bluuebunny/crossref_metadata_2025 huggingface dataset:
An equivalent medium model for wave simulation in fractured porous rocks
Authors: Qi‐Zhen Du , Xue‐Mei Wang , Jing Ba , Qiang Zhang
Published: December 2011

Seismic wave propagation in reservoir rocks is often strongly affected by fractures and micropores. Elastic properties of fractured reservoirs are studied using a fractured porous rock model, in which fractures are considered to be embedded in a homogeneous porous background. The paper presents an equivalent media model for fractured porous rocks. Fractures are described in a stress‐strain relationship in terms of fracture‐induced anisotropy. The equations of poroelasticity are used to describe the background porous matrix and the contents of the fractures are inserted into a matrix. Based on the fractured equivalent‐medium theory and Biot's equations of poroelasticity, two sets of porosity are considered in a constitutive equation. The porous matrix permeability and fracture permeability are analysed by using the continuum media seepage theory in equations of motion. We then design a fractured porous equivalent medium and derive the modified effective constants for low‐frequency elastic constants due to the presence of fractures. The expressions of elastic constants are concise and are directly related to the properties of the main porous matrix, the inserted fractures and the pore fluid.

The phase velocity and attenuation of the fractured porous equivalent media are investigated based on this model. Numerical simulations are performed. We show that the fractures and pores strongly influence wave propagation, induce anisotropy and cause poroelastic behaviour in the wavefields. We observe that the presence of fractures gives rise to changes in phase velocity and attenuation, especially for the slow P‐wave in the direction parallel to the fracture plane.
High‐resolution esophageal manometry: addressing thermal drift of the manoscan system
Authors: Robertson E. V. , Lee Y. Y. , Derakhshan M. H. , Wirz A. A. , Whiting J. R. H. , Seenan J. P. , Connolly P. , McColl K. E. L.
Published: December 2011

Background  The high resolution esophageal manometry system manufactured by Sierra Scientific Instruments is widely used. The technology is liable to ‘thermal drift’, a change in measured pressure due to change in temperature. This study aims to characterize ‘thermal drift’ and minimize its impact.

Methods  Response of the system to immediate temperature change (20 °C to 37 °C) was tested. Accuracy of pressure measurement over two hours at 37 °C was examined. Six repetitions were performed and median pressure change calculated for each sensor. Sensors were compared using Kruskal‐Wallis test. Current correction processes were tested.

Key Results  There was a biphasic response of the system to body temperature: an immediate change in recorded pressure, ‘thermal effect’ and an ongoing pressure change with time, ‘baseline drift’. Median thermal effect for all 36 sensors was 7 mmHg (IQR 3.8 mmHg). Median baseline drift was 11.1 mmHg (IQR 9.9 mmHg). Baseline drift varied between sensors but for a given sensor was linear. Interpolated thermal compensation, recommended for prolonged studies, corrects data assuming a linear drift of pressures. When pressures were corrected in this way, baseline pressure was almost restored to zero (Median 0.3 mmHg, IQR 0.3). The standard thermal compensation process did not address the error associated with baseline drift.

Conclusions & Inferences  Thermal effect is well compensated in the current operation of the system but baseline drift is not well recognized or addressed. Incorporation of a linear correction into current software would improve accuracy without impact on ease of use.
Intestinal tissue engineering: current concepts and future vision of regenerative medicine in the gut
Authors: Bitar K. N. , Raghavan S.
Published: December 2011

Background and Purpose Functional tissue engineering of the gastrointestinal (GI) tract is a complex process aiming to aid the regeneration of structural layers of smooth muscle, intrinsic enteric neuronal plexuses, specialized mucosa, and epithelial cells as well as interstitial cells. The final tissue‐engineered construct is intended to mimic the native GI tract anatomically and physiologically. Physiological functionality of tissue‐engineered constructs is of utmost importance while considering clinical translation. The construct comprises of cellular components as well as biomaterial scaffolding components. Together, these determine the immune response a tissue‐engineered construct would elicit from a host upon implantation. Over the last decade, significant advances have been made to mitigate adverse host reactions. These include a quest for identifying autologous cell sources like embryonic and adult stem cells, bone marrow‐derived cells, neural crest‐derived cells, and muscle derived‐stem cells. Scaffolding biomaterials have been fabricated with increasing biocompatibility and biodegradability. Manufacturing processes have advanced to allow for precise spatial architecture of scaffolds to mimicin vivomilieu closely and achieve neovascularization. This review will focus on the current concepts and the future vision of functional tissue engineering of the diverse neuromuscular structures of the GI tract from the esophagus to the internal anal sphincter.
‘Idiopathic’ intestinal failure – the importance of identifying and treating primary psychopathology
Authors: Bourke J. , Soldan J. , Silk D. B. A. , Aziz Q. , Libby G. W.
Published: December 2011

Background  Gastrointestinal neuromuscular disorders (GINMD) are an important cause of intestinal failure (IF). We present six cases of IF in whom a diagnosis of GINMD was initially suspected, but in whom psychopathology was discovered to be the primary etiology.

