bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding processes of sediment bleaching in glacial settings using a portable OSL reader
Authors: King Georgina E. , Sanderson David C. W. , Robinson Ruth A. J. , Finch Adrian A.
Published: May 2014

Analysis of a high‐resolution suite of modern glacial sediments from Jostedalen, southern Norway, using a portable optically stimulated luminescence (OSL) reader, provides insights into the processes of sediment bleaching in glacial environments at the catchment scale. High‐magnitude, low‐frequency processes result in the least effective sediment bleaching, whereas low‐magnitude, high‐frequency events provide greater bleaching opportunities. Changes in sediment bleaching can also be identified at the scale of individual bar features: tails of braid‐bars and side‐attached bar deposits have the lowest portable reader signal intensities, as well as the smallest conventional OSL residual doses. In addition to improving our understanding of the processes of sediment bleaching, portable reader investigations can also facilitate more rapid and comprehensive modern analogue investigations, which are commonly used to confirm that the OSL signals of modern glacial sediments are well bleached.
Luminescence dating of ice‐marginal deposits in northern Germany: evidence for repeated glaciations during the Middle Pleistocene (MIS 12 to MIS 6)
Authors: Roskosch Julia , Winsemann Jutta , Polom Ulrich , Brandes Christian , Tsukamoto Sumiko , Weitkamp Axel , Bartholomäus Werner A. , Henningsen Dierk , Frechen Manfred
Published: May 2014

The exact number, extent and chronology of the Middle Pleistocene Elsterian and Saalian glaciations in northern Central Europe are still controversial. This study presents new luminescence data from Middle Pleistocene ice‐marginal deposits in northern Germany, giving evidence for repeated glaciations during the Middle Pleistocene (MIS 12 to MIS 6). The study area is located in the Leine valley south of the North German Lowlands. The data set includes digital elevation models, high‐resolution shear wave seismic profiles, outcrop and borehole data integrated into a 3D subsurface model to reconstruct the bedrock relief surface. For numerical age determination, we performed luminescence dating on 12 ice‐marginal and two fluvial samples. Luminescence ages of ice‐marginal deposits point to at least two ice advances during MIS 12 and MIS 10 with ages ranging from 461±34 to 421±25 ka and from 376±27 to 337±21 ka. The bedrock relief model and different generations of striations indicate that the older ice advance came from the north and the younger one from the northeast. During rapid ice‐margin retreat, subglacial overdeepenings were filled with glaciolacustrine deposits, partly rich in re‐worked Tertiary lignite and amber. During MIS 8 and MIS 6, the study area may have been affected by two ice advances. Luminescence ages of glaciolacustrine delta deposits point to a deposition during MIS 8 or early MIS 6, and late MIS 6 (250±20 to 161±10 ka). The maximum extent of both the Elsterian (MIS 12 and MIS 10) and Saalian glaciations (MIS 8? and MIS 6) approximately reached the same position in the Leine valley and was probably controlled by the formation of deep proglacial lakes in front of the ice sheets, preventing a further southward advance.
Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age‐related macular degeneration
Authors: Kaneko Hiroki , Ye Fuxiang , Ijima Ryo , Kachi Shu , Kato Seiichi , Nagaya Masatoshi , Higuchi Akiko , Terasaki Hiroko
Published: May 2014

Background and Purpose

The present treatment for choroidal neovascularization (CNV) associated with age‐related macular degeneration (AMD) is not sufficient. Hence, we examined the therapeutic efficacy of reducing histamine H4 receptor expression on CNV in mice.

Experimental Approach

H4 receptor expression was examined in CNVs from patients with AMD. In mice, laser photocoagulation was performed in the retina to induce experimental CNV (laser CNV). Protein and mRNA expression levels were determined and CNV volume measured in wild‐type and Hrh4‐/‐ mice with laser CNV. The effects of JNJ7777120, an H4 receptor antagonist, administered intravitreously, on CNV volume and pathological vessel leakage were determined in mice with laser CNV and controls. Fundus imaging, retinal histology and electroretinography were performed on eyes injected with JNJ7777120 to evaluate retinal toxicity.

Key Results

Human H4 receptors were only confirmed in CNV samples from AMD patients and not in the other subretinal tissues. Mouse H4 receptors were expressed in retinal pigment epithelium only after inducing laser CNV in wild‐type mice, and were co‐localized with the macrophage marker F4/80. Laser CNV volume was reduced in Hrh4‐/‐ mice compared with that in wild‐type mice, and JNJ7777120 suppressed laser‐induced CNV volume and pathological CNV leakage in wild‐type mice. Also eyes injected with JNJ7777120 did not show retinal degeneration.

