bluuebunny/crossref_metadata_2025 huggingface dataset:
Bias and Sensitivity Analysis When Estimating Treatment Effects from the Cox Model with Omitted Covariates
Authors: Lin Nan Xuan , Logan Stuart , Henley William Edward
Published: November 2013

Omission of relevant covariates can lead to bias when estimating treatment or exposure effects from survival data in both randomized controlled trials and observational studies. This paper presents a general approach to assessing bias when covariates are omitted from the Cox model. The proposed method is applicable to both randomized and non-randomized studies. We distinguish between the effects of three possible sources of bias: omission of a balanced covariate, data censoring and unmeasured confounding. Asymptotic formulae for determining the bias are derived from the large sample properties of the maximum likelihood estimator. A simulation study is used to demonstrate the validity of the bias formulae and to characterize the influence of the different sources of bias. It is shown that the bias converges to fixed limits as the effect of the omitted covariate increases, irrespective of the degree of confounding. The bias formulae are used as the basis for developing a new method of sensitivity analysis to assess the impact of omitted covariates on estimates of treatment or exposure effects. In simulation studies, the proposed method gave unbiased treatment estimates and confidence intervals with good coverage when the true sensitivity parameters were known. We describe application of the method to a randomized controlled trial and a non-randomized study.
Modeling the impact of hepatitis C viral clearance on end‐stage liver disease in an HIV co‐infected cohort with targeted maximum likelihood estimation
Authors: Schnitzer Mireille E. , Moodie Erica E.M. , van der Laan Mark J. , Platt Robert W. , Klein Marina B.
Published: November 2013

Despite modern effective HIV treatment, hepatitis C virus (HCV) co‐infection is associated with a high risk of progression to end‐stage liver disease (ESLD) which has emerged as the primary cause of death in this population. Clinical interest lies in determining the impact of clearance of HCV on risk for ESLD. In this case study, we examine whether HCV clearance affects risk of ESLD using data from the multicenter Canadian Co‐infection Cohort Study. Complications in this survival analysis arise from the time‐dependent nature of the data, the presence of baseline confounders, loss to follow‐up, and confounders that change over time, all of which can obscure the causal effect of interest. Additional challenges included non‐censoring variable missingness and event sparsity.

In order to efficiently estimate the ESLD‐free survival probabilities under a specific history of HCV clearance, we demonstrate the double‐robust and semiparametric efficient method of Targeted Maximum Likelihood Estimation (TMLE). Marginal structural models (MSM) can be used to model the effect of viral clearance (expressed as a hazard ratio) on ESLD‐free survival and we demonstrate a way to estimate the parameters of a logistic model for the hazard function with TMLE. We show the theoretical derivation of the efficient influence curves for the parameters of two different MSMs and how they can be used to produce variance approximations for parameter estimates. Finally, the data analysis evaluating the impact of HCV on ESLD was undertaken using multiple imputations to account for the non‐monotone missing data.
These pretzels are going to make me thirsty tomorrow: Differential development of hot and cool episodic foresight in early childhood?
Authors: Mahy Caitlin E. V. , Grass Julia , Wagner Sarah , Kliegel Matthias
Published: November 2013

The current study examined 3‐ and 7‐year‐olds' performance on two types of episodic foresight tasks: A task that required ‘cool’ reasoning processes about the use of objects in future situations and a task that required ‘hot’ processes to inhibit a salient current physiological state in order to reason accurately about a future state. Results revealed that 7‐year‐olds outperformed 3‐year‐olds on the episodic foresight task that involved cool processes, but did not show age differences in performance on the task that involved hot processes. In fact, both 3‐ and 7‐year‐olds performed equally poorly on the task that required predicting a future physiological state that was in conflict with their current state. Further, performance on the two tasks was unrelated. We discuss the results in terms of differing developmental trajectories for episodic foresight tasks that differentially rely on hot and cool processes and the universal difficulties humans have with predicting later outcomes that conflict with current motivational states.
The current status of bridging anticoagulation
Authors: Patel Jignesh P. , Arya Roopen
Published: November 2013

For patients prescribed chronic vitamin K antagonist therapy requiring a surgical or invasive procedure, the question of whether or not to bridge and how to bridge is commonly encountered in clinical practice. Bridging anticoagulation has evolved over the years and the evidence base for current practice is deficient in many areas. Clinical trials currently being completed with conventional anticoagulants should help strengthen the evidence base for future practice. The availability of novel oral anticoagulants is a welcome addition, though their optimal management peri‐procedure is yet to be determined. Prospective multi‐centre controlled studies that can provide the evidence base for novel oral anticoagulant peri‐procedural management are required.
A multicentre matched‐pair analysis comparing robot‐assisted versus open partial nephrectomy
Authors: Ficarra Vincenzo , Minervini Andrea , Antonelli Alessandro , Bhayani Sam , Guazzoni Giorgio , Longo Nicola , Martorana Giuseppe , Morgia Giuseppe , Mottrie Alexander , Porter James , Simeone Claudio , Vittori Gianni , Zattoni Filiberto , Carini Marco
Published: November 2013

Objective

To compare the perioperative, pathological and functional outcomes in two contemporary, large series of patients in different institutions and who underwent open partial nephrectomy (OPN) or robot‐assisted PN (RAPN) for suspected renal tumours.

