bluuebunny/crossref_metadata_2025 huggingface dataset:
A theory of anisotropic healing and damage mechanics of materials
Authors: Voyiadjis George Z. , Shojaei Amir , Li Guoqiang , Kattan Peter I.
Published: August 2011

Self-healing smart materials have emerged into the research arena and have been deployed in industrial and biomedical applications, in which the modelling techniques and predicting schemes are crucial for designers to optimize these smart materials. In practice, plastic deformation is coupled with damage and healing in these systems, which necessitates a coupled formulation for characterization. The thermodynamics of inelastic deformation, damage and healing processes are incorporated here to establish the coupled constitutive equations for healing materials. This thermodynamic consistent formulation provides the designers with the ability to predict the irregular inelastic deformation of glassy polymers and damage and healing patterns for a highly anisotropic self-healing system. Moreover, the lack of a physically consistent method to measure and calibrate the healing process in the literature is addressed here. Within the continuum damage mechanics (CDM) framework, the physics of damage and healing processes is used to introduce the healing effect into the CDM concept and a set of two new anisotropic damage–healing variables are derived. These novel damage–healing variables together with the proposed thermodynamic consistent coupled theory constitute a well-structured method for accurately predicting the degradation and healing mechanisms in material systems. The inelastic and damage response for a shape memory polymer-based self-healing system is captured herein. While the healing experimental results are limited in the literature, the proposed theory provides the mathematical competency to capture the most nonlinear responses.
Gene Set Analysis and Network Analysis for Genome-Wide Association Studies
Authors: Pedroso Inti , Breen Gerome
Published: August 2011

INTRODUCTION

The application of high-throughput genotyping in humans has yielded numerous insights into the genetic basis of human phenotypes and an unprecedented amount of genetic data. Genome-wide association studies (GWAS) have increased in number in recent years, but the variants that have been found have generally explained only a tiny proportion of the estimated genetic contribution to phenotypic variation. This article summarizes the progress made in the development of gene set analysis (GSA) and network analysis for GWAS was a way to identify the underlying molecular processes of human phenotypes. It also highlights some promising findings and indicates future directions that may greatly enhance the analysis and interpretation of GWAS.
Urinary concentrations of 15‐epimer of lipoxin A4 are lower in patients with aspirin‐intolerant compared with aspirin‐tolerant asthma
Authors: Yamaguchi H. , Higashi N. , Mita H. , Ono E. , Komase Y. , Nakagawa T. , Miyazawa T. , Akiyama K. , Taniguchi M.
Published: August 2011

Background

Although an abnormality in arachidonic acid metabolism may be responsible for aspirin‐intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A4 (LXA4) and the 15‐epimer of LXA4 (15‐epi‐LXA4) in relation to asthma severity in AIA subjects.

Objective

The purpose of this study is to estimate urinary LXA4 and the 15‐epimer concentrations to investigate lipoxins in AIA.

Methods

In this study, we examined AIA, aspirin‐tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non‐severe asthma subgroups. Urinary LXA4, 15‐epi‐LXA4 and leukotriene E4 (LTE4) were quantified using enzyme immunoassay after separating these compounds using high‐performance liquid chromatography.

Results

The urinary LXA4 concentration was significantly lower than the 15‐epi‐LXA4 concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15‐epi‐LXA4 (P < 0.01) and higher urinary LTE4 concentrations (P < 0.05) than the ATA group. Comparison of 15‐epi‐LXA4 concentrations between the severe asthmatic and non‐severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15‐epi‐LXA4 concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE4 to 15‐epi‐LXA4 was superior to 15‐epi‐LXA4 concentration and LTE4 concentration as a predictive factor for aspirin intolerance.

Conclusions and Clinical Relevance

We have demonstrated for the first time that urinary 15‐epi‐LXA4 concentration is significantly higher than LXA4 concentration in both the AIA and ATA groups. 15‐Epi‐LXA4 concentration was significantly lower in the AIA group with an increased urinary LTE4 concentration than in the ATA group. An imbalance between proinflammatory cysteinyl‐leukotrienes and anti‐inflammatory 15‐epi‐LXA4 may be involved in AIA pathogenesis.
Consistent flowering response to global warming by European plants introduced into North America
Authors: Hulme Philip E.
Published: August 2011

1. The reliability of species distribution models (SDM) to predict the probable response of alien plants to climate change rests on the assumption that plant performance in relation to temperature in the introduced range will be similar to that observed in the native range. Yet, alien plants may exhibit enhanced performance or different environment‐distribution relationships following their introduction into a new area. Empirical data are therefore essential to test whether the responsiveness of species to climate is equivalent in the native and introduced ranges.

2. This study tests the assumption that phenological responses of plants to temperature are similar in both their native and introduced range. First flowering date (FFD) is widely used to assess the responsiveness of plants to recent warming arising from global change. For 19 species native to Europe, FFD observed in both the UK and USA between 1970 and 2000 was examined in relation to interannual variation in local temperatures. General trends, variability and responsiveness of FFD to warming were examined for consistency in the contrasting climate of Oxfordshire and Washington DC.