Conclusions and Implications

H4 receptors are expressed in macrophages that accumulate around CNVs. Suppressing H4 receptor expression prevented the pathological vessel leakage without showing retinal toxicity, indicating that the H4 receptor has potential as a novel therapeutic target in AMD.
A Re‐examination of the MDM2/p53 Interaction Leads to Revised Design Criteria for Novel Inhibitors
Authors: Vasilevich Natalya I. , Afanasyev Ilya I. , Kovalskiy Dmitry A. , Genis Dmitry V. , Kochubey Valery S.
Published: May 2014

The general model of epitope‐type MDM2 inhibitor was developed based on the structural information on the complexes between MDM2 and various low molecular weight ligands found in the PDB database. Application of this model to our in‐house library has led us to a new scaffold capable of interrupting protein–protein interactions. A synthetic library based on this and related scaffolds resulted in new classes of compounds that possess biochemical and cellular activity and good pharmacokinetic properties. We assume that such general approach to PPI inhibitors design may be useful for the development of inhibitors of various PPI types, including Bcl/XL.
Influence of individual differences in disease perception on consumer response to direct‐to‐consumer genomic testing
Authors: Boeldt D.L. , Schork N.J. , Topol E.J. , Bloss C.S.
Published: May 2014

Individuals who undergo multiplex direct‐to‐consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow‐up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer's disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services.
SWITCHING REGRESSION ESTIMATES OF THE INTERGENERATIONAL PERSISTENCE OF CONSUMPTION
Authors: GUO SHENG
Published: May 2014

The influential economic theory of intergenerational transfers predicts a negative connection between credit constraints and intergenerational mobility of consumption. Existing work has used bequest receipt to signal a parent's access to credit markets when investing in his children's human capital. However, measurement error in bequest receipt generates misclassification error and, in turn, attenuation bias. Employing switching regressions with imperfect sample separation to deal with this error, we show that the intergenerational persistence of consumption in the United States for credit constrained families is much higher than that for unconstrained families, contrary to what the theory implies. This means that children from constrained families are more likely to have consumption levels similar to those of their parents than children from unconstrained families. Our results are robust to the choice of bequest variables and other predictive variables in the switching equation. (JEL C13, D12, E21, J62)
Demographic changes following mechanical removal of exotic brown trout in an Intermountain West (USA), high‐elevation stream
Authors: Saunders W. Carl , Budy Phaedra , Thiede Gary P.
Published: May 2014

Exotic species present a great threat to native fish conservation; however, eradicating exotics is expensive and often impractical. Mechanical removal can be ineffective for eradication, but nonetheless may increase management effectiveness by identifying portions of a watershed that are strong sources of exotics. We used mechanical removal to understand processes driving exotic brown trout (Salmo trutta) populations in the Logan River, Utah. Our goals were to: (i) evaluate the demographic response of brown trout to mechanical removal, (ii) identify sources of brown trout recruitment at a watershed scale and (iii) evaluate whether mechanical removal can reduce brown trout densities. We removed brown trout from 2 km of the Logan River (4174 fish), and 5.6 km of Right Hand Fork (RHF, 15,245 fish), a low‐elevation tributary, using single‐pass electrofishing. We compared fish abundance and size distributions prior to, and after 2 years of mechanical removal. In the Logan River, immigration to the removal reach and high natural variability in fish abundances limited the response to mechanical removal. In contrast, mechanical removal in RHF resulted in a strong recruitment pulse, shifting the size distribution towards smaller fish. These results suggest that, before removal, density‐dependent mortality or emigration of juvenile fish stabilised adult populations and may have provided a source of juveniles to the main stem. Overall, in sites demonstrating strong density‐dependent population regulation, or near sources of exotics, short‐term mechanical removal has limited effects on brown trout populations but may help identify factors governing populations and inform large‐scale management of exotic species.
Antioxidant activity of Pinus pinaster infected with Fusarium circinatum is influenced by maternal effects
Authors: Vivas M. , Nunes C. , Coimbra M. A. , Solla A.
Published: May 2014

The antioxidant activity of Pinus pinaster seedlings originating from two contrasting maternal environments and inoculated with the fungal pathogen Fusarium circinatum was examined. The antioxidant activity related positively to the stem necrosis caused by the pathogen (p = 0.005), but this relationship differed significantly between maternal environments (p ≤ 0.002). Seedlings from mother trees grown under a favourable environment expressed a more variable antioxidant activity to F. circinatum than seedlings from mother trees grown in a less favourable environment. Antioxidant activity ranging from 80 to 100% resulted in shorter necrosis in seedlings from the favourable maternal environment than in seedlings from the unfavourable environment. Maternal effects caused shifts in the relationship between antioxidant activity and necrosis in offspring, and significantly modified the individual plant capacity for antioxidant response on pathogen penetration.
Equine ocular neoplasia: A review
Authors: Montgomery K. W.
Published: May 2014

The following article discusses the clinical appearance, diagnosis and therapeutic options for ocular neoplasia in the horse based on anatomic location.
New Roles for Family Therapists in the Courts: An Overview with a Focus on Custody Dispute Resolution
Authors: Emery Robert E. , Rowen Jenna , Dinescu Diana
Published: May 2014

