bluuebunny/crossref_metadata_2025 huggingface dataset:
Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile
Authors: Mercken Evi M. , Crosby Seth D. , Lamming Dudley W. , JeBailey Lellean , Krzysik‐Walker Susan , Villareal Dennis T. , Capri Miriam , Franceschi Claudio , Zhang Yongqing , Becker Kevin , Sabatini David M. , de Cabo Rafael , Fontana Luigi
Published: April 2013

Caloric restriction (CR) and down‐regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long‐term CR in humans inhibits the IGF‐1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF‐1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age‐related diseases and promote health in humans.
Sticky cost behaviour: evidence from small and medium sized companies
Authors: Dalla Via Nicola , Perego Paolo
Published: April 2013

This paper investigates whether cost stickiness occurs in small and medium sized companies using a sample of Italian nonlisted and listed firms during the period 1999–2008. Our findings show that cost stickiness emerges only for the total cost of labour and not for selling, general and administrative (SG&A) costs, cost of goods sold and operating costs. Stickiness of operating costs is only detected in a sample of listed companies. We further contribute to the literature on sticky cost behaviour by discussing critical issues associated with the extant approach of empirical analysis and interpretation of sticky cost behaviour.
Conjunctival goblet cells density and preservative‐free tafluprost therapy for glaucoma: an in vivo confocal microscopy and impression cytology study
Authors: Mastropasqua Leonardo , Agnifili Luca , Fasanella Vincenzo , Curcio Claudia , Ciabattoni Cristina , Mastropasqua Rodolfo , Toto Lisa , Ciancaglini Marco
Published: April 2013

Purpose:  To evaluate the density of conjunctival goblet cells (GCs) in glaucomatous patients treated with preservative‐free (PF) tafluprost, using laser scanning confocal microscopy (LSCM) and impression cytology (IC).

Methods:  Thirty glaucomatous patients (30 eyes) naive for therapy and thirty healthy subjects (30 eyes) were enrolled. Conjunctiva was examined by means of Heidelberg Retina Tomography/Rostock cornea module. Afterwards, the specimens for IC were obtained. Patients were randomized to PF‐tafluprost (Group 1) or preserved latanoprost (Group 2) and controls to the vehicle of latanoprost (Group 3) or physiological buffered saline solution (Group 4). Both LSCM and IC were performed at baseline, and after the 1st and 6th months of therapy, GC density (GCD) (cells/mm2) was the main outcome measurement.

Results:  Baseline. Mean GCD was 240.69 ± 25.43 and 232.65 ± 23.52, for LSCM, and 162.10 ± 23.44 and 164.71 ± 21.03 for IC in Group 1 and 2, respectively. GC density values were not significantly different in Group 3 and 4 (p > 0.05%). Month one. Mean GCD increased to 284.16 ± 43.88 and 230.62 ± 48.32 in Group 1 (p < 0.001) and to 297.86 ± 26.87 and 221.78 ± 43.02 in Group 2 (p < 0.05), measured with LSCM and IC, respectively. In Group 3, GCD decreased to 205.88 ± 25.04 and 139.54 ± 17.37 measured with LSCM and IC, respectively (p < 0.05). Month six. Mean GCD did not change in Group 1 (p > 0.05) whereas it decreased in Group 2 (p < 0.05), compared to month 1. In Group 3, GCD further decreased to 166.32 ± 22.31 and 120.76 ± 11.66, measured with LSCM and IC, respectively (p < 0.05); in Group 4, mean GCD did not change during the study period (p > 0.05).

Conclusions:  Treatment with PF tafluprost was associated with an increase in conjunctival GCD in glaucomatous eyes naïve for therapy. Further studies are mandatory to verify this finding because its validation may have important consequences in the medical management of glaucoma.
Treatment of Status Epilepticus with Ketamine, Are we There yet?
Authors: Dorandeu Frederic , Dhote Franck , Barbier Laure , Baccus Benjamin , Testylier Guy
Published: April 2013

Status epilepticus (SE), a neurological emergency both in adults and in children, could lead to brain damage and even death if untreated. Generalized convulsive SE (GCSE) is the most common and severe form, an example of which is that induced by organophosphorus nerve agents. First‐ and second‐line pharmacotherapies are relatively consensual, but if seizures are still not controlled, there is currently no definitive data to guide the optimal choice of therapy. The medical community seems largely reluctant to use ketamine, a noncompetitive antagonist of the N‐methyl‐d‐aspartate glutamate receptor. However, a review of the literature clearly shows that ketamine possesses, in preclinical studies, antiepileptic properties and provides neuroprotection. Clinical evidences are scarcer and more difficult to analyze, owing to a use in situations of polytherapy. In absence of existing or planned randomized clinical trials, the medical community should make up its mind from well‐conducted preclinical studies performed on appropriate models. Although potentially active, ketamine has no real place for the treatment of isolated seizures, better accepted drugs being used. Its best usage should be during GCSE, but not waiting for SE to become totally refractory. Concerns about possible developmental neurotoxicity might limit its pediatric use for refractory SE.
Effects of the ant Formica fusca on the transmission of microsporidia infecting gypsy moth larvae
Authors: Goertz Dörte , Hoch Gernot
Published: April 2013

