bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential for scale economies in milk powder processing: an Irish case study
Authors: Donnellan Trevor , Hennessy Thia , Fenelon Mark , O'Callaghan Donal
Published: December 2013

This paper examines the difference in costs associated with milk plants of differing dryer scale in Ireland. This is an important question for international competitiveness in the context of the removal of the EU milk quota in 2015 and the expectation that Irish milk production could increase considerably thereafter. Using confidential data obtained from a number of sources, the differential in the cost of processing at differing plant scales was established. It was found that two 7.5 tonne/h dryers at a single location provide a level flexibility which offsets the slight cost advantage associated with a 15 tonne/h dryer.
Percutaneous Mitral Repair with the MitraClip System in Patients with Mild‐to‐Moderate and Severe Heart Failure: A Single‐Centre Experience
Authors: Bozdag‐Turan Ilkay , Paranskaya Liliya , Birkemeyer Ralf , Turan R. Gökmen , Kische Stephan , Akin Ibrahim , Ortak Jasmin , Stoeckicht Yannik , Schubert Jochen , Westphal Bernd , Nienaber Christoph A. , Ince Hüseyin
Published: December 2013

Aims

Edge‐to‐edge repair of mitral regurgitation (MR) with the MitraClip® (MC) system is increasingly applied in advanced heart failure. Our objective was to compare outcomes in patients with mild‐to‐moderate and severe systolic heart failure.

Methods and results

Between February 2010 and July 2012, 121 patients with MR of at least grade 3+ and a mean EuroSCORE II of 10.6% underwent MC implantation. Thirty‐nine had a left ventricular ejection fraction (LVEF) of ≤30% (group A) and 82 of >30% (group B).

Procedural success was comparable in both groups (100% vs. 95.2%) with multiple (>2) clip implantation in 34% and 25% of patients, respectively. At 12 months, absolute reduction in MR grade (2.3 vs. 2.2) and relative reduction in mitral valve orifice area (48% vs. 42%) were also comparable. New York Heart Association class had improved independent from baseline LVEF (P < 0.001). In‐hospital mortality was low in both groups (2.6% vs. 2.4%), but there was a strong trend for higher 12‐month mortality in group A (34% vs. 18%, P = 0.05) with no significant difference in the overall rate of major adverse cerebrovascular and cardiac events (36.8% vs. 28.9%, P = 0.38). On multivariate analysis, MR grade after repair was the strongest predictor of mortality (OR 2.121, 95% CI 1.095–4.109), whereas systolic impairment was no independent predictor.

Conclusions

Percutaneous mitral valve repair led to comparable symptomatic improvement in patients with mild‐to‐moderately or severely reduced LV function. LV‐EF < 30% was not an independent predictor of short‐term mortality, which was mainly governed by residual MR after repair.
“We are Human Beings, and have a Past”: The “Adjustment” of Migrants and the Australian Assimilation Policies of the 1950s
Authors: Damousi Joy
Published: December 2013

This article argues that the assimilation policy adopted by the Australian government during the 1950s was based on a denial of a migrant's past. The assumption that the migrant would readily merge into Australian cultural life ignored the ways in which past stories and memories shape the self. Through an analysis of the Good Neighbour Councils I explore the nature of assimilation that was based on a neglect of collective war memories of immigrant groups. This perspective is distinguished from that adopted by several theorists of the day such as W.D. Borrie and Jean Martin whose studies were less crude and one‐dimensional. The experiences of Greek migrants are examined to consider how Greek war stories could not often find expression or recognition in the assimilationist climate of the post‐war period.
Eczema phenotypes are associated with multiple vitamin D pathway genes in Chinese children
Authors: Wang S. S. , Hon K. L. , Kong A. P. S. , Tang M. F. , Sy H. Y. , Chan J. C. N. , Leung T. F.
Published: December 2013

Background

Vitamin D is increasingly recognized to play crucial roles in cutaneous immunity, and vitamin D treatment improved eczema control in small clinical trials. Several vitamin D‐related genes were associated with asthma, but there are no data for eczema.

Methods

Twenty‐three single‐nucleotide polymorphisms (SNPs) of five vitamin D‐related genes (CYP27A1, CYP2R1, CYP27B1, GC and VDR) were genotyped in 1442 Chinese children with eczema and 1231 non‐allergic controls. SNPs that followed Hardy–Weinberg equilibrium and yielded ≥95% genotyping call‐rate were included. Haplotypic associations and SNP–SNP interactions for eczema diagnosis and subphenotypes were analysed.

Results

Atopic eczema was associated with rs4674343 of CYP27A1 (odds ratio 0.66, 95% confidence interval 0.53–0.83, P = 0.0004). Increased eosinophil percentage was associated with CYP2R1 rs2060793A (P = 0.001) and rs1933064A (P = 0.001). Two CYP2R1 haplotypes increased eczema risk whereas one VDR haplotype lowered eczema risk. GC rs7041 and CYP2R1 rs7935792 interacted to modulate total IgE (cross‐validation consistency 10/10, P = 0.047). Specifically, high‐risk eczema patients had higher log‐transformed total IgE than low‐risk patients (2.76 ± 0.76 vs 2.60 ± 0.80, P = 0.002).