Methods  (i) Six consecutive cases referred to our unit with IF, initially presumed to be due to GINMD, were selected. Informed consent was obtained from all patients. Case notes were reviewed for salient clinical information. (ii) A literature search was performed to ascertain the epidemiology of psychopathology in IF and the current evidence for the management of severe functional GI disorders with a multidisciplinary psychiatric approach.

Key Results  (i)All six cases required multidisciplinary psychiatric management in a specialized psychiatric unit that included the use of antidepressants, antipsychotics, mood stabilizers, and Electroconvulsive therapy in addition to nutritional support via enteral or parenteral routes. (ii) The evidence base for the treatment of severe FGIDs is sparse.

Conclusions & Inferences  There is a need for additional reporting of such cases and further research. Our experience would suggest that a delay in the involvement of a specialist liaison psychiatrist has the potential to be life threatening in such cases. This may be more likely with greater severity, where the apparent predominance of ‘physical’ symptoms generates reluctance in both patient and physician to consider a psychiatric etiology and also appears to occur due to a lengthier investigative process than existed previously. We therefore propose that the provision of a specialist psychiatric assessment for all patients presenting with IF is indicated at the point of initial clinical contact, based upon the substantial clinical benefit it has the potential to confer upon a significant minority. This process need not delay investigation, which can continue as indicated in parallel, but can be life‐saving.
Beginner's luck – the first in vivo demonstration of functioning platelets; William Duke, 1910
Authors: Boulton F.
Published: December 2011

Blood platelets remained obscure until the early 20th century although from the 1880s claims that low numbers were associated with certain types of ‘purpura’ began to gain favour. This article re‐appraises critically, but with due consideration to the limited technology of the times, the first remarkable in vivo demonstration of the effects of platelets demonstrated by the serial ‘Bleeding Times' reported by William Duke in 1910, when fresh blood was transfused to two thrombocytopenic people. It also speculates on the possible causes of the thrombocytopenia with which Duke's main patient presented.
Biological and functional characteristics of a novel low–molecular weight antagonist of glucose‐dependent insulinotropic polypeptide receptor, SKL‐14959, in vitro and in vivo
Authors: Nakamura T. , Tanimoto H. , Mizuno Y. , Tsubamoto Y. , Noda H.
Published: December 2011

Aim: We recently discovered a glucose‐dependent insulinotropic polypeptide (GIP) receptor antagonist, SKL‐14959. GIP plays a role in the glucose and lipid metabolism, and is associated with obesity and insulin resistance. Therefore, we aimed to ascertain the inhibitory potency and glucose and lipid metabolism of SKL‐14959.

Methods: SKL‐14959 was evaluated for its binding affinity to each GIP, glucagon‐like peptide‐1 (GLP‐1) and glucagon receptors by each labelled and non‐labelled ligand; GIP‐stimulated cyclic AMP (cAMP) production in CHO cells expressing human GIP receptor in vitro. Oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT) were performed to examine the insulinotropic effect on endogenous and exogenous GIP. Oil tolerance tests were also conducted to examine the lipid metabolism and the postheparin plasma lipase activity, lipoprotein lipase (LPL) and hepatic lipase (HL).

Result: SKL‐14959 selectively bound to GIP receptor and inhibited GIP‐stimulated cAMP production with the Ki value of 55 nM and an IC50 value of 2.9 µM, respectively. SKL‐14959·Na significantly increased blood glucose levels, inhibited insulin secretion in OGTT and inhibited the plasma glucose lowering of exogenous GIP in IPGTT. Furthermore, SKL‐14959 increased plasma triacylglycerol (TG) levels as well as suppressed the postheparin plasma lipase activity in an oil load test.

Conclusion: These data indicate that SKL‐14959 is distinguished in the physiological phenotype of GIP following direct binding to the receptor.
The female postabdomen of the enigmatic Nannochoristidae (Insecta: Mecopterida) and its phylogenetic significance
Authors: Hünefeld Frank , Beutel Rolf Georg
Published: December 2011

Hünefeld, F. and Beutel, R.G. 2011. The female postabdomen of the enigmatic Nannochoristidae (Insecta: Mecopterida) and its phylogenetic significance. —Acta Zoologica (Stockholm) 00: 1–8.

