bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiplatelet drugs in the elderly: prescriptions often inappropriate and reduced tolerance by associated diseases and drugs
Authors: Cadiou Gwénaëlle , Adam Magali , Caussin Marie , Landrin Isabelle , Mariette Natacha , Capet Corinne , Mouton‐Schleifer Dominique , Remy Elise , Kadri Nadir , Doucet Jean
Published: January 2011

To assess the conditions of prescriptions and tolerance of antiplatelet drugs (APD) in the elderly and to detail the parameters that influence the tolerance of these drugs. Prospective survey in a Department of Geriatric Medicine. Two hundred nineteen patients 70 years and older treated with one or two APD prior to admission were included during 7 months in 2008. We recorded the type of APD, associated diseases, main associated or co‐prescribed drugs which could interact with APD and the bleeding adverse events including cutaneous bleeding. The mean age of the 219 patients was 84.5 ± 6.7 years (70–101 years), women 59.4%. Among patients 64.8% received aspirin (mainly 75 mg), 28.3% received clopidogrel and 6.8% received their combination; 16.9% of prescriptions were off‐label; 51.6% of patients had an associated disease and/or an associated drug which could have increased risk of bleeding event. Among the patients who received a gastric‐protective drug, the prescription followed the recommendations of the French Health Authority in 38.9%. We recorded bleeding events in 24.2% of patients at admission and in 18.3% of patients during the hospitalization. Bleeding events were significantly more frequent in patients treated with aspirin than clopidogrel (40.8 vs. 24.2%, P < 0.05) and/or with an associated drug (OR = 2.36, 95% CI 1.34–4.14, P < 0.01) and/or an associated disease (OR = 1.22, 95% CI 1.01–3.42, P < 0.05). APD treatment was stopped in 28.8% of patients, mainly because lack of indication or bleeding adverse events. Off‐label prescriptions of APD were not rare in the elderly, and adverse events are frequent. The results of this preliminary study evoke that medical situations at increased risk of bleeding are perhaps insufficiently evaluated, either in case of prescription of associated drugs with increased bleeding risk or during the follow‐up of patients with associated diseases. Cutaneous bleeding events should be more taken into account in prospective studies.
Evaluation of Composite Resin Materials for Maxillomandibular Fixation in Cats for Treatment of Jaw Fractures and Temporomandibular Joint Luxations
Authors: Hoffer Melissa , Manfra Marretta Sandra , Kurath Peter , Johnson Ann , Griffon Dominique , Schaeffer David , Pijanowski Gerald , Przywara John
Published: January 2011

Objective: To identify a method of composite application for maxillomandibular fixation (MMF) in cats that ensures the material will remain bonded during convalescence but be easy to remove with a low complication rate.

Study Design: Experimental study

Sample Population: Feline cadavers (n=88).

Methods: MMF was applied using composite to 4 groups of 22 feline cadaver heads each. The protocols were: group CR: acid etch and composite resin; group CR+: acid etch, bonding agent, and composite resin; group FR50: partial surface acid etch and flowable composite resin; group FR100: complete surface acid etch and flowable composite resin. Removal time and complication rate were noted. Load to failure was determined by tensile loading.

Results: Load to failure was similar for groups CR and CR+ and for groups FR50 and FR100; however, load to failure for groups FR50 and FR100 was higher than groups CR and CR+ (P<.01). Time for material removal for group FR100 was longer (P<.01) and the complication rate was higher (P<.01) compared with the groups CR, CR+, and FR50, with no significant differences in removal times and complication rate between the latter groups. The most frequent complication during material removal in group FR100 was crown fracture.

Conclusions: Partial coronal surface acid etch before use of flowable composite maintained a strong bond, yet resulted in easy material removal with a low complication rate.
More Similarities or More Differences? Comparing Public and Nonprofit Managers’ Job Motivations
Authors: Lee Young‐joo , Wilkins Vicky M.
Published: January 2011

Existing research on career motivations tends to focus either on the difference between private and public organizations or on the difference between nonprofit and for‐profit firms. Although commonalities exist, the literature suggests that there also are many differences in what motivates public and nonprofit employees. Employing data from the National Administrative Studies Project III, this research examines how seven motivational aspects correlate with the choice between public and nonprofit employment. The authors find that managers who value advancement opportunities, a pension and retirement plan, and the ability to serve the public in their jobs are more likely to accept a job in the public sector, whereas managers who value family‐friendly policies and increased responsibility are more likely to accept a position in the nonprofit sector. Participation in volunteering is positively associated with nonprofit employment. The authors suggest a possible link between volunteering and the unique nonprofit motivation that is differentiated from public service motivation.
International Entrepreneurship and Capability Development—Qualitative Evidence and Future Research Directions
Authors: Autio Erkko , George Gerard , Alexy Oliver
Published: January 2011

