bluuebunny/crossref_metadata_2025 huggingface dataset:
USING MODEL SELECTION ALGORITHMS TO OBTAIN RELIABLE COEFFICIENT ESTIMATES
Authors: Castle Jennifer L. , Qin Xiaochuan , Robert Reed W.
Published: September 2011

This review surveys a number of common model selection algorithms (MSAs), discusses how they relate to each other and identifies factors that explain their relative performances. At the heart of MSA performance is the trade‐off between type I and type II errors. Some relevant variables will be mistakenly excluded, and some irrelevant variables will be retained by chance. A successful MSA will find the optimal trade‐off between the two types of errors for a given data environment. Whether a given MSA will be successful in a given environment depends on the relative costs of these two types of errors. We use Monte Carlo experimentation to illustrate these issues. We confirm that no MSA does best in all circumstances. Even the worst MSA in terms of overall performance – the strategy of including all candidate variables – sometimes performs best (viz., when all candidate variables are relevant). We also show how (1) the ratio of relevant to total candidate variables and (2) data‐generating process noise affect relative MSA performance. Finally, we discuss a number of issues complicating the task of MSAs in producing reliable coefficient estimates.
A protease activity–depleted environment for heterologous proteins migrating towards the leaf cell apoplast
Authors: Goulet Charles , Khalf Moustafa , Sainsbury Frank , D’Aoust Marc‐André , Michaud Dominique
Published: September 2011

Recombinant proteins face major constraints along the plant cell secretory pathway, including proteolytic processing compromising their structural integrity. Here, we demonstrate the potential of protease inhibitors as in situ stabilizing agents for recombinant proteins migrating towards the leaf apoplast. Genomic data for Arabidopsis, rice and Nicotiana spp. were assessed to determine the relative incidence of protease families in the cell secretory pathway. Transient expression assays with the model platform Nicotiana benthamiana were then performed to test the efficiency of protease inhibitors in stabilizing proteins targeted to the apoplast. Current genomic data suggest the occurrence of proteases from several families along the secretory pathway, including A1 and A22 Asp proteases; C1A and C13 Cys proteases; and S1, S8 and S10 Ser proteases. In vitro protease assays confirmed the presence of various proteases in N. benthamiana leaves, notably pointing to the deposition of A1‐ and S1‐type activities preferentially in the apoplast. Accordingly, transient expression and secretion of the A1/S1 protease inhibitor, tomato cathepsin D inhibitor (SlCDI), negatively altered A1 and S1 protease activities in this cell compartment, while increasing the leaf apoplast protein content by ∼45% and improving the accumulation of a murine diagnostic antibody, C5‐1, co‐secreted in the apoplast. SlCYS9, an inhibitor of C1A and C13 Cys proteases, had no impact on the apoplast proteases and protein content, but stabilized C5‐1 in planta, presumably upstream in the secretory pathway. These data confirm, overall, the potential of protease inhibitors for the in situ protection of recombinant proteins along the plant cell secretory pathway.
Resistance to Wheat streak mosaic virus generated by expression of an artificial polycistronic microRNA in wheat
Authors: Fahim Muhammad , Millar Anthony A. , Wood Craig C. , Larkin Philip J.
Published: September 2011

Wheat streak mosaic virus (WSMV) is a persistent threat to wheat production, necessitating novel approaches for protection. We developed an artificial miRNA strategy against WSMV, incorporating five amiRNAs within one polycistronic amiRNA precursor. Using miRNA sequence and folding rules, we chose five amiRNAs targeting conserved regions of WSMV but avoiding off‐targets in wheat. These replaced the natural miRNA in each of five arms of the polycistronic rice miR395, producing amiRNA precursor, FanGuard (FGmiR395), which was transformed into wheat behind a constitutive promoter. Splinted ligation detected all five amiRNAs being processed in transgenic leaves. Resistance was assessed over two generations. Three types of response were observed in T1 plants of different transgenic families: completely immune; initially resistant with resistance breaking down over time; and initially susceptible followed by plant recovery. Deep sequencing of small RNAs from inoculated leaves allowed the virus sequence to be assembled from an immune transgenic, susceptible transgenic, and susceptible non‐transgenic plant; the amiRNA targets were fully conserved in all three isolates, indicating virus replication on some transgenics was not a result of mutational escape by the virus. For resistant families, the resistance segregated with the transgene. Analysis in the T2 generation confirmed the inheritance of immunity and gave further insights into the other phenotypes. Stable resistant lines developed no symptoms and no virus by ELISA; this resistance was classified as immunity when extracts failed to transmit from inoculated leaves to test plants. This study demonstrates the utility of a polycistronic amiRNA strategy in wheat against WSMV.
Field performance of transgenic sugarcane expressing isomaltulose synthase
Authors: Basnayake Shiromani W. V. , Morgan Terrance C. , Wu Luguang , Birch Robert G.
Published: September 2011