Many legal issues involve conflicts that are at least as much psychological and relational as they are legal in nature. Juvenile and family courts have always embraced a helping philosophy under theparens patriaelegal doctrine. These courts address problems where family relationships are central, for example, custody and coparenting disputes, divorce, child abuse and neglect, foster care, intimate partner violence, and juvenile delinquency. Family therapists are playing a growing role in all of these matters. In this article, we use child custody disputes as a more in‐depth example for exploring new, potential roles for family therapists, particularly as mediators and parenting coordinators. To show the breadth of the role for family therapists, we also more briefly consider the topics of child abuse and neglect, foster care, juvenile delinquency, and drug and alcohol issues.
Effects of consumers and nitrogen availability on heterotrophic microbial activity during leaf decomposition in headwater streams
Authors: Cheever Beth M. , Webster Jackson R.
Published: May 2014

Microbial processes in streams may be influenced by bottom‐up factors, such as nutrient availability, and by top‐down factors, such as the activity of upper trophic levels. The latter pathway has been well described between autotrophs and grazers, but the effects of consumers on heterotrophic basal trophic levels may also be important. Consumers may influence microbial activity through consumption of microbial biomass and by altering nutrient availability via consumer nutrient recycling (CNR).

We investigated the effects of two shredder taxa, Gammarus spp. and Tipula spp., on nitrogen (N) uptake during organic matter decomposition by leaf‐associated heterotrophic microbial assemblages under conditions of ambient and enriched N availability in stream mesocosms. Colonised red maple leaves were placed in mesocosms with low (<20 μg L−1) or high (>800 μg L−1) nitrate concentration in the presence of amphipods, tipulids or no shredders. To test the importance of consumption and CNR, leaf packs were constructed from both coarse and fine mesh, which respectively allowed or prevented shredders from consuming detritus.

Nitrogen enrichment generally increased red maple breakdown rates, while shredder influence on leaf breakdown was taxon specific. Feeding by tipulids increased red maple breakdown rate compared with amphipods, although not significantly. While feeding by amphipods did not directly influence breakdown rates, amphipod nutrient recycling stimulated leaf breakdown rate by the same magnitude as the N‐enrichment treatment.

Fungal biomass increased with N enrichment. However, this did not lead to changes in N uptake, which was extremely variable and did not respond significantly to either treatment. In general, N uptake (per leaf mass) was greatest under enriched N conditions when tipulids were present.

Our results indicate that both top‐down and bottom‐up factors influence microbial activity in heterotrophic systems and suggest that consumers may play important roles in detrital processing, not only through direct consumption but also through nutrient recycling.
Winter climate change affects growing‐season soil microbial biomass and activity in northern hardwood forests
Authors: Durán Jorge , Morse Jennifer L. , Groffman Peter M. , Campbell John L. , Christenson Lynn M. , Driscoll Charles T. , Fahey Timothy J. , Fisk Melany C. , Mitchell Myron J. , Templer Pamela H.
Published: May 2014

Understanding the responses of terrestrial ecosystems to global change remains a major challenge of ecological research. We exploited a natural elevation gradient in a northern hardwood forest to determine how reductions in snow accumulation, expected with climate change, directly affect dynamics of soil winter frost, and indirectly soil microbial biomass and activity during the growing season. Soils from lower elevation plots, which accumulated less snow and experienced more soil temperature variability during the winter (and likely more freeze/thaw events), had less extractable inorganic nitrogen (N), lower rates of microbial N production via potential net N mineralization and nitrification, and higher potential microbial respiration during the growing season. Potential nitrate production rates during the growing season were particularly sensitive to changes in winter snow pack accumulation and winter soil temperature variability, especially in spring. Effects of elevation and winter conditions on N transformation rates differed from those on potential microbial respiration, suggesting that N‐related processes might respond differently to winter climate change in northern hardwood forests than C‐related processes.
Strong contribution of autumn phenology to changes in satellite‐derived growing season length estimates across Europe (1982–2011)
Authors: Garonna Irene , de Jong Rogier , de Wit Allard J.W. , Mücher Caspar A. , Schmid Bernhard , Schaepman Michael E.
Published: May 2014

Land Surface Phenology (LSP) is the most direct representation of intra‐annual dynamics of vegetated land surfaces as observed from satellite imagery. LSP plays a key role in characterizing land‐surface fluxes, and is central to accurately parameterizing terrestrial biosphere–atmosphere interactions, as well as climate models. In this article, we present an evaluation of Pan‐European LSP and its changes over the past 30 years, using the longest continuous record of Normalized Difference Vegetation Index (NDVI) available to date in combination with a landscape‐based aggregation scheme. We used indicators of Start‐Of‐Season, End‐Of‐Season and Growing Season Length (SOS, EOS and GSL, respectively) for the period 1982–2011 to test for temporal trends in activity of terrestrial vegetation and their spatial distribution. We aggregated pixels into ecologically representative spatial units using the European Landscape Classification (LANMAP) and assessed the relative contribution of spring and autumn phenology. GSL increased significantly by 18–24 days decade−1 over 18–30% of the land area of Europe, depending on methodology. This trend varied extensively within and between climatic zones and landscape classes. The areas of greatest growing‐season lengthening were the Continental and Boreal zones, with hotspots concentrated in southern Fennoscandia, Western Russia and pockets of continental Europe. For the Atlantic and Steppic zones, we found an average shortening of the growing season with hotspots in Western France, the Po valley, and around the Caspian Sea. In many zones, changes in the NDVI‐derived end‐of‐season contributed more to the GSL trend than changes in spring green‐up, resulting in asymmetric trends. This underlines the importance of investigating senescence and its underlying processes more closely as a driver of LSP and global change.
Nature, wellbeing and the transformational self
Authors: Little Jo
Published: May 2014