Conclusion

A vitamin D‐related SNP rs4674343 on CYP27A1 was found to be protective against atopic eczema. CYP2R1 and VDR haplotypes altered eczema susceptibility and eosinophil percentage, and GC and CYP2R1 interacted to determine total IgE among eczema patients.
Prevalence of the posterior superior alveolar canal in cone beam computed tomography scans
Authors: Anamali Sindhura , Avila‐Ortiz Gustavo , Elangovan Satheesh , Qian Fang , Ruprecht Axel , Finkelstein Michael , Allareddy Veeratrishul
Published: December 2013

Objective

This study was primarily aimed at determining the prevalence of the posterior superior alveolar (PSA) canal in cone beam computerized tomography (CBCT) scans in a North American population.

Materials and methods

Cone beam computed tomography scans were selected on the basis of predetermined eligibility criteria from a pool of 976 data sets. Two calibrated examiners assessed the presence of PSA canal on the postero‐lateral wall of the maxillary sinus using coronal sections. One examiner also recorded the presence of images compatible with sinus disease. Associations between the presence of PSA canal and sinus disease were investigated for males and females separately using statistical methods.

Results

A total of 254 CBCT scans were selected. The pooled prevalence of the PSA canal in CBCT scans was 94.4% and 91% on the right and left side, respectively. The ability to detect the presence of the canal was not significantly affected by the presence of intrasinusal disease. Males are more likely than females to present signs of maxillary sinus pathoses on the right (63.3% vs. 36.7%) and the left side (59.2% vs. 40.8%).

Conclusions

The prevalence of the PSA canal on CBCT images in the selected population is high. The PSA canal can be consistently visualized on CBCT scans with a high level of reproducibility regardless of the presence of radiographic signs of intrasinusal pathoses.
Retinol‐binding protein 4 levels and susceptibility to ischaemic events in men
Authors: Cubedo Judit , Padró Teresa , Cinca Juan , Mata Pedro , Alonso Rodrigo , Badimon Lina
Published: December 2013

Background

Many efforts in cardiovascular medicine have been focused in the identification of patients at risk of developing an acute ischaemic event. Biomarker discovery studies have become an essential research area, being proteomic technologies an excellent tool for biomarker identification. By applying proteomic approaches, we have detected changes in retinol‐binding protein 4 (RBP4) in acute new‐onset myocardial infarction patients (AMI) and in high‐risk patients with heterozygous familial hypercholesterolaemia (FH).

Materials and methods

Differential serum proteome was analysed by two‐dimensional electrophoresis and MALDI‐TOF/TOF. Validation studies were performed by ELISA, and functional effects of RBP4 were tested in cell culture experiments.

Results

Retinol‐binding protein 4 proteomic characterization depicted two spots (pI = 5·4;Mw = 23·01/22·78 kDa) with decreased intensity in AMI patients. Total serum RBP4 levels were decreased in AMI patients (N = 68) compared with controls (N = 132; P < 0·0001). RBP4 was also decreased in FH patients who had an ischaemic event 2 years (±0·3) after their inclusion compared with FH patients without any cardiovascular episode at follow‐up (P < 0·001; N = 187). In both cases, changes were limited to men. RBP4 induced a significant increase in eNOS expression in human endothelial vascular cells and in prostaglandin I2 release in coronary vascular smooth muscle cells.

Conclusions

We show decreased serum RBP4 levels in men in the acute phase of AMI, being this decrease already detected in men with FH previous to the presentation of an ischaemic event. The decrease in RBP4 levels could confer an increased susceptibility to the precipitation of an ischaemic event that could be mediated by the decrease in its vasculoprotective properties through NO and PGI2.
Lipid‐lowering treatment and inflammatory mediators in diabetes and chronic kidney disease
Authors: Almquist Tora , Jacobson Stefan H. , Mobarrez Fariborz , Näsman Per , Hjemdahl Paul
Published: December 2013

Background

Inflammation may contribute to the high cardiovascular risk in diabetes mellitus (DM) and chronic kidney disease (CKD). Monocyte chemoattractant protein‐1 (MCP‐1) facilitates the recruitment of monocytes into atherosclerotic lesions and is involved in diabetic nephropathy. Interferon gamma (IFNγ) is important in atherosclerosis and increases the synthesis of chemokines including MCP‐1. Lipid‐lowering treatment (LLT) with statins may have anti‐inflammatory effects, and ezetimibe cotreatment provides additional cholesterol lowering.

Methods

After a placebo run‐in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S+E) were compared in a randomized, double‐blind, cross‐over study on inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15–59 mL/min × 1·73 m2 (CKD stages 3–4) (DM‐CKD) and 21 DM patients with eGFR > 75 mL/min (DM only) were included.

Results

At baseline, monocyte chemoattractant protein 1 (MCP‐1) (P = 0·03), IFNγ (P = 0·02), tumour necrosis factor‐α (TNFα) (P < 0·01) and soluble vascular adhesion molecule (sVCAM) (P = 0·001) levels were elevated in DM‐CKD compared with DM‐only patients. LLT with S and S+E reduced MCP‐1 levels (P < 0·01 by anova) and IFNγ levels (P < 0·01) in DM‐CKD patients but not in DM‐only patients. Reductions were most pronounced with the combination treatment.