Transgenic sugarcane plants expressing a vacuole‐targeted isomaltulose (IM) synthase in seven recipient genotypes (elite cultivars) were evaluated over 3 years at a field site typical of commercial cane growing conditions in the Burdekin district of Australia. IM concentration typically increased with internode maturity and comprised up to 217 mm (33% of total sugars) in whole‐cane juice. There was generally a comparable decrease in sucrose concentration, with no overall decrease in total sugars. Sugarcane is vegetatively propagated from stem cuttings known as setts. Culture‐derived plants were slower to establish and generally gave shorter and thinner stalks at harvest than those grown from field‐sourced setts in the initial field generations. However, after several cycles of field propagation, selections were obtained with cane yields similar to the recipient genotypes. There was no apparent adverse effect of IM accumulation on vigour assessed by stalk height and diameter or other visual indicators including germination of setts and establishment of stools. There was some inconsistency in IM levels in juice, between samplings of the vegetatively propagated transgenic lines. Until the causes are resolved, it is prudent to selectively propagate from stalks with higher IM levels in the initial vegetative field generations. Pol/Brix ratio allowed rapid identification of lines with high IM levels, using common sugar industry instruments. Sucrose isomerase activity was low in these transgenic lines, and the results indicate strong potential to develop sugarcane for commercial‐scale production of IM if higher activity can be engineered in appropriate developmental patterns.
Serving the Nation: Devolution and the Civil Service in Wales
Authors: Cole Alistair
Published: September 2011

The article captures the evolution of the moving object of Welsh devolution over its first decade through a case study of the civil service in Wales. Three positions are proposed as heuristics for understanding politico-administrative relations in devolved Wales: these are administrative persistence, capacity-building and bureaucratic capture. Rather than set these dynamics against each other, the case study of the civil service in Wales demonstrates the value of reasoning in terms of a mix of administrative, political and managerial pressures, requiring the development of hybrid responses and skills. Although the institutional capacity-building dynamic clearly had the ascendancy during the first decade, as the post-devolution Welsh polity gradually becomes more settled, there is likely to be a revival of more generic administrative and/or managerial concerns.
How Has CEO Turnover Changed?
Authors: Kaplan Steven N. , Minton Bernadette A.
Published: September 2011

We study CEO turnover – both internal (board driven) and external (through takeover and bankruptcy) – from 1992 to 2007 for a sample of large US companies. Annual CEO turnover is higher than that estimated in previous studies over earlier periods. Turnover is 15.8% from 1992 to 2007, implying an average tenure as CEO of less than 7 years. In the more recent period since 2000, total CEO turnover increases to 16.8%, implying an average tenure of less than 6 years. Internal turnover is significantly related to three components of firm stock performance – performance relative to industry, industry performance relative to the overall market, and the performance of the overall stock market. The relations are stronger in the more recent period since 2000. We find similar patterns for both forced and unforced turnover, suggesting that some, if not most, turnover labeled as unforced is actually not voluntary. The turnover‐performance sensitivity is modestly related to block shareholder ownership and board independence.
Synthesis and pigmental properties of titanium phosphates with the addition of urea
Authors: Onoda H. , Yamaguchi T. , Takenaka A.
Published: September 2011

Synopsis

As a white pigment, titanium oxide is used for cosmetic application. This oxide is well known to have the photo catalytic activity. Therefore, a certain degree of sebum is decomposed by the ultraviolet radiation in the sunlight. In this work, titanium phosphates were prepared as a novel white pigment. Their chemical composition, powder properties, photo catalytic activity, moisture retention and smooth were studied with the addition of urea. These white pigments had little photo catalytic activity. The addition of urea improved the moisture retention of titanium phosphates. The slipping resistance of samples became small by heating, on the other hand, the roughness of samples became small by the addition of urea.
Asset Substitution and Debt Renegotiation
Authors: Flor Christian Riis
Published: September 2011

Abstract:  In a dynamic capital structure model we study whether asset substitution implies agency costs when the firm initially takes the substitution option into account. Asset substitution affects earnings in two directions: volatility increases and growth rate decreases. We show that substitution implies agency costs if volatility increases enough. In this case, debt renegotiation to avoid substitution mitigates the ex ante costs. However, debt renegotiation decreases the equity holders’ ex post costs. Thus, with a modest volatility increase, debt renegotiation allows equity holders to extract concessions from creditors albeit asset substitution was not chosen for non‐renegotiable debt. Hence, debt renegotiation need not improve ex ante firm value if asset substitution is allowed for.
Mouse class III myosins: kinase activity and phosphorylation sites
Authors: Dalal Jasbir S. , Stevens Stanley M. , Alvarez Sophie , Munoz Nathalie , Kempler Karen E. , Dosé Andrea C. , Burnside Beth , Battelle Barbara‐Anne
Published: September 2011

J. Neurochem. (2011) 119, 772–784.

As class III unconventional myosins are motor proteins with an N‐terminal kinase domain, it seems likely they play a role in both signaling and actin based transport. A growing body of evidence indicates that the motor functions of human class IIIA myosin, which has been implicated in progressive hearing loss, are modulated by intermolecular autophosphorylation. However, the phosphorylation sites have not been identified. We studied the kinase activity and phosphorylation sites of mouse class III myosins, mMyo3A and 3B, which are highly similar to their human orthologs. We demonstrate that the kinase domains of mMyo3A and 3B are active kinases, and that they have similar, if not identical, substrate specificities. We show that the kinase domains of these proteins autophosphorylate, and that they can phosphorylate sites within their myosin and tail domains. Using liquid chromatography‐mass spectrometry, we identified phosphorylated sites in the kinase, myosin motor and tail domains of both mMyo3A and 3B. Most of the phosphorylated sites we identified and their consensus phosphorylation motifs are highly conserved among vertebrate class III myosins, including human class III myosins. Our findings are a major step toward understanding how the functions of class III myosins are regulated by phosphorylation.
The immune molecule CD3zeta and its downstream effectors ZAP‐70/Syk mediate ephrin signaling in neurons to regulate early neuritogenesis
Authors: Angibaud Julie , Louveau Antoine , Baudouin Stéphane J. , Nerrière‐Daguin Véronique , Evain Sarah , Bonnamain Virginie , Hulin Philippe , Csaba Zsolt , Dournaud Pascal , Thinard Reynald , Naveilhan Philippe , Noraz Nelly , Pellier‐Monnin Véronique , Boudin Hélène
Published: September 2011