This paper explores the relationship between health, exercise and the body through the lens of fitness holidays. It conceptualises fitness tourism within Foucaudian ideas of the care of the self and bodily discipline, arguing that the holidays and the practices they employ need to be seen as part of the shift in health in which the individual is required to take a more active part in regulating and managing their own health and wellbeing. The paper stresses the relationship between health and beauty, and the importance of appropriately sized and shaped bodies within contemporary ideas of wellbeing. It goes on to show how nature is present in both the kinds of bodies that are seen as healthy, and the spaces and practices used to produce those bodies. Drawing on interviews, client testimonials and publicity material the paper examines the motivations behind the provision and consumption of fitness holidays. It argues that despite a set of novel and ‘transformative’ practices (incorporating strong links between diet, relaxation and exercise and an emphasis on ‘reeducation’), consumption of and satisfaction with the fitness holidays is heavily dependent on conventional outcomes of weight loss and body size reduction.
Reflections on The draining of the Somerset Levels
Authors: Clout Hugh
Published: May 2014

Several messages emerge from reading this monograph in the light of the floods of 2013–14. Michael Williams showed that attempts at water control in the Levels extended over many centuries, and that construction of farms and settlements on very low‐lying land carried major risks. There were precedents for the recent magnitude of flooding, caused in the past by very heavy rainfall, poor maintenance of channels, and insufficient investment in water management. Despite modern pumps, winter flooding remains uncontrollable without massive investment. Unlike his earlier emphasis on ‘improvement’, Williams argued in later writing that some stretches of peat moor in Somerset might be conserved as wetland rather than being subjected to further drainage.
L‐mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model
Authors: Trimmel K. , Cvikl B. , Müller H.‐D. , Nürnberger S. , Gruber R. , Moritz A. , Agis H.
Published: May 2014

Aim

To assess the pro‐angiogenic and pro‐inflammatory capacity of the dentine–pulp complex in response to the prolyl hydroxylase inhibitor L‐mimosine in a tooth slice organ culture model.

Methodology

Human teeth were sectioned transversely into 600‐μm‐thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L‐mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro‐angiogenic capacity and to immunoassays for interleukin (IL)‐6 and IL‐8 to assess the pro‐inflammatory response. Interleukin‐1 served as pro‐inflammatory control. Echinomycin was used to inhibit hypoxia‐inducible factor‐1 (HIF‐1) alpha activity. Data were analysed using Student's t‐test and Mann–Whitney U test.

Results

Pulps within tooth slices remained vital upon L‐mimosine stimulation as indicated by formazan formation and histological evaluation. L‐mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin (P < 0.01). Changes in normalized IL‐6 and IL‐8 levels upon treatment with L‐mimosine did not reach the level of significance (P > 0.05), whilst treatment with IL‐1, which served as positive control, increased IL‐6 (P < 0.05) and IL‐8 levels (P < 0.05).

Conclusions

The prolyl hydroxylase inhibitor L‐mimosine increased VEGF production via HIF‐1 alpha in the tooth slice organ culture model whilst inducing no prominent increase in IL‐6 and IL‐8. Pre‐clinical studies will reveal if these in vitro effects translate into dental pulp regeneration.
Characteristics of a large cohort of patients with diabetes having at‐risk feet and outcomes in patients with foot ulceration referred to a tertiary care diabetes unit
Authors: Riaz Musarrat , Miyan Zahid , Zaidi Syed I , Alvi Syed FD , Fawwad Asher , Ahmadani Muhammad Y , Zafar Asim B , Malik Rayaz A , Basit Abdul
Published: May 2014