Conclusions

DM patients with CKD stages 3–4 had increased inflammatory activity compared with DM patients with normal GFR. Lipid‐lowering treatment decreased the levels of MCP‐1 and IFNγ in DM patients with concomitant CKD, which may be beneficial with regard to the progression of both atherosclerosis and diabetic nephropathy.
Democracy and Legitimacy in the Shadow of Purposive Competence
Authors: Davies Gareth
Published: December 2013

This article argues that the way EU competences are defined plays an important role in the social legitimacy problems of the EU. The fact that its powers are purposive compels the EU to privilege narrow functional goals and act in a highly focused way. This has the consequence that politics cannot be meaningful within the EU, since essential choices of direction are pre‐empted. It also has the consequence that EU law is over‐instrumental and lacks expressive qualities, alienating the public. Now that EU law is so broad, the same defects are being imposed increasingly on Member States. Without another form of conferred power, the legitimacy of the EU, and of law and government in Europe, will be increasingly undermined. The constitutional DNA, which has been a functional success for Europe, may also be its political nemesis.
Climate‐change impacts on sandy‐beach biota: crossing a line in the sand
Authors: Schoeman David S. , Schlacher Thomas A. , Defeo Omar
Published: December 2013

Sandy ocean beaches are iconic assets that provide irreplaceable ecosystem services to society. Despite their great socioeconomic importance, beaches as ecosystems are severely under‐represented in the literature on climate‐change ecology. Here, we redress this imbalance by examining whether beach biota have been observed to respond to recent climate change in ways that are consistent with expectations under climate change. We base our assessments on evidence coming from case studies on beach invertebrates in South America and on sea turtles globally. Surprisingly, we find that observational evidence for climate‐change responses in beach biota is more convincing for invertebrates than for highly charismatic turtles. This asymmetry is paradoxical given the better theoretical understanding of the mechanisms by which turtles are likely to respond to changes in climate. Regardless of this disparity, knowledge of the unique attributes of beach systems can complement our detection of climate‐change impacts on sandy‐shore invertebrates to add rigor to studies of climate‐change ecology for sandy beaches. To this end, we combine theory from beach ecology and climate‐change ecology to put forward a suite of predictive hypotheses regarding climate impacts on beaches and to suggest ways that these can be tested. Addressing these hypotheses could significantly advance both beach and climate‐change ecology, thereby progressing understanding of how future climate change will impact coastal ecosystems more generally.
Modulation of sorghum biological activities by varieties and two traditional processing methods: an integrated in vitro/modelling approach
Authors: Proietti Ilaria , Tait Sabrina , Aureli Federica , Mantovani Alberto
Published: December 2013

Five sorghum cultivars (Sorghum bicolor (L.) Moench), from Nigeria, Senegal, Burkina Faso and Italy (two), were characterised by analysing the modulation of cellular functional markers and estimated iron bioavailability; the effect of traditional processing, fermentation and cooking, was also investigated. Glutathione peroxidase (Gpx) activity and total protein content were assayed in human colon‐derived DLD‐1 cell line exposed to raw and processed samples; iron bioavailability was estimated through the application of an algorithm. The Senegal variety showed promising characteristics: no effects on cell protein and GPx, and a threefold higher percentage of estimated iron bioavailability compared with the other varieties. Fermentation significantly reduced cell proteins and GPx by 26% and 58%, respectively, but improved estimated iron bioavailability from 34 to 77%, whereas cooking only reduced the cellular total protein content. The results indicate that selection of traditional varieties and processing methods can have a significant impact on parameters relevant to sorghum nutritional characteristics.
Global Stroke Statistics
Authors: Thrift Amanda G. , Cadilhac Dominique A. , Thayabaranathan Tharshanah , Howard George , Howard Virginia J. , Rothwell Peter M. , Donnan Geoffrey A.
Published: December 2013

In many countries, stroke is a lower priority than other diseases despite its public health impact. One issue is a lack of readily accessible comparative data to help make the case for the development of national stroke strategies. To assist in this process, we need to have a common repository of the latest published information on the impact of stroke worldwide. We aim to provide a repository of the most current incidence and mortality data on stroke available by country and illustrate the gaps in these data. We plan to update this repository annually and expand the scope to address other aspects of the burden of stroke. Data were compiled using two approaches: ( 1 ) an extensive literature review with a major focus on published systematic reviews on stroke incidence (between 1980 and May 14, 2013); and ( 2 ) direct acquisition and collation of data from the World Health Organization to present the most current estimates of stroke mortality for each country recognized by the World Health Organization. For mortality, ICD8, ICD9, and ICD10 mortality codes were extracted. Using population denominators crude stroke mortality was calculated, as well as adjusting for the World Health Organization world population. We used only the most recent year reported to the World Health Organization. Incidence rates for stroke were available for 52 countries, with some countries having incidence studies undertaken in more than one region. When adjusted to the World Health Organization world standard population, incidence rates for stroke ranged from 41 per 100 000 population per year in Nigeria (1971–74) to 316/ 100 000/year in urban Dar-es-Salaam (Tanzania). Some regions had three to fivefold greater incidence than other countries. Of the 123 countries reporting mortality data, crude mortality was greatest in Kazhakstan (in 2003). In many regions data were very old or nonexistent. Such country-level data are important for citizens, clinicians, and policy makers so that local and global strategies to reduce the overall burden of stroke can be implemented. Through this first annual review of country-specific stroke epidemiology, we hope to promote discussion and provide insights into the worldwide burden of stroke.
Modelo analítico de la dinámica del empleo informal en economías en transición: el caso de Ucrania
Authors: COMMANDER Simon , ISACHENKOVA Natalia , RODIONOVA Yulia
Published: December 2013