J. Neurochem. (2011) 119, 708–722.

Recent studies have highlighted the key role of the immune protein CD3ζ in the maturation of neuronal circuits in the CNS. Yet, the upstream signals that might recruit and activate CD3ζ in neurons are still unknown. In this study, we show that CD3ζ functions early in neuronal development and we identify ephrinA1‐dependent EphA4 receptor activation as an upstream regulator of CD3ζ. When newly born neurons are still spherical, before neurite extension, we found a transient CD3ζ aggregation at the cell periphery matching the initiation site of the future neurite. This accumulation of CD3ζ correlated with a stimulatory effect on filopodia extension via a Rho‐GEF Vav2 pathway and a repression of neurite outgrowth. Conversely, cultured neurons lacking CD3ζ isolated from CD3ζ−/− mice showed a decreased number of filopodia and an enhanced neurite number. Stimulation with ephrinA1 induces the translocation of both CD3ζ and its activated effector molecules, ZAP‐70/Syk tyrosine kinases, to EphA4 receptor clusters. EphrinA1‐induced growth cone collapse was abrogated in CD3ζ−/− neurons and was markedly reduced by ZAP‐70/Syk inhibition. Moreover, ephrinA1‐induced ZAP‐70/Syk activation was inhibited in CD3ζ−/− neurons. Altogether, our data suggest that CD3ζ mediates the ZAP‐70/Syk kinase activation triggered by ephrinA‐activated pathway to regulate early neuronal morphogenesis.
Smad proteins differentially regulate transforming growth factor‐β‐mediated induction of chondroitin sulfate proteoglycans
Authors: Susarla Bala T. S. , Laing Eric D. , Yu Panpan , Katagiri Yasuhiro , Geller Herbert M. , Symes Aviva J.
Published: September 2011

J. Neurochem. (2011) 119, 868–878.

Traumatic injury to the CNS results in increased expression and deposition of chondroitin sulfate proteoglycans (CSPGs) that are inhibitory to axonal regeneration. Transforming growth factor‐β (TGF‐β) has been implicated as a major mediator of these changes, but the mechanisms through which TGF‐β regulates CSPG expression are not known. Using lentiviral expressed Smad‐specific ShRNA we show that TGF‐β induction of CSPG expression in astrocytes is Smad‐dependent. However, we find a differential dependence of the synthetic machinery on Smad2 and/or Smad3. TGF‐β induction of neurocan and xylosyl transferase 1 required both Smad2 and Smad3, whereas induction of phosphacan and chondroitin synthase 1 required Smad2 but not Smad3. Smad3 knockdown selectively reduced induction of chondroitin‐4‐sulfotransferase 1 and the amount of 4‐sulfated CSPGs secreted by astrocytes. Additionally, Smad3 knockdown in astrocytes was more efficacious in promoting neurite outgrowth of neurons cultured on the TGF‐β‐treated astrocytes. Our data implicate TGF‐β Smad3‐mediated induction of 4‐sulfation as a critical determinant of the permissiveness of astrocyte secreted CSPGs for axonal growth.
Integrating detection probabilities in species distribution models of amphibians breeding in Mediterranean temporary ponds
Authors: Gómez‐Rodríguez Carola , Bustamante Javier , Díaz‐Paniagua Carmen , Guisan Antoine
Published: September 2011

Aim  The imperfect detection of species may lead to erroneous conclusions about species–environment relationships. Accuracy in species detection usually requires temporal replication at sampling sites, a time‐consuming and costly monitoring scheme. Here, we applied a lower‐cost alternative based on a double‐sampling approach to incorporate the reliability of species detection into regression‐based species distribution modelling.

Location  Doñana National Park (south‐western Spain).

Methods  Using species‐specific monthly detection probabilities, we estimated the detection reliability as the probability of having detected the species given the species‐specific survey time. Such reliability estimates were used to account explicitly for data uncertainty by weighting each absence. We illustrated how this novel framework can be used to evaluate four competing hypotheses as to what constitutes primary environmental control of amphibian distribution: breeding habitat, aestivating habitat, spatial distribution of surrounding habitats and/or major ecosystems zonation. The study was conducted on six pond‐breeding amphibian species during a 4‐year period.

Results  Non‐detections should not be considered equivalent to real absences, as their reliability varied considerably. The occurrence of Hyla meridionalis and Triturus pygmaeus was related to a particular major ecosystem of the study area, where suitable habitat for these species seemed to be widely available. Characteristics of the breeding habitat (area and hydroperiod) were of high importance for the occurrence of Pelobates cultripes and Pleurodeles waltl. Terrestrial characteristics were the most important predictors of the occurrence of Discoglossus galganoi and Lissotriton boscai, along with spatial distribution of breeding habitats for the last species.