Patients and Methods

This was a retrospective, multicentre, international, matched‐pair analysis comparing patients who underwent RAPN or OPN for suspected renal cell carcinoma.

Data on patients who underwent OPN were extracted by an Italian observational registry collecting data from 19 different centres.

Data on patients who received RAPN were extracted from a multicentre, international database collecting cases treated in four high‐volume referral centres of robotic surgery.

The matching was in a 1:1 ratio for the surgical approach and included 200 patients in each arm.

Results

The mean warm ischaemia time was shorter in the OPN group than in the RAPN group, at a mean (sd) of 15.4 (5.9) vs 19.2 (7.3) min (P < 0.001).

Conversely, the median (interquartile range) estimated blood loss was 150 (100–300) mL in the OPN group and 100 (50–150) mL in the RAPN group (P < 0.001).

There were no differences in operating time (P = 0.18) and the intraoperative complication rate (P = 0.31) between the approaches.

Postoperative complications were recorded in 43 (21.5%) patients who underwent OPN and in 28 (14%) who received RAPN (P = 0.02). Moreover, major complications (grade 3–4) were reported in nine (4.5%) patients after OPN and in nine (4.5%) after RAPN.

Positive margins were detected in nine (5.5%) patients after OPN and in nine (5.7%) after RAPN (P = 0.98). The mean (sd) 3‐month estimated glomerular filtration rate declined by 16.6 (18.1) mL/min from the preoperative value in the OPN group and by 16.4 (22.9) mL/min in the RAPN group (P = 0.28).

Conclusion

RAPN can achieve equivalent perioperative, early oncological and functional outcomes as OPN. Moreover, RAPN is a less invasive approach, offering a lower risk of bleeding and postoperative complications than OPN.
Ages and genesis of terrace flights in the middle reaches of the Yarlung Zangbo River, Tibetan Plateau, China
Authors: Zhu Song , Wu Zhenhan , Zhao Xitao , Li Jianping , Xiao Keyan
Published: November 2013

Field investigation has shown that the middle reaches of the Yarlung Zangbo River, in Tibet (known as the Bhramaputra River in reaches downstream) has 11 terraces. The ages of these terraces were determined as follows: T11>2000 ka, T10 = 1783 ka, T9 = 1238 ka, T8 = 683 ka, T7 = 382 ka, T6 = 150 ka, T5 = 82 ka, T4 = 67 ka, T3 = 43 ka, T2 = 28 ka and T1 = 10 ka. These terraces formed during several stages of the Quaternary when the Tibetan Plateau was uplifting, recording tectonic–climatic cycles or subcycles of 1.2, 0.4, 0.1, 0.04 and 0.02 million years duration. The tectonic–climatic cycles identified by this study are correlated with red soil and palaeosol records. The preservation of the Oligocene to Early Miocene conglomeratic Dazhuka Formation, close to the present altitude of the main planation surface of the Tibetan Plateau and occurring only in the Yarlung Zangbo valley, suggests that this river has existed since at least 7 Ma. Discoveries of old and thick fluvial gravel layers extending to within 630 m of the valley floor show that the Yarlung Zangbo River was already incised by 2000 m or more below the surface of the Tibetan Plateau, that much of the incision from plateau to valley floor had been accomplished and that the plateau was already substantially uplifted prior to the Quaternary. In addition to its importance for understanding the evolution of the Tibetan Plateau, this study documents the impact of varying rates of tectonic uplift on river development.
Understanding the trauma of first‐episode psychosis
Authors: Dunkley Jane E. , Bates Glen W. , Findlay Bruce M.
Published: November 2013

Aim

This study examined the distress of first‐episode psychosis (FEP) beyond the acute episode. It focused on how people understand the experience of FEP and its negative impact and how this relates to the traumagenic phenomena.

Methods

This research was a longitudinal qualitative study including interpretative phenomenological analysis of interview data. Ten people who had experienced FEP were interviewed 3–6 months following their psychotic episode (time one) and again 3 months after their initial interview (time two). Clinicians and significant others were interviewed at time two.

Results

Interpretative phenomenological analysis of the interview data supported a conceptualization of recovery from FEP within a broad trauma framework. The traumatic nature of FEP was found to be extended beyond the acute episode and was not linked to symptoms of post‐traumatic stress disorder (PTSD) but included impact on identity, relationships and worldview.

Conclusions

The diagnosis of PTSD does not appear to capture all aspects of the distress of FEP. Traumagenic distress appears explained by incorporating a range of negative emotions, viewing the impact of FEP as ongoing rather than contained to the acute episode, and recognizes disruption of the individual's views of the self, others and the world.
Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function?
Authors: Avanzini Giuliano , Depaulis Antoine , Tassinari Alberto , de Curtis Marco
Published: November 2013

Relevant to the definition of epileptic encephalopathy (EE) is the concept that the epileptic activity itself may contribute to bad outcomes, both in terms of epilepsy and cognition, above and beyond what might be expected from the underlying pathology alone, and that these can worsen over time. The review of the clinical and experimental evidence that seizures or interictal electroencephalography (EEG) discharges themselves can induce a progression toward more severe epilepsy and a regression of brain function leads to the following conclusions:

The possibility of seizure‐dependent worsening is by no means a general one but is limited to some types of epilepsy, namely mesial temporal lobe epilepsy (MTLE) and EEs.