El aumento del empleo informal observado en los países de la antigua Unión Soviética a partir de 1990 obedece, según los autores, a la estructura de la remuneración heredada de la economía centralizada, que incluye prestaciones no pecuniarias en las empresas estatales o privatizadas. Según un modelo teórico innovador que considera estas prestaciones y la probabilidad de que las empresas informales sean descubiertas para predecir la elección de los trabajadores entre trabajo formal, informal o pluriempleo mixto, tales prestaciones atraerían a los trabajadores hacia esta última opción; apoyan esta hipótesis resultados empíricos obtenidos con datos de panel de la Encuesta Longitudinal de Seguimiento de Ucrania.
The timing of diversification within the most divergent parrot clade
Authors: Rheindt Frank E. , Christidis Les , Kuhn Sylvia , de Kloet Siwo , Norman Janette A. , Fidler Andrew
Published: December 2013

The Strigopidae are an ancient parrot (Psittaciformes) family consisting of three extant species placed in two genera (Nestor, Strigops) and restricted to New Zealand. Their evolutionary history is clouded because the timing of divergence events within this family has variously been attributed to Pleistocene climate change or much earlier earth‐historic events. Here we examine new psittaciform DNA sequence data, and combine them with previously published sequences, to shed light on the poorly understood timing of diversification within the Strigopidae. Using calibrations indirectly derived from both psittaciform and non‐psittaciform fossils, our data indicate a Late Pliocene or Early Pleistocene (ca 1.2–3.6 mya) differentiation between the two Nestor species (kea and kaka), possibly in response to shifts in habitat distribution associated with sea level fluctuations. The unique, monotypic, nocturnal and flightless genus Strigops (kakapo) is shown to have diverged from the Nestor lineage probably ca 28–29 mya, coinciding with the potential Oligocene submergence of Zealandia when much of its landmass may have been fragmented into smaller islands, providing a setting for allopatric diversification.
Modularity along organism dispersal gradients challenges a prevailing view of abrupt transitions in animal landscape perception
Authors: Borthagaray Ana Inés , Barreneche Juan Manuel , Abades Sebastián , Arim Matías
Published: December 2013

A common property of landscapes and metacommunities is the occurrence of abrupt shifts in connectivity along gradients of individual dispersal abilities. Animals with short‐range dispersal capability perceive fragmented landscapes, but organisms moving across critical thresholds perceive continuous landscapes. This qualitative shift in landscape perception may determine several attributes of local communities and the dynamics of whole metacommunities. Modularity describes the existence in some communities of relatively high numbers of mutual connections favoring the movement of neighboring individuals (even when each individual is able to reach any patch in the landscape). Local patch linkages and metacommunity connectivity along gradients of dispersal ability have been reported frequently. However, the intermediate level of structure captured by modularity has not been considered. We evaluated landscape connectivity and modularity along gradients of individual dispersal abilities. Random landscapes with different degrees of cell aggregation and occupancy were simulated; we also analyzed ten real ecosystems. An expected, a shift in landscape connectivity was always detected; modularity consistently decreased gradually along dispersal gradients in both simulated networks and empirical landscapes. Neutral metacommunities within simulated landscapes demonstrated that modularity and connectivity may reflect landscape traits in the shaping of metacommunity diversity. Average beta‐diversity was strongly associated with modularity, particularly with low migration rates, while connectivity trends tracked changes in beta‐diversity at intermediate to high migrations rates. Consequently, while some species are able to perceive abrupt transitions in the landscape, many others probably experience a gradual continuum in landscape perception, contrary to predictions from previous analyses. Furthermore, the gradual behavior of modularity indicates that it may represent an exceptional early‐warning tool that measures system distance to tipping points. Our study highlights the multiple perceptions that different species may have of a single landscape and shows, for the first time, a theoretical and empirical relationship between landscape modularity, and metacommunity diversity.
Detection and evaluation of an early divergence problem in northern Fennoscandian tree‐ring data
Authors: Schneider Lea , Esper Jan , Timonen Mauri , Büntgen Ulf
Published: December 2013

Although not yet fully understood, reduced sensitivity of tree growth to temperature at high northern latitudes during the last ˜ 40 years is often linked to concurrent anthropogenic changes of atmospheric composition and global warming. The idea that a temporal localization of the problem could improve its understanding initiated a search for erratic growth‐patterns in earlier periods of high quality dendrochronological archives.

