bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinopelvic Alignment by Different Surgical Methods in the Treatment of Degenerative Sagittal Imbalance of the Lumbar Spine
Authors: Chang Dong-Gune , Ha Kee-Yong , Kim Young-Hoon , Lee Eun-Whan
Published: December 2014

Study Design:

A retrospective comparative study.

Objective:

To compare pedicle subtraction osteotomy (PSO) and iliac fixation (ILF) without osteotomy as methods of correcting lumbar spine deformities due to degenerative sagittal imbalance (DSI) through the evaluation of the changes in spinopelvic alignment.

Summary of Background Data:

Many papers have reported the surgical results after PSO and ILF for patients with fixed adult deformities. However, little is known about the difference between PSO and ILF corrections of spinopelvic alignment in adults with DSI.

Methods:

DSI patients who had undergone PSO or ILF with a minimum of 2-year follow-up (FU) were retrospectively studied in PSO (n=30) or ILF (n=25) groups. Lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis (SVA) were measured as spinal parameters and pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT) were used as measurements of pelvic parameters. Clinical outcomes were evaluated using a visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores.

Results:

There were no statistically significant differences between the PSO and ILF groups with regard to age and fused segments, but there were significant differences in operative time and estimated blood loss. Concerning spinal parameters, there were significant increases of LL and TK in PSO group immediate postoperatively (LL: P=0.014, TK: P=0.017) and at the 2-year FU (LL: P=0.021, TK: P=0.022), but no significant difference in SVA was evident between the 2 groups. Within the pelvic parameters, there was a significant increase of SS and decrease of PT in the ILF group immediate postoperatively (SS: P=0.013, PT: P=0.009) and at the 2-year FU (SS: P=0.024, PT: P=0.027), but the PI in both groups was not changed after surgery and there was no significant difference between 2 groups. VAS and ODI were significantly improved after surgery in both groups.

Conclusions:

The PSO group was better than the ILF group in the correction of the LL and TK, but not with regard to the pelvic parameters. The ILF group was superior in the correction of the pelvic orientation as compared with the PSO group when the PI was constant after surgery. Ultimately, ILF effectively achieves better correction of the pelvic parameters (SS and PT).
Too packed to change: site-specific substitution rates and side-chain packing in protein evolution
Authors: Marcos María Laura , Echave Julian
Published: December 2014

In protein evolution, due to functional and biophysical constraints, the rates of amino acid substitution differ from site to site. Among the best predictors of site-specific rates is packing density. The packing density measure that best correlates with rates is the weighted contact number (WCN), the sum of inverse square distances between the site’sCαand the otherCα. According to a mechanistic stress model proposed recently, rates are determined by packing because mutating packed sites stresses and destabilizes the protein’s active conformation. While WCN is a measure ofCαpacking, mutations replace side chains, which prompted us to consider whether a site’s evolutionary divergence is constrained by main-chain packing or side-chain packing. To address this issue, we extended the stress theory to model side chains explicitly. The theory predicts that rates should depend solely on side-chain packing. We tested these predictions on a data set of structurally and functionally diverse monomeric enzymes. We found that, on average, side-chain contact density (WCNρ) explains 39.1% of among-sites rate variation, larger than main-chain contact density (WCNα) which explains 32.1%. More importantly, the independent contribution of WCNαis only 0.7%. Thus, as predicted by the stress theory, site-specific evolutionary rates are determined by side-chain packing.
Arabidopsis Ensemble Reverse-Engineered Gene Regulatory Network Discloses Interconnected Transcription Factors in Oxidative Stress
Authors: Vermeirssen Vanessa , De Clercq Inge , Van Parys Thomas , Van Breusegem Frank , Van de Peer Yves
Published: December 2014

The abiotic stress response in plants is complex and tightly controlled by gene regulation. We present an abiotic stress gene regulatory network of 200,014 interactions for 11,938 target genes by integrating four complementary reverse-engineering solutions through average rank aggregation on an Arabidopsis thaliana microarray expression compendium. This ensemble performed the most robustly in benchmarking and greatly expands upon the availability of interactions currently reported. Besides recovering 1182 known regulatory interactions, cis-regulatory motifs and coherent functionalities of target genes corresponded with the predicted transcription factors. We provide a valuable resource of 572 abiotic stress modules of coregulated genes with functional and regulatory information, from which we deduced functional relationships for 1966 uncharacterized genes and many regulators. Using gain- and loss-of-function mutants of seven transcription factors grown under control and salt stress conditions, we experimentally validated 141 out of 271 predictions (52% precision) for 102 selected genes and mapped 148 additional transcription factor-gene regulatory interactions (49% recall). We identified an intricate core oxidative stress regulatory network where NAC13, NAC053, ERF6, WRKY6, and NAC032 transcription factors interconnect and function in detoxification. Our work shows that ensemble reverse-engineering can generate robust biological hypotheses of gene regulation in a multicellular eukaryote that can be tested by medium-throughput experimental validation.
Cell Differentiation and Development inArabidopsisAre Associated with Changes in Histone Dynamics at the Single-Cell Level
Authors: Rosa Stefanie , Ntoukakis Vardis , Ohmido Nobuko , Pendle Ali , Abranches Rita , Shaw Peter
Published: December 2014