3. Mean FFD in Oxfordshire was a powerful predictor of the same variable in Washington DC, although summer flowering plants in Oxfordshire tended to flower earlier in the season in Washington DC. FFD varied considerably over 30 years, but across all species, the range in FFD revealed a similar trend in both regions with larger ranges observed for earlier flowering species.

4. Comparable trends were found between Oxfordshire and Washington DC in the degree to which flowering advanced or regressed per unit temperature increase. In response to warming, the majority of species flowered earlier in both countries and the degree to which FFD responded to increasing temperature was greatest for species flowering earlier in the year.

5. These equivalent phenological responses to temperature across continents imply prediction of the performance of alien plants under climate change may be derived from a species’ behaviour in its native range. While these findings support the use of SDM, they also indicate that these models could be significantly improved through the integration of phenological relationships parameterized from data in the native range.
Prevalence of molar–incisor hypomineralisation observed using transillumination in a group of children from Barcelona (Spain)
Authors: MARTÍNEZ GÓMEZ TERESITA PATRICIA , GUINOT JIMENO FRANCISCO , BELLET DALMAU LUIS J. , GINER TARRIDA LUIS
Published: August 2011

International Journal of Paediatric Dentistry 2012; 22: 100–109

Objectives.  The objectives were to investigate the prevalence of the condition, by using transillumination, in a group of children. Analysed the prevalence with regard to gender, jaw affected, and the teeth that exhibited dysplasia most commonly.

Methods.  A sample of 550 children aged 6 to 14 years was selected at the Department of Paediatric Dentistry at the Universitat Internacional de Catalunya, but among those selected only 505 children were eligible for inclusion in the study. The gender and age of the child, number of permanent teeth, number of teeth affected by MIH and their position were registered.

Results.  Ninety patients (17.85%) had MIH. Of these, 45 were girls (50%) and 45 were boys (50%). A total of 8062 permanent teeth were observed. Of these, 344 (4.2%) were affected by MIH. Of the teeth affected, 198 (57.7%) were located in the maxilla and 146 (42.4%) in the mandible. This result was statistically significant (P = 0.003).

Conclusions.  The population studied showed a prevalence of MIH of 17.8%. The presence of the defect did not differ according to sex in this population. Defects were more common among teeth in the maxilla.
Functional traits shape ontogenetic growth trajectories of rain forest tree species
Authors: Hérault Bruno , Bachelot Bénédicte , Poorter Lourens , Rossi Vivien , Bongers Frans , Chave Jérôme , Paine C. E. Timothy , Wagner Fabien , Baraloto Christopher
Published: August 2011

1. Functional traits are posited to explain interspecific differences in performance, but these relationships are difficult to describe for long‐lived organisms such as trees, which exhibit strong ontogenetic changes in demographic rates. Here, we use a size‐dependent model of tree growth to test the extent to which of 17 functional traits related to leaf and stem economics, adult stature and seed size predict the ontogenetic trajectory of tree growth.

2. We used a Bayesian modelling framework to parameterize and contrast three size‐dependent diameter growth models using 16 years of census data from 5524 individuals of 50 rain forest tree species: a size‐dependent model, a size‐dependent model with species‐specific parameters and a size‐dependent model based on functional traits.

3. Most species showed clear hump‐shaped ontogenetic growth trajectories and, across species, maximum growth rate varied nearly tenfold, from 0.58 to 5.51 mm year−1. Most species attained their maximum growth at 60% of their maximum size, whereas the magnitude of ontogenetic changes in growth rate varied widely among species.

4. The Trait‐Model provided the best compromise between explained variance and model parsimony and needed considerably fewer parameters than the model with species terms.

5. Stem economics and adult stature largely explained interspecific differences in growth strategy. Maximum absolute diameter growth rates increased with increasing adult stature and leaf δ13C and decreased with increasing wood density. Species with light wood had the greatest potential to modulate their growth, resulting in hump‐shaped ontogenetic growth curves. Seed size and leaf economics, generally thought to be of paramount importance for plant performance, had no significant relationships with the growth parameters.

6. Synthesis. Our modelling approach offers a promising way to link demographic parameters to their functional determinants and hence to predict growth trajectories in species‐rich communities with little parameter inflation, bridging the gap between functional ecology and population demography.
Effects of increased payment for ventilation tube insertion on decision making for paediatric otitis media with effusion
Authors: Wang Mao‐Che , Huang Chung‐Kai , Wang Ying‐Piao , Chien Ching‐Wen
Published: August 2011

Objective  The National Health Insurance (NHI) in Taiwan raised the physician fee for myringotomy with ventilation tube insertion (VTI) from $61.5 to $117.6 in July 2004. This study aimed to evaluate if the increased payment affected the decision making of physicians.

Methods  This study is a retrospective analysis by using NHI databank in Taiwan. All children less than 12 years old who underwent VTI from 1 July 2003 to 30 June 2006 were included. Waiting time and case numbers before and after the increased VTI payment were compared. The waiting time between public and private hospitals was also examined.

Results  From the 7408 cases evaluated, there was no difference in waiting time before and after the raise of VTI payment, and no difference within each year group. The case number of VTI increased significantly after the increase in VTI payment (P < 0.05). The waiting time of VTI performed in private hospitals was shorter than that in public hospitals (P = 0.0001).

