Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review with Meta‐Analysis of Randomized Controlled Trials
Authors: Buehler Anna Maria , Cavalcanti Alexandre Biasi , Berwanger Otavio , Figueiro Mabel , Laranjeira Lígia Nasi , Zazula Ana Denise , Kioshi Bruno , Bugano Diogo G. , Santucci Eliana , Sbruzzi Grazielle , Guimaraes Helio Penna , Carvalho Vitor Oliveira , Bordin Silvana Auxiliadora
Published: December 2011

Tight control of blood glucose reduces cardiovascular events and total mortality is conflicting. To summarize clinical effects of tight versus conventional glucose control in patients with type 2 diabetes. We systematically searched MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge with no limits of language and time. Further trials were searched from the reference lists of identified studies. We included randomized controlled comparing different levels of blood glucose control intensity in type 2 diabetic patients. Two independent reviewers extracted data of eligible studies using standard case report forms. We investigated total mortality, cardiovascular and microvascular events, and hypoglycemia in patients with type 2 diabetes. We used random‐effects models to obtain relative risks (RR) with 95% confidence intervals (CI). We included 6 trials involving 27,654 patients. There was no significant effect of tight blood glucose control on all‐cause mortality (RR 1.03; 95% CI 0.90–1.17) or cardiovascular mortality (RR 1.04; 95% CI 0.83–1.29). Tight glucose control reduced the risk for nonfatal MI (RR 0.85; 95% CI 0.76–0.95), although had no effect on the incidence of nonfatal stroke (RR 1.02; 95% CI 0.88–1.17). For microvascular events, tight glucose control reduced the risk progression of retinopathy (RR 0.80; 95% CI 0.71–0.91), incidence of peripheral neuropathy (RR 0.94; 95% CI 0.89–0.99), and progression of nephropathy (RR 0.55; 95% CI 0.37–0.80), but had not significant effect on the incidence of nephropathy (RR 0.69; 95% CI 0.42–1.14). The risk of severe hypoglycemia increased with tight glucose control (RR 2.39; 95% CI 1.79–3.18). Tight blood glucose control reduces the risk for some macrovascular and microvascular events, without effect on all‐cause mortality and cardiovascular mortality. Tight glucose control increases the risk of severe hypoglycemia.
N‐Acetylcysteine in Preventing Contrast‐Induced Nephropathy Assessed by Cystatin C
Authors: Alioglu Emin , Saygi Serkan , Turk Ugur , Kirilmaz Bahadir , Tuzun Nurullah , Duman Can , Tengiz Istemihan , Yildiz Serkan , Ercan Ertugrul
Published: December 2011

Aims: Prophylactic oral N‐acetylcysteine (NAC) has been widely used for prevention of contrast‐induced nephropathy (CIN). However, clinical studies have not been demonstrating this effect consistently because of evidence that NAC can alter serum creatinine levels without affecting glomerular filtration rate (GFR). We investigated NAC for the prevention of CIN by monitoring creatinine and cystatin C.

Methods: We enrolled 113 patients (49 patients in NAC group and 64 patients in control group) with normal to subnormal GFR who were scheduled for cardiovascular procedures. Patients in NAC group receive acetylcysteine 600 mg twice a day, on the day before and on the day of cardiovascular procedure. All patients received a periprocedural intravenous infusion ("volume expansion") of 1 ml/kg/h with 0.45% saline for 24 h (12 h before and 12 h after exposure to contrast medium). Serum cystatin C and creatinine levels were measured before and at 12, 24, and 48 h after procedure.

Results: The incidence of cystatin C‐based CIN was 28.5% (n = 14) in NAC and 23.4% (n = 15) in control group (p = 0.663) and serum creatinine‐based CIN was 12.2% (n = 6) in NAC and 17.2% (n = 11) in control group (P= 0.468). In this study, oral NAC had no effect on the prevention of CIN in patients undergoing cardiovascular procedures.

Conclusion: In this study, oral NAC administration does not reduce neither the incidence of cystatin C‐based CIN nor serum creatinine‐based CIN in patients undergoing cardiovascular procedures.
Effect of Depression on the Risk and Severity of Lower Urinary Tract Symptoms in Community‐Dwelling Elderly Korean Men
Authors: PARK Hyoung Keun , PAICK Sung Hyun , KIM Hyeong Gon , LHO Yong Soo , BYUN Seok‐Soo , LEE Seok Bum , PARK Joon Hyuk , LEE Jung Jae , KIM Ki Woong
Published: December 2011

Objectives: To evaluate the association of the risk and severity of lower urinary tract symptoms (LUTS) and depression diagnosed by neuropsychiatrists according to the DSM‐IV diagnostic criteria using an objective questionnaire within community‐dwelling elderly Korean men.

Methods: A total of 392 men who completed urological and psychiatric evaluations as a participant in the Korean Longitudinal Study on Health and Aging were included in this analysis. From each subject, an interview elicited demographic characteristics and medical history, International Prostate Symptom Score was ascertained, and a psychiatric questionnaire was completed. Subjects were analyzed with regard to depression and LUTS severity.