In this article, we explore how new capabilities emerge and solidify in new ventures that are faced with fundamental uncertainty from their environment. To do so, we draw from the organizational and entrepreneurial literature on cognition and capabilities. Using initial qualitative evidence from a multifirm study in the context of new venture internationalization, we develop a cognition–based model of capability emergence in new ventures. Our findings extend the capability development and learning implications of internationalization to the fundamental character of organizing processes in start–ups. Moreover, we derive avenues for future entrepreneurship research on the origins and evolution of capabilities in new ventures.
The Rewards of Entrepreneurship: Exploring the Incomes, Wealth, and Economic Well–Being of Entrepreneurial Households
Authors: Carter Sara
Published: January 2011

The financial rewards and consequences of entrepreneurship for the individual are unknown. Prior studies have focused on self–employment income estimates and have highlighted the low median earnings that may be anticipated. The apparent financial irrationality of entrepreneurship is typically explained in terms of nonpecuniary compensating factors, such as autonomy and satisfaction. However, the financial rewards of entrepreneurship are multifaceted and include different types and amounts of rewards at different stages of the business life cycle. More accurate reflections of entrepreneurial rewards require researchers to move away from the use of narrow and static measures and instead focus on a broad set of indicators that collectively contribute to overall economic well–being. Entrepreneurial rewards are not only determined by business rationality, but are influenced by household needs that evolve over time. Hence, the analysis of entrepreneurial rewards requires an approach that captures the processes of reward decision making over the business life cycle while contextualizing reward decisions within the entrepreneurial household.
The Business Model in Practice and its Implications for Entrepreneurship Research
Authors: George Gerard , Bock Adam J.
Published: January 2011

While the term “business model” has gained widespread use in the practice community, the academic literature on this topic is fragmented and confounded by inconsistent definitions and construct boundaries. In this study, we review prior research and reframe the business model with an entrepreneurial lens. We report on a discourse analysis of 151 surveys of practicing managers to better understand their conceptualization of a business model. We find that the underlying dimensions of the business model are resource structure, transactive structure, and value structure, and discuss the nature and implications of dimensional dominance for firm characteristics and behavior. These findings provide new directions for theory development and empirical studies in entrepreneurship by linking the business model to entrepreneurial cognition, opportunity co–creation, and organizational outcomes.
Entrepreneurship as Method: Open Questions for an Entrepreneurial Future
Authors: Sarasvathy Saras D. , Venkataraman Sankaran
Published: January 2011

In this essay, we outline the provocative argument that in the realm of human affairs there exists an “entrepreneurial method” analogous to the scientific method spelled out by Francis Bacon and others with regard to the natural realm. We then suggest a series of open questions that we believe will help future scholars spell out the contents of such a method and ways in which it can be put to work in the design and achievement of socioeconomic ends. At least one normative implication of accepting the argument would be to teach entrepreneurship not only to entrepreneurs but to everyone, as a necessary and useful skill and an important way of reasoning about the world.
Contextualizing Entrepreneurship—Conceptual Challenges and Ways Forward
Authors: Welter Friederike
Published: January 2011

This paper sets out to explore contexts for entrepreneurship, illustrating how a contextualized view of entrepreneurship contributes to our understanding of the phenomenon. There is growing recognition in entrepreneurship research that economic behavior can be better understood within its historical, temporal, institutional, spatial, and social contexts, as these contexts provide individuals with opportunities and set boundaries for their actions. Context can be an asset and a liability for the nature and extent of entrepreneurship, but entrepreneurship can also impact contexts. The paper argues that context is important for understanding when, how, and why entrepreneurship happens and who becomes involved. Exploring the multiplicity of contexts and their impact on entrepreneurship, it identifies challenges researchers face in contextualizing entrepreneurship theory and offers possible ways forward.
Delineating the Domain of Development Entrepreneurship: A Market–Based Approach to Facilitating Inclusive Economic Growth
Authors: McMullen Jeffery S.
Published: January 2011

Development economists and management scholars have called for a more market–based approach to address the extreme poverty suffered by the billion people residing primarily in least developed countries. This article proposes a theory of development entrepreneurship that blends business entrepreneurship, social entrepreneurship, and institutional entrepreneurship to accelerate the institutional change necessary to make economic growth more inclusive. After examining various explanations of market failure in the base of the pyramid and social entrepreneurship literatures, I explain why entrepreneurial transformation of formal institutions is needed and what differentiates development entrepreneurship from related concepts such as social entrepreneurship, social business entrepreneurship, and socio–political activism.
Culture Change Models and Resident Health Outcomes in Long‐Term Care
Authors: Hill Nikki L. , Kolanowski Ann M. , Milone‐Nuzzo Paula , Yevchak Andrea
Published: January 2011

Purpose: To examine the scientific evidence for the effect of comprehensive culture change model implementation on resident health outcomes in long‐term care.

Design: In this integrated review, an electronic literature search was conducted for studies that examined the effect of comprehensive culture change models on long‐term care residents’ physical and psychosocial health.

Methods: Eleven articles were thoroughly reviewed for outcomes related to resident health, and findings were integrated across models. Each study was assigned a level of evidence rating using the Scottish Intercollegiate Guidelines Network guidelines and an overall recommendation grade was determined.

Findings: Evaluation of the literature indicates that results are conflicting, although potential resident benefits as a result of model implementation may exist, particularly in regard to psychosocial health outcomes.