External and internal features of the female postabdomen of Nannochorista neotropica are described in detail. The conditions found in females of Nannochoristidae come closest to the ground plan of Mecopterida. This lineage is characterised by telescoping postabdominal segments, a presumptive autapomorphic feature that is modified in some antliophoran groups, but displayed by the nannochoristid species in a typical manner. More potential autapomorphies of Mecopterida, all present in Nannochoristidae, are the neo‐formation of an intersegmental muscle, a transverse muscle spanning between the genital appendages of segment VIII, a muscle connecting these appendages and the genital chamber and the loss of an intersegmental muscle. Plesiomorphic features of Nannochoristidae are the presence of paired genital appendages on segments VIII and IX. Information on the egg‐depositing substrates of the females is not available. The telescoping postabdomen is suitable for oviposition in soft substrates such as moist soil, or rotten plant materials in the riparian zone, and this is possibly a ground‐plan feature of Mecopterida. The results of recent phylogenetic analyses based on morphological data support a placement of Nannochoristidae in Antliophora, whereas the exact position of the group remains ambiguous. No characters of the female postabdomen were found supporting the monophyly of Mecoptera as conventionally circumscribed, that is Nannochoristidae + Boreidae + Pistillifera.
Optimising repeat prostate biopsy decisions and procedures
Authors: Kirby Roger , Fitzpatrick John M.
Published: December 2011

What's known on the subject? and What does the study add?

Due to the fear of missing clinically significant cancer, it is often uncertain whether a repeat biopsy should be performed in men with ≥1 prior negative prostate biopsies but persistent suspicion of prostate cancer. However, the repeat biopsy may again be negative and a biopsy may be associated with anxiety, discomfort and complications (resulting in hospitalisation in 4.1% of men).

This review discusses strategies to optimise repeat biopsy procedures in order to better predict the biopsy outcome. Optimising repeat biopsy procedures include adjusting the location and number of cores and the use of MRI to detect suspicious areas. The use of diagnostic markers, e.g. (Prostate CAncer) gene 3, which is predictive of biopsy outcome, can aid in guiding repeat biopsy decisions and reduce the number of unnecessary and uncomfortable biopsies.

To review strategies to optimise repeat biopsy procedures and to better predict the biopsy outcome. As it is often uncertain whether a repeat biopsy should be performed in men with ≥1 previous negative prostate biopsies but persistent suspicion of prostate cancer. The repeat biopsy may also be negative and a biopsy may be associated with anxiety, discomfort and occasionally (severe) complications. A search in PubMed was performed to find English language original and review articles related to repeat prostate biopsies. Strategies to optimise repeat biopsy procedures include applying the appropriate indications and adjusting the location and number of biopsy cores. The PROGENSA™ Prostate CAncer gene 3 (PCA3) Assay is a highly prostate cancer‐specific test. A higher PCA3 Score corresponds with an increased probability of a positive repeat biopsy and including the PCA3 Score in multivariate models significantly increased their predictive accuracy for predicting repeat biopsy outcome. The PCA3 Score seems also to be predictive of future biopsy outcome. In clinical practice it is often uncertain whether a prostate biopsy should be repeated or not. Optimising repeat biopsy procedures and the use of diagnostic markers, such as PCA3, can increase the probability of a positive repeat biopsy and reduce the number of unnecessary and uncomfortable biopsies
Coronary stent management in elective genitourinary surgery
Authors: Gupta Angela D. , Streiff Michael , Resar Jon , Schoenberg Mark
Published: December 2011

What's known on the subject? and What does the study add?

Withdrawal of dual antiplatelet therapy before the recommended, 12 months for drug‐eluting stents and 1 month for bare‐metal stents increases the rate of major adverse coronary events and mortality. However, in those undergoing surgery the risk of bleeding is increased substantially for those on antiplatelet agents. Successful management in patients with coronary stents who must undergo elective or non‐elective urological surgery should be a multidisciplinary decision.

This article reviews the literature and recommends a protocol for clinical management of patients undergoing urological procedures after coronary stent placement.

To review the literature on coronary stents and genitourinary surgery and provide a protocol for perioperative. The keywords, ‘elective surgery’, ‘aspirin’, ‘clopidogrel’, ‘guidelines for percutaneous coronary intervention’, and ‘antiplatelet therapy after coronary stent placement’ were used to search PubMed for any relevant articles relating to coronary stents. Recommendations were made based on the whether the procedures patients were exposed to placed them at low‐, moderate‐ or high‐bleeding risk based on the extent of the procedure. All elective procedures should be delayed for 1 month after bare‐metal stent placement and 1 year after drug‐eluting stent placement. In patients classified as low risk (endoscopy and laser prostatectomy), aspirin should be continued throughout the perioperative period and dual antiplatelet therapy should continue 24–48 h postoperatively, if there is no concern for active bleeding. In those classified as moderate risk (scrotal procedures, transurethral resection of bladder tumours, transurethral resection of the prostate, urinary sphincter placement) dual antiplatelet therapy should be discontinued 5–7 days before the procedure and continued within 7 days after procedure, if there is no concern for active bleeding, in consultation with cardiology. In high‐risk procedures (cystectomy, nephrectomy, prostatectomy, penile prosthesis placement) dual antiplatelet therapy should be discontinued 10 days before the procedure and continued postoperatively within 7–10 days of the procedure, when there is no longer a concern for active bleeding with the assistance of a cardiologist. Coronary artery disease is becoming more prominent in our society, increasing the use of coronary stents and antiplatelet agents. With the proposed protocol, it is safe to proceed with surgical intervention in those that have adequate stent endothelialisation.
Gastrointestinal symptoms and obesity: a meta‐analysis
Authors: Eslick G. D.
Published: December 2011

Weight loss is a recognized alarm symptom for organic gastrointestinal (GI) disease, yet the association between obesity and specific GI symptoms remains poorly described. A meta‐analysis was conducted to determine which GI symptoms predominate among obese individuals.