Transmission plays an integral part in the intimate relationship between a host insect and its pathogen that can be altered by abiotic or biotic factors. The latter include other pathogens, parasitoids, or predators. Ants are important species in food webs that act on various levels in a community structure. Their social behavior allows them to prey on and transport larger prey, or they can dismember the prey where it was found. Thereby they can also influence the horizontal transmission of a pathogen in its host's population. We tested the hypothesis that an ant species like Formica fusca L. (Hymenoptera: Formicidae) can affect the horizontal transmission of two microsporidian pathogens, Nosema lymantriae Weiser (Microsporidia: Nosematidae) and Vairimorpha disparis (Timofejeva) (Microsporidia: Burenellidae), infecting the gypsy moth, Lymantria dispar L. (Lepidoptera: Erebidae: Lymantriinae). Observational studies showed that uninfected and infected L. dispar larvae are potential prey items for F. fusca. Laboratory choice experiments led to the conclusion that F. fusca did not prefer L. dispar larvae infected with N. lymantriae and avoided L. dispar larvae infected with V. disparis over uninfected larvae when given the choice. Experiments carried out on small potted oak, Quercus petraea (Mattuschka) Liebl. (Fagaceae), saplings showed that predation of F. fusca on infected larvae did not significantly change the transmission of either microsporidian species to L. dispar test larvae. Microscopic examination indicated that F. fusca workers never became infected with N. lymantriae or V. disparis after feeding on infected prey.
Longer tongues and swifter handling: why do more bumble bees (Bombus spp.) than honey bees (Apis mellifera) forage on lavender (Lavandula spp.)?
Authors: BALFOUR NICHOLAS J. , GARBUZOV MIHAIL , RATNIEKS FRANCIS L.W.
Published: April 2013

Lavender (Lavandula spp.) flowers attract more bumble bees (Bombus spp.) than honey bees (Apis mellifera). Counts of bees foraging on Lavandula × intermedia ‘Grosso’ at the University of Sussex campus, showed that bumble bees (92%) greatly outnumbered honey bees (8%). This was not due to a scarcity of honey bees, as the reverse ratio (94% honey bees vs. 6% bumble bees) occurred on borage (Borago officinalis) at the same location.

Video analysis of free‐flying bees revealed that all bumble bee species present (Bombus terrestris/lucorum, Bombus pascuorum, and Bombus lapidarius) handled lavender flowers three times faster than honey bees (mean extraction times: 0.38, 0.37, 0.34 s respectively, vs. 1.30 s; all P < 0.001). Honey bee tongue length (6.6 mm) was approximately 2 mm shorter than those of bumble bees (7.8–8.9 mm) and 1 mm shorter than the lavender corolla tube (c. 7 mm). In addition, bumble bees probed twice as many lavender flowers encountered than honey bees (86% vs. 46%).

Experimentally reducing effective corolla tube length with scalpel incisions significantly decreased extraction time for honey bees (from 1.11 to 0.76 s; P < 0.001) but not for bumble bees (0.33 to 0.28 s; P = 0.266).

Results suggest that honey bees are deterred from foraging on lavender because they are being outcompeted by bumble bees, which forage more efficiently.
Nucleic acid‐based non‐invasive prenatal diagnosis of genetic skin diseases: are we ready?
Authors: Ma Yonghui , Gong He , Wen Yaran
Published: April 2013

The discovery of circulating fetal nucleic acids is a great step on the way of developing non‐invasive prenatal diagnosis (NIPD) for genetic disorders. Here, we briefly discuss the current applications of circulating fetal nucleic acids in genetic testing for different kinds of hereditary diseases with an emphasis on using circulating cell‐free fetal DNA in diagnosis of monogenic disorders. As the genetic skin disorders impair the quality of life at different levels, we next discuss some ethical issues in NIPD for genetic skin diseases of various severities and in particular, the responsibility of doctors and parents, respectively, in the prenatal genetic testing.
Efficacy of single buccal infiltrations for maxillary first molars in patients with irreversible pulpitis: a randomized controlled clinical trial
Authors: Atasoy Ulusoy Ö. İ. , Alaçam T.
Published: April 2013

Aim

To evaluate the efficacy of a single buccal infitration using 4% articaine hydrochloride (HCl) with 1 : 100 000 epinephrine or 4% articaine HCl with 1 : 100 000 epinephrine bitartrate for obtaining adequate pulpal anaesthesia in the palatal roots of maxillary first molars associated with irreversible pulpitis.

Methodology

In this single‐blind randomized clinical trial, fifty subjects were randomly allocated to receive maxillary buccal injections of 1.5 mL 4% articaine with 1 : 100 000 epinephrine (n = 25) or 1.5 mL 4% articaine with 1 : 100 000 epinephrine bitartrate (n = 25). Visual analogue scale (VAS) scores and pulse rate measurements were recorded during access cavity preparation and initial file placement into the mesiobuccal, distobuccal and palatal canals. Data were analysed using Duncan and t‐tests.

Results

There was no significant difference between the two anaesthetic solutions regarding the VAS scores and pulse rate measurements during endodontic procedures. The mean VAS ratings of the 50 patients during file placement into the palatal canals were significantly higher compared with the other three root canal procedures (P < 0.0001). The heart rates during negotiation of palatal canals were significantly higher than when negotiating the mesiobuccal and distobuccal canals (P < 0.0001).

Conclusion

Single buccal infiltration did not achieve adequate pulpal anaesthesia in the palatal root canal of the maxillary first molars associated with irreversible pulpitis.
Acute myeloid leukaemia in Western Australia 1991–2005: a retrospective population‐based study of 898 patients regarding epidemiology, cytogenetics, treatment and outcome
Authors: Gangatharan S. A. , Grove C. S. , P'ng S. , O'Reilly J. , Joske D. , Leahy M. F. , Threlfall T. , Wright M. P.
Published: April 2013

Background

Patient characteristics and cytogenetics of acute myeloid leukaemia (AML) in clinical trials do not reflect that of the general population. There has not been a large population‐based study that has examined cytogenetic features and outcomes of AML in Australia.