Conclusions: Evidence regarding long‐term care residents’ health outcomes after comprehensive culture change model implementation is inconsistent, and the grade of the evidence makes practice recommendations difficult at this time. However, integrated findings across studies demonstrate potential psychosocial benefits to long‐term care residents.

Clinical Relevance: Nurses working in long‐term care play a crucial role in the success of culture change initiatives as well as the health outcomes of residents. Empirical evidence for the effect of comprehensive culture change models on resident health outcomes supports reasonable expectations of their implementation and indicates areas for future research and translation into practice.
Melatonin preserves the transient mitochondrial permeability transition for protection during mitochondrial Ca2+stress in astrocyte
Authors: Jou Mei‐Jie
Published: January 2011

Abstract: Cells have two modes of mitochondrial permeability transition (MPT) which produce virtually opposite pathophysiological outcomes of survival or death when responding to apoptotic insults. The transient‐MPT (t‐MPT) protects mitochondria, whereas the prolonged‐MPT (p‐MPT), once activated, triggers the ‘point of no return’ for apoptosis or necrosis. Our previous studies show that in addition to scavenging mitochondrial reactive oxygen species, melatonin targets mitochondrial Ca2+(mCa2+)‐mediated MPT for protection during mCa2+‐mediated apoptosis in astrocytes. The precise mechanism for how melatonin modulates the MPT during mCa2+stress, however, remains unelucidated. With the application of fluorescence laser scanning imaging microscopy, this study demonstrated for the first time that melatonin does not inhibit the MPT pore, rather it crucially preserves the pore in its protective mode of t‐MPT during mCa2+stress. Melatonin‐preserved t‐MPT importantly maintained mitochondrial membrane potential (ΔΨm) which not only prevented depolarized ΔΨm‐induced p‐MPT but also retained ΔΨm‐dependent ATP formation during disturbed Ca2+homeostasis. Additionally, the melatonin‐preserved t‐MPT allowed mitochondria to release the toxic overload of mCa2+to sublethal levels, which prevented mCa2+‐mediated fission and mCa2+‐dependent p‐MPT and possibly also improved mCa2+‐dependent ATP synthesis. Melatonin’s effect in reducing the Ca2+load greatly diminished when the MPT was inhibited by cyclosporine A, suggesting its pore dependency as well as that a preserved t‐MPT may be superior to a MPT inhibition in protecting mCa2+‐mediated apoptosis. The unique modulation on the MPT provided by melatonin may have extraordinary therapeutic potential in the treatment of mCa2+‐mediated astrocyte‐associated neurodegenerative pathologies and diseases.
The Power of Observation
Authors: Clark David A.
Published: January 2011

Citation  Clark DA. The power of observation. Am J Reprod Immunol 2011; 66: 71–75

Problem  In the golden age of evidence‐based medicine, how should one view the cohort‐controlled study of IVIG + anti‐TNF‐α (Humira) in recurrent in vitro fertilization (IVF) failure patients with an elevated Th1/Th2 cytokine production ratio.

Method  Critical analysis of the nature of evidence for causation.

Results A better delivery rate and a live birth rate per embryo approaching the estimated maximum possible in patients whose elevated Th1/Th2 ratio corrected to normal compared to those with an incomplete correction is a strong argument for causation. A maximal improvement when treatment was given 61–120 days before embryo transfer suggests a possible mechanism via improving the physiology during follicle development.

Conclusion  Independent replication to verify results would augment power.
Sequential Virtual Screening Approach to the Identification of Small Organic Molecules as Potential BACE‐1 Inhibitors
Authors: Chiriano Gianpaolo , Sartini Andrea , Mancini Francesca , Andrisano Vincenza , Bolognesi Maria L. , Roberti Marinella , Recanatini Maurizio , Carloni Paolo , Cavalli Andrea
Published: January 2011

In this letter, we report on the sequential application of two different in silico screening approaches combined with bioassays aimed at the identification of small organic molecules as potential BACE‐1 inhibitors. Two hits endowed of micromolar inhibitory potency were selected, and the binding mode of the most potent compound was further characterized through docking simulations.
Four newly recorded species of subfamily Olethreutinae (Lepidoptera: Tortricidae) from North Korea
Authors: BYUN Bong‐Kyu
Published: January 2011

Four species of the subfamily Olethreutinae based on the materials in the Hungarian Natural History Museum are added to the North Korean fauna: Ancylis melanostigma Kuznetsov, Ancylis sativa Liu, Eucoenogenes japonica Kawabe and Eucosma glebana (Snellen). Photographs of adults and genitalia are provided with brief comments on the distribution.
Electroantennogram and flight orientation response of Cotesia plutellae to hexane extract of cruciferous host plants and larvae of Plutella xylostella
Authors: SEENIVASAGAN Thangaraj , PAUL A. V. Navarajan
Published: January 2011