The mechanism whereby the same genome can give rise to different cell types with different gene expression profiles is a fundamental problem in biology. Chromatin organization and dynamics have been shown to vary with altered gene expression in different cultured animal cell types, but there is little evidence yet from whole organisms linking chromatin dynamics with development. Here, we used both fluorescence recovery after photobleaching and two-photon photoactivation to show that in stem cells from Arabidopsis thaliana roots the mobility of the core histone H2B, as judged by exchange dynamics, is lower than in the surrounding cells of the meristem. However, as cells progress from meristematic to fully differentiated, core histones again become less mobile and more strongly bound to chromatin. We show that these transitions are largely mediated by changes in histone acetylation. We further show that altering histone acetylation levels, either in a mutant or by drug treatment, alters both the histone mobility and markers of development and differentiation. We propose that plant stem cells have relatively inactive chromatin, but they keep the potential to divide and differentiate into more dynamic states, and that these states are at least in part determined by histone acetylation levels.
Response of non‐grassland avian guilds to adjacent herbaceous field buffers: testing the configuration of targeted conservation practices in agricultural landscapes
Authors: Riffell Samuel K. , Monroe Adrian P. , Martin James A. , Evans Kristine O. , Burger Loren W. , Smith Mark D.
Published: December 2014

A substantial part of the world's land base is dominated by agriculture, and forest habitat often consists of discrete patches of forest and linear woody corridors. These natural components provide habitat for some forest birds, but make conservation of these species difficult. In‐field practices applied outside forest patches, such as specific juxtapositions of herbaceous field buffers adjacent to forest habitat, could increase avian diversity contributions of existing forest without creation of additional forest habitat. Our prediction was that herbaceous field buffers would increase bird richness in adjacent forest, and we evaluated four potential mechanisms.

We used bird count data from a conservation buffer monitoring programme and hierarchical community models to estimate species richness of forest generalist, forest interior and shrubland (edge) species near forest edges with and without adjacent herbaceous field buffers. We accounted for heterogeneity in detection probabilities and forest cover in surrounding landscapes when estimating species‐ and guild‐level responses.

Consistent with the drift fence hypothesis, adjacent herbaceous buffers were associated with a modest increase in richness of forest interior birds in woody corridors, but not in forest blocks. Consistent with resource complementation, adjacent herbaceous buffers were associated with modest increases in richness of shrubland (edge) birds in both woody corridors and forest blocks.

Across all species and guilds, adjacent buffers were generally associated with greater abundance (e.g. 28 of 39 species), but these increases were also relatively small and highly variable (i.e. overlapping 95% credible intervals). Corroborating existing research, effects of adjacent herbaceous buffers are likely real, but neither pervasive nor strong.

Synthesis and applications. Conservation practices targeted to grassland species often produce measurable conservation benefits for target species. However, biodiversity return for investment would be further increased if targeted practices could be deployed in ways that also produce benefits for non‐target species in adjacent habitats. Our results suggest that additional benefits for non‐target species using adjacent forest habitat are likely to be modest, so conservation planning should focus on species targeted by the conservation practices and avoidance of potential negative impacts on those species when positive benefits to adjacent habitat are weak or lacking.
Changing legislation and its effects on inclusive and special education: Scotland
Authors: Riddell Sheila , Weedon Elisabet
Published: December 2014

This article, by Sheila Riddell and Elisabet Weedon of the Centre for Research in Education Inclusion and Diversity, University of Edinburgh, analyses recent policy developments and outcomes in the field of additional support needs in Scotland in the context of devolution and austerity, drawing on a critical analysis of policy and administrative data. While there is a growing tendency in Scottish policy discourse to ‘decentre’ England as a main point of comparison, in the field of special and additional support needs policy there appear to be strong correspondences between the two jurisdictions. England appears to be following Scotland's lead in producing new types of statutory support plans and placing greater emphasis on children's rights. At the same time, these policy changes are being implemented in different policy contexts, with homogenous governance arrangements characterising the Scottish school system, compared with increasing complexity within the English system. In terms of the growth of the category of social, emotional and behavioural difficulties (SEBD in Scotland, BESD in England) there are strong cross‐border parallels. Children in these categories tend to live in deprived areas and are unlikely to have statutory support plans. Overall, this indicates the importance of analysing not just policy discourse, but also policy outcomes.
Changing policy and legislation in special and inclusive education: a perspective from Northern Ireland
Authors: Smith Ron
Published: December 2014

It is now 15 years since the signing of the 1998 Belfast (or ‘Good Friday’) Peace Agreement which committed all participants to exclusively democratic and peaceful means of resolving differences, and towards a shared and inclusive society defined by the principles of respect for diversity, equality and the interdependence of people. In particular, it committed participants to the protection and vindication of the human rights of all. This is, therefore, a precipitous time to undertake a probing analysis of educational reforms in Northern Ireland associated with provision in the areas of inclusion and special needs education. Consequently, by drawing upon analytical tools and perspectives derived from critical policy analysis, this article, by Ron Smith from the School of Education, Queen's University Belfast, discusses the policy cycle associated with the proposed legislation entitled Every School a Good School: the way forward for special educational needs and inclusion. It examines how this policy text structures key concepts such as ‘inclusion’, ‘additional educational needs’ and ‘barriers to learning’, and how the proposals attempt to resolve the dilemma of commonality and difference. Conceived under direct rule from Westminster (April 2006), issued for consultation when devolved powers to a Northern Ireland Assembly had been restored, and with the final proposals yet to be made public, this targeted educational strategy tells a fascinating story of the past, present and likely future of special needs education in Northern Ireland. Before offering an account of this work, it is placed within some broader ecological frameworks.
Changing policy, legislation and its effects on inclusive and special education: a perspective from Wales
Authors: Ware Jean
Published: December 2014