Conclusion  The waiting time of VTI for children with otitis media with effusion (OME) has not been shortened after the increase in VTI payment. Waiting time in private hospitals is shorter than that in public hospitals. Increased payment for VTI has no effect on the physicians' decision making regarding to waiting time for children with OME in Taiwan.
Dietetic practice in refeeding syndrome
Authors: Wagstaff G.
Published: August 2011

Background:  The physiology and consequences of refeeding syndrome have long been recognised, although its management continues to be debated, despite the recommendations made by The National Institute for Health and Clinical Excellence (NICE) in their guideline ‘Nutrition Support in Adults’ (2006). The present study aims to assess current dietetic opinion and practice in this area, as well as whether the NICE recommendations have been adopted.

Methods:  An anonymous, self‐completed Internet survey was designed investigating current practice and opinions on the NICE (2006) guidance on this subject. A link to the questionnaire was distributed with a covering letter via e‐mail to the heads of department of National Health Service Trusts in the London region, UK, requesting that it be disseminated to all dietitians working with adults. After the closing date, all responses were collated and analysed.

Results:  The survey elicited a 30.8% response rate. Some 89.8% of respondents have read the NICE guidance on Nutrition Support in Adults (2006) and 66.9% have changed their practice regarding refeeding syndrome management as a result. Sixty‐two percent do not wait for biochemistry to normalise before commencing nutrition. Ninety‐two percent of respondents completed the mini case studies indicating that current practice is inconsistent among dietitians. Neither NICE criteria for recognising patients at risk of refeeding, nor the recommended starting rates are universally followed. Seventy‐five percent continue to supplement electrolytes reactively.

Conclusions:  Although limited by a small sample size, the findings of the present study suggest that dietetic practice regarding refeeding syndrome management remains inconsistent with the recommendations made by NICE, although some aspects have been adopted.
Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population
Authors: Handberg A. , Højlund K. , Gastaldelli A. , Flyvbjerg A. , Dekker J. M. , Petrie J. , Piatti P. , Beck‐Nielsen H. ,   the RISC Investigators
Published: August 2011

Abstract.  Handberg A, Højlund K, Gastaldelli A, Flyvbjerg A, Dekker JM, Petrie J, Piatti P, Beck‐Nielsen H (Aarhus Hospital and Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark; Odense University Hospital, Odense, Denmark; Institute of Clinical Physiology, CNR Pisa, Pisa, Italy; Aarhus University Hospital, Aarhus, Denmark; Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; BHF Glasgow Cardiovascular Research Centre, Glasgow, UK; and San Raffaele Institute, Milan, Italy). Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med 2012; 271: 294–304.

Objectives.  Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid atherosclerosis in nondiabetic subjects.

Methods.  In 1296 healthy subjects without diabetes or hypertension recruited from 19 centres in 14 European countries (RISC study), we determined the levels of sCD36, adiponectin, lipids and liver enzymes, insulin sensitivity (M/I) by euglycaemic–hyperinsulinaemic clamp, carotid atherosclerosis as intima–media thickness (IMT) and two estimates of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%).

Results.  IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose regulation, insulin and triglycerides increased across sCD36 quartiles (Q2–Q4), whereas adiponectin and M/I decreased (P ≤ 0.01). sCD36 was lower in women than in men (P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects with sCD36 within the log‐normal distribution (log‐normal population, n = 1029), sCD36 was increased in subjects with impaired glucose regulation (P = 0.045), metabolic syndrome (P = 0.006) or increased likelihood of fatty liver (P < 0.001). sCD36 correlated significantly with insulin, triglycerides, M/I and FLI (P < 0.05) after adjustment for study centre, gender, age, glucose tolerance status, smoking habits and alcohol consumption. In the log‐normal population, these relationships were stronger than in the total study population and, additionally, sCD36 was significantly associated with LF% and IMT (P < 0.05).

Conclusions.  In this cross‐sectional study of nondiabetic subjects, sCD36 was significantly associated with indices of insulin resistance, carotid atherosclerosis and fatty liver. Prospective studies are needed to further evaluate the role of sCD36 in the inter‐relationship between atherosclerosis, fatty liver and insulin resistance.
Predictors of the depressive symptomatology of the family caregivers of Chinese stroke patients in Hong Kong
Authors: LAU C. G. , TANG W. K. , WONG K. S. , MOK V. , UNGVARI G. S.
Published: August 2011

Accessible summary

No previous Hong Kong study has explored the relationship between stroke survivors and their carers' depressive symptoms.

The severity of Chinese stroke patients' depressive symptoms, their caregivers' perceptions of their own health, and the adversity of recent life events are the crucial factors associated with caregivers' depressive symptoms.

Caregivers' depressive symptoms are correlated with those of stroke survivors, although the causal connection and its direction could not be established.

Teaching effective stress management skills to caregivers and care recipients could reduce emotional stress and related depressive symptoms. Doing so would, in turn, lessen caregivers' physical health problems, resulting in better quality of life for both the providers and recipients of care, and thus a better caregiving outcome. Educational programmes for stroke caregivers and stroke survivors should be made available in the community.