Results: The mean age of the subjects was 75 years, 22% were current smokers and 45% were heavy drinkers. Two hundred and twenty‐nine subjects (59%) had moderate to severe LUTS and 6.4% of the subjects were diagnosed with major depressive disorders. Those with depression showed higher International Prostate Symptom Score and lower quality of life than the euthymic group (P = 0.03 and P = 0.02, respectively). Severe LUTS was more prevalent in the depression group compared with the euthymic group (P = 0.01). Moderate to severe LUTS was associated with higher age, lower prevalence of hypertension, and higher prevalence of depression than mild LUTS. Univariate and multivariate analyses identified age, hypertension, and depression as significant prognostic factors for moderate to severe LUTS. Depression was the most significant prognostic factor. Depression was associated with 5.81‐fold increased odds of having moderate to severe LUTS.

Conclusion: In older Korean men, depressive symptoms are associated with moderate to severe LUTS.
1997 Best Paper Award—Turbomachinery Committee: A Study of Spike and Modal Stall Phenomena in a Low-Speed Axial Compressor
Authors: Camp T. R. , Day I. J.
Published: December 2011

This paper presents a study of stall inception mechanisms in a low-speed axial compressor. Previous work has identified two common flow breakdown sequences, the first associated with a short length-scale disturbance known as a “spike,” and the second with a longer length-scale disturbance known as a “modal oscillation.” In this paper the physical differences between these two mechanisms are illustrated with detailed measurements. Experimental results are also presented that relate the occurrence of the two stalling mechanisms to the operating conditions of the compressor. It is shown that the stability criteria for the two disturbances are different: Long length-scale disturbances are related to a two-dimensional instability of the whole compression system, while short length-scale disturbances indicate a three-dimensional breakdown of the flow-field associated with high rotor incidence angles. Based on the experimental measurements, a simple model is proposed that explains the type of stall inception pattern observed in a particular compressor. Measurements from a single-stage low-speed compressor and from a multistage high-speed compressor are presented in support of the model.
1997 Best Paper Award—Structures and Dynamics Committee: A Coupled Mode Analysis of Unsteady Multistage Flows in Turbomachinery
Authors: Silkowski P. D. , Hall K. C.
Published: December 2011

A computational method is presented for predicting the unsteady aerodynamic response of a vibrating blade row that is part of a multistage turbomachine. Most current unsteady aerodynamic theories model a single blade row isolated in an infinitely long duct. This assumption neglects the potentially important influence of neighboring blade rows. The present “coupled mode” analysis is an elegant and computationally efficient method for modeling neighboring blade row effects. Using this approach, the coupling between blade rows is modeled using a subset of the so-called spinning modes, i.e., pressure, vorticity, and entropy waves, which propagate between the blade rows. The blade rows themselves are represented by reflection and transmission coefficients. These coefficients describe how spinning modes interact with, and are scattered by, a given blade row. The coefficients can be calculated using any standard isolated blade row model; here we use a linearized full potential flow model together with rapid distortion theory to account for incident vortical gusts. The isolated blade row reflection and transmission coefficients, interrow coupling relationships, and appropriate boundary conditions are all assembled into a small sparse linear system of equations that describes the unsteady multistage flow. A number of numerical examples are presented to validate the method and to demonstrate the profound influence of neighboring blade rows on the aerodynamic damping of a cascade of vibrating airfoils.
Active Stabilization of Axial Compressors With Circumferential Inlet Distortion
Authors: van Schalkwyk C. M. , Paduano J. D. , Greitzer E. M. , Epstein A. H.
Published: December 2011

This paper describes the first experimental validation of transfer function modeling and active stabilization for axial compressors with circumferential inlet distortion. The inlet distortion experiments were carried out in a three-stage low-speed compressor. Theory–experiment comparisons of steady performance, unsteady stall precursor, and forced response (transfer function) data were all used to assess a control-theoretic version of the Hynes–Greitzer distorted flow model. The tests showed good agreement between theory and data and demonstrated that a priori predictions, based on geometry and steady-state performance data, can be used to design control laws that stabilize rotating stall with inlet distortion. Based on these results, active feedback control has been used to stabilize the inlet distortion induced instability associated with rotating stall onset. The stabilization allowed stall-free operation to be extended below the natural (distorted flow) stall point by up to 3.7 percent for a 0.8 dynamic head distortion. For a 1.9 dynamic head distortion, 40 percent of the mass flow range lost due to inlet distortion was regained through active control. The paper elucidates the difficulties associated with active control with distortion, and introduces a new control law that addresses many of these challenges.
Aerothermal Performance Measurements and Analysis of a Two-Dimensional High Turning Rotor Blade
Authors: Arts T. , Duboue J.-M. , Rollin G.
Published: December 2011

The purpose of this contribution is to report on the aerothermal performance measurements and calculations carried out around a high-pressure gas turbine rotor blade profile mounted in a two-dimensional linear cascade arrangement. The measurements were performed in the CT-2 facility of the von Karman Institute, allowing a correct simulation of the operating conditions encountered in modern aero-engines. Independent variations of exit Mach (0.8−1.3) and Reynolds numbers (5×105–2×106), free-stream turbulence (1–6 percent) and incidence angle (−14–+11 deg) provided the definition of a detailed data base of test results. The measured quantities were the blade velocity and convective heat transfer coefficient distributions. The first objective of the paper is to open and analyze this data base, which is one of those used at SNECMA for validation purposes. The paper shows the degree of maturity and reliability SNECMA-ONERA Navier–Stokes solvers have now reached for daily use in turbine airfoil design and analysis.