This article, by Jean Ware of Bangor University School of Education, examines policy developments in education in Wales since devolution, and their implications for inclusive and special education. This is set in the context of the demographics of Wales, which, it is argued, have a significant influence on policy and on the nature of educational provision as a whole. The discussion initially focuses on issues related to the Welsh language. The article then discusses four policy initiatives (the Foundation Phase, the Literacy and Numeracy Framework, the Masters in Educational Practice and the proposed reform of initial teacher education and training), intended to respond to Wales's poor performance in the Programme for International Student Assessment, and their potential impact, as well as the White Paper on reforming the special educational needs system in Wales. It is too soon to discuss the impact of these special educational needs‐specific reforms, but the differences from the English special educational needs reforms highlight the inherent tensions in special educational needs systems. It is argued that the Tabberer Report's critique of the teacher education system in Wales, which emphasises the need for teacher education to be strongly connected to relevant research, provides an opportunity to improve the quality of education in Wales for all children; but that considerable investment, and a willingness to address the potential tensions between the different initiatives, is necessary to achieve such an outcome.
Association between ABCG2 Q141K polymorphism and gout risk affected by ethnicity and gender: a systematic review and meta‐analysis
Authors: Dong Zheng , Guo Shicheng , Yang Yajun , Wu Junjie , Guan Ming , Zou Hejian , Jin Li , Wang Jiucun
Published: December 2014

Aim

Original studies have employed various genetic models in association analysis between ABCG2 Q141K (rs2231142) with gout risk and different or conflicting results, especially regarding the role of gender in this association. In addition, it is not clear whether the association varies by ethnicity.

Method

Articles published before September 1, 2013 were extracted and registered into databases for the systematic review of this polymorphism. The quality of each study was scored based on predefined criteria. The genetic model was identified through stratification analysis, then a meta‐analysis including all publically available data was preformed to test the association between rs2231142 and gout risk. Potential sources of heterogeneity were sought out via stratification analysis and meta‐regression analysis.

Results

Nine case–control studies involving 17 942 individuals were eligible for the meta‐analysis of rs2231142. Codominant model was the most appropriate genetic model to interpret the susceptibility cause. It showed that the rs2231142 T allele obviously increased gout risk, and TT was much stronger than GT (TT vs. GG: OR, 4.10; 95% CI, 2.90–5.80; GT vs. GG: OR, 1.71, 95% CI, 1.39–2.10). In addition, gender and ethnicity were found to affect the association between the susceptibility of gout and rs2231142.

Conclusion

ABCG2 rs2231142 is an important genetic factor in increasing gout risk, and the difference in genetic association has been found between male and female populations. In addition, the degree of association has been found to vary with ethnicity.
Social and spatial heterogeneity in psychosis proneness in a multilevel case–prodrome–control study
Authors: Kirkbride J. B. , Stochl J. , Zimbrón J. , Crane C. M. , Metastasio A. , Aguilar E. , Webster R. , Theegala S. , Kabacs N. , Jones P. B. , Perez J.
Published: December 2014

Objective

To test whether spatial and social neighbourhood patterning of people at ultra‐high risk (UHR) of psychosis differs from first‐episode psychosis (FEP) participants or controls and to determine whether exposure to different social environments is evident before disorder onset.

Method

We tested differences in the spatial distributions of representative samples of FEP, UHR and control participants and fitted two‐level multinomial logistic regression models, adjusted for individual‐level covariates, to examine group differences in neighbourhood‐level characteristics.

Results

The spatial distribution of controls (n = 41) differed from UHR (n = 48; P = 0.04) and FEP participants (n = 159; P = 0.01), whose distribution was similar (P = 0.17). Risk in FEP and UHR groups was associated with the same neighbourhood‐level exposures: proportion of single‐parent households [FEP adjusted odds ratio (aOR): 1.56 95% CI: 1.00–2.45; UHR aOR: 1.59; 95% CI: 0.99–2.57], ethnic diversity (FEP aOR: 1.27; 95% CI: 1.02–1.58; UHR aOR: 1.28; 95% CI: 1.00–1.63) and multiple deprivation (FEP aOR: 0.88; 95% CI: 0.78–1.00; UHR aOR: 0.86; 95% CI: 0.76–0.99).