The aim of this cross‐sectional study was to determine the socio‐demographic and clinical factors associated with depressive symptoms in the family caregivers of Hong Kong Chinese stroke patients. One hundred and twenty‐three patients at a stroke clinic and their family caregivers formed the study sample. The depressive symptoms of both the patients and their family caregivers were rated with the Chinese version of the 15‐item Geriatric Depression Scale (GDS). Participants' socio‐demographic data and clinical characteristics served as the independent variables in relation to the caregivers' GDS scores. Patients' and caregivers' somatic and psychological conditions were measured with 10 scales. In univariate analysis, caregivers' GDS scores were significantly correlated with certain of their characteristics [Modified Life Event Scale (MLES), Cumulative Illness Rating Scale (CIRS) and Lubben Social Network Scale (LSNS) scores, sex and being a housewife] and those of the patients (GDS score and being a housewife). Multiple regression analysis showed caregivers' MLES and CIRS scores and patients' GDS scores to be independent correlates of caregivers' GDS scores. Adverse events encountered by caregivers in the past 6 months, their current health problems and patients' depressive symptoms were found to be the principal factors associated with caregivers' depressive symptoms.
High‐amplitude theta wave bursts during REM sleep and cataplexy in hypocretin‐deficient narcoleptic mice
Authors: BASTIANINI STEFANO , SILVANI ALESSANDRO , BERTEOTTI CHIARA , LO MARTIRE VIVIANA , ZOCCOLI GIOVANNA
Published: August 2011

Neurons that release hypocretin (HCRT; orexin) peptides control wake–sleep states and autonomic functions, and are lost in patients with narcolepsy with cataplexy. Bursts of high‐amplitude electroencephalographic (EEG) activity have been reported during behavioural arrests and rapid eye movement sleep (REMS) episodes at sleep onset in HCRT‐deficient narcoleptic mice. Quantitative information on these EEG phenomena is lacking. We aimed to quantify EEG frequency, occurrence rate, daily rhythm and cardiovascular correlates of high‐amplitude EEG bursts during REMS and cataplexy. Twenty HCRT‐deficient mice and 15 congenic wild‐type controls were instrumented with electrodes for sleep recordings and a telemetric blood pressure transducer. Short (1–2 s) high‐amplitude bursts of pointed theta waves (7 Hz) occurred during either REMS or cataplexy in 80% of HCRT‐deficient mice without any significant accompanying modification in systolic blood pressure or heart period. Theta bursts were significantly more likely to occur during the dark period and in the last third of REMS episodes. Similar EEG events were detected in a significantly lower fraction (27%) of wild‐type mice and with a significantly lower occurrence rate (0.8 versus 5 per hour of REMS). These data demonstrate that occurrence of high‐amplitude theta bursts is facilitated during REMS and cataplexy in narcoleptic mice. Analysis of EEG frequency and daily and intra‐episode patterns of event occurrence do not support interpretation of theta bursts as temporally displaced pre‐REMS spindles. Facilitation of high‐amplitude theta bursts may thus represent a novel neurophysiological abnormality associated with chronic HCRT deficiency.
Activation status of integrated stress response pathways in neurones and astrocytes of HIV‐associated neurocognitive disorders (HAND) cortex
Authors: Akay C. , Lindl K. A. , Shyam N. , Nabet B. , Goenaga‐Vazquez Y. , Ruzbarsky J. , Wang Y. , Kolson D. L. , Jordan‐Sciutto K. L.
Published: August 2011

C. Akay, K. A. Lindl, N. Shyam, B. Nabet, Y. Goenaga‐Vazquez, J. Ruzbarsky, Y. Wang, D. L. Kolson and K. L. Jordan‐Sciutto (2012) Neuropathology and Applied Neurobiology38, 175–200

Activation status of integrated stress response pathways in neurones and astrocytes of HIV‐associated neurocognitive disorders (HAND) cortex

Aims: Combined anti‐retroviral therapy (cART) has led to a reduction in the incidence of HIV‐associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV‐associated neurocognitive disorders (HAND), continues to escalate in the post‐cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV‐infected/activated macrophages/microglia in the brain, might underlie the pathogenesis of HAND in the post‐cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV‐infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. Methods: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV‐infected patients. Results: The ISR does not respond in an all‐or‐none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. Conclusion: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.
Novel immunomic technologies for schistosome vaccine development
Authors: McWILLIAM H. E. G. , DRIGUEZ P. , PIEDRAFITA D. , McMANUS D. P. , MEEUSEN E. N. T.
Published: August 2011