The braconid wasp Cotesia plutellae is an important larval parasitoid of the diamondback moth (DBM) Plutella xylostella, which a major pest of crucifers in the tropics and subtropics. The peripheral olfactory responses of antennal chemoreceptors of C. plutellae to various cruciferous host plants of DBM and host larval body (cuticle) extracts were examined by electroantennogram (EAG) detection and the behavioral response to a concentration of 1% was analyzed in a Y‐tube olfactometer. Females of C. plutellae exhibited dose‐dependant EAG response for all the extracts tested. Antennal stimulation with 0.1 and 1% concentrations elicited stronger EAG responses than lower concentrations for all the extracts. Host plant extracts were more stimulatory to virgin females, while gravid females exhibited increased antennal sensitivity to host larval body extract odors. In the flight orientation studies, virgin females exhibited increased orientation toward host plant extracts, while gravid females oriented more toward host larval body odors. The EAG response profile and the corresponding orientation behavior revealed a differential preference by the parasitoid wasp to host plant and host‐related cues. Mustard and cauliflower extracts were more attractive to females than other extracts. The possible behavioral manipulation of this specialist parasitoid using these extracts for effective biological control of diamondback moth is discussed.
Cellular and humoral immune defenses of Oxya japonica (Orthoptera: Acrididae) to entomopathogenic fungi Metarhizium anisopliae
Authors: ANGGRAENI Tjandra , MELANIE  , PUTRA Ramadhani Eka
Published: January 2011

One Indonesian isolate of the fungus Metarhizium anisopliae, named Majalengka strain, was evaluated not only for its virulence but also for the immune response of rice grasshopper Oxya japonica (Orthoptera: Acrididae) as a target organism. Five aqueous suspensions with different conidia concentrations in logarithmic series were prepared. The fungus showed high virulence as it caused 100% mortality at low conidia concentration (1.5 × 102 conidia/mL). Remarkable changes in the cellular and humoral responses were also observed when adult grasshoppers were infected with the fungus. The number of hemocytes decreased significantly within 12 h after infection. In addition, the total number of granulocytes increased rapidly in the first 12 h then gradually decreased 24 and 48 h after infections, while the number of coagulocytes fluctuated over time. The infection influenced the humoral response by increasing the phenoloxidase activity.
Black light trap collections in Wangging county and Yanji city, Jilin Province, China, August 2006–2007
Authors: SHIN E‐Hyun , LEE Wook‐Gyo , CHANG Kyu‐Sik , CHOI Young‐Mi , LEE Hee‐Il , JIN Longzhu , LI Jixu , CHEN Longnan , LEE Dong‐Kyu , PARK Chan
Published: January 2011

Adult mosquito surveillance was conducted using black light traps in August of 2006 and 2007 at Wangging county and Yanji city, Jilin Province, China to identify the distribution of anopheline mosquitoes in northern China. A total of 2459 female mosquitoes comprising three genera and eight species including Anopheles (Anopheles) lesteri, An. (Ano.) kleini, An. (Ano.) pullus, Culex inatomii, Cx. orientalis, Cx. pipiens, Cx. bitaeniorhynchus and Aedes vexans nipponii were collected. The most commonly collected species was An. kleini which had not been previously reported from China. Anopheles sinensis sensu stricto is commonly collected throughout China, but was not collected from these areas.
Hvmar1, a mariner‐like element from the tobacco budworm Heliothis virescens, can transpose in Drosophila melanogaster
Authors: KIM Yu Jung , HAN Tiffany S. , MILLER Thomas A.
Published: January 2011

Transposable elements of the mariner family are widespread and have been found in the genome of plants, animals and insects. However, most of these elements contain multiple inactivating mutations and so far, only three naturally occurring mariner elements are known to be functional. In a previous study, a mariner‐like element called Hvmar1 was discovered in the genome of the tobacco budworm Heliothis virescens. Further analysis of the Hvmar1 nucleotide sequence revealed the presence of 30‐bp imperfect inverted terminal repeats and an intact open reading frame, which is considered to encode a functional transposase. In the present study, we show that the Hvmar1 element is active using interplasmid transposition assays in Drosophila melanogaster embryos. When injected into Drosophila embryos, the helper plasmid produced a transposase that was able to mediate transposition of the Hvmar1 element from a donor to a target plasmid. The transposition efficiency of Hvmar1 in D. melanogaster is approximately 11‐fold lower than that of the well‐known Mos1 mariner transposon. However, this efficiency is comparable to those observed previously with Mos1 in non‐Drosophila insects. We identified 10 independent interplasmid transposition events, albeit the recovery of these events was rare. In each case the Hvmar1 element transposed in a precise manner, with the characteristic TA dinucleotides being duplicated on insertion. Furthermore, two of the target sites identified have been used previously by Mos1 for insertion. The active transposition of Hvmar1 in D. melanogaster provides a basis for examining the mobility of this element in its natural host as well as a starting point for comparative studies with Mos1 and other functional mariner transposons.
Photoexcitation of Aqueous Suspensions of Titanium Dioxide Nanoparticles: An Electron Spin Resonance Spin Trapping Study of Potentially Oxidative Reactions
Authors: Dodd Nicholas J. F. , Jha Awadhesh N.
Published: January 2011