A search of the literature using the databases MEDLINE, EMBASE PubMed and Current Contents (1950 – November 2011) was conducted. All studies assessing GI symptoms and increasing body mass index (BMI)/obesity were included. English and non‐English articles were searched. A random effect model of the studies was undertaken.

Overall, significant associations between GI symptoms and increasing BMI were found for upper abdominal pain (odds ratio [OR] = 2.65, 95% confidence interval [CI]: 1.23–5.72), gastroesophageal reflux (OR = 1.89, 95% CI: 1.70–2.09), diarrhoea (OR = 1.45, 95% CI: 1.26–1.64), chest pain/heartburn (OR = 1.74, 95% CI: 1.49–2.04), vomiting (OR = 1.76, 95% CI: 1.28–2.41), retching (OR = 1.33, 95% CI: 1.01–1.74) and incomplete evacuation (OR = 1.32, 95% CI: 1.03–1.71). However, no significant associations were found for all abdominal pain, lower abdominal pain, bloating, constipation/hard stools, fecal incontinence, nausea and anal blockage.

Several key GI symptoms are associated with increasing BMI and obesity. In addition, there were a number of other GI symptoms that had no relationship with obesity. A greater knowledge of the GI symptoms associated with obesity along with the physiology will be important in the clinical management of these patients.
Looking on the Bright Side: Children’s Knowledge About the Benefits of Positive Versus Negative Thinking
Authors: Bamford Christi , Lagattuta Kristin Hansen
Published: December 2011

Five‐ to 10‐year‐olds (N = 90) listened to 6 illustrated scenarios featuring 2 characters that jointly experience the same positive event (and feel good), negative event (and feel bad), or ambiguous event (and feel okay). Afterward, one character thinks a positive thought and the other thinks a negative thought. Children predicted and explained each character’s emotions. Results showed significant development between 5 and 10 years in children’s understanding that thinking positively improves emotions and thinking negatively makes one feel worse, with earliest knowledge demonstrated when reasoning about ambiguous and positive events. Individual differences in child and parental optimism and hope predicted children’s knowledge about thought–emotion connections on some measures, including their beliefs about the emotional benefits of thinking positively in negative situations.
“Independent” Consultants' Role in the Executive Remuneration Design Process under Restrictive Guidelines
Authors: Kostiander Leena , Ikäheimo Seppo
Published: December 2011

Manuscript Type: Empirical

Research Question/Issue: This study explores the remuneration consultant–client relationship in a non‐Anglo‐American context, focusing on what consultants do under heavy political remuneration guidance.

Research Findings/Insights: A qualitative social constructivist approach was adopted, drawing on interviews with the CEO and “independent” chairman of the board of 23 Finnish state‐owned enterprises, as well as four leading consultants. The research context considerably differs from that of the US, since the State takes an active role in providing remuneration guidelines. Finland also represents a country with a high level of corporate governance and low level of corruption. Nonetheless, our results strongly support the managerial entrenchment perspective fraught with problems and filled with game playing, where “specialized” consultants and CEOs play the major roles, resulting in increased salary levels, slack, an emphasis on share‐based incentives, and public outrage. The effectiveness of these guidelines would be hard, even impossible, to understand, without proper analysis of human interaction related to it.

Theoretical/Academic Implications: The study questions the definition of consultant independence based on external data. Second, routine practices commonly bypass rules, leading to the unintended consequence of forced change. Third, the structure of consultancy markets and long consultant–client relationships play an important role in the services offered by consultants.

Practioner/Policy Implications: The findings show that restrictive remuneration guidelines can be ineffective and lead to standardized pay designs without providing competitive advantage. Shareholders should request greater transparency concerning remuneration design. The role of consultants should be considered proactively in the guidelines, even by limiting the length of the consultant–client relationship or increasing their transparency.
Spending, saving, or investing? Risk management in sixteenth‐century Dutch households1
Authors: ZUIJDERDUIJN JACO , DE MOOR TINE
Published: December 2011

In the past one of the main challenges to households was that of coping with adversity. War, plague, famine, and flood were a constant threat, and could reduce what little improvements families had made in productivity. Economic growth therefore required a means of absorbing external adversities. To see how well late medieval households coped with adversity, this investigation focuses on the households of a small town and its surroundings in early modern Holland. Our findings reveal that several severe external shocks around 1500 had little effect on the general level or distribution of wealth, which suggests that certain forms of insurance may have protected the population. The results show that households increasingly invested in capital markets rather than employing such techniques as scattered holdings and hoarding. This fact indicates that such investment played a vital role in a household's risk aversion strategy. The change from unproductive to more productive risk‐aversion strategies also provides some clues about progress with respect to insurance during Holland's financial revolution.
(Re)Placing Path Dependence: A Response to the Debate
Authors: MARTIN RON
Published: December 2011