Conclusion

Similar neighbourhood‐level exposures predicted UHR and FEP risk, whose residential patterning was closer to each other's than controls. Adverse social environments are associated with psychosis before FEP onset.
Mycophenolic acid in dermatology a century after its discovery
Authors: Strathie Page Sarah J , Tait Clare P
Published: December 2014

Mycophenolic acid was first discovered in 1913 and first used clinically in the 1970s as an immunosuppressant to prevent organ transplantation rejection. It was later used in the treatment of psoriasis. However due to its side‐effect profile and fears over its carcinogenic potential it was abandoned. From the late 1990s a prodrug, mycophenolate mofetil (MMF), was developed and more recently, enteric‐coated mycophenolate sodium (EC‐MPS), both of which have gained increasing use in the field of dermatology for a variety of skin conditions. This review discusses the pharmacology, mechanisms of action, side‐effects and current clinical applications in dermatology of MMF and EC‐MPS.
Antenatal care provider's advice is the key determinant of influenza vaccination uptake in pregnant women
Authors: Mak Donna B. , Regan Annette K. , Joyce Sarah , Gibbs Robyn , Effler Paul V.
Published: December 2014

Background

Although influenza vaccination is an important component of antenatal care and is recommended and funded by the Australian government, vaccination uptake has been low.

Aims

This study compared seasonal influenza vaccination uptake among pregnant Western Australian (WA) women and identified factors associated with vaccination uptake.

Materials and Methods

Adult women who were pregnant during the 2012 and 2013 influenza vaccination seasons were selected at random and invited to complete a computer‐assisted telephone interview survey about whether they received influenza vaccination during pregnancy. Data analyses were weighted to the age distribution of women of reproductive age in WA. Multivariate logistic regression was used to identify factors associated with vaccination uptake.

Results

Between 2012 and 2013, the proportion of WA women whose antenatal care provider recommended influenza vaccination increased from 37.6 to 62.1% and vaccination uptake increased from 23.0 to 36.5%. The antenatal care provider's advice to have influenza vaccine was the single most important factor associated with vaccination (OR 11.1, 95% CI 7.9–15.5). Most women (63.7%) were vaccinated in general practice, 18.8% in a public hospital antenatal clinic and 11.0% at their workplace. Wanting to protect their infant from infection (91.2%) and having the vaccine recommended by their GP (60.0%) or obstetrician (51.0%) were commonly reported reasons for vaccination; worrying about side effects was a common reason for nonvaccination.

Conclusions

To optimise maternal and infant health outcomes, Australian antenatal care providers and services need to incorporate both the recommendation and delivery of influenza vaccination into routine antenatal care.
Using Qualitative Information to Improve Causal Inference
Authors: Glynn Adam N. , Ichino Nahomi
Published: December 2014

Using the Rosenbaum (2002, 2009) approach to observational studies, we show how qualitative information can be incorporated into quantitative analyses to improve causal inference in three ways. First, by including qualitative information on outcomes within matched sets, we can ameliorate the consequences of the difficulty of measuring those outcomes, sometimes reducing p‐values. Second, additional information across matched sets enables the construction of qualitative confidence intervals on effect size. Third, qualitative information on unmeasured confounders within matched sets reduces the conservativeness of Rosenbaum‐style sensitivity analysis. This approach accommodates small to medium sample sizes in a nonparametric framework, and therefore it may be particularly useful for analyses of the effects of policies or institutions in a small number of units. We illustrate these methods by examining the effect of using plurality rules in transitional presidential elections on opposition harassment in 1990s sub‐Saharan Africa.
The effect of hyperglycaemia on haemostasis testing – a volunteer study
Authors: Lippi G. , Buonocore R. , Musa R. , Ippolito L. , Picanza A. , Favaloro E. J.
Published: December 2014

We investigated whether the contamination of samples with glucose subsequently tested for haemostasis affected the results, including prothrombin time, activated partial thromboplastin time and fibrinogen concentration. Venous blood was collected from 12 healthy subjects and divided into four aliquots, which were subjected to different degrees of contamination with standard glucose solution (0%, 5%, 10%, 20%). With increasing glucose contamination, prothrombin time increased from mean (SD) 11.0 (0.7) s to 11.2 (0.7) s, 11.5 (0.7) s and 12.2 (0.8) s, all p < 0.001. Activated partial thromboplastin time decreased from 32.3 (0.9) s to 30.9 (0.8) s, 30.8 (0.8) s, and 29.7 (0.7) s, all p < 0.001. Fibrinogen concentration decreased from 3.8 (0.7) g.l−1 to 3.7 (0.6) g.l−1, 3.6 (0.6) g.l−1, and 3.4 (0.6) g.l−1, all p < 0.001. Bias was clinically meaningful from 5% contamination for activated partial thromboplastin time, 10% contamination for prothrombin time and 20% contamination for fibrinogen concentration. We conclude that if glucose contamination of haemostasis samples is suspected or has occurred, the specimens should not be analysed.
Growth hormone treatment of Prader–Willi syndrome has long‐term, positive effects on body composition
Authors: Höybye Charlotte
Published: December 2014

Aim

Growth hormone (GH) treatment is a relatively new concept in adults, and the knowledge of its long‐term effects is limited. We studied ten men with Prader–Willi Syndrome (PWS) after more than 5 years of GH treatment.

Methods

Study participants underwent a detailed physical examination, including blood tests. Five had received GH as childhood and five had started GH as adults.