It is well‐established that exposure of aqueous suspensions of titanium dioxide (TiO2) nanoparticles to ultraviolet A (UVA) light produces reactive oxygen species which leads to biological damage. However, there is disagreement in the literature as to the exact nature of these species and how they are formed. Using a number of different spin traps (i.e.PBN, POBN, DMPO, DEPMPO), we have shown that the primary damaging species produced on irradiation of an aqueous suspension of TiO2is the hydroxyl radical, which is formed at the valence band hole under both aerobic and hypoxic conditions. Hydroxyl radical production is enhanced by the presence of oxygen which probably reacts with the conduction band electrons or resultant Ti3+, inhibiting hole‐electron recombination, although we find no evidence of reaction of oxygen to form free superoxide radical anions or of the formation of any other radical at that site. The present results suggest that the resulting O2•−species may not be as labile as previously thought and may possibly undergo further reduction to the O22−dianion. Hydroxyl radicals formed at the surface of the TiO2readily react with substrates containing an abstractable hydrogen to produce secondary radicals that, in biological systems, could lead to cell damage.
Peripheral and Central Blood Pressure Responses of Combination Aliskiren/Hydrochlorothiazide and Amlodipine Monotherapy in African American Patients With Stage 2 Hypertension: The ATLAAST Trial
Authors: Ferdinand Keith C. , Pool James , Weitzman Richard , Purkayastha Das , Townsend Raymond
Published: January 2011

Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8‐week double‐blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren/hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1‐ to 4‐week washout, initial therapy was aliskiren/HCTZ 150/12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced‐titrated to aliskiren/HCTZ 300/25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments (−28.6 mm Hg with aliskiren/HCTZ vs −28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren/HCTZ vs amlodipine (−30.1 mm Hg vs −21.2; P=.031), although 24‐hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients. J Clin Hypertens (Greenwich). 2011;13:366–375. ©2011 Wiley Periodicals, Inc.
Wolbachia detection: an assessment of standard PCR Protocols
Authors: SIMÕES P. M. , MIALDEA G. , REISS D. , SAGOT M.‐F. , CHARLAT S.
Published: January 2011

Wolbachia is a large monophyletic genus of intracellular bacteria, traditionally detected using PCR assays. Its considerable phylogenetic diversity and impact on arthropods and nematodes make it urgent to assess the efficiency of these screening protocols. The sensitivity and range of commonly used PCR primers and of a new set of 16S primers were evaluated on a wide range of hosts and Wolbachia strains. We show that certain primer sets are significantly more efficient than others but that no single protocol can ensure the specific detection of all known Wolbachia infections.
The semantic‐similarity effect in children: Influence of long‐term knowledge on verbal short‐term memory
Authors: Monnier Catherine , Bonthoux Françoise
Published: January 2011

The present research was designed to highlight the relation between children's categorical knowledge and their verbal short‐term memory (STM) performance. To do this, we manipulated the categorical organization of the words composing lists to be memorized by 5‐ and 9‐year‐old children. Three types of word list were drawn up: semantically similar context‐dependent (CD) lists, semantically similar context‐independent (CI) lists, and semantically dissimilar lists. In line with the procedure used by Poirier and Saint‐Aubin (1995), the dissimilar lists were produced using words from the semantically similar lists. Both 5‐ and 9‐year‐old children showed better recall for the semantically similar CD lists than they did for the unrelated lists. In the semantic similar CI condition, semantic similarity enhanced immediate serial recall only at age 9 but contributed to item information memory both at ages 5 and 9. These results, which indicate a semantic influence of long‐term memory (LTM) on serial recall from age 5, are discussed in the light of current models of STM. Moreover, we suggest that differences between results at 5 and 9 years are compatible with pluralist models of development.
Distribution of electrical activation to the external intercostal muscles during high frequency spinal cord stimulation in dogs
Authors: DiMarco Anthony F. , Kowalski Krzysztof E.
Published: January 2011

Non‐technical summary  Normal breathing is controlled by specialized neurons in the central nervous system including the brainstem and spinal cord. Signals generated in the brainstem and transmitted to the major inspiratory muscles, including the diaphragm and intercostal muscles, are necessary to sustain life. However, we show that the specific pattern of intercostal muscle activation during breathing does not require input from the brainstem. In other words, the neural circuitry controlling this pattern of activation exists within the spinal cord. This knowledge furthers our understanding of the mechanisms that control breathing and has implications for patients with certain disease states such as cervical spinal cord injury.
The microcirculation: physiology at the mesoscale
Authors: Secomb Timothy W. , Pries Axel R.
Published: January 2011

Abstract The microcirculation exemplifies the mesoscale in physiological systems, bridging larger and smaller scale phenomena. Microcirculatory research represents an example of a ‘middle‐out,’ rather than ‘top‐down’ or ‘bottom‐up,’ approach to the study of biological function. Computational and mathematical approaches can be used to analyse the functioning of the microcirculation and to establish quantitative relationships between microvascular processes and phenomena occurring on larger and smaller scales, leading to insights which could not be obtained solely by reductionist biological experiments. Given its integrative approach to processes occurring on disparate scales and its emphasis on theoretical as well as experimental approaches, microcirculatory research belongs within current definitions of systems biology.
Spinal 5‐HT7 receptor activation induces long‐lasting phrenic motor facilitation
Authors: Hoffman M. S. , Mitchell G. S.
Published: January 2011