Aim

Investigation of epidemiological, prognostic, treatment and outcome data in adults diagnosed with AML in Western Australia between 1991 and 2005.

Methods

Patients were identified utilising the Western Australia Cancer Registry, cytogenetic databases and hospital inpatient discharge diagnoses. Data were retrospectively collected from patients presenting to tertiary hospitals on patient characteristics, karyotype, induction therapy, remission, transplantation and survival.

Results: 

A total of 987 patients with AML was identified, of which 91% (898) attended a tertiary hospital. Median age was 67 years and 45% of cases represented secondary AML. Cytogenetic analysis was available in 81% of patients. Frequent karyotypes were normal (38.8%), complex (13.8%) and −7/add(7q)/del(7q) (12.1%). Aggressive therapy was initiated in 62.6%. Less than 15% were enrolled in clinical trials. Overall 16.5% received a stem cell transplant. Median overall survival for all patients was 5.6 months. In patients treated aggressively, complete remission was achieved in 56.9% and median overall survival was 12.2 months. Age, secondary disease and karyotype were significantly predictive of remission and overall survival.

Conclusion

Age distribution, remission and survival rates were comparable with published population‐based studies. High median age was reflected in the rate of secondary AML and trial eligibility. These findings highlight the need for prospective data collection.
Supporting home care for the dying: an evaluation of healthcare professionals' perspectives of an individually tailored hospice at home service
Authors: Jack Barbara A , Baldry Catherine R , Groves Karen E , Whelan Alison , Sephton Janice , Gaunt Kathryn
Published: April 2013

Aims and objectives

To explore health care professionals' perspective of hospice at home service that has different components, individually tailored to meet the needs of patients.

Background

Over 50% of adults diagnosed with a terminal illness and the majority of people who have cancer, prefer to be cared for and to die in their own home. Despite this, most deaths occur in hospital. Increasing the options available for patients, including their place of care and death is central to current UK policy initiatives. Hospice at home services aim to support patients to remain at home, yet there are wide variations in the design of services and delivery. A hospice at home service was developed to provide various components (accompanied transfer home, crisis intervention and hospice aides) that could be tailored to meet the individual needs of patients.

Design

An evaluation study.

Methods

Data were collected from 75 health care professionals. District nurses participated in one focus group (13) and 31 completed an electronic survey. Palliative care specialist nurses participated in a focus group (9). One hospital discharge co‐ordinator and two general practitioners participated in semi‐structured interviews and a further 19 general practitioners completed the electronic survey.

Results

Health care professionals reported the impact and value of each of the components of the service, as helping to support patients to remain at home, by individually tailoring care. They also positively reported that support for family carers appeared to enable them to continue coping, rapid access to the service was suggested to contribute to faster hospital discharges and the crisis intervention service was identified as helping patients remain in their own home, where they wanted to be.

Conclusions

Health care professionals perceived that the additional individualised support provided by this service contributed to enabling patients to continue be cared for and to die at home in their place of choice.

Relevance to clinical practice

This service offers various components of a hospice at home service, enabling a tailor made package to meet individual and local area needs. Developing an individually tailored package of care appears to be able to meet specific needs.
Differences Between Aggressive and Non‐Aggressive Single Spore Lines of Leptosphaeria maculans in Cultural Characteristics and Phytotoxin Production
Authors: Koch E. , Badawy H. M. A. , Hoppe H. H.
Published: April 2013

Stems of oilseed rape (Brassica napus) bearing pseudothecia of Leptosphaeria maculans were collected in different parts of West Germany. From single ascospores of this material a total of 352 fungal lines were derived, tested on rape cotyledons and devided into 124 aggressive and 228 non‐aggressive pathotypes. The two groups could be distinguished by certain characteristics. On nutrient agar, aggressive strains grew more slowly. In liquid cultures, non‐aggressive types produced a yellow‐brown pigment whereas the culture filtrates of aggressive strains remained unpigmented. The culture filtrates of aggressive lines contained phytotoxic compounds which were identified as sirodesmins. These compounds were absent in culture filtrates of non‐aggressive pathotypes. The very close correlation between aggressiviness as a pathogen and the phytotoxin production indicates that phytotoxins of Leptosphaeria maculans could be involved in the disease development.

Unterschiede zwischen aggressiven und nichtaggressiven Einzelsporlinien von Leptosphaeria maculaos in den Kulturcharakteristiken und der Phytotoxinproduktion

Rapsstengel (Brassica napus) mit Pseudothecien von Leptosphaeria maculans wurden in verschiedenen Teilen der Bundesrepublik gesammelt. Aus einzelnen Ascosporen dieses Materials wurden insgesamt 352 Pilzisolate hergestellt, an Rapskotyledonen getestet und in 124 aggressive und 228 nichaggressive Pathotypen unterteilt. Die beiden Gruppen unterschieden sich in bestimmten charakteristischen Eigenschaften voneinander. Auf Nährböden wuchsen die aggressiven Stämme langsamer. In Flüssigkulturen bildeten die nichtaggressiven Pathotypen gelb‐braune Pigmente, während die Kultur‐filtrate der aggressiven Stämme ungefärbt blieben. Die Kulturfiltrate der aggressiven Linien enthielten dagegen phytotoxische Verbindungen, die als Sirodesmine identifiziert wurden. Diese Verbindungen fehlten in den Kulturfiltraten der nichtaggressiven Pathotypen. Die sehr enge Korrelation zwischen der Aggressivität als Pathogen und der Toxinproduktion deutet darauf hin, daß die Phytotoxine von Leptosphaeria maculans an der Krankheitsentwicklung beteiligt sein könnten.
Comparison of Pathogenesis Related “b1” Protein Determination Obtained by ELISA and HPLC Techniques
Authors: Abad P. , Cardin L. , Poupet A. , Ponchet M.
Published: April 2013

