bluuebunny/crossref_metadata_2025 huggingface dataset:
Geochronology and geochemistry of the enderbite series in the Lapland Granulite Belt: generation, tectonic setting, and correlation of the belt1NORDSIM Publication No. 322.
Authors: Tuisku P. , Huhma H. , Whitehouse M.J.
Published: December 2012

The Lapland Granulite Belt of the northeastern Fennoscandian Shield is dominated by blastomylonitic migmatitic metagreywackes and a deformed, structurally conformable norite–enderbite series. The belt contains minor granodiorites and one major anorthosite massif and is crosscut by post-tectonic granite plutons and diabase dykes. The major and trace element composition of the enderbite series is similar to that of arc-related igneous rocks. Magmatically zoned zircon yield U–Pb secondary ion mass spectrometry ages of 1.91–1.92 Ga, while homogeneous metamorphic zircon domains are aged 1.88–1.90 Ga. Major enderbite bodies reveal only a few older inherited, xenocrystic zircon cores or grains, mainly Archaean in age, while a tonalite body and a narrow quartz norite vein have abundant inherited zircons comparable with the detrital zircon population in the metagreywackes. The intrusive series has slightly positive initial εNdvalues, while the tonalite body has a slightly negative initial εNd, consistent with the occurrences of inherited zircon grains. The major intrusive series, interpreted to have been emplaced in an arc environment, has juvenile character and assimilated only a minor amount of older crustal material during ascent, intrusion, and cooling. Narrow veins and more evolved bodies had more interaction with the metasediments and other crustal rocks. The enderbite series of the Lapland Granulite Belt may be correlated with arc-related plutonism in the Nagssugtoqidian and Torngat orogens, but metamorphic and structural evolution took place considerably later in Greenland and the northeastern Canadian Shield, with the exception of the Inglefield Belt of northwestern Greenland.
A CENTRAL LIMIT THEOREM FOR LATIN HYPERCUBE SAMPLING WITH DEPENDENCE AND APPLICATION TO EXOTIC BASKET OPTION PRICING
Authors: AISTLEITNER CHRISTOPH , HOFER MARKUS , TICHY ROBERT
Published: December 2012

We consider the problem of estimating 𝔼[f(U1, …, Ud)], where (U1, …, Ud) denotes a random vector with uniformly distributed marginals. In general, Latin hypercube sampling (LHS) is a powerful tool for solving this kind of high-dimensional numerical integration problem. In the case of dependent components of the random vector (U1, …, Ud) one can achieve more accurate results by using Latin hypercube sampling with dependence (LHSD). We state a central limit theorem for the d-dimensional LHSD estimator, by this means generalising a result of Packham and Schmidt. Furthermore we give conditions on the function f and the distribution of (U1, …, Ud) under which a reduction of variance can be achieved. Finally we compare the effectiveness of Monte Carlo and LHSD estimators numerically in exotic basket option pricing problems.
EFFICIENT PRICING AND RELIABLE CALIBRATION IN THE HESTON MODEL
Authors: LEVENDORSKIĬ SERGEI
Published: December 2012

We suggest a general scheme for improvement of FT-pricing formulas for European options and give efficient recommendations for the choice of the parameters of the numerical scheme, which allow for very accurate and fast calculations. The efficiency of the method stems from the properties of functions analytical in a strip, which were introduced to finance by Feng and Linetsky (2008). We demonstrate that an indiscriminate choice of parameters of a numerical scheme leads to an inaccurate pricing and calibration. As applications, we consider the Heston model and its generalization. For many parameter sets documented in empirical studies of financial markets, relative accuracy better than 0.01% can be achieved by summation of less than 10-20 terms even in the situations in which the standard approach requires more than 200. In some cases, the one-term formula produces an error of several percent, and the summation of two terms — less than 0.5%. Typically, 10 terms and fewer suffice to achieve the error tolerance of several percent and smaller.
UTILITY BASED PRICING AND HEDGING OF JUMP DIFFUSION PROCESSES WITH A VIEW TO APPLICATIONS
Authors: ZAHN JOCHEN
Published: December 2012

We discuss utility based pricing and hedging of jump diffusion processes with emphasis on the practical applicability of the framework. We point out two difficulties that seem to limit this applicability, namely drift dependence and essential risk aversion independence. We suggest to solve these by a re-interpretation of the framework. This leads to the notion of an implied drift. We also present a heuristic derivation of the marginal indifference price and the marginal optimal hedge that might be useful in numerical computations.
Talking about bioelectrical potentials using rings of the mesenteric artery without glass micropipettes
Authors: Ribeiro-Filho H. V. , Brito T. S. , Lima F. J. B. , Pinho J. P. M. , Sousa D. F. , Silva M. T. B. , de Siqueira R. J. B. , Cosker F. , Bastos V. P. D. , Santos A. A. , Magalhães P. J. C.
Published: December 2012

