bluuebunny/crossref_metadata_2025 huggingface dataset:
From Branch Plant Economies to Knowledge Economies? Manufacturing Industry, Government Policy, and Economic Development in Britain's Old Industrial Regions
Authors: Phelps Nicholas A
Published: August 2009

In this paper I present an ex post review of the failure of mobile private investment to contribute to the formation of competitive industry agglomerations in the UK's old industrial regions. The UK's industrial districts were the inspiration for the concept of external economies with which we understand the competitiveness of agglomerations of economic activity. Yet long-standing disarticulation between UK government inward investment, regional, industrial, and technology policy has ensured that mobile investment (notably, but not exclusively, foreign direct investment) has rarely contributed to the genesis of competitive agglomerations of new economic activity. Up until the 1980s the nature of mobile investment actually offered considerable scope for successive UK governments to leverage on synergies between it and established industry specialisms in the formation of viable new agglomerations of economic activity. Since the 1980s the difficulties of creating synergies between new mobile and existing industry arguably have increased, leaving new regional economic strategies as little more than wishful thinking regarding the formation of new agglomerations of knowledge-based economic activity.
Endogenous versus Exogenous Development: A Comparative Study of Biotechnology Industry Cluster Policies in South Korea and Singapore
Authors: Lee Yong-Sook , Tee Ying-Chian , Kim Dong-Wan
Published: August 2009

With this study we aim to develop a theoretical understanding and to assess policy implications of cluster development in the context of a knowledge-driven, globalizing Asian economy. We will examine both the strengths and the limitations of recent biotechnology cluster policies in South Korea and Singapore. We argue that the two states share similar experiences in terms of the state's proactive role as a cluster creator, but that they have promoted biotechnology industry clusters in contrasting ways due to different national politics and political institutions. South Korea places more emphasis on endogenous capabilities, while Singapore highlights the importance of exogenous capabilities in biotechnology cluster development. By analyzing the advantages and disadvantages of these contrasting cluster policies, we evaluate the long-standing debate between endogenism and exogenism in the study of regional development. Instead of these dualistic approaches, we employ a global production network analytical lens for understanding the dynamic interactions between localized growth factors (endogenous) and globalizing external factors (exogenous) in the context of Asian biotechnology cluster development. We adopt a multipart strategy that includes archives, surveys, in-depth interviews, and secondary source data collection in order to enhance the validity and reliability of the data.
A New Era of Federal Involvement in Regional Economic Development? The Case of the Wired Initiative
Authors: Renski Henry
Published: August 2009

In November 2005 the US Department of Labor's Employment and Training Administration announced a bold new initiative—Workforce Innovations in Regional Economic Development (known as WIRED). In its first iteration the WIRED initiative awarded thirteen three-year regional planning and development grants to assist regions in integrating their workforce and economic development systems to better serve emerging technologies and high employment growth sectors. In this paper I discuss the WIRED initiative as a model for federal involvement in regional economic development. Despite a sound basis in regional development theory, the implementation of WIRED fell short of its original goals that, in many cases, stymied regional attempts at innovation. The difficulties experienced by first-generation WIRED recipients led to a stark revision of the federal WIRED concept and a reversion to more traditional workforce development approaches. To be truly effective, future federal endeavors in regional economic development must overcome the persistent institutional divisions, legal impediments, and political pressures that work contrary to the desired goal of a flexible and competitive regional development strategy.
Policy-Driven University – Industry Linkages and Regional Innovation Networks in Korea
Authors: Sohn Dong-Won , Kim Hyungjoo , Lee Jeong Hyop
Published: August 2009

In this paper we examine the role of the Korean government in creating university – industry linkages and in promoting the role of universities as knowledge providers in regional innovation systems. We investigate the different types of universities' roles in the capital region of Seoul and in the noncapital regions. We argue that government policy is the main determinant that drives Korean universities to play the role of knowledge provider for industrial innovation. This policy has also brought about regional differences in the way universities participate in innovation activities in the capital region and outside the capital region. In the Korean context, universities in noncapital regions act as a backbone for creating and managing regional innovation networks as well as a close and easily accessible knowledge provider to local industry. However, universities in the capital region play the role of a close knowledge provider only to local industry, while corporate research and development centres are the key players in developing and managing innovation networks in the capital region. To arrive at our conclusions we use social networks analysis and government document analysis to demonstrate the structure of innovation networks and to analyze two types of universities' roles in the regional innovation networks of four Korean industrial clusters.
Illusory-Contour Figures Prime Matching of Real Shapes
Authors: Barlasov-Ioffe Anna , Hochstein Shaul
Published: August 2009