A comparison was done between HPLC and ELISA for quantitative determination of the PR‐b1 protein, the major pathogenesis related “b” protein (PR‐b), in both healthy and TMV infected Nicotiana tabacum cv. Xanthi nc leaves. The PR‐b1 protein antiserum, used for double antibody sandwich (DAS) Enzyme linked Immunosorbant Assay (ELISA), was sensitive enough to detect PR‐b1 and other PR‐b1 related proteins at concentrations as low as 250 pg/ml. Since N. tabacum cv. Xanthi nc PR‐b2 and PR‐b3 proteins were shown to be serologically closely related to PR‐b1 protein, the validity of determining PR‐b1 by DAS ELISA test had to be established. By comparing PR‐b1 protein levels in healthy and TMV infected plants, it was found that PR‐b2 and PR‐b3 interfered little with PR‐b1 estimations. A good correlation existed between PR‐b1 determinations by HPLC and ELISA.

Ein Vergleich der pathogenesegekoppelten “b1”‐Proteinbestimmung durch ELISA‐ und HPLC‐Verfahren

Verglichen wurden ELISA‐ und HPLC‐Verfahren bei der quantitativen Bestimmung des PR‐bl‐Proteins, ein bedeutendes pathogenesegekoppeltes “b1”‐Protein (PR‐b), in gesunden und TMV‐infizierten Nicotiana tabacum cv. Xanthi nc‐Blättern. Das PR‐bl‐Protein‐Antiserum, das beim Double Antibody Sandwich (DAS) enzymgekoppelte Immunosorbant Assay (ELISA) angewandt wurde, hatte eine Empfindlichkeit, die PR‐bl und andere PR‐bl verwandte Proteine bei Konzentrationen ab 250 pg/ml wahrnehmen konnte. Da die PR‐b2‐ und PR‐b3‐Proteine von N. tabacum cv. Xanthi nc serologisch eng mit dem PR‐bl‐Protein verwandt sind, wurde die Gültigkeit einer PR‐bl‐Bestimmung durch einen DAS ELISA‐Test erstmals festgestellt. Nach einem Vergleich der PR‐bl ‐Proteingehalte in gesunden bzw. TMV‐infizierten Pflanzen wurde ermittelt, daß PR‐b2 und PR‐b3 die PR‐bl‐Bestimmungen kaum beeinflussen. Eine gute Korrelation wurde zwischen den PR‐bl‐Bestimmungen nach HPLC‐ und ELISA‐Verfahren beobachtet.
Ultrastructure of Antagonism of Sclerotium cepivorum by Bacillus subtilis
Authors: Backhouse D. , Stewart A.
Published: April 2013

Ultrastructural changes in hyphae of Sclerotium cepivorum antagonized by Bacillus subtilis in culture were studied. At early stages, mitochondria became swollen, but retained their longitudinal orientation. Antagonized hyphae became more vacuolated than controls. Cell death followed rupture of hyphal walls and leakage of cytoplasm. The walls of many burst hyphae had abnormal ultrastructure. It is suggested that antibiotics of B. subtilis act on the fungal metabolism, rather than on membranes or cytoskeleton.

Ultrastruktur des Antagonismus von Sclerotium cepivorum durch Bacillus subtilis

Untersucht wurden die ultrastrukturellen Änderungen in Sclerotium cepivorum‐Hyphen, die in Kultur durch Barillus subtilis antagonisiert waren. In früheren Stadien wurde eine Anschwellung der Mitochondrien beobachtet, diese aber ihre Längsorientierung beibehielten. Verglichen mit der Kontrolle entwickelten sich mehr Vakuolen in antagonisierten Hyphen. Hyphenwandbrüche und das Auslaufen von Cytoplasma verursachte Zelltod. Die Wände von aufgrissenen Hyphen besaßen häufig eine atypische Ultrastruktur. Es wird vorgeschlagen, daß die B. subtilis‐Antibiotika eher den pilzlichen Metabolismus als die Membrane oder das Cytoskelett beeinflussen.
Response to Seow: Biological mechanisms of early childhood caries
Authors: Bowen W. H.
Published: April 2013

Abstract—

For more than three decades, it has been recognized that dental caries is an infectious and transmissible disease in which diet plays a key role. Nevertheless, in treating patients with early childhood caries, scant attention is placed on exploring the source of infection and the prevalence of caries in other family members. Results from studies conducted in animals clearly show that the virulence of mutans streptococci can be enhanced by a highly cariogenic environment. For example, offspring from a highly caries‐active dam develop significantly more caries than pups from a low caries‐active dam. Considerable attention has been placed on the role of the nursing bottle in early childhood caries. Milk and some infant formulas do not promote caries and the role of the remainder of the diet has been largely ignored. The nursing bottle can effectively block salivary access to tooth surfaces, thereby increasing the cariogenicity of any food remaining in the mouth. Recent evidence shows that salivary gland function is impaired by iron deficiency and by prenatal exposure to lead. Clearly, early childhood caries is a complex disease that requires careful and extensive investigation.
Psychosocial and behavioral issues in early childhood caries
Authors: Reisine Susan , Douglass Joanna M.
Published: April 2013