Non‐technical summary  Acute intermittent hypoxia elicits a serotonin‐dependent form of respiratory plasticity known as phrenic long‐term facilitation via synthesis of brain‐derived neurotrophic factor (BDNF) and activation of its receptor TrkB. Recently we demonstrated that spinal activation of Gs protein‐coupled adenosine A2A receptors ‘trans‐activates’ the BDNF receptor, TrkB, and induces phrenic motor facilitation (PMF). Therefore we hypothesized that perhaps other Gs protein‐coupled serotonin receptors elicit PMF, specifically serotonin receptor type‐7 (5‐HT7) which are expressed in phrenic motor neurons and underlie multiple forms of spinal respiratory plasticity. We demonstrate that spinal 5‐HT7 receptor activation in anaesthetized rats elicits long‐lasting PMF. 5‐HT7 agonist‐induced PMF appears to require TrkB receptor activity and/or new synthesis of TrkB protein, in addition to activity of the signalling molecule PI3K. A more complete understanding of signalling mechanisms involved in PMF may guide development of novel therapeutic strategies to treat ventilatory control disorders.
l‐Dopa activates histaminergic neurons
Authors: Yanovsky Yevgenij , Li Sha , Klyuch Boris P. , Yao Qiaoling , Blandina Patrizio , Passani M. Beatrice , Lin Jian‐Sheng , Haas Helmut L. , Sergeeva Olga A.
Published: January 2011

Non‐technical summary L‐Dopa is an effective medication for Parkinson's disease (PD), but loses efficiency with time. This can be delayed by treatment with histamine antagonists. We show histaminergic neurons in the hypothalamus controlling wakefulness are excited by L‐Dopa, which they can take up and transform to dopamine. They innervate the whole brain, in particular the striatum which is deficient of dopamine in PD. We revealed mechanisms of excitation of histaminergic neurons by L‐Dopa and dopamine opening new avenues for the treatment of PD and sleep disorders.
Impaired β‐adrenergic responsiveness accentuates dysfunctional excitation–contraction coupling in an ovine model of tachypacing‐induced heart failure
Authors: Briston Sarah J. , Caldwell Jessica L. , Horn Margaux A. , Clarke Jessica D. , Richards Mark A. , Greensmith David J. , Graham Helen K. , Hall Mark C. S. , Eisner David A. , Dibb Katharine M. , Trafford Andrew W.
Published: January 2011

Non‐technical summary  Heart failure is where the heart is unable to pump sufficient blood in order to meet the requirements of the body. Symptoms of heart failure often first present during exercise. During exercise the blood levels of a hormone, noradrenaline, increase and activate receptors on the muscle cells of the heart known as β‐receptors causing the heart to contract more forcefully. We show that in heart failure the response to β‐receptor stimulation is reduced and this appears to be due to a failure of the β‐receptor to signal correctly to downstream targets inside the cell. However, by‐passing the β‐receptor and directly activating one of the downstream targets, an enzyme known as adenylyl cyclase, inside the cell restores the function of the muscle cells in failing hearts. These observations provide a number of potential targets for therapies to improve the function of the heart in patients with heart failure.
Current instabilities in rare-earth oxides-HfO2 gate stacks grown on germanium based metal-oxide-semiconductor devices due to Maxwell–Wagner instabilities and dielectrics relaxation
Authors: Rahman M. S. , Evangelou E. K. , Dimoulas A. , Mavrou G. , Galata S.
Published: January 2011

The authors report the current instabilities in rare-earth oxides-HfO2 gate stacks grown on Ge (001) based metal-oxide-semiconductor devices under constant voltage stress (CVS). The devices have been subjected to CVS and show relaxation effect and charge accumulation/trapping at the interface of the high-k bilayers known as Maxwell–Wagner (MW) polarization; both cause current instabilities (i.e., current decay). The experimental data can only be explained when co-occurrent effects of MW instability and dielectric relaxation are taken into consideration. On the contrary, any single effect alone is unable to fit and/or explain the results completely. It is interesting that these effects show field dependent behavior; that is, at low CVS, the authors observe the current instabilities (follow J∼t−n law), whereas at higher field, the charge trapping and/or the creation of new defects in the oxides, which eventually lead to breakdown, are significant. These results are also confirmed by capacitance-voltage (C−Vg) measurements in respective conditions.
Changes of B and T lymphocytes and selected apopotosis markers in Hashimoto's thyroiditis
Authors: Kaczmarek Elzbieta , Lacka Katarzyna , Jarmolowska-Jurczyszyn Donata , Sidor Anna , Majewski Przemyslaw
Published: January 2011