To identify in a large population cohort the clinical and biochemical characteristics of patients with diabetes at risk of foot ulceration and outcomes in those with foot ulcers. All patients with diabetes attending Baqai Institute of Diabetology and Endocrinology from January 2004 to April 2012 included in the study. Clinical, biochemical and socio‐demographic data were collected and patients were categorised into those at no risk of ulceration, at risk of ulceration and those with foot ulcer, according to the University of Texas classification. Patients with foot ulceration followed for their final outcome, that is complete healing, persisted non‐healed ulcer, lower extremity amputation, lost to follow‐up or death. A total of 18 119 patients with diabetes underwent assessment, 3576 (19·7%) patients defined as at high risk for foot ulceration and 3731 (20·6%) presented with foot ulcer. Age, male gender, hypertension, higher glycated haemoglobin (HbA1c), history of smoking and presence of neuropathy were risk factors (P < 0·000) for foot ulceration. Amputation rate in patients with foot ulceration was significantly related to severity of ulceration at presentation. Preventive foot care practices were followed by 19·02% patients. One thousand eight hundred seventy three (50·2%) patients completely healed, 293 (11%) patients underwent amputation and 397 (10·1%) patients continued to be treated in the foot clinic. All patients with diabetes should be screened for neuropathy to identify those at risk of foot ulceration, as it is the major contributory factor for foot ulceration. The final outcome of foot ulceration was determined by the severity and grade of ulcer at presentation.
Reassessment of Hydrofluoric Acid Desilicification in the Carius Tube Digestion Technique for Re–Os Isotopic Determination in Geological Samples
Authors: Li Jie , Zhao Pei‐Pei , Liu Jingao , Wang Xuan‐Ce , Yang Alexandra Yang , Wang Gui‐Qing , Xu Ji‐Feng
Published: May 2014

In this study, Re and Os isotopes were systematically determined in six geological reference materials (RMs; covering a wide range of lithologies) using the Carius tube (CT) digestion technique with and without hydrofluoric acid desilicification. Our results show that the HF desilicification increased the Re extraction efficiency (by 9–15%) evidenced from basaltic and andesitic rocks (e.g., BHVO‐2, TDB‐1 and AGV‐2). This implies that a small proportion of Re resides in silicate phases. For mafic–ultramafic rocks (e.g., BCR‐2, WGB‐1 and WPR‐1), Re extraction efficiencies obtained by the CT digestion with and without HF desilicification were similar. This may indicate that Re in these rocks may dominantly reside in some phases (e.g., magnetite and sulfides) that could be completely dissolved in aqua regia solutions without the aid of HF desilicification. Our results also show that the HF desilicification increased Os extraction efficiency (by 13–99%) in some RMs (e.g., BHVO‐2, WGB‐1 and AGV‐2). This observation suggests that a portion of Os‐rich trace phases may occur as inclusions in the silicate phases that act as isolators at ~ 200 mesh sizes. This study demonstrates that the HF desilicification step prior to CT digestion is important for complete extraction of Re and Os in geological samples.
Single, escalating dose pharmacokinetics, safety and food effects of a new oral androgen dimethandrolone undecanoate in man: a prototype oral male hormonal contraceptive
Authors: Surampudi P. , Page S. T. , Swerdloff R. S. , Nya‐Ngatchou J. J. , Liu P. Y. , Amory J. K. , Leung A. , Hull L. , Blithe D. L. , Woo J. , Bremner W. J. , Wang C.
Published: May 2014

The novel androgen, dimethandrolone (DMA) has both androgenic and progestational activities, properties that may maximize gonadotropin suppression. We assessed the pharmacokinetics of dimethandrolone undecanoate (DMAU), an orally bioavailable, longer acting ester of DMA, for male contraceptive development. Our objective was to examine the safety and pharmacokinetics of single, escalating doses of DMAU (powder in capsule formulation) administered orally with or without food in healthy men. We conducted a randomized, double‐blind Phase 1 study. For each dose of DMAU (25–800 mg), 10 male volunteers received DMAU and two received placebo at two academic medical centres. DMAU was administered both fasting and after a high‐fat meal (200–800 mg doses). Serial serum samples were collected over 24 h following each dose. DMAU was well tolerated without significant effects on vital signs, safety laboratory tests or electrocardiograms. When administered while fasting, serum DMA (active compound) was detectable in only 4/10 participants after the 800 mg dose. When administered with a 50% fat meal, serum DMA was detectable in all participants given 200 mg DMAU and showed a dose‐incremental increase up to 800 mg, with peak levels 4–8 h after taking the dose. Serum gonadotropins and sex hormone concentrations were significantly suppressed 12 h after DMAU administration with food at doses above 200 mg. This first‐in‐man study demonstrated that a single, oral dose of DMAU up to 800 mg is safe. A high‐fat meal markedly improved DMAU/DMA pharmacokinetics.
Atrial Structure and Function 5 Years After Successful Ablation for Persistent Atrial Fibrillation: An MRI Study
Authors: COCHET HUBERT , SCHERR DANIEL , ZELLERHOFF STEPHAN , SACHER FREDERIC , DERVAL NICOLAS , DENIS ARNAUD , KNECHT SEBASTIEN , KOMATSU YUKI , MONTAUDON MICHEL , LAURENT FRANÇOIS , PIESKE BURKERT M. , HOCINI MÉLÈZE , HAÏSSAGUERRE MICHEL , JAÏS PIERRE
Published: May 2014

Atrial Function After Persistent AF Ablation

Introduction

The atrial outcome after extensive ablation is unknown. We sought to quantify atrial structure and function years after successful ablation for persistent atrial fibrillation (PsAF).