Abstract—

Rampant caries in infants and young children has long been recognized as a clinical syndrome referred to by various names, including nursing caries, nursing bottle syndrome, night bottle mouth, and baby bottle tooth decay. The common theme among these terms is the perceived central role of inappropriate use of the baby bottle in the etiology and progression of carious lesions. Use of the baby bottle is not the only, and may not be the most important, factor in caries development. Because of questions about the role of the baby bottle in caries among young children, the Centers for Disease Control and Prevention recently suggested that the term for this clinical syndrome be replaced with early childhood caries (ECC). The purpose of this paper is to evaluate the literature on the influence of psychosocial and behavioral factors in early childhood caries. Prevalence of caries and maxillary anterior decay varies greatly in developed and undeveloped countries and among socioeconomic groups in developed countries. However, relatively little is known about the onset and progression of the disease or the antecedents of ECC, such as high risk behaviors, cultural norms, health beliefs and attitudes, or health care delivery factors. Furthermore, studies that do exist are limited by small and possibly biased samples and a lack of clear case definition. Future research should aim to develop a clear case definition of ECC, differentiate patterns of caries and conduct community‐based epidemiological studies in order to obtain accurate estimates of the etiology and epidemiology of ECC in the general population, as well as in high risk groups.
Relationships between Leisure Participation and Quality of Life of People with Developmental Disabilities
Authors: Badia Marta , Orgaz María Begoña , Verdugo Miguel Á. , Ullán Ana M. , Martínez Magdalena
Published: April 2013

Background

Studies of people with developmental disabilities suggest that participation in leisure activities might be a key factor for good quality of life. This study explores the relationships between objective and subjective quality of life and leisure participation of adults with developmental disabilities.

Materials and Methods

A cross‐sectional design was used with a convenience sample of 125 people, aged 17–65, living in the community. Participants completed the subjective scale of Integral Quality Scale and the Leisure Assessment Inventory in the form of an individual interview. Staff completed the GENCAT Scale.

Results

No relationship was found between objective quality of life and leisure participation. However, correlations between some leisure participation dimensions and specific subjective quality of life domains were observed. The results establish a predictive relationship between leisure participation and material, emotional, and physical well‐being. Personal and environmental variables analyzed were not found to have a moderating effect on the relationship between leisure participation and quality of life.

Conclusions

These findings indicate that some aspects of leisure participation may significantly contribute to enhancing the quality of life of young people and adults with developmental disabilities living in the community.
Geographical sampling bias in a large distributional database and its effects on species richness–environment models
Authors: Yang Wenjing , Ma Keping , Kreft Holger
Published: April 2013

Aim

Recent advances in the availability of species distributional and high‐resolution environmental data have facilitated the investigation of species richness–environment relationships. However, even exhaustive distributional databases are prone to geographical sampling bias. We aim to quantify the inventory incompleteness of vascular plant data across 2377 Chinese counties and to test whether inventory incompleteness affects the analysis of richness–environment relationships and spatial predictions of species richness.

Location

China.

Methods

We used the most comprehensive database of Chinese vascular plants, which includes county‐level occurrences for 29,012 native species derived from 4,236,768 specimen and literature records. For each county, we computed smoothed species accumulation curves and used the mean slope of the last 10% of the curves as a proxy for inventory incompleteness. We created a series of data subsets with different levels of inventory incompleteness by excluding successively more under‐sampled counties from the full data set. We then applied spatial and non‐spatial regression models to each of these subsets to investigate relationships between the species richness of subsets and environmental factors, and to predict spatial patterns of vascular plant species richness in China.

Results

Log10‐transformed numbers of records and documented species were strongly correlated (r = 0.97). In total, 91% of Chinese counties were identified as under‐sampled. After controlling for inventory incompleteness, the overall explanatory power of environmental factors markedly increased, and the strongest predictor of species richness switched from elevational range to annual wet days. Environmental models calibrated with more complete inventories yielded better spatial predictions of species richness.

Main conclusions

Our results indicate that inventory incompleteness strongly affects the explanatory power of environmental factors, the main determinants of species richness obtained from regression analyses, and the reliability of environment‐based spatial predictions of species richness. We conclude that even large distributional databases are prone to geographical sampling bias, with far‐reaching implications for the perception of and inferences about macroecological patterns.
Inhibition of the PI3K/AKT pathway potentiates cytotoxicity of EGFR kinase inhibitors in triple‐negative breast cancer cells
Authors: Yi Yong Weon , Hong Wooyoung , Kang Hyo Jin , Kim Hee Jeong , Zhao Wenjing , Wang Antai , Seong Yeon‐Sun , Bae Insoo
Published: April 2013