The aim was to assess changes of B and T lymphocytes and selected apoptotic markers in Hashimoto thyroiditis (HT) cases on the basis of quantitative immunohistochemical studies (CD20, CD43, CD8, Bcl-2, caspase-3). The control group comprised colloid goitres without inflammatory infiltrate taken from 10 female patients. Thyroid specimens were obtained retrospectively from 40 patients. The immunohistochemical reactions were subject to quantitative evaluation performed using image-processing methods, including a spatial visualisation of the markers' expression. The percentage of Bcl-2 reactions in HT (mean 3.65%, SD 2.94%) was significantly lower than in the control group (mean 13.99%, SD 5.04%), while the thyroid follicles in HT samples exhibited a higher degree of staining for caspase-3 (mean 1.10%, SD 1.03%) in contrast to normal control tissues (mean 0.48%, SD 1.02%). The results from this study indicate that apoptosis plays a major role in the patogenesis of autoimmune thyroid diseases containing the main pathogenic events in the lesion of thyroid follicular cells in HT. Moreover, the reactivity of CD43 and CD20 was significantly higher in Hashimoto disease, while CD8 was not significantly different from the control group.
Acute severe ulcerative colitis: timing is everything
Authors: Gulliford Stephen R , Limdi Jimmy K
Published: January 2011

The idiopathic inflammatory bowel diseases comprise mainly two types of intestinal disorder, Crohn disease and ulcerative colitis. The clinical course is marked by exacerbations and remissions that occur spontaneously in response to treatment or intercurrent illness. The disease affects approximately 240 000 patients in the UK. Acute severe ulcerative colitis is a medical emergency; prompt effective treatment at the point of admission can avoid significant morbidity and be potentially life-saving. Although such patients need specialist management, it is imperative that emergency care physicians are aware of the important principles of management of this condition to achieve successful outcomes. Corticosteroids remain the cornerstone of initial therapy, but a third of patients will fail to respond, and further management involves critical and timely decisions on whether to use rescue therapy in the form of ciclosporin or infliximab without compromising the health or safety of the patient or to offer timely surgery. The evidence base for the choices for optimal management of this condition is presented.
Orogen-parallel tangential motion in the Late Devonian – Early Carboniferous southern Appalachians internides
Authors: Vauchez Alain , Babaie Hassan A. , Babaei Abdolali
Published: January 2011

In the internal southern Appalachians, orogen-parallel lineation in flat-lying amphibolite facies mylonites occurs over more than 700 km, from North Carolina to Alabama, along the Inner Piedmont western boundary. In several areas distributed along this zone, evidence of orogen-parallel tangential movement is consistently associated with the lineation, suggesting the amphibolite facies mylonites mark an orogen-scale movement zone, probably a décollement zone that formed in the middle crust.Amphibolite facies mylonites occur in the Clairmont Formation north of Atlanta, Georgia. Abundant mesoscopic and microscopic kinematic indicators together with a dominant southwest-trending lineation on a subhorizontal mylonitic foliation reveal a ductile southwestward movement of the Inner Piedmont on subhorizontal shear planes during the mylonitization. Synkinematic hornblende and biotite crystals extracted from a specimen of amphibolite suggest minimum K–Ar cooling ages of, respectively, 349 and 327 Ma. A minimum age of 350 Ma is thus suggested for the main activity of the western Piedmont décollement zone.Orogen-parallel tangential movement along the western Piedmont décollement zone is coeval with orogen-parallel strike-slip faulting in the high-angle Ocmulgee fault in central Piedmont. These faults shape a shear zone system that probably formed at the boundary of the North American craton, in relation with a transpressional regime of deformation.
Evidence for early Mesozoic extensional faulting in Carboniferous rocks, southern New Brunswick, Canada
Authors: Roberts Wyn , Williams Paul F.
Published: January 2011

The high-grade sylvinite orebody (28% K2O) mined by the Potacan Mining Company (formerly the Denison Potacan Potash Company) near Sussex, New Brunswick, Canada, has undergone intense internal folding. The folds vary in size from centimetres to hundreds of metres, are mostly tight to isoclinal, recumbent and asymmetrically overfolded towards the southeast, and belong to a single varied style group suggesting one deformation event. Folds are noncylindrical to sheath-like locally and have highly variable cross-sectional morphologies. Slickensides are locally common and penetrative. Slickenline trends in all parts of the mine are northwest–southeast. All the evidence is consistent with a southeast-directed movement across the top of the evaporite body having caused extensive ductile drag folding within both the sylvinite and halite lithologies. The evaporites, in fact, have all the characteristics of a near-horizontal mylonite zone. Variscan deformation during the Late Carboniferous is generally cited as being the most recent tectonic activity immediately north of the Caledonia Highlands, and the evaporite deformation has, in the past, been attributed to these events. This viewpoint is here reexamined, since reverse faults that are locally associated with the Variscan orogeny do not adequately explain the evaporite deformation. With increasing evidence for significant Mesozoic extensional faulting and the need for low-angle detachments, it is more likely that the evaporite deformation is linked to these later events than to earlier Palaeozoic deformation.
Les déformations ordoviciennes dans la zone des Sehoul (Maroc septentrional) : une orogenèse calédonienne en Afrique du Nord
Authors: Piqué Alain , Hassani Ahmed El , Hoepffner Christian
Published: January 2011