Main conclusions  We did not find a single best supported hypothesis valid for all species, which stresses the importance of multiscale and multifactor approaches. More importantly, this study shows that estimating the reliability of non‐detection records, an exercise that had been previously seen as a naïve goal in species distribution modelling, is feasible and could be promoted in future studies, at least in comparable systems.
Identifying hotspots for biodiversity management using rank abundance distributions
Authors: Dunstan Piers K. , Bax Nicholas J. , Foster Scott D. , Williams Alan , Althaus Franziska
Published: September 2011

Aim Identification of biodiversity hotspots has typically relied on species richness. We extend this approach to include prediction to regional scales of other attributes of biodiversity based on the prediction of Rank Abundance Distributions (RADs). This allows us to identify areas that have high numbers of rare species and areas that have a rare assemblage structure.

Location Continental slope and shelf of south‐western Australia, between 20.5 and 30° S and depths of 100–1500 m.

Methods We use a recently developed method to analyse RADs from biological surveys and predict attributes of RADs to regional scales from spatially abundant physical data for demersal fish and invertebrates. Predictions were made for total abundance (N), species richness (S) and relative evenness at 147,996 unsampled locations using data from two spatially limited surveys. The predictions for S and relative evenness were then independently split into categories, creating a bivariate distribution. The RAD categories are mapped spatially between 20.5 and 30° S to depths of 1500 m to allow identification of areas with rare species and assemblage structure across this region.

Results Rank abundance distributions for demersal fish vary with large scale oceanographic patterns. Peaks in abundance and unevenness are found on the shelf break. The bivariate distributions for richness and evenness for both fish and invertebrates show that all assemblage structures are not equally likely. The RAD categories identify regions that have high numbers of rare species and areas with unique assemblage structure.

Main conclusions Predicted RADs over large regions can be used to identify biodiversity hotspots in more detail than richness alone. Areas of rare species and rare assemblage structure identified from fish and invertebrates largely overlap, despite the underlying data coming from two different data sets with two different collection methods. This approach allows us to target conservation management at species that would otherwise be missed.
Clinical effects and outcomes with new P2Y12 inhibitors in ACS
Authors: Collet Jean‐Philippe , O’Connor Stephen
Published: September 2011

Thienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, characteristics that make them particularly attractive for high‐risk percutaneous coronary intervention (PCI). Four new P2Y12 inhibitors have been tested each of them having particular individual properties. Prasugrel is an oral pro‐drug leading to irreversible blockade of the P2Y12 receptor and is approved worldwide for ACS PCI. Ticagrelor is a direct‐acting and reversible inhibitor of the P2Y12 receptor with potentially more pleiotropic effects. Cangrelor is an intravenous direct and reversible inhibitor of the P2Y12 receptor providing the highest level of inhibition, and elinogrel is an intravenous and oral P2Y12 antagonist with a direct and reversible action. Both prasugrel and ticagrelor, opposed to clopidogrel, have shown that stronger P2Y12 inhibition led respectively to significant 19 and 16% relative risk reduction of a similar primary end point combining cardiovascular death, non‐fatal myocardial infarction, or non‐fatal stroke. Both drugs showed a significant 0.6% absolute excess of TIMI major bleeding not related to CABG surgery. Because in clinical trials, patients perceived to be at higher risk of bleeding usually are excluded, the risk of major and even fatal bleeding might even be higher in a ‘real‐world’ setting, i.e. in the elderly patient with comorbidities. On the other hand, these newly developed P2Y12 inhibitors decrease mortality after PCI compared with clopidogrel. The risk/benefit ratio is particularly favorable in PCI for patients with STEMI.
Pharmacokinetic basis of the antiplatelet action of prasugrel
Authors: Schrör Karsten , Siller‐Matula Jolanta M. , Huber Kurt
Published: September 2011

Prasugrel is the most recent development of thienopyridine‐type antiplatelet drugs. Like the earlier‐generation thienopyridines, i.e. ticlopidine and clopidogrel, prasugrel is also an inactive prodrug that requires metabolic processing in vivo to generate the active antiplatelet metabolite. The efficacy of this bioactivation is the key determinant for the pharmacodynamic potency of the compound, i.e. the irreversible blockade of the platelet P2Y12‐ADP receptor. Prasugrel is rapidly absorbed from the gut. After oral administration of standard‐loading doses of 60 mg, maximum plasma levels of the active metabolite are achieved within 1 h, effective, maximum inhibition of platelet aggregation at 1–2 h. Bioconversion of prasugrel into the active metabolite requires two metabolic steps that occur in sequence. The first is the generation of a thiolactone‐intermediate, mainly by carboxyesterases‐2 in the intestine, the second the cytochrome (CYP)‐dependent conversion of the thiolactone into the active metabolite. This second step involves several cytochromes, most notably CYP3A4, CYP2C19, CYP2B6, and CYP2C9. The enzymatic generation of the active metabolite of prasugrel is much more effective than that of clopidogrel where only about 5% of oral clopidogrel is transformed into the active compound by two‐step CYP‐dependent procedures. About 70% of prasugrel metabolites are excreted in the urine and 30% in the feces. The molar potency of the respective active metabolites of prasugrel and clopidogrel is identical. Thus, the more rapid onset, higher potency and lower interindividual variability of antiplatelet effects of prasugrel as compared to clopidogrel in vivo are entirely because of its more efficient pharmacokinetics.
Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues
Authors: Lin Ligen , Saha Pradip K. , Ma Xiaojun , Henshaw Iyabo O. , Shao Longjiang , Chang Benny H. J. , Buras Eric D. , Tong Qiang , Chan Lawrence , McGuinness Owen P. , Sun Yuxiang
Published: September 2011

Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show that ablation of the ghrelin receptor (growth hormone secretagogue receptor, GHS‐R) improves insulin sensitivity during aging. Compared to wild‐type (WT) mice, old Ghsr−/− mice have reduced fat and preserve a healthier lipid profile. Old Ghsr−/− mice also exhibit elevated energy expenditure and resting metabolic rate, yet have similar food intake and locomotor activity. While GHS‐R expression in white and brown adipose tissues was below the detectable level in the young mice, GHS‐R expression was readily detectable in visceral white fat and interscapular brown fat of the old mice. Gene expression profiles reveal that Ghsr ablation reduced glucose/lipid uptake and lipogenesis in white adipose tissues but increased thermogenic capacity in brown adipose tissues. Ghsr ablation prevents age‐associated decline in thermogenic gene expression of uncoupling protein 1 (UCP1). Cell culture studies in brown adipocytes further demonstrate that ghrelin suppresses the expression of adipogenic and thermogenic genes, while GHS‐R antagonist abolishes ghrelin’s effects and increases UCP1 expression. Hence, GHS‐R plays an important role in thermogenic impairment during aging. Ghsr ablation improves aging‐associated obesity and insulin resistance by reducing adiposity and increasing thermogenesis. Growth hormone secretagogue receptor antagonists may be a new means of combating obesity by shifting the energy balance from obesogenesis to thermogenesis.
Depressive symptomatology and service utilisation among refugee children and adolescents living in South Australia
Authors: Ziaian Tahereh , de Anstiss Helena , Antoniou Georgia , Sawyer Michael , Baghurst Peter
Published: September 2011

Background:  Young refugees resettled in Western countries are at increased risk of mental health problems. However, most research has centred on post traumatic stress disorder (PTSD), with depression, other mental health disorders, and problems receiving comparatively less attention.

Method:  Depressive symptomatology was assessed using the Children’s Depression Inventory (CDI) in a multiethnic community sample of 348 refugee children (n = 180) and adolescents (n = 168) aged 7–17 years living in South Australia.

Results:  According to parent reports, 7.1% of children and adolescents had depressive symptomatology for which services were available and yet only 21.5% of these accessed services.

Conclusions:  Young refugees need improved access to culturally appropriate mental health care.
ARCHAEOMETALLURGICAL CHARACTERIZATION OF HELLENISTIC METAL OBJECTS: THE CONTRIBUTION OF THE BRONZE OBJECTS FROM RISHON LE‐ZION (ISRAEL)*
Authors: ASHKENAZI D. , IDDAN N. , TAL O.
Published: September 2011

An archaeometallurgical analysis is presented of 14 bronze artefacts retrieved from an Early Hellenistic–period farmstead in controlled archaeological excavations at Rishon Le‐Zion, Israel, and dated to the first quarter of the third century bce according to coins and pottery vessels. The bronze assemblage includes a needle, pins, spatulas and fibulas. The aims of the research are to determine the composition, microstructure and manufacturing process of these artefacts, and to discover their place of production. This will provide a better understanding of Hellenistic technological abilities and material culture. The examination included optical microscopy, microhardness, SEM including EDS, and XRD. The results show that the collection consists of Cu–Sn binary alloys, with evidence for a controlled alloying process and the absence of recycling. Furthermore, the microstructure of the objects indicates that all artefacts were produced by a cold‐working process. Moreover, the manufacturing process of the rectangular cross‐section fibulas included sophisticated joining techniques of copper and iron.
Remains of Hipparion (Equidae, Perissodactyla) from Puente Minero (Teruel Province, Spain) and their implications for the systematics of the Turolian Hipparionini
Authors: PESQUERO MARÍA D. , ALBERDI MARÍA T. , ALCALÁ LUIS
Published: September 2011

Abstract:  Morphological and biometrical variability of the equid Hipparion from Puente Minero and other localities from the Teruel Basin, Spain (MN10–MN13), is analysed. Three species of Hipparion are recognized in Puente Minero, H. laromae, H. matthewi and Hipparion sp. cf. H. longipes, through comparison with other Spanish and Eurasian species (Samos, Greece; Höwenegg, Germany; Pavlodar, Kazakhstan, small and large forms; Akkaşdaği, Turkey; and the following Spanish sites, La Roma 2, Los Aljezares, Concud, Milagros, Las Casiones and Venta de Moro). The majority of the Hipparion remains from Puente Minero and determined to be Hipparion laromae based on their size and morphology. This interpretation was confirmed by bivariate and multivariate analyses. These results suggest a Eurasian immigration of different Hipparion species into the Teruel Basin.
Is the Age Gradient in Self‐Reported Material Hardship Explained By Resources, Needs, Behaviors, or Reporting Bias?
Authors: Siminski Peter , Yerokhin Oleg
Published: September 2011

Older people report much less hardship than younger people in a range of contexts, despite lower incomes. Hardship indicators are increasingly influential, so the source of this age gradient has considerable policy implications. We propose a theoretical and empirical strategy to decompose the sources of this relationship. We exploit a unique feature of the Household, Income and Labour Dynamics Australia (HILDA) survey, which collects reports of hardship from all adult household members. This facilitates within‐couple estimates, allowing us to identify age‐related reporting bias. The majority of the raw age–hardship gradient is explained by observed resources, particularly wealth and home ownership. One third of the relationship is explained by unobserved differences between households, which we interpret as age‐related behavioral choices. Reporting error does not appear to contribute to the age gradient.
FOOD INSECURITY AND INSUFFICIENCY AT LOW LEVELS OF FOOD EXPENDITURES
Authors: GUNDERSEN CRAIG , RIBAR DAVID
Published: September 2011