Clinical and experimental data concur in indicating that prolonged seizures/status epilepticus (SE) are a risky initial event that can set in motion an epileptogenic process leading to persistent, possibly drug‐refractory epilepsies.

The mechanisms for SE‐related epileptogenic process are incompletely known; they seem to involve inflammation and/or glutamatergic transmission.

The evidence of the role of recurrent individual seizures in sustaining epilepsy progression is ambiguous. The correlation between high seizure frequency and bad outcome does not necessarily demonstrate a cause–effect relationship, rather high seizure frequency and bad outcome can both depend on a particularly aggressive epileptogenic process.

The results of EE studies challenge the idea of a common seizure‐dependent mechanism for epilepsy progression/intellectual deterioration.
Epileptic encephalopathy as models of system epilepsy
Authors: Capovilla Giuseppe , Moshé Solomon L. , Wolf Peter , Avanzini Giuliano
Published: November 2013

The pathophysiology of epileptic encephalopathies has long been debated. Recently, some authors proposed the new concept of so‐called system epilepsies. This hypothesis postulates that system epilepsies are produced by the enduring propensity to generate seizures in different cerebral areas that, alone, are unable to create a specific electroclinical phenotype. This goes beyond the classical dichotomy between focal and generalized epilepsy. Epileptic encephalopathies, in general, have the ideal profile to be considered as system epilepsies, andWest syndrome andLennox‐Gastaut syndrome are two of the best examples. Apart from the conventional neurophysiologic methods for studying brain activities and the pathophysiologic mechanisms underlying epileptic syndromes, other new methods of neuroimaging support this hypothesis.
Therapeutic approach to epileptic encephalopathies
Authors: Vigevano Federico , Arzimanoglou Alexis , Plouin Perrine , Specchio Nicola
Published: November 2013

Epileptic encephalopathies (EEs) are electroclinical entities with a peculiar course of disease; seizures and electroencephalographic (EEG) epileptiform abnormalities, ictal and interictal, contribute to progressive disturbance of cerebral functions. FrequentlyEEs are drug resistant, and consequences may be catastrophic. The main goal of treatment is to stop the peculiar course of epilepsy, operating on three parameters: seizure control, reduction ofEEGabnormalities, and developmental outcome. For a correct therapeutic approach it is mandatory to have an as accurate as possible syndromic and etiologic diagnosis. Given the poor efficacy of conventional antiepileptic drugs (AEDs), the use of specific drugs forEEs, such as adrenocorticotropic hormone (ACTH) and corticosteroids or stiripentol is suggested. In some cases the choice of treatment is strictly related to the etiology: vigabatrin in tuberous sclerosis, ketogenic diet in glucose transporter type 1 (GLUT‐1) deficiency, and pyridoxine in pyridoxine deficiency. Some AEDs combinations, such as sodium valproate with lamotrigine, have also provided interesting results, for example, in Lennox‐Gastaut syndrome, although controlled studies are lacking. Finally, early surgery can be an option in children with focal structural abnormalities responsible forEEspreferably before irreversible damage on developmental outcome. Multispecialist support is recommended inEE. Management should be global from the onset, integrating not only seizure control but also all issues related to comorbidities, particularly neuropsychological and psychiatric.
Tribute to Tinbergen: Questions and How to Answer Them
Authors: Dawkins Marian Stamp
Published: November 2013

Despite the major advances that have occurred in the study of animal behaviour in the 50 years since the publication of Tinbergen's (ZeitschriftfürTierpsychologie, 20, 1963, 410) ‘Aims and Methods’ paper, the framework he outlined still remains the best way we have of guiding and organizing behavioural research. His distinction between four different types of question – adaptation, phylogeny, immediate causal mechanism and development – and his insistence on being clear on what would count as answers to each of them are still as good an introduction to the subject today as they ever were.
Beyond modules and hubs: the potential of gene coexpression networks for investigating molecular mechanisms of complex brain disorders
Authors: Gaiteri C. , Ding Y. , French B. , Tseng G. C. , Sibille E.
Published: November 2013

In a research environment dominated by reductionist approaches to brain disease mechanisms, gene network analysis provides a complementary framework in which to tackle the complex dysregulations that occur in neuropsychiatric and other neurological disorders. Gene–gene expression correlations are a common source of molecular networks because they can be extracted from high‐dimensional disease data and encapsulate the activity of multiple regulatory systems. However, the analysis of gene coexpression patterns is often treated as a mechanistic black box, in which looming ‘hub genes’ direct cellular networks, and where other features are obscured. By examining the biophysical bases of coexpression and gene regulatory changes that occur in disease, recent studies suggest it is possible to use coexpression networks as a multi‐omic screening procedure to generate novel hypotheses for disease mechanisms. Because technical processing steps can affect the outcome and interpretation of coexpression networks, we examine the assumptions and alternatives to common patterns of coexpression analysis and discuss additional topics such as acceptable datasets for coexpression analysis, the robust identification of modules, disease‐related prioritization of genes and molecular systems and network meta‐analysis. To accelerate coexpression research beyond modules and hubs, we highlight some emerging directions for coexpression network research that are especially relevant to complex brain disease, including the centrality–lethality relationship, integration with machine learning approaches and network pharmacology.
A Small‐Diameter NMR Logging Tool for Groundwater Investigations
Authors: Walsh David , Turner Peter , Grunewald Elliot , Zhang Hong , Butler James J. , Reboulet Ed , Knobbe Steve , Christy Tom , Lane John W. , Johnson Carole D. , Munday Tim , Fitzpatrick Andrew
Published: November 2013