My aim in this contribution is to respond to the three preceding critiques of my Roepke Lecture on ‘Rethinking Regional Path Dependence: Beyond Lock‐in to Evolution’. Each critique raises some pertinent and challenging issues: specifically that Marxist regional political economy is a more powerful perspective with which to ‘take history seriously’; that I should have given due recognition to the idea of ‘punctuated evolution’; and that my attempt to revise and extend the concept of path dependence has ontological problems. I welcome these commentaries, as they contribute to the very debate that my Roepke Lecture was intended to initiate. But I argue that these critiques are themselves contestable, and that none of them undermines the main thrust of that lecture. My aim in the latter was to suggest that we need to widen and revise the concept of path dependence if it is to function as a an evolutionary concept, to set it free from the overly restrictive and conservative interpretation (of ‘lock‐in’) that it has all too often been given in economic‐geographic applications. I defend that aim here.

Cette contribution répond aux trois critiques présentées précédemment sur ma ‘Roepke Lecture’ intitulée ‘Rethinking regional path dependence: Beyond lock‐in to evolution’. Chacune soulève des questions pertinentes et passionnantes, à savoir: l’économie politique régionale marxiste offre une perspective plus efficace pour ‘prendre l’histoire au sérieux’; j’aurais dû donner une place à la notion d’‘évolution ponctuelle’; ma tentative de réexamen et d’extension du concept de sentier de dépendance présente des problèmes ontologiques. Ces commentaires sont bienvenus car ils nourrissent le débat que cette intervention cherchait à susciter. Toutefois, selon moi, ces critiques sont elles‐mêmes contestables et aucune ne compromet les idées‐forces de mon propos. Le but de celui‐ci était de proposer d’élargir et de corriger le concept de sentier de dépendance pour qu’il puisse opérer en tant que concept évolutionniste et pour qu’il s’affranchisse de l’interprétation conventionnelle et trop restrictive (de ‘blocage’) qui lui a trop souvent été attribuée dans les applications de géographie économique. C’est cet objectif qui est défendu ici.
Genome‐Wide Patterns of Genetic Distances Reveal Candidate Loci Contributing to Human Population‐Specific Traits
Authors: de Magalhães João Pedro , Matsuda Alex
Published: December 2011

Modern humans originated in Africa before migrating across the world with founder effects and adaptations to new environments contributing to their present phenotypic diversity. Determining the genetic basis of differences between populations may provide clues about our evolutionary history and may have clinical implications. Herein, we develop a method to detect genes and biological processes in which populations most differ by calculating the genetic distance between modern populations and a hypothetical ancestral population. We apply our method to large‐scale single nucleotide polymorphism (SNP) data from human populations of African, European and Asian origin. As expected, ancestral alleles were more conserved in the African populations and we found evidence of high divergence in genes previously suggested as targets of selection related to skin pigmentation, immune response, senses and dietary adaptations. Our genome‐wide scan also reveals novel candidates for contributing to population‐specific traits. These include genes related to neuronal development and behavior that may have been influenced by cultural processes. Moreover, in the African populations, we found a high divergence in genes related to UV protection and to the male reproductive system. Taken together, these results confirm and expand previous findings, providing new clues about the evolution and genetics of human phenotypic diversity.
Harpagoside attenuates MPTP/MPP+ induced dopaminergic neurodegeneration and movement disorder via elevating glial cell line‐derived neurotrophic factor
Authors: Sun Xiaoyu , Xiong Zhongkui , Zhang Yongfang , Meng Ya , Xu Gang , Xia Zhiming , Li Jiamei , Zhang Rui , Ke Zunji , Xia Zongqin , Hu Yaer
Published: December 2011

J. Neurochem. (2012) 120, 1072–1083.

Parkinson’s disease is a chronic neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. New therapeutic approaches aiming at delaying or reversing the neurodegenerative process are under active investigations. In this work, we found that harpagoside, an iridoid purified from the Chinese medicinal herb Scrophularia ningpoensis, could not only prevent but also rescue the dopaminergic neurodegeneration in MPTP/MPP+ intoxication with promising efficacy. Firstly, in cultured mesencephalic neurons, harpagoside significantly attenuated the loss of TH‐positive neuron numbers and the shortening of axonal length. Secondly, in a chronic MPTP mouse model, harpagoside dose‐dependently improved the loco‐motor ability (rotarod test), increased the TH‐positive neuron numbers in the substantia nigra pars compacta (unbiased stereological counting) and increased the striatal DAT density (125I‐FP‐CIT autoradiography). Thirdly, harpagoside markedly elevated the GDNF mRNA and GDNF protein levels in MPTP/MPP+ lesioned models. However, the protecting effect of harpagoside on the dopaminergic degeneration disappeared when the intrinsic GDNF action was blocked by either the Ret inhibitor PP1 or the neutralizing anti‐GDNF antibody. Taken together, we conclude that harpagoside attenuates the dopaminergic neurodegeneration and movement disorder mainly through elevating glial cell line‐derived neurotrophic factor.
Enhanced neuronal plasticity and elevated endogenous sAPPα levels in mice over‐expressing MMP9
Authors: Fragkouli Apostolia , Papatheodoropoulos Costas , Georgopoulos Spiros , Stamatakis Antonios , Stylianopoulou Fotini , Tsilibary Effie C. , Tzinia Athina K.
Published: December 2011