The Sehoul Zone of northern Morocco differs from the remainder of the Hercynides in having the structural signature of an earlier event of deformation. Folds and thrusts overturned to the south affect an area in which Cambrian rocks are represented. The schistose epizonal metamorphism and a granodiorite intrusion have been dated by various methods as being Middle to Late Ordovician in age. This structurally particular Sehoul Zone was subsequently refolded during the Hercynian orogenesis at early Carboniferous time. The tectono-metamorphic evolution of the Sehoul Zone is contemporaneous with the deformation recognized in oceanic drill holes on the Atlantic margin of Morocco, offshore from El Jadida. This orogenic evolution that affected the northern and western margins of Morocco was contemporaneous with the known Taconic events of the Appalachian chain. [Journal Translation]
Across-strike geometry of the Grand Pabos fault zone: evidence for Devonian dextral transpression in the Quebec Appalachians
Authors: Kirkwood Donna , Malo Michel
Published: January 2011

The principal faults of southeastern Gaspé Peninsula in Quebec consist of a central high-strain zone that is characterized by mainly ductile deformation structures and bordered by low-strain zones each dominated by brittle deformation structures. The overall geometry of shear fractures within the low-strain zones is quite similar to the expected geometry of Riedel shear fractures. The brittle structures overprint the dominant C–S-type fabric of the high-strain zone, which implies that brittle deformation outlasted ductile deformation. The asymmetry of local micro- to meso-scale deformation features along the fault zones reflects the non-coaxiality of the shear. Other features described within the fault zone (stylolitic cleavage, shear bands, and reverse faults) are evidence for a component of shortening perpendicular or oblique to the fault zone. The geometry of the Grand Pabos fault zone (GPFZ), a major fault of southern Gaspé, indicates that deeper seated fault rocks (high-strain zone) have been brought up to higher crustal levels and are presently in contact with brittlely deformed fault rocks (low-strain zone). The proposed model for the evolution of the GPFZ involves Early to Late Devonian, dextral, transcurrent movement accompanied by relatively minor amounts of vertical slip within a dextral transpressive regime. The main pulse of the Acadian orogeny in Gaspé is restricted to the Devonian and therefore occurred later than elsewhere in the Canadian Appalachians.
U–Pb zircon age of the southwest lobe of the Havre-Saint-Pierre Anorthosite Complex, Grenville Province, Canada
Authors: Breemen Otto van , Higgins Michael D.
Published: January 2011

U–Pb zircon dating of the southwest lobe of the Havre-Saint-Pierre anorthosite intrusion indicates that it is 1062 ± 4 Ma old. Parallelism of magmatic and solid-state foliations with the adjacent Abbé–Huard lineament suggest that anorthosite parental magmas rose up this shear zone, which was active at that time. The age of igneous crystallization is much younger than that of a spatially associated mangerite intrusion, but accords with age data from other granitoid intrusions elsewhere in the Grenville Province. Evidence points to a widespread 1.09–1.05 Ga magmatic event that included massif anorthosite intrusions. This magmatic event coincided with late stage convergent tectonics in the southwestern Grenville Province.
Early Proterozoic deformation along the southern margin of the Kisseynew gneiss belt, Trans-Hudson Orogen: a 30 Ma progressive deformation cycle
Authors: Norman A. R. , Williams P. F. , Ansdell K. M.
Published: January 2011

Fold axes and lineations across the southern margin of the Kisseynew gneiss belt were progressively reoriented from northwesterly to northeasterly during an Early Proterozoic, southwest-directed, compressive deformation cycle. Partitioning of deformation resulted in a concentration of non-coaxial strain along the boundary between the Kisseynew gneiss belt and Flin Flon–Snow Lake belt. The structural evolution was complicated by streamlining of the movement vector around the comparatively rigid Flin Flon–Snow Lake belt. The relationship of metamorphic assemblages to kinematic fabrics indicates that deformation was coeval with a prograde–retrograde metamorphic cycle. Progressive deformation occurred during a period of 30 Ma, which is consistent with Phanerozoic orogenic time scales.
Lower Ordovician scolecodonts from the Cow Head Group, western Newfoundland
Authors: Underhay Nicole K. , Williams S. Henry
Published: January 2011

A scolecodont (polychaete jaw) fauna from the latest Tremadoc and Arenig strata of the Cow Head Group includes some of the earliest representatives of these fossils in the world. No biostratigraphically useful changes seem to occur within the interval, although rapid diversification follows their appearance in the latest Tremadoc. Insufficient data were recovered to permit conclusions regarding ecological control of assemblages in early Paleozoic, down-slope environments.
An azhdarchid pterosaur eaten by a velociraptorine theropod
Authors: Currie Philip J. , Jacobsen Aase Roland
Published: January 2011

Tooth-marked bones are more common in the fossil record than published accounts would lead us to believe, but with rare exceptions, the animals that made the marks cannot be identified. A partial skeleton of an azhdarchid pterosaur found in Upper Cretaceous strata of Dinosaur Provincial Park was eaten by the theropod Saurornitholestes langstoni, which left tooth marks and the broken tip of one tooth imbedded in one of the bones. The presence of the broken dinosaur tooth is the first reported in association with tooth-marked bone, and probably indicates that the dromaeosaur was a scavenger in this case. Because the bitten pterosaur bone was thin walled, the bone must have been very tough to have broken the theropod tooth.