A small‐diameter nuclear magnetic resonance (NMR) logging tool has been developed and field tested at various sites in the United States and Australia. A novel design approach has produced relatively inexpensive, small‐diameter probes that can be run in open or PVC‐cased boreholes as small as 2 inches in diameter. The complete system, including surface electronics and various downhole probes, has been successfully tested in small‐diameter monitoring wells in a range of hydrogeological settings. A variant of the probe that can be deployed by a direct‐push machine has also been developed and tested in the field. The new NMR logging tool provides reliable, direct, and high‐resolution information that is of importance for groundwater studies. Specifically, the technology provides direct measurement of total water content (total porosity in the saturated zone or moisture content in the unsaturated zone), and estimates of relative pore‐size distribution (bound vs. mobile water content) and hydraulic conductivity. The NMR measurements show good agreement with ancillary data from lithologic logs, geophysical logs, and hydrogeologic measurements, and provide valuable information for groundwater investigations.
CO2 Capture and Geologic Storage: The Possibilities
Authors: Loáiciga Hugo A.
Published: November 2013

Carbon dioxide (CO2) capture and geologic storage has been postulated as one possible method to stabilize the atmospheric concentration of CO2 by injecting and storing it in deep geologic formations. This issue paper analyzes the viability of capture and geologic storage of becoming an effective method to aid in stabilizing the atmospheric concentration of CO2. It is herein shown that such viability is contingent on overcoming major obstacles that are hydrogeological, technical, and economic in nature. Our analysis indicates that capture and geologic storage is likely to have negligible success in reducing the atmospheric buildup of CO2 in the coming decades. The magnitude of the anthropogenic emissions of CO2 indicates that a transition of the world economy away from reliance on fossil fuels might be the only path to stabilize its atmospheric concentration.
Optimising the retrieval of information on adverse drug effects
Authors: Golder Su
Published: November 2013

Pharmaceutical interventions have brought about many benefits to health, improving the population's well‐being and life expectancy. However, these interventions are not without potential harmful side‐effects and yet searching for the evidence on adverse effects is challenging. This article summarises a PhD whose main aim was to develop a better understanding of the implications of using different sources and approaches to identifying relevant data on adverse effects. The author is Su Golder, who has recently completed her PhD at the University of York and who has already published several articles on specific aspects of her research, including this journal. This article is the first in the Dissertations into Practice series to report on a PhD study, and it summarises her research in a way which emphasises the implications for practice.

AM
Juvenile‐like (inflammatory/hyperplastic) mucosal polyps of the gastrointestinal tract in neurofibromatosis type 1
Authors: Agaimy Abbas , Schaefer Inga‐Marie , Kotzina Leopoldina , Knolle Jürgen , Baumann Irith , Ströbel Philipp , Vieth Michael
Published: November 2013

Aims

Diffuse neurofibromatosis/ganglioneuromatosis, solitary/plexiform neurofibroma, periampullary carcinoids and gastrointestinal stromal tumour (GIST) are the main gastrointestinal manifestations of neurofibromatosis type 1 (NF‐1, von Recklinghausen disease). Inflammatory (juvenile‐like) polyps have not been recognised to date as specific gastrointestinal (GI) manifestations ofNF‐1.

Methods and results

We describe four males aged 23–65 years withNF‐1 and inflammatory (juvenile‐like) gastrointestinal polyps, and review the literature for similar cases. Two patients had single polyps (sigmoid colon and antrum, respectively), one had two polyps (left colon), and one had three polyps (distal oesophagus and colon). Histological appearances were variable, ranging from juvenile‐like to granulation tissue‐rich, predominantly inflammatory and hyperplastic. Three lesions showed obliterative vasculopathic changes. None had neurofibromatous or ganglioneuromatous polyps. A review of the literature disclosed 11 similar cases. Most patients presented with severe gastrointestinal symptoms and/or anaemia.