An extensive network of maximum latewood density (MXD) measurements from northern Fennoscandia likely represents one of the most reliable regional summer‐temperature reconstructions. The strong coherence between proxy and instrumental data is, however, interrupted by a short, but significant correlation decrease from ˜ 1900 till 1925, a period of distinct summer‐temperature warming. Here we analyze this early 20th century divergence period (EDP). We therefore use long instrumental station records and tree‐ring density chronologies including 878 Pinus sylvestris and 126 Picea abies samples. Our results indicate that EDP was accompanied by a simultaneous decline of inter‐site and inter‐station correlations. This could be ascribed to substantially reduced inter‐annual summer temperature variability from 1905–1919. Stable correlations of the MXD network with high‐pass filtered sea level pressure and precipitation records imply tree‐growth to be additionally controlled by other factors, e.g. light conditions, in periods of low summer temperature variability. Within the scope of this study, the causes for EDP could be confined to a limited area and a short period. Calibration of proxy data and reconstruction skills thus remain unaffected in this case of divergence.
Microstructure and Thermal Conductivity of Silicon Carbide with Yttria and Scandia
Authors: Kim Young‐Wook , Lim Kwang‐Young , Seo Won‐Seon
Published: December 2013

A fully dense SiC ceramic with high thermal conductivity was obtained by conventional hot pressing, with 1 vol% Y2O3–Sc2O3 additives. The ceramic had a bimodal microstructure consisting of large and small equiaxed SiC grains. Observation with high‐resolution transmission electron microscopy (HRTEM) showed two kinds of homophase (SiC/SiC) boundaries, that is crystallized and clean boundaries, and a fully crystallized junction phase. The thermal conductivity of the SiC ceramic was 234 W (m·K)−1 at room temperature. The high thermal conductivity was attributed to a clean SiC lattice and good contiguity between SiC grains.
Dispersal capacity of Monochamus galloprovincialis, the European vector of the pine wood nematode, on flight mills
Authors: David G. , Giffard B. , Piou D. , Jactel H.
Published: December 2013

The pine wood nematode (Bursaphelenchus xylophilus), which causes the symptoms of pine wilt disease, is recognized worldwide as a major forest pest. It was introduced into Portugal in 1999. It is transmitted between trees almost exclusively by longhorn beetles of the genus Monochamus, including, in particular, M. galloprovincialis (Coleoptera: Cerambycidae) in maritime pine forests. Accurate estimates of the flight capacity of this insect vector are required if we are to understand and predict the spread of pine wilt disease in Europe. Using computer‐linked flight mills, we evaluated the distance flown, the flight probability and speed of M. galloprovincialis throughout adulthood and investigated the effects of age, sex and body weight on these flight performances, which are proxies for dispersal capacity. The within‐population variability of flight performance in M. galloprovincialis was high, with a mean distance of 16 km flown over the lifetime of the beetle. Age and body weight had a significant positive effect on flight capacity, but there was no difference in performance between males and females. These findings have important implications for managing the spread of the pine wood nematode in European forests.
The Relationship Between Emergency Department Crowding and Patient Outcomes: A Systematic Review
Authors: Carter Eileen J. , Pouch Stephanie M. , Larson Elaine L.
Published: December 2013

Purpose

Emergency department (ED) crowding is a significant patient safety concern associated with poor quality of care. The purpose of this systematic review is to assess the relationship between ED crowding and patient outcomes.

Design

We searched the Medline search engine and relevant emergency medicine and nursing journals for studies published in the past decade that pertained to ED crowding and the following patient outcome measures: mortality, morbidity, patient satisfaction, and leaving the ED without being seen. All articles were appraised for study quality.

Findings

A total of 196 abstracts were screened and 11 articles met inclusion criteria. Three of the eleven studies reported a significant positive relationship between ED crowding and mortality either among patients admitted to the hospital or discharged home. Five studies reported that ED crowding is associated with higher rates of patients leaving the ED without being seen. Measures of ED crowding varied across studies.

Conclusions

ED crowding is a major patient safety concern associated with poor patient outcomes. Interventions and policies are needed to address this significant problem.

Clinical Relevance

This review details the negative patient outcomes associated with ED crowding. Study results are relevant to medical professionals and those that seek care in the ED.
BEYOND GDP: AN OVERVIEW OF MEASUREMENT ISSUES IN REDEFINING ‘WEALTH’
Authors: Munda Giuseppe
Published: December 2013

In the last decades, a growing quantity of literature has been written about concepts such as quality of life and well‐being as a proxy for evaluating societal prosperity and progress. This paper analyses the theoretical foundations and the empirical validity of multi‐dimensional technical tools that can be used for well‐being measurement. There is no doubt that there is a lot of complexity and fuzziness inherent in multi‐dimensional concepts such as well‐being. A possible reduction of this complexity, a pre‐condition for policy‐making, introduces the problem of the descriptors used: indicators and indexes. In a multi‐dimensional framework, multi‐criteria evaluation is a consistent approach for the construction of so‐called composite indicators. Often, some individual indicators improve while others deteriorate. This is the classical conflictual situation dealt with in multi‐criteria evaluation; in particular non‐compensatory methods are quite relevant, since compensability implies complete substitutability between different types of capital. Uncertainty and sensitivity analysis can estimate the robustness of the results obtained and help the framing of the debate around the conceptual framework used, that is, which representation of reality (and thus which societal values and interests) has been considered.
Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design
Authors: Djuris Jelena , Ioannis Nikolakakis , Ibric Svetlana , Djuric Zorica , Kachrimanis Kyriakos
Published: December 2013

Objectives

This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene–polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated.