Triple‐negative breast cancers (TNBCs) are known to be intrinsically resistant to inhibitors for epidermal growth factor receptor (EGFR). Until now, clinical trials for TNBCs using EGFR inhibitors (EGFRis) as single agents have yielded disappointing results. Here, we report that combinatorial treatment using EGFRis, such as gefitinib or erlotinib, with PI3K/AKT pathway inhibitors (PI3K/AKTis) demonstrated a synergistic, anti‐proliferative effect in cell lines of the basal‐like (BL) subtype, a subtype of TNBC. Western blot analysis revealed that the gefitinib/PI‐103 combination significantly reduced the level of both phospho‐AKT and phospho‐ERK in two susceptible BL subtype cell lines, SUM149PT and MDA‐MB‐468, whereas it had little or no effect on the level of phospho‐ERK in two non‐susceptible cell lines (HS578T and MDA‐MB‐231) of mesenchymal stem‐like (MSL) TNBC subtype. The gefitinib/PI‐103 combination also significantly induced caspase‐3/7‐mediated PARP cleavage and reduced two anti‐apoptotic proteins, XIAP and Bcl‐2 in the susceptible cell lines. In addition, the level of myeloid cell leukemia 1 (Mcl‐1) protein was markedly decreased by gefitinib/PI‐103 combination in the BL TNBC cells, but showed no significant change by this combination in MSL subtype cells. These results suggest that pharmacological inhibition of EGFR used in combination of PI3K/AKTis is a potential therapeutic approach to treat a subtype of TNBCs.
Saving the Euro at the Cost of Democracy?
Authors: Crum Ben
Published: April 2013

This article explores the implications of the financial crisis for the relationship between monetary integration and democratic government in the European Union (EU). As the crisis has exposed the original balance that economic and monetary union (EMU) sought to maintain between monetary integration and policy diversity to be unsustainable, the eurozone is put before the choice of one of three governance models: executive federalism, democratic federalization or EMU dissolution. Notably, these three governance models perfectly illustrate Dani Rodrik's ‘trilemma of the world economy’, which maintains that of the three goods – economic (and monetary) integration, the nation‐state and democratic politics – one will always have to give. In light of this, the article concludes that the present course towards executive federalism can be justified for preventing euro dissolution and recognizing the value of national self‐government. Nevertheless, it threatens to come at a democratic price. Hence, it is imperative to consider possible flanking measures that can mitigate this effect.
Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience
Authors: Brazzelli V. , Grasso V. , Borroni G.
Published: April 2013

In the last years, several tyrosine kinase inhibitors (TKIs) have been developed and approved for human cancer treatment. Imatinib mesylate was the first of this novel family of drugs that target cancer‐specific molecules and signalling pathways. The appearance of imatinib resistances led to the introduction of second‐generation TKIs with higher potency and selectivity, such as dasatinib and nilotinib. However, the range of activity of these agents is not simply directed at tumour cells. Patients and their clinicians are indeed frequently confronted with the cutaneous side‐effects associated with the employ of these drugs, which represent the most common non‐hematological adverse reactions. For this reason, a systematic dermatological survey of patients receiving these therapies is highly important, and an early and appropriate dermatological treatment is required. In this review, we analyse the clinical and pathological characteristics of the most commonly reported adverse skin events associated with first‐ and second‐generation tyrosine kinase inhibitors, with a particular emphasis on our clinical experience.
Effects of maternal nutrient restriction, intrauterine growth restriction, and glucocorticoid exposure on phosphoenolpyruvate carboxykinase‐1 expression in fetal baboon hepatocytes in vitro
Authors: Li Cun , Shu Zhen‐Ju , Lee Shuko , Gupta Madhulika B. , Jansson Thomas , Nathanielsz Peter W. , Kamat Amrita
Published: April 2013

Background

The objective of this study was to develop a cell culture system for fetal baboon hepatocytes and to test the hypotheses that (i) expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase‐1 (PEPCK‐1) is upregulated in hepatocytes isolated from fetuses of nutrient‐restricted mothers (MNR) compared with ad libitum‐fed controls (CTR), and (ii) glucocorticoids stimulate PEPCK‐1 expression.

Methods

Hepatocytes from 0.9G CTR and MNR fetuses were isolated and cultured. PEPCK‐1 protein and mRNA levels in hepatocytes were determined by Western blot and quantitative PCR, respectively.

Results

Fetuses of MNR mothers were intrauterine growth restricted (IUGR). Feasibility of culturing 0.9G fetal baboon hepatocytes was demonstrated. PEPCK‐1 protein levels were increased in hepatocytes isolated from IUGR fetuses, and PEPCK‐1 mRNA expression was stimulated by glucocorticoids in fetal hepatocytes.

Conclusions

Cultured fetal baboon hepatocytes that retain their in vivo phenotype provide powerful in vitro tools to investigate mechanisms that regulate normal and programmed hepatic function.
Ethanol induces TLR4/TLR2 association, triggering an inflammatory response in microglial cells
Authors: Fernandez‐Lizarbe Sara , Montesinos Jorge , Guerri Consuelo
Published: April 2013

Alcohol consumption can induce brain damage, demyelination, and neuronal death, although the mechanisms are poorly understood. Toll‐like receptors are sensors of the innate immune system and their activation induces inflammatory processes. We have reported that ethanol activates and recruits Toll‐like receptor (TLR)4 receptors within the lipid rafts of glial cells, triggering the production of inflammatory mediators and causing neuroinflammation. Since TLR2 can also participate in the glial response and in the neuroinflammation, we investigate the effects of ethanol on TLR4/TLR2 responses. Here, we demonstrate that ethanol up‐regulates TLR4 and TLR2 expression in microglial cells, inducing the production of inflammatory mediators which triggers reactive oxygen species generation and neuronal apoptosis. Ethanol also promotes TLR4/TLR2 recruitment into lipid rafts‐caveolae, mimicking their activation by their ligands, lipopolysaccharide, and lipoteichoic acid (LTA). Immunoprecipitation and confocal microscopy studies reveal that ethanol induces a physical association between TLR2 and TLR4 receptors, suggesting the formation of heterodimers. Using microglia from either TLR2 or TLR4 knockout mice, we show that TLR2 potentiates the effects of ethanol on the TLR4 response reflected by the activation of MAPKs and inducible NO synthase. In summary, we provide evidence for a mechanism by which ethanol triggers TLR4/TLR2 association contributing to the neuroinflammation and neurodegeneration associated with alcohol abuse.
Diet and risk of oral potentially malignant disorders in rural Sri Lanka
Authors: Amarasinghe Hemantha K. , Usgodaarachchi Udaya , Kumaraarachchi Menaka , Johnson Newell W. , Warnakulasuriya Saman
Published: April 2013

Background

While the protective role of antioxidant nutrients against cancer is well established, data on Asian diets in patients with oral cancer are meagre.