Conclusions

NF‐1‐associated inflammatory polyps probably represent specificGImanifestations of this disorder, and should be considered, particularly in patients withGIsymptoms. They should be distinguished from inflammatory fibroid polyps and from juvenile‐like changes associated with ganglioneuroma/ganglioneuromatosis and neurofibroma/neurofibromatosis. Their aetiology remains obscure, but different mechanisms, includingNF‐1inactivation,NF‐1‐associated vasculopathy, and localised mucosal prolapse/damage caused by motility disorders, might be involved.
The effects of a smoking cessation programme on health‐promoting lifestyles and smoking cessation in smokers who had undergone percutaneous coronary intervention
Authors: Park Ai Hee , Lee Suk Jeong , Oh Seung Jin
Published: November 2013

Smoking is a major risk factor for not only the occurrence of myocardial ischaemia but also recurrences of vascular stenosis. This study aimed to evaluate health‐promoting lifestyles and abstinence rate after a smoking cessation programme. Sixty‐two smokers who had undergone percutaneous coronary intervention were randomly assigned to either the experimental or control group. The experimental group (n = 30) received 10 phone counselling sessions and 21 short message service messages for abstinence and coronary disease prevention, whereas the control group (n = 32) received only the standard education. After the intervention, 14 members of the experimental group had switched to a non‐smoking status, confirmed biochemically; moreover, their physical activity and stress management scores increased significantly. However, self‐efficacy of smoking cessation was not reflected in the cotinine levels. Thus, it is necessary not only to increase self‐efficacy but also to determine the factors that affect the success of smoking cessation so that they can be included in the intervention. Our results suggest that phone counselling and short message service messaging might be important tools for the realization of smoking cessation and lifestyle changes among patients who have undergone percutaneous coronary intervention.
T cell receptor (TCR) V gene usage in patients with systemic necrotizing vasculitis
Authors: GISCOMBE R , GRUNEWALD J , NITYANAND S , LEFVERT A K
Published: November 2013

Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN) are systemic necrotizing vasculitides of unknown etiology. These disorders run a fatal course if untreated. T lymphocytes are implicated in the pathogenesis of WG, since they have been found to infiltrate affected organs, and sIL-2R correlates with disease activity. To elucidate further the role of T cells in necrotizing vasculitis, we have used a panel of 12 TCR V-specific MoAbs to investigate the number of cells expressing certain Vα and Vβ gene segments in the CD4+ and CD8+ subsets of altogether 11 patients with WG or PAN. In the group of patients, we found abnormal expansions of T cells using particular TCR Vα or β gene products. These T cell expansions were more numerous, of a dramatically higher magnitude, and frequently more often found in the CD4 subset, compared with T cell expansions identified in healthy individuals. In long-term studies of the T cell expansions for up to 18 months, a heterogeneous pattern was revealed, with no obvious correlation to clinical features such as disease activity or treatment. Studies of TCR V gene usage in this group of patients may help in understanding the pathogenesis of necrotizing vasculitis, and in the identification of unknown antigens, and may open the possibility to a highly selective immunotherapy by targeting disease-mediating T cells.
Mechanochemical Treatment of Amorphous Silica Powder for Glasses Without Firing
Authors: Hien Tran Thi Thu , Shirai Takashi , Fuji Masayoshi
Published: November 2013

An amorphous silica powder was subjected to mechanical and hydrothermal treatment. Silanol surface groups, which play an active role in the chemical modification of silica, were produced by these two treatments. The surface activity of raw and treated powders was measured as the amount of dissolved Si4+ ion in ammonia (NH3) and potassium hydroxide (KOH) solutions at different concentrations. KOH solution was more effective than NH3 solution in activating the surface of the silica powder. Nonfiring glass was successfully fabricated using mechanochemically treated silica powder. Glass properties such as morphology and transparency were analyzed using scanning electron microscope and UV–vis–NIR techniques. Possible reaction mechanisms of powder surface activation occurring during hydrothermal and condensation processes are also discussed.
Thermodynamic Properties of LaCrO4, La2CrO6, and La2Cr3O12, and Subsolidus Phase Relations in the System Lanthanum–Chromium–Oxygen
Authors: Kallarackel Thomas Jacob , Gupta Sapna , Singh Prabhakar
Published: November 2013

In the system La–Cr–O, there are three ternary oxides (LaCrO4, La2Cr3O12, and La2CrO6) that contain Cr in higher valence states (V or VI). On heating, LaCrO4 decomposes to LaCrO3, La2Cr3O12 to a mixture of LaCrO4 and Cr2O3, and La2CrO6 to LaCrO3 and La2O3 with loss of oxygen. The oxygen potentials corresponding to these decomposition reactions are determined as a function of temperature using solid‐state cells incorporating yttria‐stabilized zirconia as the electrolyte. Measurements are made from 840 K to the decomposition temperature of the ternary oxides in pure oxygen. The standard Gibbs energies of formation of the three ternary oxides are derived from the reversible electromotive force (EMF) of the three cells. The standard enthalpy of formation and standard entropy of the three ternary oxides at 298.15 K are estimated. Subsolidus phase relations in the system La–Cr–O are computed from thermodynamic data and displayed as isothermal sections at several temperature intervals. The decomposition temperatures in air are 880 (±3) K for La2Cr3O12, 936 (±3) K for LaCrO4, and 1056 (±4) K for La2CrO6.
Theoretical Prediction and Experimental Investigation on the Thermal and Mechanical Properties of Bulk β‐Yb2Si2O7
Authors: Zhou Yan‐Chun , Zhao Cen , Wang Feng , Sun Yin‐Jie , Zheng Li‐Ya , Wang Xiao‐Hui
Published: November 2013