In the present study, a practical activity is proposed to adopt an experimental approach to demonstrate the relationship between the equilibrium potential for K+and transmembrane electrical potential without glass micropipettes. A conventional setup for recording contractile activity of isolated smooth muscle preparations was used based on the events elegantly described by Somlyo and Somlyo in the 1960s. They showed that, in response to a given stimulus, smooth muscle cells may contract, recruiting electromechanical or pharmacomechanical coupling by mechanisms that involve, or not, changes in transmembrane potential, respectively. By means of contractions and relaxations of a ring-like preparation from the rat mesenteric artery, it is possible to observe the functional consequences of handling K+concentration in the extracellular compartment and the effects caused by opening K+channels in that preparation, which are significant when the cell membrane establishes an electrical potential difference between intra- and extracellular compartments (driven mainly by K+permeability under resting conditions). The effects observed by students fit well with values predicted by Nernst and Goldman-Hodgin-Katz equations, and we demonstrated that the activity is able to improve students' comprehension regarding basic principles of bioelectricity.
On systolic murmurs and cardiovascular physiological maneuvers
Authors: Salazar Sergio A. , Borrero Jose L. , Harris David M.
Published: December 2012

Physiological principles that directly apply to physical diagnosis provide opportune occasions to bring basic science to the bedside. In this article, we describe the effect of cardiac maneuvers on systolic murmurs and how physiological principles apply to the explanation of the changes noted at the bedside. We discuss the effect of Valsalva, squatting, and hand grip maneuvers on different physiological parameters influencing preload, afterload, chamber dimensions, and pressure gradients. The clinical manifestations noted during the aforementioned maneuvers are described in common cardiac conditions responsible for the production of certain systolic murmurs.
Fenofibrate Therapy in Carnitine Palmitoyl Transferase Type 2 Deficiency
Authors: Hamilton-Craig I. , Yudi M. , Johnson L. , Jayasinghe R.
Published: December 2012

Bezafibrate therapy has been shown to improve beta-oxidation of fatty acids and to reduce episodes of rhabdomyolysis in patients with carnitine palmitoyltransferase type-2 (CPT2) deficiency. We report the efficacy of fenofibrate in a patient with CPT2 deficiency, in whom beta-oxidation was improved but an episode of rhabdomyolysis nevertheless occurred. This suggests additional methods to avoid rhabdomyolysis in patients with CPT2 deficiency should accompany fibrate therapy, including avoidance of muscular overexertion, dehydration, and heat exposure.
Why People Play: Artificial Lives Acquiring Play Instinct to Stabilize Productivity
Authors: Tamura Shinichi , Inabayashi Shoji , Hayakawa Waichi , Yokouchi Takahiro , Mitsumoto Hiroshi , Taketani Hisashi
Published: December 2012

We propose a model to generate a group of artificial lives capable of coping with various environments which is equivalent to a set of requested task, and likely to show that the plays or hobbies are necessary for the group of individuals to maintain the coping capability with various changes of the environment as a whole. This may be an another side of saying that the wide variety of the abilities in the group is necessary, and if the variety in a species decreased, its species will be extinguished. Thus, we show some simulation results, for example, in the world where more variety of abilities are requested in the plays, performance of the whole world becomes stable and improved in spite of being calculated only from job tasks, and can avoid the risk of extinction of the species. This is the good effect of the play.
Influence ofTriatoma dimidiatain Modulating the Virulence ofTrypanosoma cruziMexican Strains
Authors: Guzman-Marin E. , Jimenez-Coello M. , Puerto-Solis M. , Ortega-Pacheco A. , Acosta-Viana K. Y.
Published: December 2012

The epidemiology of Chagas disease is complex. There are different vectors and reservoirs and different clinical manifestations. In order to assess whether the biological behavior of three strains isolated in southeastern Mexico (H4 isolated from human, Z17 isolated fromDidelphissp., and V isolated fromT. dimidiata) could be modified during passage through the vectorT. dimidiata, the parasitemia curve, the amount of amastigote nests, and mortality of BALB/c infected with blood trypomastigotes ofT. cruziwere evaluated. Strains were maintained in continuous passage from mouse to mouse and in animals infected with metacyclic trypomastigotes. The parasitemia curves were significantly different () between mice to mice and triatoma to mice groups in strains H4 and Z17, and was also observed fewer amastigote nests in cardiac tissue ( strain H4 with higher number versus all groups and Z17 between mice to mice and triatoma to mice) 45 days after inoculation. It is concluded thatT. dimidiatainfluences in modulating the virulence of strains ofT. cruziin the region. Further studies of the intestinal tract of the insect in search for some protein molecules involved in regulating may clarify the virulence of the parasite.
The Immune Response: Targets for the Treatment of Severe Sepsis
Authors: Bernard Aline M. , Bernard Gordon R.
Published: December 2012