We investigated explicit and implicit properties of the internal representation of illusory-contour figures by studying potential priming effects of this representation. Using a primed matching paradigm (Beller 1971, Journal of Experimental Psychology87 176–182), we found that illusory ‘Kanizsa’ squares and triangles prime later matching of the same shapes, respectively, and not of the alternative shape. This priming effect is present despite the use of an illusory figure as a prime and real shapes as tests. To determine whether implicit processing mechanisms sufficiently induce a representation of the illusory shape so that it can lead to this priming effect, we used a novel method of presentation of the inducing pattern, based on Rock and Linnet's (1993, Perception22 61–76) method for separating (implicit) retinal and (explicit) world-coordinate images. Presence of the implicit retinal image is confirmed by its producing an afterimage. While the retinal image is only implicitly produced by the inducing pattern of pacmen, it is nevertheless available for real-shape match priming. We conclude that Kanizsa-type inducer patterns are processed implicitly until formation of illusory-figure shapes. These are represented at relatively high cortical levels, and shape-matching priming must occur here, too. These results are consistent with the claim of the reverse hierarchy theory that bottom–up processing is generally implicit and that conscious perception originates at high cortical levels.
Timing Flickers across Sensory Modalities
Authors: Vicario Carmelo Mario , Rappo Gaetano , Pepi Anna Maria , Oliveri Massimiliano
Published: August 2009

In tasks requiring a comparison of the duration of a reference and a test visual cue, the spatial position of test cue is likely to be implicitly coded, providing a form of a congruency effect or introducing a response bias according to the environmental scale or its vectorial reference. The precise mechanism generating these perceptual shifts in subjective duration is not understood, although several studies suggest that spatial attentional factors may play a critical role. Here we use a duration comparison task within and across sensory modalities to examine if temporal performance is also modulated when people are exposed to spatial distractors involving different sensory modalities. Different groups of healthy participants performed duration comparison tasks in separate sessions: a time comparison task of visual stimuli during exposure to spatially presented auditory distractors; and a time comparison task of auditory stimuli during exposure to spatially presented visual distractors. We found the duration of visual stimuli biased depending on the spatial position of auditory distractors. Observers underestimated the duration of stimuli presented in the left spatial field, while there was an overestimation trend in estimating the duration of stimuli presented in the right spatial field. In contrast, timing of auditory stimuli was unaffected by exposure to visual distractors. These results support the existence of multisensory interactions between space and time showing that, in cross-modal paradigms, the presence of auditory distractors can modify visuo-temporal perception but not vice versa. This asymmetry is discussed in terms of sensory–perceptual differences between the two systems.
Emerging principles and neural substrates underlying tonic sleep-state-dependent influences on respiratory motor activity
Authors: Horner Richard L.
Published: August 2009

Respiratory muscles with dual respiratory and non-respiratory functions (e.g. the pharyngeal and intercostal muscles) show greater suppression of activity in sleep than the diaphragm, a muscle almost entirely devoted to respiratory function. This sleep-related suppression of activity is most apparent in the tonic component of motor activity, which has functional implications of a more collapsible upper airspace in the case of pharyngeal muscles, and decreased functional residual capacity in the case of intercostal muscles. A major source of tonic drive to respiratory motoneurons originates from neurons intimately involved in states of brain arousal, i.e. neurons not classically involved in generating respiratory rhythm and patternper se. The tonic drive to hypoglossal motoneurons, a respiratory motor pool with both respiratory and non-respiratory functions, is mediated principally by noradrenergic and glutamatergic inputs, these constituting the essential components of thewakefulness stimulus. These tonic excitatory drives are opposed by tonic inhibitory glycinergic and γ-amino butyric acid (GABA) inputs that constrain the level of respiratory-related motor activity, with the balance determining net motor tone. In sleep, the excitatory inputs are withdrawn and GABA release into the brainstem is increased, thus decreasing respiratory motor tone and predisposing susceptible individuals to hypoventilation and obstructive sleep apnoea.
Serotonin targets inhibitory synapses to induce modulation of network functions
Authors: Manzke Till , Dutschmann Mathias , Schlaf Gerald , Mörschel Michael , Koch Uwe R. , Ponimaskin Evgeni , Bidon Olivier , Lalley Peter M. , Richter Diethelm W.
Published: August 2009

The cellular effects of serotonin (5-HT), a neuromodulator with widespread influences in the central nervous system, have been investigated. Despite detailed knowledge about the molecular biology of cellular signalling, it is not possible to anticipate the responses of neuronal networks to a global action of 5-HT. Heterogeneous expression of various subtypes of serotonin receptors (5-HTR) in a variety of neurons differently equipped with cell-specific transmitter receptors and ion channel assemblies can provoke diverse cellular reactions resulting in various forms of network adjustment and, hence, motor behaviour.