The thermal and mechanical properties of β‐Yb2Si2O7 were investigated using a combination of first‐principles calculations and experimental investigations. Theoretically, anisotropic chemical bonding and elastic properties, weak interatomic (010) and (001) planes in the crystal structure, damage tolerance, and low thermal conductivity are predicted. Experimentally, preferred orientation, superior mechanical properties, and damage tolerant behavior for hot‐pressed bulk β‐Yb2Si2O7 are approved. Slipping along the weakly bonded {010}, {001}, or {100} planes, grain delamination, buckling, and kinking of nanolaminated grains are identified as main mechanisms for damage tolerance. The anisotropic linear thermal expansion coefficients (CTEs) are: αa = (3.57 ± 0.18) × 10−6 K−1, αb = (2.49 ± 0.14) × 106 K−1, and αc = (1.48 ± 0.22) × 10−6 K−1 (673–1273 K). A low thermal conductivity of ~2.1 W (m·K)−1 at 1273 K has been confirmed. The unique combination of these properties endow it a potential candidate for thermal barrier coating (TBC)/environmental barrier coating of silicon‐based ceramics.
Correlations Between Microstructure and Mechanical Properties of Air Plasma‐Sprayed Thermal Barrier Coatings Exposed to a High Temperature
Authors: Osorio Julián D. , Maya Deiby , Barrios Augusto C. , Lopera Adrián , Jiménez Freddy , Meza Juan M. , Hernández‐Ortiz Juan P. , Toro Alejandro
Published: November 2013

An indentation method is used to study the variations in Young's modulus, hardness and fracture toughness of air plasma‐sprayed thermal barrier coatings at a high temperature. The coatings were exposed to 1100°C during 1700 h. A sudden increase in Young's modulus for the first 600 h was observed, while the hardness increased after 800 h as a consequence of sintering. Conversely, there was a reduction of 25% in fracture toughness after 1700 h, evidencing the thermal barrier coating degradation. The evolution of these mechanical properties was correlated with microstructural changes. After 1700 h, the thermally grown oxide thickness reached 6.8 μm, the volumetric percentage of porosity was reduced from 6.8% to 4.7% and the amount of monoclinic phase increased to 23.4 wt%. These characteristics are closely related to the stress distribution in the top coat, which promotes cracks nucleation and propagation, compromising the coating durability.
Role of diet and nutritional management in non‐alcoholic fatty liver disease
Authors: Fan Jian‐Gao , Cao Hai‐Xia
Published: November 2013

Non‐alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non‐alcoholic steatohepatitis, which causes an increased risk of cirrhosis, type 2 diabetes, and cardiovascular complications. With the worldwide growing incidence of obesity, sedentary lifestyle, and unhealthy dietary pattern, NAFLD has currently been recognized as a major health burden. Dietary patterns and nutrients are the important contributors to the development, progression, and treatment of NAFLD and associated metabolic comorbidities. Generally, hypercaloric diet, especially rich in trans/saturated fat and cholesterol, and fructose‐sweetened beverages seem to increase visceral adiposity and stimulate hepatic lipid accumulation and progression into non‐alcoholic steatohepatitis, whereas reducing caloric intake, increasing soy protein and whey consumption, and supplement of monounsaturated fatty acids, omega‐3 fatty acids, and probiotics have preventive and therapeutic effects. In addition, choline, fiber, coffee, green tea, and light alcohol drinking might be protective factors for NAFLD. Based on available data, at least 3–5% of weight loss, achieved by hypocaloric diet alone or in conjunction with exercise and behavioral modification, generally reduces hepatic steatosis, and up to 10% weight loss may be needed to improve hepatic necroinflammation. A sustained adherence to diet rather than the actual diet type is a major predictor of successful weight loss. Moreover, a healthy diet has benefits beyond weight reduction on NAFLD patients whether obese or of normal weight. Therefore, nutrition serves as a major route of prevention and treatment of NAFLD, and patients with NAFLD should have an individualized diet recommendation.
Non‐nutritional effects of food: An underutilized and understudied therapeutic tool in chronic gastrointestinal diseases
Authors: Gibson Peter R , Muir Jane G
Published: November 2013

The use of diet has traditionally been used to improve the nutrition of patients. However, diet also can be utilized to modify disease processes and manage symptoms independently of its nutritional role. There are few chronic gastrointestinal conditions where dietary modification is utilized therapeutically and backed by a high degree of evidence. This is not due to a lack of ideas but is more likely to lie in the difficulties associated with translating those ideas into evidence‐based practice. Long lead‐in times and low incidence hinders interventional studies of prevention for many conditions. The design and execution of dietary clinical trials is challenging and funding them even more so. The knowledge base of doctors in nutrition and food composition is often poor, and attitudes toward the success of and adherence to dietary therapies create additional problems. However, ideas can be successfully translated into evidence‐based practice, as exemplified but the low fermentable, oligo‐, di‐, and mono‐saccharides and polyols (FODMAP) (poorly‐absorbed short‐chain carbohydrates) diet for patients with functional bowel symptoms. Showing efficacy is, however, insufficient for non‐nutritional dietary manipulations. Adverse effects, such as nutritional adequacy of the diet and effect on pathogenesis of other diseases, must also be carefully addressed. The physiological principles upon which the diet is based should be matched to the physiology associated with the condition being targeted, as it can be hazardous to extrapolate findings in healthy persons. There is a need for greater attention to the evaluation of dietary therapies for many chronic gastrointestinal disorders.
Distribution of interferon lambda‐3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: Analysis from the PREDICT and CHARIOT studies
Authors: Roberts Stuart K , Mitchell Joanne , Leung Reynold , Booth David , Bollipo Steven , Ostapowicz George , Sloss Andrew , McCaughan Geoffrey W , Dore Gregory J , Thompson Alexander , Crawford Darrell HG , Sievert William , Weltman Martin , Cheng Wendy , George Jacob ,   Australian Liver Association Clinical Research Network
Published: November 2013

Background and Aims

The aim of this study was to examine the distribution of interferon lambda‐3 (IFN‐λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN‐λ3 genotype frequency among the different ethnic populations.