Schistosomiasis remains one of the most common human helminthiases, despite the availability of an effective drug against the causative parasites. Drug treatment programmes have several limitations, and it is likely that a vaccine is required for effective control. While decades of vaccine development have seen the discovery and testing of several candidate antigens, none have shown consistent and acceptable high levels of protection. The migrating larval stages are susceptible to immunity, however few larval‐specific antigens have been discovered. Therefore, there is a need to identify novel larval‐specific antigens, which may prove to be more efficacious than existing targets. Immunomics, a relatively new field developed to cope with the recent large influx of biological information, holds promise for the discovery of vaccine targets, and this review highlights some immunomic approaches to schistosome vaccine development. Firstly, a method to focus on the immune response elicited by the important and vulnerable larval stage is described, which allows a targeted study of the immunome at different tissue sites. Then, two high‐throughput arrays are discussed for the identification of protein and carbohydrate antigens. It is anticipated that these approaches will progress vaccine development against the schistosomes, as well as other parasites.
A stratigraphic model to account for complexity in aeolian dune and interdune successions
Authors: MOUNTNEY NIGEL P.
Published: August 2011

Wet aeolian systems, in which the water table or its capillary fringe are in contact with the accumulation surface, such that moisture influences sedimentation, are well‐known from modern aeolian systems and several ancient preserved successions are recognized from outcrop. One common mechanism by which accumulation of wet aeolian system deposits occurs is via a progressive rise in the relative water‐table level that is coincident with ongoing dune and interdune migration, the angle of dune climb being determined by the ratio between the rate of relative water‐table rise and the rate of downwind migration of the bedforms. Accumulations of wet aeolian system deposits tend to be characterized by units of climbing dune strata separated by units of damp or wet interdune strata. For simple geometric configurations, where the size of the dune and interdune units, the rate of bedform migration and the rate of aggradation all remain constant over space and time, the resulting accumulation has a simple architecture characterized by sets of uniform thickness inclined at a constant angle. However, the dynamic nature of most aeolian dune systems means that such simple configurations are unlikely in nature. The complexity inherent in these systems is accounted for here by a numerical model in which key controlling parameters, including dune and interdune wavelength and spacing, migration rate and aggradation rate, are allowed to vary systematically both spatially (from a dune‐field centre to its margin) and temporally (in response to changes in sediment availability or water‐table level). The range of synthetic stratigraphic architectures generated by the model accounts for all the best‐known examples of aeolian dune and interdune stratigraphic configurations documented from the stratigraphic record. Modelling results have enabled the erection of a scheme for the classification of dune system type whereby the many elaborate stratal architectures known to exist in nature can effectively be accounted for by only four parameters that are allowed to vary over space and time: dune and interdune wavelength and spacing, rate of bedform migration and rate of accumulation. Results have applied implications, including the modelling of reservoir heterogeneity and the prediction of fluid flow pathways of hydrocarbons, water, CO2 and contaminants in subsurface reservoirs and aquifers, in which low permeability interdune units might act as baffles or barriers.
Calcineurin inhibitor minimization using sirolimus leads to improved renal function in pediatric heart transplant recipients
Authors: Chinnock Timothy J. , Shankel Tamara , Deming Douglas , Cutler Drew , Sahney Shobha , Fitts James , Chinnock Richard E.
Published: August 2011

Chinnock TJ, Shankel T, Deming D, Cutler D, Sahney S, Fitts J, Chinnock RE. Calcineurin inhibitor minimization using sirolimus leads to improved renal function in pediatric heart transplant recipients. Pediatr Transplantation 2011: 15: 746–749. © 2011 John Wiley & Sons A/S.

Abstract:  The introduction of cyclosporine revolutionized the practice of immunosuppression for solid organ transplant recipients, and has resulted in a significant increase in survival. While CNI use has been the mainstay of immunosuppressive therapy in pediatric heart transplantation, CNIs have been associated with an increased risk of nephropathy leading to significant morbidity and mortality. We evaluated the effect on renal function of a CNI minimization protocol using SRL in pediatric heart transplant patients with CNI induced renal insufficiency. An IRB approved retrospective chart review and case control study was performed. There were 20 patients identified with renal insufficiency who had been converted to SRL (target 5–8 ng/mL) and cyclosporine (target 50–75 vs. 125–150 ng/mL). Renal insufficiency was defined as isotopic (Indium 111 DTPA) GFR <60 mL/min per 1.73 m2 or sCr >1 mg/dL. Outcome variables evaluated were GFR and sCr at time of conversion and at two yr post conversion. Comparison was made with case control subjects matched for age at Tx, time from Tx to conversion, and initial GFR. The median age at Tx = 81 days (S.D. ±26), median time of conversion after Tx = 10 yrs (s.d. ±0.65). Self‐limited/treatable side effects included hypercholesterolemia (10), neutropenia (6), aphthous ulcer (3), edema (2), anemia (2), and tremor (1). One patient rejected in the two yr prior to conversion, and one patient had two rejection episodes following conversion. GFR at conversion for study group was 51 ± 14 vs. 60 ± 22 at two yr, p = 0.018. GFR at inclusion for control group was 56 ± 20 vs. 53 ± 21, p = 0.253. This report demonstrates that minimizing CNI exposure by addition of SRL to the immunosuppressant regimen in pediatric heart transplant recipients result in improved renal function in comparison to historically managed patients. Furthermore, immunotherapy with SRL and lower‐dose CNI can effectively prevent rejection with an acceptable side‐effect profile.
Selecting predictors for discriminant analysis of species performance: an example from an amphibious softwater plant
Authors: Vanderhaeghe F. , Smolders A. J. P. , Roelofs J. G. M. , Hoffmann M.
Published: August 2011