Methods

A total of 1029 subjects over 30 years of age were investigated on their dietary practices in the Sabaragamuwa province (Sri Lanka) in 2006–07. Data collection tools were an interviewer‐administered questionnaire, a three‐day food diary and an examination of the oral cavity. Subjects identified with Oral Potentially Malignant Disorders (OPMD) and disease‐free controls were analysed in a case–control fashion. Among the OPMDs, those with leukoplakia were separately considered. A further subgroup analysis was undertaken for β‐carotene‐rich foods. The analysis was stratified by portions of fruit/vegetables consumed as five or more portions and two or more portions daily.

Results

A low BMI (<18.5) was a significant independent risk factor for the development of OPMD. More than half of both cases and controls consumed less than two portions of fruit/vegetables per day and only 20 subjects consumed more than five portions per day. Intake of more than two portions per day of β‐carotene‐containing fruits/vegetables significantly reduced the risk of having an OPMD and leukoplakia (OR = 0.5; 95% CI, 0.3–0.9). The significant differences observed with BMI and fruits/vegetables were attenuated when adjusted for betel quid chewing, smoking and alcohol use.

Conclusions

This study discloses prevailing under‐nutrition in this rural population with very low daily consumption of fruit/vegetables. Cancer preventive properties in their diets are limited and are swamped by the known carcinogenic agents associated with use of betel quid, tobacco and alcohol.
Immunohistochemical expression of oestrogen receptor‐α and progesterone receptor in salivary gland tumours
Authors: Kolude Bamidele , Adisa Akinyele , Adeyemi Bukola , Lawal Ahmed
Published: April 2013

Background

The mammary and salivary glands are tubulo‐acinar exocrine glands, sharing similar morphological characteristics and tumour histology. It is logical to postulate that they may have similar tumour biology. This study was carried out to define the expression of oestrogen‐α (ER‐α) and progesterone (PR) in salivary gland tumours (SGTs) presenting at the University College Hospital, Ibadan.

Methods

Formalin‐fixed, paraffin‐embedded tissue samples of different salivary gland neoplasms were processed for antibodies to ER‐α and PR using the specifications of the manufacturer. Two independent investigators reviewed the slides scoring the pattern and intensity of staining as follows: negative (0), weakly positive (+1), moderately positive (+2) and strongly positive (+3). Data were analysed using version 16 of the Statistical Package for Social Sciences (SPSS16). The level of significance was set at P < 0.05.

Results

A total of 40 SGTs from 19 males (47.5%) and 21 females (52.5%) were utilised. There were 15 benign and 25 malignant SGTs. ER expression in benign SGTs was 6.7%, while in malignant SGTs, it was 28.0%. There was no statistically significant difference in the gender and mean age distribution between patients with or without positive ER‐α expression (χ2 = 0.37, P = 0.59 Fisher's exact test; t = 0.054, P = 0.96, respectively). About 66.7% of high‐grade SGTs was positive for ER while only 20% of the low‐grade lesions were positive.

Conclusion

This study showed that ER‐α was expressed more in the high‐grade malignant SGTs compared with the low‐grade malignant SGTs and the benign SGTs.
BORDERS AS BOUNDARIES TO FISCAL POLICY INTERACTIONS? AN EMPIRICAL ANALYSIS OF POLITICIANS’ OPINIONS ON RIVALS IN THE COMPETITION FOR FIRMS
Authors: Geys Benny , Osterloh Steffen
Published: April 2013

Studies of spatial policy interdependence in (local) public policies usually concentrate on the relations between jurisdictions within a single analyzed region, and disregard possible extraregional effects. However, the theoretical spatial statistics literature shows that biased estimates might emerge if spatial interactions extend beyond the boundaries of the available data (i.e., the boundary value problem). This paper empirically assesses the practical relevance of this concern by studying German local politicians’ assessments of their jurisdictions’ main competitors in the struggle to attract firms. We find that location near a border significantly undermines politicians’ perception that the fiercest competitive pressure derives from jurisdictions within their own state. This effect sets in about 20 km (10.2 km) from a national (international) border. These results indicate that nearest municipalities perceive each other as competitors regardless of the state or country where they are located, which has important implications for estimating spatial dependence models.
Sleep patterns and insomnia among adolescents: a population‐based study
Authors: Hysing Mari , Pallesen Ståle , Stormark Kjell M. , Lundervold Astri J. , Sivertsen Børge
Published: April 2013