Methods

This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN‐λ3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay.

Results

Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high‐dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN‐λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN‐λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN‐λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001).

Conclusions

The distribution of IFN‐λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self‐reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans.
Role of glycine N‐methyltransferase in experimental ulcerative colitis
Authors: Chou Wen‐Yueh , Zhao Jin‐Feng , Chen Yi‐Ming Arthur , Lee Kuan‐I , Su Kuo‐Hui , Shyue Song‐Kun , Lee Tzong‐Shyuan
Published: November 2013

Background and Aim

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with unclear etiology and mechanism(s). Glycine N‐methyltransferase (GNMT) plays a central role in inflammatory diseases such as hepatitis and atherosclerosis. However, little is known about the impact of GNMT and the involved mechanism in the pathogenesis of IBD. In the current study, we investigated the role of GNMT in the mouse model of dextran sulfate sodium (DSS)‐induced colitis.

Methods

Protein expression was determined by Western blotting or immunohistochemistry. Histopathology was examined by hematoxylin and eosin staining. Levels of pro‐inflammatory cytokines were evaluated by ELISA kits.

Results

GNMT was expressed in the epithelium of the colon under normal conditions, and with DSS treatment, its expression was predominant in infiltrated leukocytes of lesions. Mice with genetic deletion of GNMT (GNMT−/−) showed increased susceptibility to DSS induction of colitis, as revealed by the progression of colitis. Additionally, severe colonic inflammation, including increased crypt loss, leukocyte infiltration, and hemorrhage, was greater with DSS treatment in GNMT−/− than wild‐type mice. Furthermore, the expression of adhesion molecule and inflammatory mediators in the colon was significantly higher with DSS treatment in GNMT−/− than wild‐type mice. Moreover, loss of GNMT decreased cell apoptosis in colitis lesions with DSS treatment.

Conclusions

Collectively, our findings suggest that GNMT may be a crucial molecule in the pathogenesis of DSS‐induced colitis. This finding may provide new information for a potential therapeutic target in treating IBD.
Relationship between serum circulating insulin‐like growth factor‐1 and liver fat in the United States
Authors: Runchey Shauna S , Boyko Edward J , Ioannou George N , Utzschneider Kristina M
Published: November 2013

Background and Aim

Nonalcoholic fatty liver disease (NAFLD), circulating insulin‐like growth factor‐1 (IGF‐1), and IGF‐1/IGF‐binding protein‐3 (IGFBP‐3) concentrations are associated with adiposity and insulin resistance. We aimed to determine whether serum IGF‐1, IGFBP‐3, and IGF‐1/IGFBP‐3 are associated with presence or severity of NAFLD independent of potential confounding.

Methods

We performed a cross‐sectional analysis of data from the Third National Health and Nutrition Examination Survey, 1988–1994, a representative sample of the United States adult population. Among participants who had a fasting blood draw and ultrasound examination, we excluded those with missing data, viral hepatitis, iron overload, excessive alcohol intake, pregnancy, or taking glucose‐lowering therapy, yielding 4172 adults for this analysis.

Results

In logistic regression analyses adjusted for age, gender, and race/ethnicity, higher IGF‐1 and IGF‐1/IGFBP‐3 quartiles were associated with lower likelihood of NAFLD and lower grade steatosis. These associations became non‐significant when further adjusted for adiposity (body mass index, waist circumference) with the exception of the association between IGF‐1/IGFBP‐3 and severity of NAFLD which remained significant after adjustment for homeostasis model assessment for insulin resistance (HOMA‐IR) (odds ratio [95% CI]: Q3: 0.71 [0.53–0.96], Q4: 0.62 [0.43–0.89]) and adiposity (Q4: 0.67 [0.47–0.96]). Full adjustment (age, gender, race/ethnicity, adiposity, HOMA‐IR, A1C%) further attenuated associations between IGF‐1 or IGF‐1/IGFBP‐3 and liver fat such that they were no longer significant.

Conclusions

Adiposity explains much of the observed association between IGF‐1 or IGF‐1/IGFBP‐3 and liver fat. These findings do not support a direct role for the growth hormone‐IGF‐1/IGFBP‐3 axis in the pathophysiology of NAFLD.
P2X7 receptor–Pannexin1 interaction mediates stress‐induced interleukin‐1 beta expression in human periodontal ligament cells
Authors: Kanjanamekanant K. , Luckprom P. , Pavasant P.
Published: November 2013

Background and Objective

Pannexin 1 (Panx1) has been found to form nonjunctional hemichannels. It is also proposed to combine with the P2X7 receptor, forming a complex involved in adenosine triphosphate (ATP)‐induced interleukin‐1beta (IL‐1β) release in macrophages. Previously, we reported that mechanical stress induced IL‐1β expression via the ATP/P2X7 receptor‐dependent pathway in human periodontal ligament (HPDL) cells and that ATP was released through the connexin 43 (Cx43) hemichannel. In the present work, we examined the role of Panx1 in stress‐induced IL‐1β induction in HPDL cells.