Results

The total duration of GH treatment was 16 ± 4 years in the childhood PWS group and 15 ± 1 years in the adulthood PWS group. Their respective mean ages were 27 ± 4 years and 44 ± 4 years, mean heights were 178 ± 11 cm and 156 ± 5 cm, and mean body mass indexes were 32.4 ± 10.3 kg/m2 and 28.9 ± 4.6 kg/m2. There were no differences in body composition between the groups and all lipids and insulin‐like growth factor 1 were normal or close to normal. Four had well‐controlled type 2 diabetes. The GH doses in the childhood and adulthood groups were 0.4 mg and 0.3 mg, respectively.

Conclusion

Men with PWS who received GH treatment displayed positive effects on body composition independent of when the GH treatment had started. Only patients who gained weight developed diabetes. The duration of GH treatment should balance the benefits and observed side effects.
Sites of cell proliferation during scute morphogenesis in turtle and alligator are different from those of lepidosaurian scales
Authors: Alibardi Lorenzo , Minelli Daniela
Published: December 2014

Cell proliferation in forming shield scutes has been studied by immunofluorescence in embryos of turtle, alligator and snake after injection of 5‐bromo‐deoxy‐uridine. Hinge regions of scutes in alligator and turtle carapace derive from an initial waving and invagination of the epidermis that contains 5‐bromo‐deoxy‐uridine‐labelled cells. This suggests that down growth of the epidermis into the dermis is driven by local proliferation in addition to dermal anchorage and stabilization of hinge regions. Few keratinocytes migrate into suprabasal layers 1 day after injection of 5‐bromo‐deoxy‐uridine and keratinocytes reach the precorneous layer in about 5 days. Proliferating keratinocytes are randomly distributed in the outer scale surface of symmetric scutes but are more numerous in the outer scale surface of asymmetric or overlapped scutes indicating epidermal expansion. Higher localization of proliferating cells along hinge regions of embryonic turtle and alligator scutes is maintained in adult scutes where most growth occurs. In snake, skin proliferation becomes prevalent on the elongating outer side of the asymmetric scale. Comparison between proliferation sites in turtle–alligator–chick scales with lepidosaurian scales indicates that placodes are present only in turtle–alligator–chick scales. Conversely, scale primordia detected only using gene markers are found in most crocodilian and lepidosaurians embryonic skin.
Single‐sweep spectral analysis of contact heat evoked potentials: a novel approach to identify altered cortical processing after morphine treatment
Authors: Hansen Tine M. , Graversen Carina , Frøkjær Jens B. , Olesen Anne E. , Valeriani Massimiliano , Drewes Asbjørn M.
Published: December 2014

Aims

The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single‐sweep characteristics to identify alterations induced by morphine.

Methods

In a crossover study 15 single‐sweep CHEPs were analyzed from 62 electroencephalography electrodes in 26 healthy volunteers before and after administration of morphine or placebo. Each sweep was decomposed by a continuous wavelet transform to obtain normalized spectral indices in the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–32 Hz) and gamma (32–80 Hz) bands. The average distribution over all sweeps and channels was calculated for the four recordings for each volunteer, and the two recordings before treatments were assessed for reproducibility. Baseline corrected spectral indices after morphine and placebo treatments were compared to identify alterations induced by morphine.

Results

Reproducibility between baseline CHEPs was demonstrated. As compared with placebo, morphine decreased the spectral indices in the delta and theta bands by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04).

Conclusion

The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response after morphine administration. Hence, assessment of spectral indices in single‐sweep CHEPs can be used to study cortical mechanisms induced by morphine treatment.
Effect of grapefruit juice on the bioactivation of prasugrel
Authors: Holmberg Mikko T. , Tornio Aleksi , Hyvärinen Hanna , Neuvonen Mikko , Neuvonen Pertti J. , Backman Janne T. , Niemi Mikko
Published: December 2014

Aims

The P2Y12 inhibitor prasugrel is a prodrug, which is activated after its initial hydrolysis partly by cytochrome P450 (CYP) 3A4. Grapefruit juice, a strong inactivator of intestinal CYP3A4, greatly reduces the activation and antiplatelet effects of clopidogrel. The aim of this study was to investigate the effects of grapefruit juice on prasugrel.

Methods

In a randomized crossover study, seven healthy volunteers ingested 200 ml of grapefruit juice or water three times daily for 4 days. On day 3, they ingested a single 10 mg dose of prasugrel with an additional 200 ml of grapefruit juice or water. Plasma concentrations of prasugrel metabolites and the antiplatelet effect were measured.

Results

Grapefruit juice increased the geometric mean area under the plasma concentration–time curve (AUC0–∞) of the primary, inactive metabolite of prasugrel to 164% of the control value (95% confidence interval 122–220%, P = 0.008), without a significant effect on its peak plasma concentration (Cmax). The Cmax and AUC0–∞ of the secondary, active metabolite were decreased to 51% (95% confidence interval 32–84%, P = 0.017) and 74% of the control value (95% confidence interval 60–91%, P = 0.014) by grapefruit juice (P < 0.05). The average platelet inhibition, assessed with the VerifyNow® method at 0–24 h after prasugrel intake, was 5 percentage points (95% confidence interval 1–10 percentage points) lower in the grapefruit juice phase than in the water phase (P = 0.034).