J. Neurochem. (2012) 121, 239–251.

Evidence accumulating during the past few years points to a significant role of matrix metalloproteinase 9 (MMP9) enzymatic activity in synaptic plasticity and cognitive processes. We have previously demonstrated that MMP9 is involved in receptor‐mediated α‐secretase‐like cleavage of APP in vitro, resulting in increased secretion of sAPPα, the soluble N‐terminal product of the non‐amyloidogenic pathway known to be involved in neuronal plasticity and memory formation. To study the in vivo role of MMP9, we have generated transgenic mice over‐expressing MMP9 in the brain. Herein, we demonstrate that MMP9 transgenic animals display enhanced performance in the non‐spatial novel object recognition and the spatial water‐maze task and that their enhanced performance was accompanied by increased dendritic spine density in the hippocampus and cortex following behavioural testing. Consistent with the above observations, the electrophysiological analysis revealed prolonged maintenance of long‐term synaptic potentiation in hippocampal slices from MMP9 transgenic mice. Moreover, elevated sAPPα levels in the hippocampus and cortex of MPP9 transgenic animals were also observed. Overall, our results extend previous findings on the physiological role of MMP9 in neuronal plasticity and furthermore reveal that, APP may be one of the physiological proteolytic targets of MMP9 in vivo.
Two Center, Randomized Pilot Study of Migraine Prophylaxis Comparing Paradigms Using Pre‐Emptive Frovatriptan or Daily Topiramate: Research and Clinical Implications
Authors: Cady Roger K. , Voirin James , Farmer Kathleen , Browning Rebecca , Beach M.E. , Tarrasch Jeanne
Published: December 2011

(Headache 2012;52:749‐764)

Objective.— To compare the efficacy and clinical benefit of 2 paradigms of migraine prevention using pre‐emptive frovatriptan and daily topiramate. The study compares the paradigms of pre‐emptive use of frovatriptan, a drug approved for acute migraine, and the daily use of topiramate, a Federal Drug Administration‐approved and ‐accepted standard for migraine prophylaxis.

Background.— Traditionally, preventive treatment of migraine required daily medication. However, recent studies suggest that pre‐emptive prophylaxis may be beneficial to those migraineurs who can predict an attack of migraine based on premonitory symptoms and treat during that phase.

Methods.— A total of 76 adult subjects with a diagnosis of migraine were screened for the study. During a 1‐month baseline period, subjects demonstrated through a daily diary that they predicted at least 50% of migraine attacks during the premonitory phase and treated with their usual medication. Of these, 55 were randomized to either Group A (daily topiramate) or Group B (frovatriptan during premonitory symptoms); 44 completed the study. The treatment period lasted 2 months. The subjects answered the Migraine‐Specific Quality of Life Questionnaire at randomization, and at Weeks 4 and 8. The revised Patient Perception of Migraine Questionnaire was answered 24 hours after taking frovatriptan (Group A, for break‐through headaches; Group B, treatment during premonitory symptoms).

Results.— The number of migraine attacks and headache days per month decreased significantly from baseline for both Groups A and B. Subjects in Group A had considerably more adverse events leading to study withdrawal than in Group B (18% vs 4%). Though this study was not powered to directly compare the efficacy of the 2 drugs, topiramate showed superiority over frovatriptan at Month 2 in reduction of headache days, which was a secondary end point in the study (P = .036).

Conclusions.— This pilot study demonstrated that statistical benefit for reduction of headache days over baseline for both pre‐emptive frovatriptan and daily topiramate. Subjects utilizing pre‐emptive frovatriptan experienced fewer adverse events leading to study withdrawal. Subjects utilizing daily topiramate had fewer headache days at Month 2.
Familial clustering of epilepsy and behavioral disorders: Evidence for a shared genetic basis
Authors: Hesdorffer Dale C. , Caplan Rochelle , Berg Anne T.
Published: December 2011

Purpose:  To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders.

Methods:  We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first‐degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9‐year follow‐up. Clinical cutoffs for CBCL problem and Diagnostic and Statistical Manual of Mental Disorders (DSM)–Oriented scales were examined. The association between first‐degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first‐degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, was adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations.