In this study we investigate the external validity of the food insecurity and insufficiency measures—specifically, how these measures correlate with food expenditures—using the December 2003 Food Security Supplement of the Current Population Survey. We focus on a special segment of the population—households with low incomes and low food expenditures. If reports of food problems are based on a lack of food, reports should be nearly ubiquitous at the bottom of the expenditure distribution. We find, however, that this is not the case. We define and scale food expenditures several different ways and find that the reported incidence of food insecurity never rises above one‐half anywhere along the corresponding expenditure distributions, leading to concerns about the external validity of the measure.
Evaluation of minichromosome maintenance protein 7 as a prognostic marker in canine cutaneous mast cell tumours*
Authors: Berlato D. , Stewart J. , Newton R. , Maglennon G. A. , Monti P. , Flindall A. , Murphy S.
Published: September 2011

Minichromosome maintenance proteins (MCMs) are sensitive markers of cellular proliferation and have been shown to be significant predictors of survival in several human malignancies. MCM7 was evaluated as a prognostic marker in canine cutaneous mast cell tumours (MCTs). MCM7 immunohistochemistry was performed and an index of MCM7‐positive cells calculated in dogs with known outcome. The Receiver Operating Characteristics method was used to individuate the best cut‐off value of MCM7 score as predictor of survival. Survival analysis and prognostic variables were analysed with statistical methods. Ninety‐five dogs were included with 31 dying of MCTs. A value of 0.18 was used as cut‐off value of MCM7 score as a binary variable. The median survival time for MCM7 score ≤0.18 was not reached at 3668 days, whereas for MCM7 score >0.18 was 187 days (log‐rank test;P< 0.0001). In the multivariable analysis, MCM7 was significantly associated with survival after controlling for age, surgical margins and histological grade (hazard ratio 9.2;P= 0.001).
Retracted: Unrecognized High Brachial Artery Bifurcation is Associated with Higher Rate of Dialysis Access Failure
Authors: Kirksey Lee
Published: September 2011

A thorough consideration of all factors contributing to successful dialysis access creation is necessary to achieve optimal outcomes. A high bifurcation of the brachial artery (brachioradial variant) occurs in greater than 20% of patients. Dialysis access was created in 22 limbs with this variant—15 fistula, and 7 prosthetic grafts. Nonmaturation occurred in 33% of fistula. Early thromboses occurred in 29% of prosthetic bridge grafts. In this experience, the brachioradial variant is associated with a relatively higher rate of fistula nonmaturation and prosthetic graft thromboses. These findings reinforce the critical role of preoperative imaging studies in dialysis access creation. A sound algorithm for the surgical management of the brachioradial variation facilitates decision making and will improve dialysis access outcomes.
A Vascular Access Coordinator Improves the Prevalent Fistula Rate
Authors: Dwyer Amy , Shelton Paula , Brier Michael , Aronoff George
Published: September 2011

The Centers for Medicare and Medicaid Services set the prevalent arteriovenous fistula (AVF) rate of 66% as a national standard. To test the hypothesis that the use of a clinical vascular access coordinator could increase the rate of AVF in a large Nephrology group practice, we implemented an aggressive, multidisciplinary vascular access improvement program led by a trained vascular access coordinator (VAC). In early 2009, we established protocols, approved by all physicians, for the care of vascular access and implemented by a nurse VAC. We retrospectively reviewed Network vascular access data reports from January 2008 through December 2010. The data show that after the implementation of a comprehensive access program led by a VAC, the prevalent AVF rate increased from 50% to 65%. The number of grafts decreased while the percentage of dialysis catheters used for more than 90 days was cut in half. These data suggest that despite an unchanged catheter rate at dialysis initiation, the use of a VAC implementing an aggressive, multidisciplinary access program can significantly increase the AVF rate while decreasing grafts and prevalent catheter use.
Resource Utilization and Quality of Life Associated with Congenital Ichthyoses
Authors: Kamalpour Loebat , Gammon Bryan , Chen Kuang‐Ho , Veledar Emir , Pavlis Michelle , Rice Zakiya P. , Chen Suephy C.
Published: September 2011

Abstract:  We explored resource utilization (ResUtil) and quality of life (QOL) associated with congenital ichthyoses (CI). Subjects completed an online survey related to clinical severity, demographics, ResUtil, and QOL as measured according to the Dermatology Life Quality Index (DLQI). Validated Likert scales were used to evaluate severity of hyperkeratosis, erythema, and alopecia. ResUtil was determined according to time spent daily treating CI symptoms (TimeTx) and number of ichthyosis‐related dermatology visits (DermVisits) per year. We used linear regression to investigate predictors of a transformed DLQI (sqrtDLQI) and logistic regression for ResUtil. Of 235 subjects, 60.2% were female, 83.8% were Caucasian, 42.3% had a family history (FamHx) of CI, and the mean age was 28.7 years (SD 20.3). Predictors for worse QOL were hyperkeratosis severity (β = 0.27, p < 0.01), erythema (β = 0.27, p < 0.01), TimeTx (β = 0.21, p < 0.01), ichthyosis type (β = 0.09, p < 0.01), and age (β = 0.01, p = 0.02). Predictors for DermVisits were hyperkeratosis severity (odds ratio [OR] = 1.38, 95% confidence limit [CL] = 1.01, 1.87), FamHx (OR = 0.28, 95% CL = 0.09, 0.85), age (OR = 0.97, 95% CI = 0.96, 0.99), and alopecia severity (OR = 1.43, 95% CL = 1.12, 1.82). Predictors for treatment duration were erythema (OR = 1.35, 95% CL = 1.02, 1.78), age (OR = 0.98, 95% CL = 0.96, 0.99), and DLQI (OR = 1.09, 95% CL = 1.03, 1.15). Increased hyperkeratosis severity and erythema negatively impact QOL in the CI. Furthermore, increased disease severity predicted greater ResUtil, whereas increased age and FamHx predicted less ResUtil. Our findings suggest that better therapies and increased patient education may improve QOL and decrease ResUtil.
Clonality of Staphylococcus aureus Colonization over Time in Attendees of a Camp for Children with Chronic Dermatoses
Authors: Graber Christopher J. , Shane Andi L. , Weintrub Peggy , Chambers Henry F.
Published: September 2011