Methods

Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates.

Key findings

Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate.

Conclusions

Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.
Phenylephrine eye drops in pediatric patients undergoing ophthalmic surgery: incidence, presentation, and management of complications during general anesthesia
Authors: Sbaraglia Fabio , Mores Nadia , Garra Rossella , Giuratrabocchetta Giuseppe , Lepore Domenico , Molle Fernando , Savino Gustavo , Piastra Marco , Pulitano' Silvia , Sammartino Maria
Published: December 2013

Background

Phenylephrine eye drops are widely used as mydriatic agent to reach the posterior segment of the eye. In literature, many reports suggest a systemic absorption of this agent as a source of severe adverse drug reactions. Hence, we reviewed our experience with topical phenylephrine in ophthalmic surgery.

Methods

In May 2006, following US guidelines publication, a standard operating procedure was issued in our operating rooms to standardize the use of phenylephrine eye drops in our practice. Two years later, after the occurrence of a cluster of serious adverse drug reactions in infants undergoing surgery, a review of phenylephrine safety and systemic complications incidence was performed.

Results

We observed 451 pediatric patients, and 187 met the inclusions criteria: Among them, 4 experienced hemodynamic complications due to phenylephrine eye drops. The incidence of major complications was 2.1%.

Conclusions

Two different patterns of side effects occurred. The first one was a cardiovascular derangement with severe hypertension and heart rate alterations; the other one involved exclusively pulmonary circuit causing early edema. These clinical manifestations, their duration, and treatment responses are all explainable by alfa1‐adrenergic action of phenylephrine. This hypothetic pathogenesis has been confirmed also by the usefulness of direct vasodilators (anesthetic agents) and by the negative outcome occurred in the past with the use of beta‐blockers.
Dietary mineral supplies in Africa
Authors: Joy Edward J. M. , Ander E. Louise , Young Scott D. , Black Colin R. , Watts Michael J. , Chilimba Allan D. C. , Chilima Benson , Siyame Edwin W. P. , Kalimbira Alexander A. , Hurst Rachel , Fairweather‐Tait Susan J. , Stein Alexander J. , Gibson Rosalind S. , White Philip J. , Broadley Martin R.
Published: December 2013

Dietary micronutrient deficiencies (MNDs) are widespread, yet their prevalence can be difficult to assess. Here, we estimateMNDrisks due to inadequate intakes for seven minerals in Africa using food supply and composition data, and consider the potential of food‐based and agricultural interventions. Food Balance Sheets (FBSs) for 46 countries were integrated with food composition data to estimate per capita supply of calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn), and also phytate. Deficiency risks were quantified using an estimated average requirement (EAR) ‘cut‐point’ approach. Deficiency risks are highest for Ca (54% of the population), followed by Zn (40%), Se (28%) and I (19%, after accounting for iodized salt consumption). The risk of Cu (1%) and Mg (<1%) deficiency are low. Deficiency risks are generally lower in the north and west of Africa. MultipleMNDrisks are high in many countries. The population‐weighted mean phytate supply is 2770 mg capita−1day−1. Deficiency risks for Fe are lower than expected (5%). However, ‘cut‐point’ approaches for Fe are sensitive to assumptions regarding requirements; e.g. estimates of Fe deficiency risks are 43% under very low bioavailability scenarios consistent with high‐phytate, low‐animal protein diets. Fertilization and breeding strategies could greatly reduce certainMNDs. For example, meetingHarvestPlusbreeding targets for Zn would reduce dietary Zn deficiency risk by 90% based on supply data. Dietary diversification or direct fortification is likely to be needed to address Ca deficiency risks.
Working memory impairment and cardiovascular hyperarousal in young primary insomniacs
Authors: Cellini Nicola , de Zambotti Massimiliano , Covassin Naima , Sarlo Michela , Stegagno Luciano
Published: December 2013

We investigated memory performance and cardiovascular activity in 13 primary insomniacs (PI) compared to 13 good sleepers (GS). Cardiovascular and hemodynamic measures, including heart rate, pre‐ejection period, and blood pressure, were continuously recorded at rest and during two memory tasks. PI showed working memory impairment under high cognitive load, but performed as well as GS in an easy memory task. In addition, PI exhibited markers of hyperarousal both at rest and during the execution of the two tasks. However, we failed to find a clear‐cut relationship between cardiovascular hyperarousal and cognitive performance in insomniacs. Our data provide further evidence of both cognitive impairment and cardiovascular hyperarousal in primary insomnia, while not supporting the hypothesis of hyperarousal as a compensatory mechanism to overcome cognitive challenges.
Ichnofabric characterization of a deep‐marine clastic system: a subsurface study of the Middle Eocene Ainsa System, Spanish Pyrenees
Authors: Heard Thomas G. , Pickering Kevin T. , Clark Julian D.
Published: December 2013