Methods and Results

We studied after 80 ± 15 months 26 patients (54 ± 8 years, 1 woman) with PsAF successfully treated by ablation (2.2 ± 0.7 stepwise approach procedures, cumulative RF duration 126 ± 37 minutes). At follow‐up atrial scar burden and atrial outflows were quantified using delayed–enhanced and velocity‐encoded MRI, respectively. Cine imaging was used to quantify atrial conduit function (CF), active emptying fraction (AEF), expansion index (EI), and the inter‐appendage mechanical activation delay. Patients underwent exercise testing at baseline and follow‐up. LA and RA scar extent were 29 ± 6 and 4.3 ± 2.8%, respectively. LA and RA AEF were 10.0 ± 5.3 and 30 ± 8%. Mean inter‐appendage delay was 83 ± 47 ms [42–217]. Complete LAA isolation was found in 3 patients. A wave was absent in 9/26 patients. LA scar extent related to the number of procedures (R = 0.58, P = 0.002) and total RF duration (R = 0.56, P = 0.003). Among follow‐up characteristics, LA scar extent related to LAAEF (R = −0.73, P < 0.0001), LAEI (R = −0.64, P = 0.0003), A‐wave peak (R = −0.72, P < 0.0001), and inter‐appendage mechanical delay (R = 0.47, P = 0.02). At multivariable analysis, LA scar extent was independently related to LAAEF and LAEI. LAAEF and LA scar extent correlated with exercise capacity at follow‐up (R = 0.44, P = 0.02, and R = −0.40; P = 0.04).

Conclusion

LA contractility and compliance are markedly impaired years after successful PsAF ablation. LA dysfunction is closely related to scar burden.
EU Confidential: The European Parliament's Involvement in EU Security and Defence Policy
Authors: Rosén Guri
Published: May 2014

In 2002, the European Parliament (EP) and the Council concluded an Interinstitutional Agreement that gave the EP privileged access to sensitive documents in the area of security and defence. It is argued that the Council let the EP become involved in this sensitive policy area because it accepted the legislature's argument for its right to access. In addition, the EP's bargaining strategy concretized the procedures and contributed to finalizing the deal after two years of negotiation. It is shown in this article that despite the EP's marginal powers in the area of security and defence and the traditional conception of this policy as an executive prerogative, it cannot be isolated from democratic principles. This article provides new evidence for previous claims that the EP's involvement in EU foreign policy is increasing due to legitimacy concerns. It also offers a theoretical account for why this is so.
Australian practice nursing: collaboration in context
Authors: Merrick Eamon , Fry Margaret , Duffield Christine
Published: May 2014

Aims and objectives

To explore whether or not the context of Australian practice nursing supports collaborative decision‐making about organisation and delivery of patient care.

Background

Positive patient outcomes depend on Australian practice nurses participating in collaborative and interprofessional services, particularly for patients with chronic disease(s). It is unclear whether Australian practice nurses have the opportunity to collaborate in decision‐making or how traditional organisational structures may support or hinder collaboration.

Design

This is a descriptive exploratory study. Semi‐structured interviews were conducted using a purposive sample of practice nurses (n = 15). Thematic analysis was used to provide meaningful and contextual insights into how practice nurses participate in decision‐making.

Method

An interview tool, based on available literature, was developed and consisted of thirty open‐ended questions to direct discussion during telephone interviews. Transcribed data were imported into NVivotm for analysis and interpretation. The collection, analysis and thematic interpretation of data were an iterative process.

Findings

Participants fostered trusting interprofessional relationships, which enabled them to influence medical decision‐making and thereby advocate for patient need. Trusting interprofessional relationships were perceived to alter the relative roles of the medical practitioner and practice nurse and enhance the opportunities for collaborative decision‐making.

Conclusions and relevance to clinical practice

Collaborative interprofessional care in Australian general practice must occur if increased demands for care are to be met. It is timely to consider how government policy, financial regulations and the organisation of Australian general practice can better support and enhance a collaborative contribution to care by practice nurses.
Fear of falling in robust community‐dwelling older people: results of a cross‐sectional study
Authors: Liu Justina YW
Published: May 2014

Aims and objectives

To identify the prevalence and risk factors for fear of falling among robust community‐dwelling older people.

Background

Different models including various risk factors emerged when previous studies attempted to explore the factors’ multivariate associations with fear of falling. Attempting to detect fear of falling by a single question in some previous studies may not have been sufficiently sensitive, particularly in a robust population. Although some studies used a validated instrument to detect participants’ fear of falling, their self‐perceived efficacy in performing various activities was seldom reported. Information to provide an insight into the planning of well‐targeted interventions to reduce fear of falling has been lacking.

Design

A cross‐sectional study of 445 robust community‐dwelling older people aged ≥65.

Methods

Besides their demographic and fall‐related background, participants’ fear of falling level was assessed using the Chinese Fall Efficacy Scale–International. Other instruments included the timed up and go test, the Chinese Geriatric Depression Scale–Short Form, the Chinese Anxiety Disorder Scale, the Chinese Lubben Social Network Scale and the Chinese Personal Wellbeing Index, which were used to assess different variables that may be associated with fear of falling.