Abstract:  Chronic dermatoses are risk factors for Staphylococcus aureus colonization; little is known about the significance of transmission between persons with chronic dermatoses (CD) and their contacts. We collected nasal, axillary, and skin swabs for S. aureus from 50 attendees of a camp for children with CD and their families at three time points: start and end of 2005 camp and start of 2006 camp (times A, B, and C, respectively). Thirty‐one persons had CD, including epidermolysis bullosa (n = 14), atopic dermatitis (n = 7), ichthyosis (n = 5), and psoriasis (n = 5). Methicillin susceptibility and genotype were determined for all S. aureus isolates. Seventy‐one unique S. aureus isolate from 10 clonal complexes (CC) were isolated; 14 (20%) were methicillin‐resistant (MRSA). Persons with CD were more likely than those without CD to be colonized with S. aureus at the start of the 2005 (p = 0.01) and 2006 (p = 0.02) camp or at any time or site (p = 0.04) or to be persistently colonized with the same S. aureus CC at the start and end of the 2005 camp. Persons with atopic dermatitis had the highest burden of S. aureus colonization, whereas MRSA was isolated most frequently from attendees with epidermolysis bullosa. Three hospitalizations for skin infections were noted in people with CD between the 2005 and 2006 camps, versus three hospitalizations in the 6 months before the 2005 camp. Although S. aureus colonization was frequent among camp attendees (and in persons with CD in particular), it was diverse and variable. Camp attendance did not appear to affect infection‐related clinical outcomes.
Budesonide‐Induced Periorificial Dermatitis Presenting as Chalazion and Blepharitis
Authors: HENNINGSEN EMIL , BYGUM ANETTE
Published: September 2011

Abstract:  We report a case of periorificial dermatitis caused by suboptimal inhalation of budesonide for asthma. The initial skin lesions presented in the eye surroundings, leading to diagnostic difficulties and treatment of presumed chalazion and staphylococcal folliculitis. After several months, the patient developed perioral papules and pustules and was diagnosed with periorificial dermatitis. He was efficiently treated with topical metronidazole and oral erythromycin.
Aleukemic Leukemia Cutis in a Child Preceding T‐Cell Acute Lymphoblastic Leukemia
Authors: Najem Nabeel , Zadeh Valid B. , Badawi Mona , Kumar Ramesh , Al‐Otaibi Sultan , Al‐Abdulrazzaq Adel
Published: September 2011

Abstract:  An 8‐year‐old boy presented with a widespread cutaneous eruption featuring macules, papules, nodules, and ulcers. The histologic infiltrate showed T lymphoblasts, but there was no sign of systemic involvement, so aleukemic leukemia cutis was diagnosed. Two months later, he developed leukemia in peripheral blood and bone marrow that was characterized as T‐cell acute lymphoblastic leukemia.
Atrial Fibrillation Hospitalization Is Not Increased with Short‐Term Elevations in Exposure to Fine Particulate Air Pollution
Authors: BUNCH T. JARED , HORNE BENJAMIN D. , ASIRVATHAM SAMUEL J. , DAY JOHN D. , CRANDALL BRIAN G. , WEISS J. PETER , OSBORN JEFFREY S. , ANDERSON JEFFREY L. , MUHLESTEIN JOSEPH B. , LAPPE DONALD L. , POPE III C. ARDEN
Published: September 2011

Background: Previous studies have observed that short‐term exposure to elevated concentrations of particulate matter (PM) air pollution increases risk of acute ischemic heart disease events and heart failure hospitalization, alters cardiac autonomic function, and increases risk of arrhythmias. This study explored the potential associations between short‐term elevations in PM exposure and atrial fibrillation (AF).

Methods and Results: A case‐crossover study design was used to explore associations between fine PM (PM2.5, particles with an aerodynamic diameter ≤2.5 μm) and 10,457 AF hospitalizations from 1993 to 2008 of patients who lived on Utah's Wasatch Front. Patients were hospitalized at Intermountain Healthcare facilities with a primary diagnosis of AF. Concurrent day exposure and cumulative lagged exposures for up to 21 days were explored and the data were stratified by sex, age, and previous or subsequent admission for myocardial infarction. Although the estimated associations between PM2.5 and AF hospitalizations for the various lag structures and strata were consistently positive suggestive of risk, they were not statistically significant and they were extremely small compared to previously observed associations with ischemic heart disease events and heart failure hospitalizations. Further, we observed no additive risk between PM2.5 and AF hospitalization in those with respiratory disease or sleep apnea.