Conclusions

Grapefruit juice reduces the bioactivation of prasugrel, but this has only a limited effect on the antiplatelet effect of prasugrel.
Population pharmacokinetic model of free and total ropivacaine after transversus abdominis plane nerve block in patients undergoing liver resection
Authors: Ollier Edouard , Heritier Fabrice , Bonnet Caroline , Hodin Sophie , Beauchesne Brigitte , Molliex Serge , Delavenne Xavier
Published: December 2014

Aims

The aim of this study was to develop a pharmacokinetic model in order to characterize the free and total ropivacaine concentrations after transversus abdominis plane block in a population of patients undergoing liver resection surgery. In particular, we evaluated the impact of the size of liver resection on ropivacaine pharmacokinetics.

Methods

This work is based on a single‐centre, double‐blinded, randomized, placebo‐controlled study. Among the 39 patients included, 19 patients were randomized to the ropivacaine group. The free and total ropivacaine concentrations were measured in nine or 10 blood samples per patient. A pharmacokinetic model was built using a nonlinear mixed‐effect modelling approach.

Results

The free ropivacaine concentrations remained under the previously published toxic threshold. A one‐compartment model, including protein binding site with a first‐order absorption, best described the data. The protein binding site concentration was considered as a latent variable. Bodyweight, the number of resected liver segments and postoperative fibrinogen evolution were, respectively, included in the calculation of the volume of distribution, clearance and binding site production rate. The resection of three or more liver segments was associated with a 53% decrease in the free ropivacaine clearance.

Conclusions

Although large liver resections were associated with lower free ropivacaine clearance, the ropivacaine pharmacokinetic profile remained within the safe range after this type of surgery.
Altered intracellular region of MUC1 and disrupted correlation of polarity‐related molecules in breast cancer subtypes
Authors: Iizuka Misato , Nakanishi Yoko , Fuchinoue Fumi , Maeda Tetsuyo , Murakami Eriko , Obana Yukari , Enomoto Katsuhisa , Tani Mayumi , Sakurai Kenichi , Amano Sadao , Masuda Shinobu
Published: December 2014

MUC1 glycoprotein is overexpressed and its intracellular localization altered during breast carcinoma tumorigenesis. The present study aimed to clarify the relationship of cytoplasmic localization of MUC1 with the breast cancer subtype and the correlation of 10 molecules associated with cell polarity in breast cancer subtypes. We immunostained 131 formalin‐fixed and paraffin‐embedded breast cancer specimens with an anti‐MUC1 antibody (MUC1/CORE). For 48 of the 131 tumor specimens, laser‐assisted microdissection and real‐time quantitative RT‐PCR were performed to analyze mRNA levels of MUC1 and 10 molecules, β‐catenin, E‐cadherin, claudin 3, claudin 4, claudin 7, RhoA, cdc42, Rac1, Par3 and Par6. Localization of MUC1 protein varied among breast cancer subtypes, that is, both the apical domain and cytoplasm in luminal A‐like tumors (P < 0.01) and both the cytoplasm and cell membrane in luminal B‐like (growth factor receptor 2 [HER2]+) tumors (P < 0.05), and no expression was found in triple negative tumors (P < 0.001). Estrogen receptor (ER)+ breast cancers showed higher MUC1 mRNA levels than ER− breast cancers (P < 0.01). The incidence of mutual correlations of expression levels between two of the 10 molecules (55 combinations) was 54.5% in normal breast tissue and 38.2% in luminal A‐like specimens, 16.4% in luminal B‐like (HER2+), 3.6% in HER2 and 18.2% in triple negative specimens. In conclusion, each breast cancer subtype has characteristic cytoplasmic localization patterns of MUC1 and different degrees of disrupted correlation of the expression levels between the 10 examined molecules in comparison with normal breast tissue.
An outcome and cost analysis of anal fistula plug insertion vs endorectal advancement flap for complex anal fistulae
Authors: Fisher O. M. , Raptis D. A. , Vetter D. , Novak A. , Dindo D. , Hahnloser D. , Clavien P.‐A. , Nocito A.
Published: December 2014

Aim

The study aimed to compare the rate of success and cost of anal fistula plug (AFP) insertion and endorectal advancement flap (ERAF) for anal fistula.

Method

Patients receiving an AFP or ERAF for a complex single fistula tract, defined as involving more than a third of the longitudinal length of of the anal sphincter, were registered in a prospective database. A regression analysis was performed of factors predicting recurrence and contributing to cost.

Results

Seventy‐one patients (AFP 31, ERAF 40) were analysed. Twelve (39%) recurrences occurred in the AFP and 17 (43%) in the ERAF group (P = 1.00). The median length of stay was 1.23 and 2.0 days (P < 0.001), respectively, and the mean cost of treatment was €5439 ± €2629 and €7957 ± €5905 (P = 0.021), respectively. On multivariable analysis, postoperative complications, underlying inflammatory bowel disease and fistula recurring after previous treatment were independent predictors of de novo recurrence. It also showed that length of hospital stay ≤ 1 day to be the most significant independent contributor to lower cost (P = 0.023).