Selecting an appropriate variable subset in linear multivariate methods is an important methodological issue for ecologists. Interest often exists in obtaining general predictive capacity or in finding causal inferences from predictor variables. Because of a lack of solid knowledge on a studied phenomenon, scientists explore predictor variables in order to find the most meaningful (i.e. discriminating) ones. As an example, we modelled the response of the amphibious softwater plant Eleocharis multicaulis using canonical discriminant function analysis. We asked how variables can be selected through comparison of several methods: univariate Pearson chi‐square screening, principal components analysis (PCA) and step‐wise analysis, as well as combinations of some methods. We expected PCA to perform best. The selected methods were evaluated through fit and stability of the resulting discriminant functions and through correlations between these functions and the predictor variables. The chi‐square subset, at P < 0.05, followed by a step‐wise sub‐selection, gave the best results. In contrast to expectations, PCA performed poorly, as so did step‐wise analysis. The different chi‐square subset methods all yielded ecologically meaningful variables, while probable noise variables were also selected by PCA and step‐wise analysis. We advise against the simple use of PCA or step‐wise discriminant analysis to obtain an ecologically meaningful variable subset; the former because it does not take into account the response variable, the latter because noise variables are likely to be selected. We suggest that univariate screening techniques are a worthwhile alternative for variable selection in ecology.
Impact of dietary manganese concentration on status criteria to determine manganese requirement in piglets
Authors: Pallauf J. , Kauer C. , Most E. , Habicht S. D. , Moch J.
Published: August 2011

The Mn requirement for pigs is not well established. This study aimed to find criteria for assessing growing piglet supply status for Mn and to determine whether the current Mn recommendations meet the requirements for piglets. Thirty‐six weaned male castrated 27‐day‐old piglets (7.24 ± 0.69 kg) were randomized into six groups of six piglets each and housed individually in stainless steel metabolic cages for 42 days. The piglets were fed a diet based on skimmed milk powder and corn starch with increasing Mn concentrations (0.24; 2; 4; 8; 16; or 32 mg Mn/kg diet as‐fed). In week 6, Mn0.24 led to reduced feed intake (p < 0.05). Manganese concentrations in blood, liver, kidney, lung, heart, phalanx proximalis, pancreas and skeletal muscle were influenced by the dietary Mn supply (p < 0.05). The activity of the Mn‐containing superoxide dismutase in the heart as well as relative arginase activity in the liver were lower in groups Mn0.24, Mn2 and Mn4 compared with the higher supplemented groups (p < 0.05). The relative arginase activity increased clearly with enhanced dietary Mn up to 16 mg/kg and correlated with Mn concentration in the liver. Manganese concentrations in the liver, kidney and phalanx proximalis seem to be suitable biomarkers for Mn status. A 4 mg/kg dietary Mn concentration recommended by NRC (1998, Nutrient Requirements of Swine. National Academy Press, Washington DC.) did not fulfil piglet requirements. Under the conditions investigated, 16 mg Mn/kg diet were necessary to reach a plateau in specific enzyme activity and Mn concentration in organs.
Heritability and gene effect estimates for components of partial resistance to grey leaf spot of maize by generation mean analysis*
Authors: Lyimo Herman J. F. , Pratt Richard C. , Mnyuku Reuben S. O. W.
Published: August 2011

With 1 figure and 6 tables

Heritability and gene effect estimates for components of partial resistance to grey leaf spot were evaluated in Eastern Tanzania, using three populations derived from grey leaf spot partial‐resistant maize inbred lines K36 and P103 and susceptible inbred lines CML 395‐5 and L37 by generation mean analysis. Populations included the resistant parents (P1), susceptible parents (P2), F1 and F2 generations and backcross BC1 and BC2 generations. Significant differences between generations, crosses and generation × cross and generation × location interactions were detected. Measurements for components conferring partial resistance to grey leaf spot behaved in a quantitative manner. The magnitude of additive, dominance and epistatic effects varied between crosses and components. Broad‐ and narrow‐sense heritability estimates were high for disease severity, lesion length and lesion size but lower for incubation period. Results have shown that lesion size, lesion length, lesion numbers and disease severity could be used for selection of partial resistance to grey leaf spot based on field measurements.
Outcome of hepatitis C virus infection in Chinese paid plasma donors: A 12–19‐year cohort study
Authors: Rao Hui‐Ying , Sun De‐Gui , Yang Rui‐Feng , Liu Feng , Wang Jian , Feng Bo , Wu Nan , Fang Ji‐Lian , Song Guang‐Jun , Ma Hui , Guo Fang , Wang Jiang‐Hua , Li Xiao‐Bo , Jin Qian , Qin Hong , Zhuang Hui , Wei Lai
Published: August 2011

Background and Aims:  Commercial plasma donation was introduced in China in the 1970s. Cases of non‐A, non‐B hepatitis (hepatitis C) continued to occur, with multiple outbreaks among plasma donors in Guan county, Hebei province between 1972 and 1990. The outcomes of hepatitis C virus (HCV) infection in these paid plasma donors from six villages of Guan county were followed up for 12–19 years.

