bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discussion of the reply by R.L. Romer and U. Kroner on “Geochemical signature of Ordovician Mn-rich sedimentary rocks on the Avalonian shelf” 1Appears in Canadian Journal of Earth Sciences, 49(6): 775–780, 10.1139/e2012-006.
Authors: Schofield David I. , Waldron John W.F. , White Chris E. , Barr Sandra M. 
Published: December 2012

In their article ‘Reply to the discussion by J.W.F. Waldron and C.E. White on “Geochemical signature of Ordovician Mn-rich sedimentary rocks on the Avalonian shelf”’, R.L. Romer and U. Kroner reinterpret geochronological data presented by J.W.F. Waldron, D.I. Schofield, C.E. White, and S.M. Barr to imply an Ordovician, not a Cambrian, depositional age for the succession of the Harlech Dome, North Wales, and Meguma Supergroup, Nova Scotia. However, an extensive history of biostratigraphic and geological survey data refutes this interpretation and shows that the rocks are unequivocally Cambrian. Waldron et al. used the U–Pb zircon laser-ablation – multicollector – inductively coupled plasma – mass spectrometry technique primarily to provide information on sediment provenance and not depositional age. Investigation of anomalously young 206Pb/238U ages showed evidence of Pb loss. These data provide little constraint on depositional age and cannot be used to infer that the Harlech Grits Group is Ordovician.
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

Abstract
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

AbstractBackgroundThe 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).MethodsThe 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.ResultsOf 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).ConclusionsHUS 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

AbstractBackgroundEarly 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.MethodsThis 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.ResultsThere 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.ConclusionsThis 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractCiliopathies 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

Abstract
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

SummaryAcademic 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 methodWe 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.ResultsAs 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 implicationsThe 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.