This paper documents a subsurface trace fossil and ichnofabric study of the proximal parts of a structurally confined and channelized sand‐rich, lower slope and proximal basin‐floor deep‐marine system in the Middle Eocene Ainsa basin, Spanish Pyrenees. Five depositional environments are recognized based on sedimentary facies associations, depositional architecture and stratigraphic context (channel axis, channel off‐axis, channel margin, leveé‐overbank and interfan), as well as a channel abandonment phase. Each environment is characterized by distinct and recurring ichnofabrics. Ichnological measurements and observations were recorded from six cores recovered from six wells drilled at a spacing of between 400 m and 500 m at outcrop, and totalling 1213 m in length. From channel axis to levée‐overbank environments, there is a trend of increasing bioturbation intensity and ichnodiversity. Ichnofabrics in channel axis and channel off‐axis environments are characterized by low bioturbation intensity and low ichnodiversity. Thalassinoides‐dominated firmground ichnofabrics associated with erosive sediment gravity flows are common in these environments. In contrast, channel margin and levée‐overbank environments are characterized by ichnofabrics associated with high bioturbation intensity and ichnodiversity. Sediments of the interfan are characterized by the highest bioturbation intensity, associated with burrow mottling and an absence of primary sedimentary structures. This paper demonstrates that in core‐based studies, ichnofabric analysis is an important and valuable tool in discriminating between different environments in channelized deep‐marine siliciclastic systems. The results of this study should find wide applicability in reservoir characterization studies in the petroleum industry, in field‐based analogue ichnofabric studies and other core‐based studies in deep‐water siliciclastic systems worldwide such as the Integrated Ocean Drilling Program.
Effect of pubic bone marrow edema on recovery from endoscopic surgery for athletic pubalgia
Authors: Kuikka L. , Hermunen H. , Paajanen H.
Published: December 2013

Athletic pubalgia (sportsman's hernia) is often repaired by surgery. The presence of pubic bone marrow edema (BME) in magnetic resonance imaging (MRI) may effect on the outcome of surgery. Surgical treatment of 30 patients with athletic pubalgia was performed by placement of totally extraperitoneal endoscopic mesh behind the painful groin area. The presence of pre‐operative BME was graded from 0 to 3 using MRI and correlated to post‐operative pain scores and recovery to sports activity 2 years after operation. The operated athletes participated in our previous prospective randomized study. The athletes with (n = 21) or without (n = 9) pubic BME had similar patients' characteristics and pain scores before surgery. Periostic and intraosseous edema at symphysis pubis was related to increase of post‐operative pain scores only at 3 months after surgery (P = 0.03) but not to long‐term recovery. Two years after surgery, three athletes in the BME group and three in the normal MRI group needed occasionally pain medication for chronic groin pain, and 87% were playing at the same level as before surgery. This study indicates that the presence of pubic BME had no remarkable long‐term effect on recovery from endoscopic surgical treatment of athletic pubalgia.
HLA frequencies and associations in cystic fibrosis
Authors: Adriaanse M. P. M. , Vreugdenhil A. C. E. , Groeneweg M. , Brüggenwirth H. T. , Castelijns S. J. A. M. , van der Ent C. K. , Voorter C. E. M. , Tilanus M. G. J.
Published: December 2013

Cystic fibrosis (CF) is classically attributed to the dysfunction of the single CF transmembrane conductance regulator gene. The incidence of human leukocyte antigen (HLA) polymorphisms in different CF‐associated diseases raises the question of an unequal distribution of HLA genotypes in CF. This study aimed to evaluate HLA gene frequencies and possible associations in CF patients compared with a control population. Frequencies of HLA‐DRB1, HLA‐DQA1 and HLA‐DQB1, performed by intermediate resolution typing using Luminex sequence‐specific oligonucleotide, and epitope counts were similar in 340 CF patients when compared with 400 control subjects. In conclusion, HLA‐DRB1, ‐DQA1 and ‐DQB1 do not seem to influence susceptibility to CF. Whether HLA plays a role in the severity of CF disease needs to be investigated.
Revealing Nature’s Cellulase Diversity: The Digestion Mechanism of
Caldicellulosiruptor bescii
CelA
Authors: Brunecky Roman , Alahuhta Markus , Xu Qi , Donohoe Bryon S. , Crowley Michael F. , Kataeva Irina A. , Yang Sung-Jae , Resch Michael G. , Adams Michael W. W. , Lunin Vladimir V. , Himmel Michael E. , Bomble Yannick J.
Published: December 2013

An Enzyme Drill

Cellulase enzymes degrade the cell walls of plants by breaking down cellulose into its constituent sugar fragments and thus have attracted interest for biofuels production. Using transmission electron microscopy

Brunecky
et al.

(p.
1513
; see the Perspective by

Berlin

) discovered that an especially active cellulase, CelA, from
Caldicellulosiruptor bescii
bacteria does not move along the surface of the substrate, but drills into the cellulose to form cavities.
CRL4 Complex Regulates Mammalian Oocyte Survival and Reprogramming by Activation of TET Proteins
Authors: Yu Chao , Zhang Yin-Li , Pan Wei-Wei , Li Xiao-Meng , Wang Zhong-Wei , Ge Zhao-Jia , Zhou Jian-Jie , Cang Yong , Tong Chao , Sun Qing-Yuan , Fan Heng-Yu
Published: December 2013

Ubiquitin Fertility Insurance

The female mammal's reproductive lifespan is determined by a pool of ovarian primordial follicles that are generated early in life.

Yu
et al.