Material and Methods

Cultured HPDL cells were treated with compressive loading or ATP to stimulate IL‐1β expression. Inhibitors, antagonists and the small interfering RNA technique were used to investigate the involvement of Panx1 in IL‐1β induction. Co‐immunoprecipitation (Co‐IP) and immunostaining were used to determine the association of Panx1 with the P2X7 receptor. The IL‐1β release mechanism was analyzed using inhibitors.

Results

Blocking Panx1 significantly decreased ATP release, as well as IL‐1β up‐regulation, upon stimulation with stress or ATP. Co‐IP revealed the association of Panx1 and the P2X7 receptor in HPDL cells, which was increased in response to mechanical loading. Pretreatment with vesicular trafficking inhibitors significantly reduced the amount of IL‐1β released from stimulated cells, suggesting that IL‐1β might be released through vesicles.

Conclusion

We clearly illustrated the contribution of Panx1 in ATP release, as well as in IL‐1β induction in HPDL cells. The association of Panx1 and the P2X7 receptor might be required for IL‐1β induction, and their possible novel role in IL‐1β vesicular release was indicated.
Hepatitis C virus core antigen testing in liver and kidney transplant recipients
Authors: Heidrich B. , Pischke S. , Helfritz F. A. , Mederacke I. , Kirschner J. , Schneider J. , Raupach R. , Jäckel E. , Barg‐Hock H. , Lehner F. , Klempnauer J. , von Hahn T. , Cornberg M. , Manns M. P. , Ciesek S. , Wedemeyer H.
Published: November 2013

HCV RNA levels correlate with the long‐term outcome of hepatitis C in liver transplant recipients. Nucleic acid testing (NAT) is usually used to confirm HCV reinfection and to examine viral loads after liver transplantation. HCV core antigen (HCVcoreAg) testing could be an alternative to NAT with some potential advantages including very low intra‐ and interassay variabilities and lower costs. The performance of HCVcoreAg testing in organ transplant recipients is unknown. We prospectively studied 1011 sera for HCV RNA and HCVcoreAg in a routine real‐world setting including 222 samples obtained from patients after liver or kidney transplantation. HCV RNA and HCVcoreAg test results showed a consistency of 98% with a very good correlation in transplanted patients (r > 0.85). The correlation between HCV RNA and HCVcoreAg was higher in sera with high viral loads and in samples from patients with low biochemical disease. Patients treated with tacrolimus showed a better correlation between both parameters than individuals receiving cyclosporine A. HCV RNA/HCVcoreAg ratios did not differ between transplanted and nontransplanted patients, and HCV RNA and HCVcoreAg kinetics were almost identical during the first days after liver transplantation. HCVcoreAg testing can be used to monitor HCV viral loads in patients after organ transplantation. However, the assay is not recommended to monitor antiviral therapies.
Sphericity Index and E‐Point‐to‐Septal‐Separation (EPSS) to Diagnose Dilated Cardiomyopathy in Doberman Pinschers
Authors: Holler P.J. , Wess G.
Published: November 2013

Background

E‐point‐to‐septal‐separation (EPSS) and the sphericity index (SI) are echocardiographic parameters that are recommended in theESVC‐DCMguidelines. However,SIcutoff values to diagnose dilated cardiomyopathy (DCM) have never been evaluated.

Objectives

To establish reference ranges, calculate cutoff values, and assess the clinical value ofSIandEPSSto diagnoseDCMin Doberman Pinschers.

Animals

One hundred seventy‐nine client‐owned Doberman Pinschers.

Methods

Three groups were formed in this prospective longitudinal study according to established Holter and echocardiographic criteria using the Simpson method of disk (SMOD): control group (97 dogs),DCMwith echocardiographic changes (75 dogs) and “last normal” group (n = 7), which included dogs that developedDCMwithin 1.5 years, but were still normal at this time point. In a substudy, dogs with earlyDCMbased uponSMODvalues above the reference range but still normal M‐Mode measurements were selected, to evaluate ifEPSSorSIwere abnormal using the established cutoff values.

Results

ROC‐curve analysis determined <1.65 for theSI(sensitivity 86.8%; specificity 87.6%) and >6.5 mm forEPSS(sensitivity 100%; specificity 99.0%) as optimal cutoff values to diagnoseDCM. Both parameters were significantly different between the control group and theDCMgroup (P < 0.001), but were not abnormal in the “last normal” group. In the substudy,EPSSwas abnormal in 13/13 dogs andSIin 2/13 dogs.

Conclusions and Clinical Importance

E‐point‐to‐septal‐separation is a valuable additional parameter for the diagnosis ofDCM, which can enhance diagnostic capabilities of M‐Mode and which performs similar as well asSMOD.