The clinical process of severe sepsis is characterized by extreme inflammation interlinked with potent stimulation of the coagulation cascade often followed by a state of relative immune paralysis. In this paper, we will review many of the potential therapies directed at various steps along the inflammatory cascade from modulation of inflammatory mediators eliciting the immune response, alteration of the host's immune response in both a stimulatory and depressive manner, and taming the overexuberant coagulation response triggered by the fierce coagulation-inflammation cycle. Finally, we will discuss further opportunities for research to improve our ability to design effective therapies.
Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder
Authors: Kim Woojun , Kim Su-Hyun , Huh So-Young , Kim Ho Jin
Published: December 2012

Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.
Two Types of Distributed CFAR Detection Based on Weighting Functions in Fusion Center for Weibull Clutter
Authors: Zaimbashi Amir
Published: December 2012

Two types of distributed constant false alarm rate (CFAR) detection using binary and fuzzy weighting functions in fusion center are developed. In the two types of distributed detectors, it was assumed that the clutter parameters at the local sensors are unknown and each local detector performs CFAR processing based on ML and OS CFAR processors before transmitting data to the fusion center. At the fusion center, received data is weighted either by a binary or a fuzzy weighting functions and combined according to deterministic rules, constructing global test statistics. Moreover, for the Weibull clutter, the expression of the weighting functions, based on ML and OS CFAR processors in local detectors, is obtained. In the binary type, we analyzed various distributed detection schemes based on maximum, minimum, and summation rules in fusion center. In the fuzzy type, we consider the various distributed detectors based on algebraic product, algebraic sum, probabilistic OR, and Lukasiewicz t-conorm fuzzy rules in fusion center. The performance of the two types of distributed detectors is analyzed and compared in the homogenous and nonhomogenous situations, multiple targets, or clutter edge. The simulation results indicate the superiority and robust performance of fuzzy type in homogenous and non homogenous situations.
China and Vietnam in the South China Sea Dispute: A Creeping ‘Conflict–Peace–Trepidation’ Syndrome
Authors: Chakraborti Tridib
Published: December 2012

The South China Sea dispute which has spilled over from the twentieth to the twenty-first century, is yet to find an amicable solution. The root cause of this tension is the dispute among the various claimants as regards the procurement of energy resources and securing territorial legitimacy. The entry of the US into the picture has further complicated the problem. In order to evolve a congenial regional environment, the disputing countries must evolve a collaborative outlook, not confrontationist, and adopt a regional perspective rather than proceed from their national interest only and take recourse to multilateral mechanisms as a means to reduce tension in the region. If the prognosis that the ‘21st century is the century of Asia’ is to be made a reality, then the economic prosperity and development of the Asian region will be essential, for which, all the disputing countries should change their mindset from local to global level and keep the South China Sea region as less tension-prone as possible.
ASEAN’s Response to the Rise of China: Deploying a Hedging Strategy
Authors: Shekhar Vibhanshu
Published: December 2012

The rise of China has brought forth new sets of opportunities and challenges for Southeast Asia. A new politico-strategic landscape has emerged in which, ASEAN not only seeks China’s economic support perceived to be crucial for the development of the region, but also worries about China’s growing power and the possibility of Chinese domination over the region. ASEAN as a regional interlocutor has responded to the new phenomenon by deploying a hedging strategy that seeks to benefit from the opportunities and manage the challenges emanating from the rise of China. While ASEAN’s policy of ‘honest brokerage’ has allowed the presence of other powers to balance China, its policy of enmesh China has facilitated China’s role as a stakeholder in the ASEAN cooperative processes.
Studying Intellectual Outliers
Authors: Wai Jonathan , Putallaz Martha , Makel Matthew C.
Published: December 2012

By studying samples of intellectual outliers across 30 years, researchers can leverage right-tail data (i.e., samples at or above the 95th percentile on tests of ability) to uncover missing pieces to two psychological puzzles: whether there are sex differences in cognitive abilities among smart people, and whether test scores are rising (a phenomenon known as the Flynn effect) among smart people. For the first puzzle, data indicate that the high male-to-female ratio among extremely high scorers on measures of math ability has decreased dramatically, but is still likely one factor among many explaining female underrepresentation in some professions. For the second puzzle, data indicate that the right tail has risen at a similar rate as the general (or middle portion of the) distribution; it is thus likely that the entire curve is rising at a relatively constant rate, consistent with the Flynn effect, which may explain why a greater number of gifted students have been identified in recent years. However, the causes for these gains and whether they reflect real gains in intelligence continue to remain a mystery. We show how these two puzzles are linked and stress the importance of paying attention to the entire distribution when attempting to address some scientific questions.
Penal tourism and the ‘dream of order’: Exhibiting early penology in Argentina and Australia
Authors: Welch Michael
Published: December 2012