Results

Of the 64·73% of participants who had fear of falling, 65·63% had no history of fall but still had fear of falling. This result was higher than in most previous studies. Participants’ main concerns were walking on slippery/uneven surfaces, in crowded places and up/down a slope. Multivariate analyses showed that being female, suffering from poor vision and arthritis, poor performance in the timed up and go test, expressing more depressive and anxiety symptoms and low self‐perceived well‐being are multiply associated with fear of falling.

Conclusion

Fear of falling is prevalent among robust community‐dwelling older people regardless of their fall history. They showed lack of self‐perceived efficacy in performing various outdoor activities.

Relevance to clinical practice

The findings can assist in developing multidimensional strategies for reducing fear of falling in robust community‐dwelling older people.
Person‐centred ward climate as experienced by mentally lucid residents in long‐term care facilities
Authors: Bergland Ådel , Hofoss Dag , Kirkevold Marit , Vassbø Tove , Edvardsson David
Published: May 2014

Aims and objectives

To assess the content validity and reliability of the Person‐centred Climate Questionnaire‐Patient version in long‐term care facilities, to describe residents' perceptions of the extent to which their ward climate was person‐centred and to explore whether person‐centredness was associated with facility and resident characteristics, such as facility and ward size, having a sensory garden and having a primary caregiver.

Background

The importance of the physical environment to persons with dementia has been investigated. However, research is lacking regarding the extent to which mentally lucid residents experience their physical and psycho‐social ward climate as person‐centred and the factors influencing their experience.

Design

Cross‐sectional survey design.

Methods

The Person‐centred Climate Questionnaire–Patient version was translated into Norwegian with forward and backward translation. The content validity index for scales was assessed. The Person‐centred Climate Questionnaire –Patient version was completed by 145 mentally lucid residents in 17 Norwegian long‐term care facilities. Reliability was assessed by Cronbach's α and item–total correlations. Test–retest reliability was assessed by paired samples t‐test and Spearman's correlation. To explore differences based on facility and resident characteristics, independent‐samples t‐test and one‐way anova were used.

Results

The content validity index for scales was satisfactory. The Person‐centred Climate Questionnaire–Patient version was internally consistent and had satisfactory test–retest reliability. The climate was experienced as highly person‐centred. No significant differences were found, except that residents in larger facilities experienced the climate as more person‐centred in relation to everyday activities (subscale 2) than residents in smaller facilities.

Conclusion

The Norwegian version of the Person‐centred Climate Questionnaire–Patient version can be regarded as reliable in a long‐term care facility context. Perceived degree of person‐centredness was not associated with facility or resident characteristics, such as the number of residents, having a sensory garden or knowing that one has a primary caregiver.

Relevance to clinical practice

A person‐centred climate can be attained in different kinds of long‐term care facilities.
Genetic diagnosis of familial hypercholesterolaemia by targeted next‐generation sequencing
Authors: Maglio C. , Mancina R. M. , Motta B. M. , Stef M. , Pirazzi C. , Palacios L. , Askaryar N. , Borén J. , Wiklund O. , Romeo S.
Published: May 2014

Objectives

The aim of this study was to combine clinical criteria and next‐generation sequencing (pyrosequencing) to establish a diagnosis of familial hypercholesterolaemia (FH).

Design, setting and subjects

A total of 77 subjects with a Dutch Lipid Clinic Network score of ≥3 (possible, probable or definite FH clinical diagnosis) were recruited from the Lipid Clinic at Sahlgrenska Hospital, Gothenburg, Sweden. Next‐generation sequencing was performed in all subjects using SEQPRO LIPO RS, a kit that detects mutations in the low‐density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLR adapter protein 1 (LDLRAP1) genes; copy‐number variations in the LDLR gene were also examined.

Results

A total of 26 mutations were detected in 50 subjects (65% success rate). Amongst these, 23 mutations were in the LDLR gene, two in the APOB gene and one in the PCSK9 gene. Four mutations with unknown pathogenicity were detected in LDLR. Of these, three mutations (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH, but their pathogenicity has not been proved. The fourth, a mutation in LDLR affecting a splicing site (exon 6–intron 6) has not previously been reported; it was found to segregate with high cholesterol levels in the family of the proband.

Conclusions

Using a combination of clinical criteria and targeted next‐generation sequencing, we have achieved FH diagnosis with a high success rate. Furthermore, we identified a new splicing‐site mutation in the LDLR gene.
Antitumour activity of melatonin in a mouse model of human prostate cancer: relationship with hypoxia signalling
Authors: Paroni Rita , Terraneo Laura , Bonomini Francesca , Finati Elena , Virgili Eleonora , Bianciardi Paola , Favero Gaia , Fraschini Franco , Reiter Russel J. , Rezzani Rita , Samaja Michele
Published: May 2014