Conclusion

Anal fistula plug and ERAF were equally effective in treating fistula‐in‐ano, but AFP has a mean cost saving of €2518 per procedure compared with ERAF. The higher cost for ERAF is due to a longer median length of stay.
Sarcopenic obesity with metabolic syndrome: a newly recognized entity following living donor liver transplantation
Authors: Choudhary Narendra S. , Saigal Sanjiv , Saraf Neeraj , Mohanka Ravi , Rastogi Amit , Goja Sanjay , Menon Palat B. , Mishra Sunil , Mittal Ambrish , Soin Arvinder S.
Published: December 2014

Objective

There are limited data about sarcopenic obesity in liver transplant recipients.

Methods

Living donor liver transplant recipients with at least 12 months of follow‐up were included. Metabolic syndrome (MS) was defined as ≥3 ATP III criteria. Body composition was assessed by bioelectrical impedance. Immunosuppression protocol included short‐term steroids, mycophenolate and calcineurin inhibitors (mainly tacrolimus). Data are shown as percentage, mean ± SD, or median (25–75 IQR).

Results

The study comprised 82 patients (males 69), aged 50.5 ± 10.65 yr, and follow‐up 24 (12–38.5) months. Etiology for cirrhosis was alcohol 29%, hepatitis C 22%, hepatitis B 17%, cryptogenic 24%, and others 7%. Post‐transplant sarcopenic obesity was present in 72 (88%), and MS was present in 43 (52%) of recipients with no significant difference among etiologies. There were significant differences between pre‐ and post‐transplant body mass index, triglycerides, high‐density lipoprotein, low‐density lipoprotein (p = 0.000 for all), prevalence of hypertension (18% vs. 39%), and diabetes (20% vs. 56%). Patients with sarcopenic obesity had significantly higher body mass index, waist circumference, and MS (57% vs. 20%, p = 0.041) when compared to patients without sarcopenic obesity.

Conclusion

Despite resuming routine activities, the majority of liver transplant recipients develop sarcopenic obesity and MS. The importance and role of appropriate nutrition and exercise after transplantation merits further investigation.
Non‐classical mechanism of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor channel block by fluoxetine
Authors: Barygin Oleg I. , Komarova Margarita S. , Tikhonova Tatiana B. , Tikhonov Denis B.
Published: December 2014

Antidepressants have many targets in the central nervous system. A growing body of data demonstrates the influence of antidepressants on glutamatergic neurotransmission. In the present work, we studied the inhibition of native Ca2+‐permeable and Ca2+‐impermeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in rat brain neurons by fluoxetine. The Ca2+‐impermeable AMPA receptors in CA1 hippocampal pyramidal neurons were weakly affected. The IC50 value for the inhibition of Ca2+‐permeable AMPA receptors in giant striatal interneurons was 43 ± 7 μm. The inhibition of Ca2+‐permeable AMPA receptors was voltage dependent, suggesting deep binding in the pore. However, the use dependence of fluoxetine action differed markedly from that of classical AMPA receptor open‐channel blockers. Moreover, fluoxetine did not compete with other channel blockers. In contrast to fluoxetine, its membrane‐impermeant quaternary analog demonstrated all of the features of channel inhibition typical for open‐channel blockers. It is suggested that fluoxetine reaches the binding site through a hydrophobic access pathway. Such a mechanism of block is described for ligands of sodium and calcium channels, but was never found in AMPA receptors. Molecular modeling suggests binding of fluoxetine in the subunit interface; analogous binding was proposed for local anesthetics in closed sodium channels and for benzothiazepines in calcium channels.
Charcoal‐inferred Holocene fire and vegetation history linked to drought periods in the Democratic Republic of Congo
Authors: Hubau Wannes , Van den Bulcke Jan , Van Acker Joris , Beeckman Hans
Published: December 2014

The impact of Holocene drought events on the presumably stable Central African rainforest remains largely unexplored, in particular the significance of fire. High‐quality sedimentary archives are scarce, and palynological records mostly integrate over large regional scales subject to different fire regimes. Here, we demonstrate a direct temporal link between Holocene droughts, palaeofire and vegetation change within present‐day Central African rainforest, using records of identified charcoal fragments extracted from soil in the southern Mayumbe forest (Democratic Republic of Congo). We find three distinct periods of local palaeofire occurrence: 7.8–6.8 ka BP, 2.3–1.5 ka BP, 0.8 ka BP – present. These periods are linked to well‐known Holocene drought anomalies: the 8.2 ka BP event, the 3rd millennium BP rainforest crisis and the Mediaeval Climate Anomaly. During and after these Holocene droughts, the Central African rainforest landscape was characterized by a fragmented pattern with fire‐prone open patches. Some fires occurred during the drought anomalies although most fires seem to lag behind them, which suggests that the open patches remained fire‐prone after the actual climate anomalies. Charcoal identifications indicate that mature rainforest patches did persist through the Early to Mid‐Holocene climatic transition, the subsequent Holocene thermal optimum and the third millennium BP rainforest crisis, until 0.8 ka BP. However, disturbance and fragmentation were probably more prominent near the boundary of the southern Mayumbe forest. Furthermore, the dominance of pioneer and woodland savanna taxa in younger charcoal assemblages indicates that rainforest regeneration was hampered by increasingly severe drought conditions after 0.8 ka BP. These results support the notion of a dynamic forest ecosystem at multicentury time scales across the Central African rainforest.
X‐ray Absorption Spectroscopy Studies of the Room‐Temperature Ferromagnetic Fe‐Doped 6H–BaTiO3
Authors: Mikulska Iuliia , Valant Matjaz , Arčon Iztok , Lisjak Darja
Published: December 2014