Aimed at delivering a didactic – as well as a recreational – experience, former prisons have been transformed into museums of past incarceration regimes. That development has become part of a larger phenomenon known as penal tourism. Indeed, visits to famous institutions tap into a timeless curiosity and fascination with the infliction of punishment. Penal tourism also puts on display practices previously hidden behind closed doors, including prisoner abuse, torture, and execution. This analysis builds on previous research at the Argentine Penitentiary Museum and expands to Australia where the Hyde Park Barracks and the Old Melbourne Gaol are explored. Moving beyond mere description, this comparative study considers theoretical implications embodied in the dream of order. Toward that end, the interpretation takes into account both instrumental (power-based, Foucauldian) and expressive (semiotic, neo-Durkheimian) perspectives on the exhibition of early penology.
Parole, snitch, or die: California’s supermax prisons and prisoners, 1997–2007
Authors: Reiter Keramet A
Published: December 2012

Supermaximum security prisons (‘supermaxes’) across the United States detain thousands in long-term solitary confinement, under conditions of extreme sensory deprivation. In 1988 and 1989, California opened two of the first and largest of the modern supermaxes: Corcoran and Pelican Bay State Prisons. Today, California houses more than 3300 prisoners in supermaxes. Each month, between 50 and 100 people are released directly from these supermaxes onto parole. Using statistics obtained from the California Department of Corrections and Rehabilitation, this article explores who these prisoners and parolees are: what race are these prisoners, how long did they spend in solitary confinement, and how frequently are they released? Relative to non-supermax prisoners and parolees in California, supermax prisoners and parolees are disproportionately Latinos, who have served long prison sentences, under severe conditions. Analysis of interviews with correctional department administrators about the original goals and purposes of the supermaxes further contextualizes these data, revealing that supermaxes today function rather differently than their designers envisioned 20 years ago. In sum, this research provides one of the first evaluations of how supermaxes function, in terms of whom they detain and for how long, and how these patterns relate to the originally articulated purposes of the institutions.
Latina/o Achievement at Predominantly White Universities
Authors: Cerezo Alison , Chang Tai
Published: December 2012

In this exploratory study, the authors examined the influence of cultural fit on the achievement of Latina/o college students by testing whether cultural integration factors (i.e., cultural congruity, ethnic identity, connection with ethnic minority peers) predict college GPA (grade point average). Participants were 113 Latina/o students enrolled at 4 predominantly White institutions (PWIs) in the Pacific Northwest. Findings revealed that in addition to high school GPA, connection with ethnic minority peers and cultural congruity were significant predictors of college GPA.
The Birth of a Stereoscopic Nation: Hollywood, Digital Empire and the Cybernetic Attraction
Authors: Gurevitch Leon
Published: December 2012

This article argues that Avatar (James Cameron, 2009) is a key moment in the development of stereoscopy, cinematography and animation. On both an aesthetic/formal level and in terms of its narrative, Avatar talks back to the origins of Victorian stereography, American cinematography and the racist discourses of ethnography and ecocide that ensued. Echoing 19th-century stereographs of ‘natives’ and their resource-rich environments, together with DW Griffith’s Birth of a Nation, Avatar also attempts to negotiate the atrocities of the past and to relate them to our present. But this negotiation also takes place on a more subtle ontological level: originating within the structures of a ‘cybernetic empire’, Victorian stereographic imaging is strikingly indicative of Avatar’s contemporary position as a work of culture in the age of cybernetic systems. It has been argued that monographic imaging reputedly replaced stereographic forms in popularity because the latter disrupted the scopic regimes of modernity by emphasizing the role of the body in the process of vision. Avatar’s computer generated composite form circumvents this equation, however; while photography may have sought to minimize viewers’ awareness of their own bodies in the process of beholding the indexical form, such a framework is questionable in an age of fabricated CG composites. If the origins of stereography predated photography, and if its founding image was hand drafted, then what originally appeared a technical footnote in the history of stereography now becomes a key factor in understanding Avatar and the new ‘cybernetic regime of modernity’.
Where Codes Collide: The Emergent Ecology of Avatar
Authors: Wood Aylish
Published: December 2012

Ecological approaches give an insight to the story-world of Avatar. They are extended in this article to facilitate an exploration of the connectivity between the feature film and its associated texts (production culture disclosures, making of featurettes, interviews). Drawing on the ecological thinking of Gregory Bateson, Félix Guattari and Jane Bennett, this article argues that Avatar and its associated texts are considered as an ecology of emergent space. The materiality of such a space is drawn from the various entities involved in its configuration: animation software, motion capture technologies, actors, designers and filmmakers. This argument is pursued primarily through a discussion of the ways in which real-time motion capture technologies alter our understandings of the ecologies of CG imagery in Avatar. Remaining focused on only the realism of these images, or the traces of humanness within them, misses the way in which such spaces emerge at an intersection of codes.
Prevention of sudden cardiac death in patients with chronic kidney disease
Authors: Franczyk-Skóra Beata , Gluba Anna , Banach Maciej , Kozłowski Dariusz , Małyszko Jolanta , Rysz Jacek
Published: December 2012

Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients’ prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient.
End-stage kidney disease due to haemolytic uraemic syndrome – outcomes in 241 consecutive ANZDATA registry cases
Authors: Tang Wen , Mohandas Janaki , McDonald Stephen P , Hawley Carmel M , Badve Sunil V , Boudville Neil , Brown Fiona G , Clayton Philip A , Wiggins Kathryn J , Bannister Kym M , Campbell Scott B , Johnson David W
Published: December 2012

Background

The aim of this study was to investigate the characteristics and outcomes of patients receiving renal replacement therapy for end-stage kidney disease (ESKD) secondary to haemolytic uraemic syndrome (HUS).

Methods

The study included all patients with ESKD who commenced renal replacement therapy in Australia and New Zealand between 15/5/1963 and 31/12/2010, using data from the ANZDATA Registry. HUS ESKD patients were compared with matched controls with an alternative primary renal disease using propensity scores based on age, gender and treatment era.

Results

Of the 58422 patients included in the study, 241 (0.4%) had ESKD secondary to HUS. HUS ESKD was independently associated with younger age, female gender and European race. Compared with matched controls, HUS ESKD was not associated with mortality on renal replacement therapy (adjusted hazard ratio [HR] 1.14, 95% CI 0.87-1.50, p = 0.34) or dialysis (HR 1.34, 95% CI 0.93-1.93, p = 0.12), but did independently predict recovery of renal function (HR 54.01, 95% CI 1.45-11.1, p = 0.008). 130 (54%) HUS patients received 166 renal allografts. Overall renal allograft survival rates were significantly lower for patients with HUS ESKD at 1 year (73% vs 91%), 5 years (62% vs 85%) and 10 years (49% vs 73%). HUS ESKD was an independent predictor of renal allograft failure (HR 2.59, 95% CI 1.70-3.95, p < 0.001). Sixteen (12%) HUS patients experienced failure of 22 renal allografts due to recurrent HUS. HUS ESKD was not independently associated with the risk of death following renal transplantation (HR 0.92, 95% CI 0.35-2.44, p = 0.87).

Conclusions

HUS is an uncommon cause of ESKD, which is associated with comparable patient survival on dialysis, an increased probability of renal function recovery, comparable patient survival post-renal transplant and a heightened risk of renal transplant graft failure compared with matched ESKD controls.
MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis
Authors: Gervais Julien , Périé Delphine , Parent Stefan , Labelle Hubert , Aubin Carl-Eric
Published: December 2012

Background

Early stages of scoliosis and spondylolisthesis entail changes in the intervertebral disc (IVD) structure and biochemistry. The current clinical use of MR T2-weighted images is limited to visual inspection. Our hypothesis is that the distribution of the MRI signal intensity within the IVD in T2-weighted images depends on the spinal pathology and on its severity. Therefore, this study aims to develop the AMRSID (analysis of MR signal intensity distribution) method to analyze the 3D distribution of the MR signal intensity within the IVD and to evaluate their sensitivity to scoliosis and spondylolisthesis and their severities.

Methods

This study was realized on 79 adolescents who underwent a MRI acquisition (sagittal T2-weighted images) before their orthopedic or surgical treatment. Five groups were considered: low severity scoliosis (Cobb angle ≤50°), high severity scoliosis (Cobb angles >50°), low severity spondylolisthesis (Meyerding grades I and II), high severity spondylolisthesis (Meyerding grades III, IV and V) and control. The distribution of the MRI signal intensity within the IVD was analyzed using the descriptive statistics of histograms normalized by either cerebrospinal fluid or bone signal intensity, weighted centers and volume ratios. Differences between pathology and severity groups were assessed using one- and two-way ANOVAs.

Results

There were significant (p < 0.05) variations of indices between scoliosis, spondylolithesis and control groups and between low and high severity groups. The cerebrospinal fluid normalization was able to detect differences between healthy and pathologic IVDs whereas the bone normalization, which reflects both bone and IVD health, detected more differences between the severities of these pathologies.

Conclusions

This study proves for the first time that changes in the intervertebral disc, non visible to the naked eye on sagittal T2-weighted MR images of the spine, can be detected from specific indices describing the distribution of the MR signal intensity. Moreover, these indices are able to discriminate between scoliosis and spondylolisthesis and their severities, and provide essential information on the composition and structure of the discs whatever the pathology considered. The AMRSID method may have the potential to complement the current diagnostic tools available in clinics to improve the diagnostic with earlier biomarkers, the prognosis of evolution and the treatment options of scoliosis and spondylolisthesis.
Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial
Authors: Boissonnat Pascale , Gaillard Ségolène , Mercier Catherine , Redonnet Michel , Lelong Bernard , Mattei Marie-Françoise , Mouly-Bandini Annick , Pattier Sabine , Sirinelli Agnès , Epailly Eric , Varnous Shaida , Billes Marc-Alain , Sebbag Laurent , Ecochard René , Cornu Catherine , Gueyffier François
Published: December 2012

Background

Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes.