Melatonin is known to exert antitumour activity in several types of human cancers, but the underlying mechanisms as well as the efficacy of different doses of melatonin are not well defined. Here, we test the hypothesis whether melatonin in the nanomolar range is effective in exerting antitumour activity in vivo and examine the correlation with the hypoxia signalling mechanism, which may be a major molecular mechanism by which melatonin antagonizes cancer. To test this hypothesis, LNCaP human prostate cancer cells were xenografted into seven‐wk‐old Foxn1nu/nu male mice that were treated with melatonin (18 i.p. injections of 1 mg/kg in 41 days). Saline‐treated mice served as control. We found that the melatonin levels in plasma and xenografted tissue were 4× and 60× higher, respectively, than in control samples. Melatonin tended to restore the redox imbalance by increasing expression of Nrf2. As part of the phenotypic response to these perturbations, xenograft microvessel density was less in melatonin‐treated animals, indicative of lower angiogenesis, and the xenograft growth rate was slower (P < 0.0001). These changes were accompanied by a reduced expression of Ki67, elevated expression of HIF‐1α and increased phosphorylation of Akt in melatonin than saline‐treated mice. We conclude that the beneficial effect of melatonin in reducing cancer growth in vivo was evident at melatonin plasma levels as low as 4 nm and was associated with decreased angiogenesis. Higher HIF‐1α expression in xenograft tissue indicates that the antitumour effect cannot be due to a postulated antihypoxic effect, but may stem from lower angiogenesis potential.
The effect of season and track condition on injury rate in racing greyhounds
Authors: Iddon J. , Lockyer R. H. , Frean S. P.
Published: May 2014

OBJECTIVES

To identify environmental and management factors affecting injury rate in racing greyhounds.

METHODS

Surveys of racing injuries at two greyhound tracks in the UK were conducted using injury data collected by track veterinary surgeons. At Track A the relative frequency of common injuries was determined and compared with previously published studies conducted in the UK. At Track B the effects of month of the year, ambient temperature and track condition (“going”) on injury rate were determined.

RESULTS

Comparison of common injuries at Track A with previous studies suggested a change in the relative frequency of some injury types following a change in track surface from grass to sand. Estimated injury rates suggest improved track safety with the change in track surface. At Track B, injury rate increased significantly with faster track conditions. Time of year and ambient temperature had no significant effect on injury rate.

CLINICAL SIGNIFICANCE

Changes in track maintenance resulting in a slower track may reduce injury rate in racing greyhounds, with associated welfare benefits.
Does Authoritarianism Breed Corruption? Reconsidering the Relationship Between Authoritarian Governance and Corrupt Exchanges in Bureaucracies
Authors: Zaloznaya Marina
Published: May 2014

This article advocates for ethnographic and historical study of the political roots of corruption. Focusing on informal economies of Belarusian universities, it reexamines two theoretical propositions about corruption in autocracies. The first proposition is that authoritarianism breeds bureaucratic corruption; the second is that autocrats grant disloyal subjects corruption opportunities in exchange for political compliance. Using qualitative data, the author finds that autocracies can generate favorable as well as unfavorable preconditions for bureaucratic corruption. The author argues that lenient autocratic governance, characterized by organizational decoupling, creates favorable conditions for bureaucratic corruption. In contrast, consolidated autocracy, defined by rigid organizational controls, is unfavorable to such corruption. The author also concludes that in autocracies, disloyal populations may be cut off from rather than granted opportunities for bureaucratic corruption. These findings suggest that the relationship between autocratic governance and corruption is more complex than current studies are able to reveal due to their methodological limitations.
Diversification of an emerging pathogen in a biodiversity hotspot: Leptospira in endemic small mammals of Madagascar
Authors: Dietrich Muriel , Wilkinson David A. , Soarimalala Voahangy , Goodman Steven M. , Dellagi Koussay , Tortosa Pablo
Published: May 2014

Biodiversity hotspots and associated endemism are ideal systems for the study of parasite diversity within host communities. Here, we investigated the ecological and evolutionary forces acting on the diversification of an emerging bacterial pathogen, Leptospira spp., in communities of endemic Malagasy small mammals. We determined the infection rate with pathogenic Leptospira in 20 species of sympatric rodents (subfamily Nesomyinae) and tenrecids (family Tenrecidae) at two eastern humid forest localities. A multilocus genotyping analysis allowed the characterization of bacterial diversity within small mammals and gave insights into their genetic relationships with Leptospira infecting endemic Malagasy bats (family Miniopteridae and Vespertilionidae). We report for the first time the presence of pathogenic Leptospira in Malagasy endemic small mammals, with an overall prevalence of 13%. In addition, these hosts harbour species of Leptospira (L. kirschneri, L. borgpetersenii and L. borgpetersenii group B) which are different from those reported in introduced rats (L. interrogans) on Madagascar. The diversification of Leptospira on Madagascar can be traced millions of years into evolutionary history, resulting in the divergence of endemic lineages and strong host specificity. These observations are discussed in relation to the relative roles of endemic vs. introduced mammal species in the evolution and epidemiology of Leptospira on Madagascar, specifically how biodiversity and biogeographical processes can shape community ecology of an emerging pathogen and lead to its diversification within native animal communities.