(p.
1518
) found that in mice, the ubiquitin E3 ligase complex CRL4 is essential for oocyte survival within primordial follicles and for development after fertilization. CRL4 binds to and activates an adaptor protein that mediates ubiquitination, but if any component is deleted, the genes required for oocyte maintenance and early embryo development are silenced and the female mice become infertile.
Relaxation Mechanism of the Hydrated Electron
Authors: Elkins Madeline H. , Williams Holly L. , Shreve Alexander T. , Neumark Daniel M.
Published: December 2013

Relaxing in a Water Jet

High-energy irradiation of liquid water and its solutes can transiently liberate electrons, which act as potent chemical reductants, but they are challenging to characterize precisely. Seeking to bridge the gap between liquid and gas,

Elkins
et al.

(p.
1496
) report results from photoelectron spectroscopy of hydrated electron dynamics in a liquid jet. The results reveal a very rapid transition from the electronic excited state to the ground state, prior to full relaxation of the solvent shell.
Dynamical Resonances Accessible Only by Reagent Vibrational Excitation in the F + HD→HF + D Reaction
Authors: Wang Tao , Chen Jun , Yang Tiangang , Xiao Chunlei , Sun Zhigang , Huang Long , Dai Dongxu , Yang Xueming , Zhang Dong H.
Published: December 2013

Access via Vibration

Molecular beam studies over the past decade have elucidated many subtle quantum mechanical factors governing the influence of vibrational excitation on the outcome of elementary chemical reactions. However, these studies have generally had to focus on reagents that can be easily made to vibrate by direct absorption in the infrared (IR).
Wang et al.
(p.
1499
) show that a variation on stimulated Raman pumping can efficiently excite the IR-inactive stretch vibration in the diatomic molecule, hydrogen deuteride (HD). As a result, they can probe the influence of that vibration on the outcome of the HD + F reaction. Through a combined spectroscopic and theoretical investigation, they uncover Feshbach resonances along the reaction coordinate that are only accessible through vibrational preexcitation.
Reformulating Table Salt Under Pressure
Authors: Ibáñez Insa Jordi
Published: December 2013

Sodium chloride transforms into exotic compounds such as NaCl
3
or Na
3
Cl with compression, laser heating, and excess of Cl or Na.

[Also see Report by

Zhang
et al.

]
A Common Pathway for a Rare Disease?
Authors: Vafai Scott B. , Mootha Vamsi K.
Published: December 2013

A rare childhood disorder caused by mitochondrial dysfunction is treated by the drug rapamycin in a mouse model of the disease.

[Also see Report by

Johnson
et al.

]
Genomic Clues to the Ancestral Flowering Plant
Authors: Adams Keith
Published: December 2013

The genome sequence of
Amborella trichopoda
provides insights into the molecular evolution of flowering plants.

[Also see Research Articles by
Amborella Genome Project
and

Rice
et al.

]
Ronning After the Adiponectin Receptors
Authors: Holland William L. , Scherer Philipp E.
Published: December 2013

A small-molecule drug mimics the beneficial effects of adiponectin in cells and in animal models of diabetes and obesity.
Neisseria meningitidis Native Outer Membrane Vesicles Containing Different Lipopolysaccharide Glycoforms as Adjuvants for Meningococcal and Nonmeningococcal Antigens
Authors: Nagaputra Jerry C. , Rollier Christine S. , Sadarangani Manish , Hoe J. Claire , Mehta Ojas Hrakesh , Norheim Gunnstein , Saleem Muhammad , Chan Hannah , Derrick Jeremy P. , Feavers Ian , Pollard Andrew J. , Moxon E. Richard
Published: December 2013

We evaluated the adjuvant effect of a modified glycoform of lipopolysaccharide (LPS) (LgtB-LpxL1) compared to that of the nonmodified glycoform Lpxl1 serogroup B meningococcal H44/76 native outer membrane vesicles (nOMVs) on immune responses to vaccination with the recombinant meningococcal protein, rPorA, tetanus toxoid, or meningococcal serogroup C capsular polysaccharide. We used LgtB-LpxL1 LPS because the disruption of thelgtBgene, which results in the exposure ofN-acetylglucosamine-galactose-glucose residues in the LPS outer core, has been shown to enhance the activation of human dendritic cellsin vitro. The responses were compared to those of a monophosphoryl lipid A (MPL)-based adjuvant and to an aluminum hydroxide suspension. The nOMVs induced blood serum IgG responses against each of the three antigens comparable to those obtained with MPL or aluminum salt. However, nOMVs elicited (i) a lower IgG1/IgG2a ratio against rPorA and (ii) serum bactericidal antibody titers superior to those achieved with aluminum salt, reaching similar titers to those obtained with MPL. Similarly, bactericidal antibody titers induced by immunization with meningococcal serogroup C polysaccharide and nOMVs were similar to those obtained using MPL but were better than those with aluminum salt. Immunization with tetanus toxoid and nOMVs resulted in tetanus toxoid-specific IgG responses similar to those obtained when adjuvanted with aluminum salt. These results highlight the potential utility of meningococcal LpxL1 LPS-containing nOMVs as an adjuvant for recombinant meningococcal protein vaccines and suggest their possible use with a variety of other antigens.