The aim of the current study was to examine sleep patterns and rates of insomnia in a population‐based study of adolescents aged 16–19 years. Gender differences in sleep patterns and insomnia, as well as a comparison of insomnia rates according to DSM‐IV, DSM‐V and quantitative criteria for insomnia (Behav. Res. Ther., 41, 2003, 427), were explored. We used a large population‐based study in Hordaland county in Norway, conducted in 2012. The sample included 10 220 adolescents aged 16–18 years (54% girls). Self‐reported sleep measurements included bedtime, rise time, time in bed, sleep duration, sleep efficiency, sleep onset latency, wake after sleep onset, rate and frequency and duration of difficulties initiating and maintaining sleep and rate and frequency of tiredness and sleepiness. The adolescents reported short sleep duration on weekdays (mean 6:25 hours), resulting in a sleep deficiency of about 2 h. A majority of the adolescents (65%) reported sleep onset latency exceeding 30 min. Girls reported longer sleep onset latency and a higher rate of insomnia than boys, while boys reported later bedtimes and a larger weekday–weekend discrepancy on several sleep parameters. Insomnia prevalence rates ranged from a total prevalence of 23.8 (DSM‐IV criteria), 18.5 (DSM‐V criteria) and 13.6% (quantitative criteria for insomnia). We conclude that short sleep duration, long sleep onset latency and insomnia were prevalent in adolescents. This warrants attention as a public health concern in this age group.
Helping to sort the liars from the truth‐tellers: The gradual revelation of information during investigative interviews
Authors: Dando Coral J. , Bull Ray , Ormerod Thomas C. , Sandham Alexandra L.
Published: April 2013

Research examining detection of verbal deception reveals that lay observers generally perform at chance. Yet, in the criminal justice system, laypersons that have not undergone specialist investigative training are frequently called upon to make veracity judgements (e.g., solicitors; magistrates; juries). We sought to improve performance by manipulating the timing of information revelation during investigative interviews. A total of 151 participants played an interactive computer game as either a truth‐teller or a deceiver, and were interviewed afterwards. Game information known to the interviewer was revealed either early, at the end of the interview, or gradually throughout. Subsequently, 30 laypersons individually viewed a random selection of interviews (five deceivers and five truth‐tellers from each condition), and made veracity and confidence judgements. Veracity judgements were most accurate in the gradual condition, p < .001, η2 = .97 (above chance), and observers were more confident in those judgements, p < .001, η2 = .99. Deceptive interviewees reported the gradual interviews to be the most cognitively demanding, p < .001; η2 = .24. Our findings suggest that the detection of verbal deception by non‐expert observers can be enhanced by employing interview techniques that maximize deceivers' cognitive load, while allowing truth‐tellers the opportunity to respond to evidence incrementally.
Vasovagal Syncope Related to Emotional Stress Predicts Coronary Events in Later Life
Authors: ZYSKO DOROTA , MELANDER OLLE , FEDOROWSKI ARTUR
Published: April 2013

Background

The aim of the study was to assess whether history of vasovagal syncope (VVS) mediated by emotional (emotional VVS) or orthostatic stress (orthostatic VVS) is associated with an increased risk of cardiovascular (CV) events in later life.

Methods

Retrospective analysis based on medical records of the consecutive 3,288 cardiologic outpatients (mean age, 61 ± 12 years; 43% men).

Results

A total of 254 patients (7.7%) reported emotional VVS, whereas 294 (9.0%) had history of orthostatic VVS. First‐ever syncopal episode was reported at a median age of 16 years (interquartile range [IQR], 12 years to 28 years), and the median total number of episodes was two (IQR, 1 to 5). There were 779 patients (23.7%) with at least one CV event, and the median age for the first CV event was 59 years (IQR, 52 years to 67 years). In the fully adjusted model, history of emotional VVS was predictive of CV event (hazard ratio [95% confidence interval]: 1.63, [1.27–2.09]; P < 0.001), myocardial infarction (1.99, [1.49–2.66]; P < 0.001), and percutaneous coronary intervention (1.84, [1.31–2.60]; P = 0.001). There was one significant interaction (P = 0.07) between history of emotional VVS and gender. Emotional VVS was predictive of CV event in men (1.89 [1.41–2.53]; P < 0.001) but not in women (1.24 [0.79–1.94]; P = 0.35).

Conclusions

History of emotional but not orthostatic VVS is independently associated with increased risk of coronary events in later life. The relationship between predisposition to emotional VVS in adolescence and development of cardiovascular disease requires further studies.
Spatial Variation of Soil Lead in an Urban Community Garden: Implications for Risk‐Based Sampling
Authors: Bugdalski Lauren , Lemke Lawrence D. , McElmurry Shawn P.
Published: April 2013

Soil lead pollution is a recalcitrant problem in urban areas resulting from a combination of historical residential, industrial, and transportation practices. The emergence of urban gardening movements in postindustrial cities necessitates accurate assessment of soil lead levels to ensure safe gardening. In this study, we examined small‐scale spatial variability of soil lead within a 15 × 30 m urban garden plot established on two adjacent residential lots located in Detroit, Michigan, USA. Eighty samples collected using a variably spaced sampling grid were analyzed for total, fine fraction (less than 250 μm), and bioaccessible soil lead. Measured concentrations varied at sampling scales of 1–10 m and a hot spot exceeding 400 ppm total soil lead was identified in the northwest portion of the site. An interpolated map of total lead was treated as an exhaustive data set, and random sampling was simulated to generate Monte Carlo distributions and evaluate alternative sampling strategies intended to estimate the average soil lead concentration or detect hot spots. Increasing the number of individual samples decreases the probability of overlooking the hot spot (type II error). However, the practice of compositing and averaging samples decreased the probability of overestimating the mean concentration (type I error) at the expense of increasing the chance for type II error. The results reported here suggest a need to reconsider U.S. Environmental Protection Agency sampling objectives and consequent guidelines for reclaimed city lots where soil lead distributions are expected to be nonuniform.