Key Findings:  In probands with uncomplicated epilepsy, first‐degree family history of unprovoked seizure was significantly associated with clinical cutoffs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cutoffs for Withdrawn/Depressed, and DSM‐Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cutoffs for Aggressive Behavior and Delinquent Behavior, and DSM‐Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first‐degree family history of unprovoked seizure and Total Problems and Aggressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed, and Anxiety Disorder. There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First‐degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy.

Significance:  Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it.
Do antiepileptic drugs or generalized tonic–clonic seizure frequency increase SUDEP risk? A combined analysis
Authors: Hesdorffer Dale C. , Tomson Torbjorn , Benn Emma , Sander Josemir W. , Nilsson Lena , Langan Yvonne , Walczak Thaddeus S. , Beghi Ettore , Brodie Martin J. , Hauser W. Allen ,   for the ILAE Commission on Epidemiology; Subcommission on Mortality
Published: December 2011

Purpose:  In an analysis of four case–control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic–clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently.

Methods:  We combined data from the three case–control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case–control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency.

Key Findings:  In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP.

Significance:  Our findings—that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account—provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.
Prenatal stress promotes development of spasms in infant rats
Authors: Yum Mi‐Sun , Chachua Tamar , Velíšková Jana , Velíšek Libor
Published: December 2011

We have developed a new model of cryptogenic infantile spasms with prenatal betamethasone brain priming to increase susceptibility to development‐specific spasms triggered by N‐methyl‐d‐aspartate (NMDA). A recent clinical study linked severe prenatal stress to increased risk for development of infantile spasms. Here, we determined whether prenatal restraint stress (2 × 45 min) in rats on gestational day 15 would increase susceptibility to develop spasms on postnatal day 15. Prenatal stress significantly accelerated onset and increased number of NMDA‐triggered spasms compared to handled controls. A single adrenocorticotropic hormone (ACTH or corticotropin) dose delivered acutely had no effects, whereas long‐term (3 day) ACTH pretreatment significantly increased latency to onset and decreased number of spasms (an effect similar to that in the human condition). Our data support the notion that extra care should be provided during pregnancy to minimize stress.
Unifying the definitions of sudden unexpected death in epilepsy
Authors: Nashef Lina , So Elson L. , Ryvlin Philippe , Tomson Torbjörn
Published: December 2011

Sudden unexpected death in epilepsy (SUDEP) is a category of death in people with epilepsy occurring in the absence of a known structural cause of death and is most likely heterogeneous with regard to mechanisms and circumstances. SUDEP is particularly difficult to investigate in research studies for several reasons, including its relatively low incidence, its unpredictable occurrence often in unwitnessed settings, and its low rate of complete autopsy examinations. Over the past two decades, two complementary definitions have been used in most SUDEP studies, but often with variations. We propose here a unified SUDEP definition and classification to resolve current ambiguities and to retrieve cases that would not have been further studied if the previous definitions were used. The proposed Unified SUDEP Definition and Classification contains, in addition to concepts inherent in the previous definitions, nine main recommendations. (1) The word “unexpected,” and not the word “unexplained,” should be uniformly used in the term SUDEP. (2) The SUDEP category should be applied when appropriate, whether or not a terminal seizure is known to have occurred. (3) The “Possible SUDEP” category should be used only for cases with competing causes of death, with cases left unclassified when data are insufficient to reasonably permit their classification. (4) Cases that would otherwise fulfill the definition of SUDEP should be designated as “SUDEP Plus” when evidence indicates that a preexisting condition, known before or after autopsy, could have contributed to the death, which otherwise is classified as SUDEP (e.g., coronary insufficiency with no evidence of myocardial infarction or long‐QT syndrome with no documented primary ventricular arrhythmia leading to death). (5) To be considered SUDEP, the death should have occurred within 1 h from the onset of a known terminal event. (6) For status epilepticus as an exclusion criterion for SUDEP, the duration of seizure activity should be 30 min or more. (7) A specific category of SUDEP due to asphyxia should not be designated, the distinction being largely impractical on circumstantial or autopsy evidence, with more than one mechanism likely to be contributory in many cases. (8) Death occurring in water but without circumstantial or autopsy evidence of submersion should be classified as “Possible SUDEP.” If any evidence of submersion is present, the death should not be classified as SUDEP. (9) A category of “Near‐SUDEP” should be agreed to include cases in which cardiorespiratory arrest was reversed by resuscitation efforts with subsequent survival for more than 1 h. Scenarios that demonstrate the basis for each SUDEP category are described. If disagreement exists about which category fits a particular case, we suggest the use of consensus decision by a panel of informed reviewers to adjudicate the classification of the case.
Ictal “hemiballic‐like” movement: Lateralizing and localizing value
Authors: Fluchère Frédérique , McGonigal Aileen , Villeneuve Nathalie , Chauvel Patrick , Bartolomei Fabrice
Published: December 2011