Methods:  A total of 402 plasma donors with HCV infection were enrolled since anti‐HCV‐positive in 1991 or 1998. Follow up was maintained until death or the end of the observation period. No antiviral treatment was applied during the period of infection.

Results:  Follow up was lost in 23 cases. After a 12–19‐year follow up, 31 donors died, with the cause of death directly related to liver disease in 15 cases, and an overall mortality of 8.18% (31/379). The incidence of liver cirrhosis was 10.03%, and hepatocellular carcinoma (HCC) was 2.90%. The rate of viral spontaneous clearing was 20.32% (77/379), and 13.69% (23/168) in males and 25.59% (54/211) in females. In May 2010, detections were performed in 348 cases. Abnormality of liver function was related to HCV viremia. Sex and alcohol intake impacted the outcome of HCV infection. There was no correlation between the viral spontaneous clearance with age of infection and genotype.

Conclusions:  This area has a high rate of chronicity in HCV infection due to plasma donation. Twenty‐five years after virus infection, liver cirrhosis or HCC developed in one‐tenth of patients, with an overall mortality of 8.18%.
DR‐70 immunoassay for the surveillance of hepatocellular carcinoma
Authors: Lin Shan‐Zu , Chen Chun‐Chia , Lee Kuei‐Chuan , Tseng Chih‐Wei , Lin Hsiao‐Yi , Chen Yi‐Chou , Lin Han‐Chieh
Published: August 2011

Background and Aim:  Although alpha‐fetoprotein (AFP) is a widely used serological marker for hepatocellular carcinoma (HCC), its utility is limited due to its unsatisfactory sensitivity. Meanwhile, a newly developed immunoassay—DR‐70—has been reported to have a good sensitivity for HCC in a small‐scale study. The aim of this study was to determine the clinical value of DR‐70 for the surveillance of HCC.

Methods:  Serum levels of DR‐70 and AFP were measured in 103 patients with HCC, 50 healthy volunteers, and 33 patients with chronic liver disease. In addition, we investigated the prognostic value of DR‐70 in patients with HCC correlating with the clinical staging—Cancer of the Liver Italian Program (CLIP) score and Barcelona Clinic Liver Cancer (BCLC) classification.

Results:  Based on the receiver operating characteristic curve with area under the curve of 0.836, the DR‐70 cut‐off value for detecting HCC was determined to be 0.75 µg/mL. DR‐70 provided a sensitivity of 81.6% and a specificity of 77.1%, and correlated well with the CLIP score and BCLC classification. The combination of DR‐70 and AFP increased the sensitivity to 91.2%. The prognosis for patients with HCC with DR‐70 level > 0.75 µg/mL was worse than that for those with DR‐70 ≤ 0.75 µg/mL. Among the patients with early stage HCC (CLIP score 0–2), DR‐70 > 0.75 µg/mL independently predicted a poor survival.

Conclusions:  DR‐70 immunoassay is complementary to AFP for the detection of HCC and has a good correlation with clinical staging and prognosis.
Associations of muscle stiffness and thickness with muscle strength and muscle power in elderly women
Authors: Ikezoe Tome , Asakawa Yasuyoshi , Fukumoto Yoshihiro , Tsukagoshi Rui , Ichihashi Noriaki
Published: August 2011

Aim:  The aims of this study were to investigate the influence of age on muscle stiffness and to examine the relationships among muscle stiffness, muscle thickness, subcutaneous fat thickness, muscle strength and muscle power in elderly women.

Methods:  The subjects were 16 young (mean age 20.3 years) and 34 elderly (mean age 84.2 years) women. Muscle stiffness of the right quadriceps femoris muscle was measured at rest and during a maximal voluntary isometric muscle contraction using a myotonometer, a computerized, electronic tissue compliance meter. Thicknesses of the rectus femoris and the vastus intermedius muscles and the overlying subcutaneous fat were measured using ultrasound. Quadriceps strength and the chair stand test were used to represent muscle strength and muscle power, respectively.

Results:  There were significant differences in muscle stiffness between rest and contraction conditions among the young but not the elderly women. Muscle stiffness during contraction, the rate of change in muscle stiffness during contraction, and muscle thickness were significantly greater in young than in elderly subjects. Pearson correlation coefficient analyses showed that muscle stiffness was significantly associated with muscle power, but not with muscle strength.

Conclusion:  This study suggests that the increase in muscle stiffness during voluntary muscle contraction is limited in elderly women compared with young women, and that muscle stiffness may be related to muscle power rather than muscle strength in elderly persons. Geriatr Gerontol Int 2012; 12: 86–92.
The role of a standardized 36 core template‐assisted transperineal prostate biopsy technique in patients with previously negative transrectal ultrasonography‐guided prostate biopsies
Authors: Pal Raj P. , Elmussareh Muhammad , Chanawani Malek , Khan Masood A.
Published: August 2011

Study Type – Diagnostic (exploratory cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

Template assisted transperineal biopsy of the prostate has become increasingly popular over the past decade. Several studies have demonstrated that transperineal prostate biopsy (TPB) is associated with an increased rate of cancer detection, increased histological concordance with final prostatectomy samples and an increase in anterior and apical prostate cancers than standard TRUS biopsy. However, interpretation of the literature is difficult due to considerable variation between studies in terms of technique and equipment.