Methods

In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations<300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids. Participants had a stable haemodynamic status, a serum creatinine level <250 μmol/L and the donors’ cold ischemia time was under six hours; multiorgan transplants were excluded. The change in serum creatinine level over 12 months was used as the main criterion for renal function. Intention-to-treat analysis was performed on the 95 randomised patients and a mixed generalised linear model of covariance was applied.

Results

At 12 months, the mean (± SD) creatinine value was 120.7 μmol/L (± 35.8) in the low-dose group and 132.3 μmol/L (± 49.1) in the standard-dose group (P = 0.162). Post hoc analyses suggested that patients with higher creatinine levels at baseline benefited significantly from the lower Cyclosporine A target. The number of patients with at least one rejection episode was not significantly different but one patient in the low-dose group and six in the standard-dose group required dialysis.

Conclusions

In patients with de novo cardiac transplantation, early Cyclosporine A dose reduction was not associated with renal benefit at 12 months. However, the strategy may benefit patients with high creatinine levels before transplantation.

Trial registration

ClinicalTrials.gov NCT00159159
Toll-like receptor 3 in Epstein-Barr virus-associated nasopharyngeal carcinomas: consistent expression and cytotoxic effects of its synthetic ligand poly(A:U) combined to a Smac-mimetic
Authors: Vérillaud Benjamin , Gressette Mélanie , Morel Yannis , Paturel Carine , Herman Philippe , Lo Kwok Wai , Tsao Sai Wah , Wassef Michel , Jimenez-Pailhes Anne-Sophie , Busson Pierre
Published: December 2012

Background

Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Though NPCs are more radiosensitive and chemosensitive than other tumors of the upper aero-digestive tract, many therapeutic challenges remain. In a previous report, we have presented data supporting a possible therapeutic strategy based on artificial TLR3 stimulation combined to the inhibition of the IAP protein family (Inhibitor of Apoptosis Proteins). The present study was designed to progress towards practical applications of this strategy pursuing 2 main objectives: 1) to formally demonstrate expression of the TLR3 protein by malignant NPC cells; 2) to investigate the effect of poly(A:U) as a novel TLR3-agonist more specific than poly(I:C) which was used in our previous study.

Methods

TLR3 expression was investigated in a series of NPC cell lines and clinical specimens by Western blot analysis and immunohistochemistry, respectively. The effects on NPC cells growth of the TLR3 ligand poly(A:U) used either alone or in combination with RMT5265, an IAP inhibitor based on Smac-mimicry, were assessed using MTT assays and clonogenic assays.

Results

TLR3 was detected at a high level in all NPC cell lines and clinical specimens. Low concentrations of poly(A:U) were applied to several types of NPC cells including cells from the C17 xenograft which for the first time have been adapted to permanent propagation in vitro. As a single agent, poly(A:U) had no significant effects on cell growth and cell survival. In contrast, dramatic effects were obtained when it was combined with the IAP inhibitor RMT5265. These effects were obtained using concentrations as low as 0.5 μg/ml (poly(A:U)) and 50 nM (RMT5265).

Conclusion

These data confirm that TLR3 expression is a factor of vulnerability for NPC cells. They suggest that in some specific pathological and pharmacological contexts, it might be worth to use Smac-mimetics at very low doses, allowing a better management of secondary effects. In light of our observations, combined use of both types of compounds should be considered for treatment of nasopharyngeal carcinomas.
A cooperative strategy for parameter estimation in large scale systems biology models
Authors: Villaverde Alejandro F , Egea Jose A , Banga Julio R
Published: December 2012

Background

Mathematical models play a key role in systems biology: they summarize the currently available knowledge in a way that allows to make experimentally verifiable predictions. Model calibration consists of finding the parameters that give the best fit to a set of experimental data, which entails minimizing a cost function that measures the goodness of this fit. Most mathematical models in systems biology present three characteristics which make this problem very difficult to solve: they are highly non-linear, they have a large number of parameters to be estimated, and the information content of the available experimental data is frequently scarce. Hence, there is a need for global optimization methods capable of solving this problem efficiently.

Results

A new approach for parameter estimation of large scale models, called Cooperative Enhanced Scatter Search (CeSS), is presented. Its key feature is the cooperation between different programs (“threads”) that run in parallel in different processors. Each thread implements a state of the art metaheuristic, the enhanced Scatter Search algorithm (eSS). Cooperation, meaning information sharing between threads, modifies the systemic properties of the algorithm and allows to speed up performance. Two parameter estimation problems involving models related with the central carbon metabolism of E. coli which include different regulatory levels (metabolic and transcriptional) are used as case studies. The performance and capabilities of the method are also evaluated using benchmark problems of large-scale global optimization, with excellent results.