Conclusions: Unlike previously observed associations with ischemic heart disease events and heart failure hospitalizations using similar study design and approaches, this study found that hospitalization for AF was not significantly associated with elevations in short‐term exposure to fine PM air pollution. (PACE 2011; 34:1475–1479)
Ranolazine Reduces Ventricular Tachycardia Burden and ICD Shocks in Patients with Drug‐Refractory ICD Shocks
Authors: BUNCH T. JARED , MAHAPATRA SRIJOY , MURDOCK DAVID , MOLDEN JAMIE , WEISS J. PETER , MAY HEIDI T. , BAIR TAMI L. , MADER KATY M. , CRANDALL BRIAN G. , DAY JOHN D. , OSBORN JEFFREY S. , MUHLESTEIN JOSEPH B. , LAPPE DONALD L. , ANDERSON JEFFREY L.
Published: September 2011

Background:
 There are limited options for patients who present with antiarrhythmic‐drug (AAD)‐refractory ventricular tachycardia (VT) with recurrent implantable cardioverter defibrillator (ICD) shocks. Ranolazine is a drug that exerts antianginal and antiischemic effects and also acts as an antiarrhythmic in isolation and in combination with other class III medications. Ranolazine may be an option for recurrent AAD‐refractory ICD shocks secondary to VT, but its efficacy, outcomes, and tolerance are unknown.

Methods and Results:
 Twelve patients (age 65 ± 9.7 years) were treated with ranolazine. Eleven (92%) were male, and 10 (83%) had ischemic heart disease with an average ejection fraction of 0.34 ± 0.13. All patients were on a class III AAD (11 amiodarone, one sotalol), with six (50%) receiving mexilitene or lidocaine. Five patients had a prior ablation and two were referred for a VT ablation at the index presentation. The QRS increased nonsignificantly from 128 ± 31 ms to 133 ± 31 ms, and the QTc increased nonsignificantly from 486 ± 32 ms to 495 ± 31 ms after ranolazine initiation. Over a follow‐up of 6 ± 6 months, 11 (92%) patients had a significant reduction in VT and no ICD shocks were observed. VT ablation was not required in those referred. In two patients, gastrointestinal side effects limited long‐term use. Of these two patients, one died due to progressive heart failure. In one patient, severe hypoglycemia limited dosing to 500 mg daily, but this was sufficient for VT control.

Conclusion:
 Ranolazine proved effective in reducing VT burden and ICD shocks in patients with AAD‐refractory VT. Ranolazine should be further tested for this indication and considered for clinical application when other options have proven ineffective. (PACE 2011; 34:1600–1606)
Radiofrequency Catheter Ablation of Posterior Paraseptal Accessory Pathway with Atresia of the Coronary Sinus Ostium
Authors: YOSHIDA SUSUMU , YOKOE HIROSHI , MURAKAWA KOUSUKE , TAKAGI MASAHIKO , YUASA FUMIO , KAMIHATA HIROSHI , IWASAKA TOSHIJI
Published: September 2011

A 42‐year‐old man was referred to our hospital for an electrophysiologic study because of recurrent episodes of palpitation. On coronary angiogram, an anomalous atresia of the coronary sinus (CS) ostium was discovered. The ablation catheter was inserted from the right femoral artery to the accessory pathway (AP) of posterior paraseptal area. The earliest retrograde atrial activation was recorded in the 5–6 o'clock region of the mitral annulus. Radiofrequency energy was delivered to this site, resulting in elimination of the AP. After this application, there was persistent ventriculoatrial dissociation and led to successful ablation of the AP. PACE 2012; 35:e80–e83)
Immune response to human embryonic stem cell‐derived cardiac progenitors and adipose‐derived stromal cells
Authors: Calderon Damelys , Planat‐Benard Valérie , Bellamy Valérie , Vanneaux Valérie , Kuhn Chantal , Peyrard Severine , Larghero Jéröome , Desnos Michel , Casteilla Louis , Pucéat Michel , Menasché Philippe , Chatenoud Lucienne
Published: September 2011

Transplantation of allogeneic human embryonic stem cell‐derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of adipose‐derived stromal cells (ADSC). Peripheral blood mononuclear cells were collected from 40 patients with coronary artery disease (CAD) and nine healthy controls. Cardiac progenitors (CD15+ Mesp1+) were generated as already reported from the I6 cell line treated with bone morphogenetic protein (BMP)‐2. Adipose‐derived stromal cells were obtained from abdominal dermolipectomies. We assessed the proliferative response of peripheral lymphocytes from patients and controls to cardiac progenitors cultured on a monolayer of ADSC, to allogeneic lymphocytes in mixed lymphocyte culture and to the T cell mitogen phytohemaglutin A in presence or absence of ADSC. Cardiac progenitors cultured on a monolayer of ADSC triggered a proliferation of lymphocytes from both patients and controls albeit lower than that induced by allogeneic lymphocytes. When cultured alone, ADSC did not induce any proliferation of allogeneic lymphocytes. When added to cultures of lymphocytes, ADSC significantly inhibited the alloantigen or mitogen‐induced proliferative response. Compared to healthy controls, lymphocytes from patients presenting CAD expressed a decreased proliferative capacity, in particular to mitogen‐induced stimulation. Adipose‐derived stromal cells express an immunomodulatory effect that limits both alloantigen and mitogen‐induced lymphocyte responses. Furthermore, lymphocytes from patients with CAD are low responders to conventional stimuli, possibly because of their age and disease‐associated treatment regimens. We propose that, in combination, these factors may limit the in vivo immunogenicity of cardiac progenitors co‐implanted with ADSC in patients with CAD.