We examined a small cohort (n= 40) of patients using a standardized 36 core template assisted TPB technique. We show that utilising this technique is associated with high cancer (68%) detection rate in patients with two previous negative TRUS biopsies. Of patients were found to have anterior gland tumours which would not have been detected by standard TRUS guided biopsy.

OBJECTIVE

• To determine the efficacy and safety of a standardized 36 core template‐assisted transperineal biopsy technique for detecting prostate cancer in patients with previously negative transrectal ultrasonography‐guided prostate biopsies and elevated prostate‐specific antigen (PSA) levels.

PATIENTS AND METHODS

• Between April 2008 to September 2010, a total of 40 patients with a mean (range) age of 63 (49–73) years, a mean (range) elevated PSA level of 21.9 (4.7–87) ng/mL and two previous sets of negative TRUS‐guided prostate biopsies underwent standardized 36 core template‐assisted transperineal prostate biopsies under general anaesthetic as a day case procedure.

• The cancer detection rate and complications for all cases were evaluated.

RESULTS

• In total, 27 of 40 (68%) patients were found to have adenocarcinoma of the prostate, two patients (5.0%) had atypical small acinar proliferation, one had high‐grade prostatic intraepithelial neoplasia (2.5%), four (10%) had chronic active inflammation and six (15%) had benign histology.

• Gleason scores were in the range 6–9, with a median Gleason score of 7.

• There were no cases of urosepsis, urinary tract infections or haematuria. A single patient experienced acute urinary retention, with a subsequent succesful trial without a catheter, and haematospermia was common, although minor.

CONCLUSIONS

• Our standardized 36 core template‐assisted transperineal prostate biopsy technique is safe and associated with a high detection rate of prostate cancer.

• This technique should be considered in patients with elevated PSA levels and previously negative TRUS‐guided prostate biopsies.
Bilateral pudendal afferent stimulation improves bladder emptying in rats with urinary retention
Authors: Chen Shih‐Ching , Grill Warren M. , Fan Wen‐Jia , Kou Yu Ru , Lin You Shuei , Lai Chien‐Hung , Peng Chih‐Wei
Published: August 2011

Study Type – Therapy (individual cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

Previous study demonstrated that unilateral electrical stimulation of the proximal transected sensory pudental nerve during distention‐evoked voiding contractions significantly improved voiding efficiency. The current study extends previous study from unilateral (UniES) to bilateral (BiES) stimulation of pudental afferent nerve fibres to determine whether this approach further enhances the improved voiding efficiency (VE) that we reported previously which unilateral stimulation. Our results show in most instances BiES consistently generated more efficient bladder emptying than did UniES but these differences were not significant.

OBJECTIVE

To determine whether bilateral electrical stimulation (BiES) of the transected pudendal sensory nerves could further enhance the voiding efficiency beyond that produced by unilateral electrical stimulation (UniES) of transected pudendal afferents in rats with urinary retention.

MATERIALS AND METHODS

The efficiency of bladder emptying with either UniES or BiES of pudendal nerve afferents was measured after acute bilateral transection of the sensory branch of the pudendal nerve.

The effects of UniES and BiES on voiding in a partially denervated bladder and acute spinal transection, respectively, were determined.

RESULTS

The voiding efficiency (VE) was reduced from 69 to 22% after bilateral transection of the sensory branch of the pudendal nerve. UniES or BiES increased the VE to 49–62%.

Although in most instances BiES consistently generated more efficient bladder emptying than did UniES, these differences were not significant.

Both UniES and BiES increased VE after unilateral pelvic nerve transection, demonstrating efficacy in a partially denervated bladder.

The enhancement of VE by either UniES or BiES was preserved after acute T9–T10, demonstrating the spinal origin of this augmenting reflex.

CONCLUSIONS

The results of the present study are consistent with an essential role for pudendal sensory feedback in efficient bladder emptying, and unilateral and bilateral electrical activation of pudendal nerve afferents are equally efficient in improving bladder emptying in an animal model of urinary retention.

This could provide an approach to improve bladder emptying in patients with non‐obstructive urinary retention.
Risk‐based explanation for the book‐to‐market effect
Authors: Chen Jerry W.
Published: August 2011

This paper proposes a risk‐based explanation for the book‐to‐market (B/M) effect. I decompose B/M into net operating asset‐to‐market (NOA/M) and net financing asset‐to‐market (NFA/M) components. Portfolio analysis shows that (i) positive B/M, NOA/M and NFA/M are positively related to future returns and (ii) negative B/M, NOA/M and NFA/M are negatively related to future returns. To the extent that positive B/M, NOA/M and NFA/M act as measures of asset risk and negative B/M, NOA/M and NFA/M act as inverse measures of borrowing risk, the nonlinear relations between B/M, NOA/M and NFA/M and future returns provide some evidence to support the risk‐based explanation for the book‐to‐market effect in stock returns.