Conclusions

The cooperative CeSS strategy is a general purpose technique that can be applied to any model calibration problem. Its capability has been demonstrated by calibrating two large-scale models of different characteristics, improving the performance of previously existing methods in both cases. The cooperative metaheuristic presented here can be easily extended to incorporate other global and local search solvers and specific structural information for particular classes of problems.
Diagnostic accuracy of loop-mediated isothermal amplification (LAMP) for detection of Leishmania DNA in buffy coat from visceral leishmaniasis patients
Authors: Khan Md Gulam Musawwir , Bhaskar Khondaker Rifat Hasan , Salam Md Abdus , Akther Tania , Pluschke Gerd , Mondal Dinesh
Published: December 2012

Background

Visceral leishmaniasis (VL) remains as one of the most neglected tropical diseases with over 60% of the world’s total VL cases occurring in the Indian subcontinent. Due to the invasive risky procedure and technical expertise required in the classical parasitological diagnosis, the goal of the VL experts has been to develop noninvasive procedure(s) applicable in the field settings. Several serological and molecular biological approaches have been developed over the last decades, but only a few are applicable in field settings that can be performed with relative ease. Recently, loop-mediated isothermal amplification (LAMP) has emerged as a novel nucleic acid amplification method for diagnosis of VL. In this study, we have evaluated the LAMP assay using buffy coat DNA samples from VL patients in Bangladesh and compared its performance with leishmania nested PCR (Ln-PCR), an established molecular method with very high diagnostic indices.

Methods

Seventy five (75) parasitologically confirmed VL patients by spleen smear microcopy and 101 controls (endemic healthy controls −25, non-endemic healthy control-26, Tuberculosis-25 and other diseases-25) were enrolled in this study. LAMP assay was carried out using a set of four primers targeting L. donovani kinetoplast minicircle DNA under isothermal (62 °C) conditions in a heat block. For Ln-PCR, we used primers targeting the parasite’s small-subunit rRNA region.

Results

LAMP assay was found to be positive in 68 of 75 confirmed VL cases, and revealed its diagnostic sensitivity of 90.7% (95.84-81.14, 95% CI), whereas all controls were negative by LAMP assay, indicating a specificity of 100% (100–95.43, 95% CI). The Ln-PCR yielded a sensitivity of 96% (98.96-87.97, 95% CI) and a specificity of 100% (100–95.43, 95% CI).

Conclusion

High diagnostic sensitivity and excellent specificity were observed in this first report of LAMP diagnostic evaluation from Bangladesh. Considering its many fold advantages over conventional PCR and potential to be used as a simple and rapid test in the VL endemic areas of the Indian subcontinent, our findings are encouraging, but further evaluation of LAMP is needed.
Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins
Authors: Rachel Rivka A , Li Tiansen , Swaroop Anand
Published: December 2012

Ciliopathies encompass a broad array of clinical findings associated with genetic defects in biogenesis and/or function of the primary cilium, a ubiquitous organelle involved in the transduction of diverse biological signals. Degeneration or dysfunction of retinal photoreceptors is frequently observed in diverse ciliopathies. The sensory cilium in a photoreceptor elaborates into unique outer segment discs that provide extensive surface area for maximal photon capture and efficient visual transduction. The daily renewal of approximately 10% of outer segments requires a precise control of ciliary transport. Here, we review the ciliopathies with associated retinal degeneration, describe the distinctive structure of the photoreceptor cilium, and discuss mouse models that allow investigations into molecular mechanisms of cilia biogenesis and defects. We have specifically focused on two ciliary proteins – CEP290 and RPGR – that underlie photoreceptor degeneration and syndromic ciliopathies. Mouse models of CEP290 and RPGR disease, and of their multiple interacting partners, have helped unravel new functional insights into cell type-specific phenotypic defects in distinct ciliary proteins. Elucidation of multifaceted ciliary functions and associated protein complexes will require concerted efforts to assimilate diverse datasets fromin vivoandin vitrostudies. We therefore discuss a possible framework for investigating genetic networks associated with photoreceptor cilia biogenesis and pathology.
Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model
Authors: Tsuchida Anika I , Beekhuizen Michiel , Rutgers Marijn , van Osch Gerjo JVM , Bekkers Joris EJ , Bot Arjan GJ , Geurts Bernd , Dhert Wouter JA , Saris Daniel BF , Creemers Laura B
Published: December 2012

Introduction

This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.