We aimed at determining the lateralizing and localizing values of “hemiballic‐like” ictal movements observed in some partial seizures. Among 20 patients disclosing ictal hyperkinetic features and explored by stereotactic‐EEG (SEEG), this sign was observed in four patients. In these cases, hemiballic movement was ipsilateral to the ictal‐onset zone and was associated with contralateral ictal dystonia. Noninvasive and subsequent invasive recording revealed seizure origin in the inferior parietal lobule or the parietal operculum in three patients and in the inferior prefrontal cortex in one.
Impact Assessment of Biodiversity and Carbon Pools from Land Use and Land Use Changes in Life Cycle Assessment, Exemplified with Forestry Operations in Norway
Authors: Michelsen Ottar , Cherubini Francesco , Strømman Anders Hammer
Published: December 2011

There is a strong need for methods within life cycle assessment (LCA) that enable the inclusion of all complex aspects related to land use and land use change (LULUC). This article presents a case study of the use of one hectare (ha) of forest managed for the production of wood for bioenergy production. Both permanent and temporary changes in above‐ground biomass are assessed together with the impact on biodiversity caused by LULUC as a result of forestry activities. The impact is measured as a product of time and area requirements, as well as by changes in carbon pools and impacts on biodiversity as a consequence of different management options. To elaborate the usefulness of the method as well as its dependency on assumptions, a range of scenarios are introduced in the study. The results show that the impact on climate change from LULUC dominates the results, compared to the impact from forestry operations. This clearly demonstrates the need to include LULUC in an LCA of forestry products. For impacts both on climate change and biodiversity, the results show large variability based on what assumptions are made; and impacts can be either positive or negative. Consequently, a mere measure of land used does not provide any meaning in LCA, as it is not possible to know whether this contributes a positive or negative impact.
K‐ras mutations are correlated to lymph node metastasis and tumor stage, but not to the growth pattern of colon carcinoma
Authors: MANNAN ABDUL , HAHN‐STRÖMBERG VICTORIA
Published: December 2011

Mannan A, Hahn‐Strömberg V. K‐ras mutations are correlated to lymph node metastasis and tumor stage, but not to the growth pattern of colon carcinoma. APMIS 2012; 120: 459–68.

In colorectal carcinoma, pathological assessment of tumors is essential for determining therapy and prognosis of the disease. Molecular associations of tumor complexity index and genetic alternations can be helpful to understand the tumor progression mechanism. Oncogenic K‐ras is one of the major colorectal cancer associated genes, and is mutated in up to 50% of colorectal cancers. In this current study, we correlated tumor complexity index with mutations in K‐ras codon 12, 13, and 61 in association with different clinicopathological parameters such as TNM stage, localization, sex, and age. Formalin‐fixed paraffin embedded tissue blocks from colon cancer samples was selected from 88 patients diagnosed with adenocarcinoma. Mutations in the K‐ras gene were detected using pyrosequencing technique. Tumor complexity index was calculated using immunohistochemically stained images of the tumor outline of the specimens and then analyzing these pictures using Photoshop CS, Fovea Pro, and Image J computer programs. Statistical analysis was performed with SPSS. K‐ras mutations were detected in 17 (19.3%) colon cancer samples. Most of the samples were at a lower complexity index. No correlation was observed between K‐ras mutations and complexity index. However, K‐ras mutations were correlated with regional lymph node metastasis and tumor stages and complexity index with tumor wall penetration. In conclusion, complexity index and K‐ras mutations are independent events; however, both correlate with tumor progression and are important in the biologic development of colon carcinoma.
The restricted seed rain of a mistletoe specialist
Authors: Rawsthorne John , Watson David M. , Roshier David A.
Published: December 2011

Specialist frugivores are the dominant consumers of mistletoe fruit in many regions and have been shown to intensify infections of host plants as a result of their rapid gut passage rates and dependence on existing infections. The role of specialist frugivores in long distance dispersal of mistletoe and establishment of new infections is unclear, and has not been explicitly evaluated previously. Here we critically examine the premise that specialists are the dominant dispersers by examining the role of an Australian mistletoe specialist (mistletoebird Dicaeum hirundinaceum Dicaeidae) in dispersing mistletoe (Amyema preissii Santalales: Loranthaceae) seeds beyond infected host stands. We use two primary lines of evidence – presence of birds using remote call recorders, and presence of dispersed seeds via surveys for defecated seeds on host branches. The observed and inferred movements of the mistletoebird were wholly restricted to habitat patches containing mistletoe, and this bird was not observed to transport seeds to nearby uninfected host stands within the study system. While mistletoe specialists may provide much of the within‐stand dispersal service for mistletoes, this serves only to aggregate and intensify existing infections. We suggest that long distance dispersal of mistletoe seeds beyond existing hosts and infection centres is not performed by these dietary specialists, these services more likely to be provided by generalist frugivores and other occasional mistletoe fruit consumers.