We investigated the effect of annealing temperature on magnetic properties of 2% and 10% Fe‐doped BaTiO3. To understand the possible structural differences between samples treated at different annealing temperatures, and to correlate them with the magnetic properties, several characterization techniques, such as X‐ray diffraction and X‐ray absorption spectroscopic methods (XANES and EXAFS) were employed. We found that the 2% Fe‐doped BaTiO3 pseudocubic perovskite is paramagnetic regardless of the heat‐treatment conditions. Initially paramagnetic 10% Fe‐doped 6H–BaTiO3, treated at 1250°C, became ferromagnetic after additional annealing at higher temperature. We have crystalographically characterized the cation ordering processes in the 6H–BaTiO3 that occurred during the high‐temperature annealing. The ferromagnetism that is induced in this stage is most probably associated with the observed diffusion processes but it extrinsic character still cannot be fully disregarded.
Tough Alumina/Polymer Layered Composites with High Ceramic Content
Authors: Livanov Konstantin , Jelitto Hans , Bar‐On Benny , Schulte Karl , Schneider Gerold A. , Wagner Daniel H.
Published: December 2014

Ceramic composites found in nature, such as bone, nacre, and sponge spicule, often provide an effective resolution to a well‐known conflict between materials' strength and toughness. This arises, on the one hand, from their high ceramic content that ensures high strength of the material. On the other hand, various pathways are provided for stress dissipation, and thus toughness, due to their intricate hierarchical architectures. Such pathways include crack bridging, crack deflection, and delamination in the case of layered structures. On the basis of these inspiring ideas, we attempted here to create simultaneously strong and tough laminated alumina composite with high ceramic content. Composites were prepared from high‐grade commercial alumina with spin‐coated interlayers of ductile polymers (PMMA and PVA). The specimens' ultimate properties (strength, fracture toughness, and work of fracture) were measured by a four‐point bending method. In some cases, fracture toughness of the composites was increased by up to an order of magnitude, reminiscent of the natural layered composites. It is proposed that this increase may be attributed to an interlocking mechanism, often encountered in biological composites. The significance of sample architecture and the role of the interfacial and bulk properties of the interlayer material are discussed.
Effects of He Irradiation on Yttria‐Stabilized Zirconia Ceramics
Authors: Yang Tengfei , Taylor Caitlin A. , Wang Chenxu , Zhang Yanwen , Weber William J. , Xiao Jingren , Xue Jianming , Yan Sha , Wang Yugang
Published: December 2014

Effects of He irradiation on polycrystalline yttria‐stabilized zirconia (YSZ) are studied with the focus on irradiation‐induced damage buildup, He behavior, and volume swelling. The evolution of irradiation‐induced structural damage in polycrystalline YSZ, which is independent of grain orientation, is described by a multistep damage accumulation model. A three‐step damage evolution process was found, and different types of defects were observed in the different damage steps. Compared with single‐crystal YSZ, the second damage step occurs at a lower dose in polycrystalline YSZ due to the initial defects and strain. The implanted He ions are readily trapped along the grain boundaries and the mobility of He ions is greatly increased. The enhanced He mobility along the grain boundary leads to a lower threshold irradiation dose and a larger penetration depth for bubble formation. Similar morphologies are observed for the He bubbles in the polycrystalline YSZ and in single‐crystal YSZ, and the formation of He bubbles in polycrystalline YSZ is not influenced by grain orientation. As both the extended defects and He bubbles can induce volume swelling, the variation in volume swelling as a function of dose can be divided into a two stage process.
Squamate hatchling size and the evolutionary causes of negative offspring size allometry
Authors: Meiri S. , Feldman A. , Kratochvíl L.
Published: December 2014

Although fecundity selection is ubiquitous, in an overwhelming majority of animal lineages, small species produce smaller number of offspring per clutch. In this context, egg, hatchling and neonate sizes are absolutely larger, but smaller relative to adult body size in larger species. The evolutionary causes of this widespread phenomenon are not fully explored. The negative offspring size allometry can result from processes limiting maximal egg/offspring size forcing larger species to produce relatively smaller offspring (‘upper limit’), or from a limit on minimal egg/offspring size forcing smaller species to produce relatively larger offspring (‘lower limit’). Several reptile lineages have invariant clutch sizes, where females always lay either one or two eggs per clutch. These lineages offer an interesting perspective on the general evolutionary forces driving negative offspring size allometry, because an important selective factor, fecundity selection in a single clutch, is eliminated here. Under the upper limit hypotheses, large offspring should be selected against in lineages with invariant clutch sizes as well, and these lineages should therefore exhibit the same, or shallower, offspring size allometry as lineages with variable clutch size. On the other hand, the lower limit hypotheses would allow lineages with invariant clutch sizes to have steeper offspring size allometries. Using an extensive data set on the hatchling and female sizes of > 1800 species of squamates, we document that negative offspring size allometry is widespread in lizards and snakes with variable clutch sizes and that some lineages with invariant clutch sizes have unusually steep offspring size allometries. These findings suggest that the negative offspring size allometry is driven by a constraint on minimal offspring size, which scales with a negative allometry.