Methods

IL-6 concentrations were determined by ELISA in synovial fluid and in conditioned media of chondrocytes regenerating cartilage. Chondrocytes were obtained from donors with symptomatic cartilage defects, healthy and osteoarthritic donors. The effect of IL-6 on cartilage regeneration and on metabolism of the resident cartilage in the knee was studied by both inhibition of endogenous IL-6 and addition of IL-6, in a regeneration model and in osteoarthritic explants in the presence of synovial fluid, respectively. Readout parameters were DNA and glycosaminoglycan (GAG) content and release. Differences between controls and IL-6 blocked or supplemented samples were determined by univariate analysis of variance using a randomized block design.

Results

Synovial fluid of patients with symptomatic cartilage defects contained more IL-6 than synovial fluid of healthy donors (P = 0.001) and did not differ from osteoarthritic donors. IL-6 production of osteoarthritic chondrocytes during cartilage regeneration was higher than that of healthy and defect chondrocytes (P < 0.001). Adding IL-6 increased GAG production by healthy chondrocytes and decreased GAG release by osteoarthritic chondrocytes (P < 0.05). Inhibition of IL-6 present in osteoarthritic synovial fluid showed a trend towards decreased GAG content of the explants (P = 0.06).

Conclusions

Our results support a modest anabolic role for IL-6 in cartilage matrix production. Targeting multiple cytokines, including IL-6, may be effective in improving cartilage repair in symptomatic cartilage defects and osteoarthritis.
Rebalancing academic psychiatry: why it needs to happen - and soon
Authors: Kleinman Arthur
Published: December 2012

Academic psychiatry is in trouble, becoming the narrowest of biological research approaches of decreasing relevance to clinical practice and global health. What is required is a rebalancing of the psychiatric academy to include greater support for researchers conducting social, clinical and community studies within a broad, more humanistic biosocial framework.
The Mental Health Clustering Tool for people with severe intellectual disability
Authors: Radhakrishnan Vishwa , Smith Kevin , O'Hara Jean
Published: December 2012

Aims and method

We assessed 92% (117/127) of the patients in our community mental health learning disability team using the Mental Health Clustering Tool (MHCT) to establish whether their needs could be captured sufficiently well to enable assignment to a care cluster for payment by results in mental health. We explored the characteristics of those assigned to Cluster 0 to identify how they differed from those who could be assigned to Clusters 1-21.

Results

As expected, nearly half of the case-load (48%) could not be assigned to any cluster except Cluster 0, the variance cluster, which is used when the needs of patients cannot be captured by the current 21 care clusters but a service is, or will be, provided.

Clinical implications

The MHCT in its current form does not adequately capture the needs of people with more severe intellectual disability. An integrated mental health and learning disability clustering tool is in development. This is expected to include new rating scales and new clusters, however until the development is completed and validated it will not be possible to implement payment by results in mental health in learning disability services.
Structure-Property Relations in Ionic Liquids: 1,2,3-Trimethyl-imidazolium and 1,2,3-Trimethyl-benzimidazolium bis-(trifluorsulfonyl)imide
Authors: Zaitsau Dzmitry H. , Yermalayeu Andrei V. , Emel'yanenko Vladimir N. , Schick Christoph , Verevkin Sergey P. , Samarov Artemiy A. , Schlenk Stefan , Wasserscheid Peter
Published: December 2012

Vaporization enthalpies for a pairs of the ionic liquids (ILs) 1,2,3-trimethyl-imidazolium and 1,2,3-trimethyl-benzimidazolium bistrifluorsulfonylimide and the corresponding molecular liquids 1,2-dimethyl-imidazole and 1,2-dimethyl-benzimidazole were determined using a quartz crystal microbalance method and TGA (for ILs) and the transpiration method (for molecular compounds). Differences in vaporization enthalpies in molecular and ionic liquids are discussed in context of structure-property relations.
Thermodynamic Properties of Gaseous Argon from the Ab Initio Virial Equation of State
Authors: Jäger Benjamin
Published: December 2012

A previously developed ab initio virial equation of state for argon (B. Jäger, R. Hellmann, E. Bich, E. Vogel, J. Chem. Phys. 135 (2011) 084308) was applied to calculate related thermophysical properties for the gaseous and supercritical region. Virial coefficients up to B
7 were included considering also nonadditive three-body interactions and quantum corrections (for B
2, B
3, and B
4). The results for the isothermal compressibility, the thermal expansivity, the isochoric and isobaric heat capacity, and for the speed of sound were compared with experimental data and with values obtained from a highly accurate empirical equation of state. It was generally found that the theoretical predictions are in very good agreement with the reference data except for the near-critical region and for higher densities. Hence, the theoretically calculated data can be useful for the improvement of equations of state, particularly for toxic or corrosive substances and for thermodynamic conditions, where experiments are difficult to perform (e.g. at high temperatures). The speed of sound was found to be the most suitable property to evaluate the quality of the underlying interaction potentials.