Using the respiratory network as a model for reciprocal synaptic inhibition, we demonstrate that 5-HT1AR modulation primarily affects inhibition through glycinergic synapses. Potentiation of glycinergic inhibition of both excitatory and inhibitory neurons induces a functional reorganization of the network leading to a characteristic change of motor output. The changes in network operation are robust and help to overcome opiate-induced respiratory depression. Hence, 5-HT1AR activation stabilizes the rhythmicity of breathing during opiate medication of pain.
The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons
Authors: Kasparov S. , Teschemacher A. G.
Published: August 2009

In contrast to some other neuronal populations, for example hippocampal or cortical pyramidal neurons, mechanisms of synaptic integration and transmitter release in central neurons that contain noradrenaline (NA) and serotonin (5HT) are not well understood. These cells, crucial for a wide range of autonomic and behavioural processes, have long un-myelinated axons with hundreds of varicosities where transmitters are synthesized and released. Both seem to signal mostly in ‘volume transmission’ mode. Very little is known about the rules that apply to this type of transmission in the brain and the factors that regulate the release of NA and 5HT. We discuss some of our published studies and more recent experiments in which viral vectors were used to investigate the physiology of these neuronal populations. We also focus on currently unresolved issues concerning the mechanism of volume transmission by NA and 5HT in the brain. We suggest that clarifying the role of astroglia in this process could be essential for our understanding of central noradrenergic and 5HT signalling.
Differential regulation of the central neural cardiorespiratory system by metabotropic neurotransmitters
Authors: Pilowsky Paul M. , Lung Mandy S. Y. , Spirovski Darko , McMullan Simon
Published: August 2009

Central neurons in the brainstem and spinal cord are essential for the maintenance of sympathetic tone, the integration of responses to the activation of reflexes and central commands, and the generation of an appropriate respiratory motor output. Here, we will discuss work that aims to understand the role that metabotropic neurotransmitter systems play in central cardiorespiratory mechanisms. It is well known that blockade of glutamatergic, gamma-aminobutyric acidergic and glycinergic pathways causes major or even complete disruption of cardiorespiratory systems, whereas antagonism of other neurotransmitter systems barely affects circulation or ventilation. Despite the lack of an ‘all-or-none’ role for metabotropic neurotransmitters, they are nevertheless significant in modulating the effects of central command and peripheral adaptive reflexes. Finally, we propose that a likely explanation for the plethora of neurotransmitters and their receptors on cardiorespiratory neurons is to enable differential regulation of outputs in response to reflex inputs, while at the same time maintaining a tonic level of sympathetic activity that supports those organs that significantly autoregulate their blood supply, such as the heart, brain, retina and kidney. Such an explanation of the data now available enables the generation of many new testable hypotheses.
Videothoracoscopy in Pleural Empyema Following Methicillin-ResistantStaphylococcus aureus(MRSA) Lung Infection
Authors: Divisi Duilio , Imbriglio Giovanna , Crisci Roberto
Published: August 2009

Our study shows the different therapeutic procedures in 64 patients with pleural effusion due to MRSA pneumonia. The thoracostomy tube associated with pleural washing was decisive in 10 simple effusion patients. Video-assisted thoracic surgery allowed a complete resolution of the disease in 22 complex parapneumonic effusion patients. In 20 of 32 patients with frank pus in the pleural cavity, the videothoracoscopic insufflation of carbon dioxide (CO2) before thoracotomy facilitated the dissection of the lung tissue. In 12 patients, this approach was not applied because of cardiac insufficiency. Videothoracoscopy and decortication after thoracotomy ensured the recovery of functions.
Peyronie's Disease: Evaluation and Review of Nonsurgical Therapy
Authors: Abern Michael R. , Levine Laurence A.
Published: August 2009

The purpose of our study was to outline the evaluation of the Peyronie's disease (PD) patient and review the available nonsurgical treatments. A review of the literature on oral, intralesional, external energy, iontophoresis, and mechanical therapies for PD was performed. PubMed was utilized to find all published articles, and several meeting abstracts were reviewed for data ahead of publication. Our medical evaluation of the PD patient is described. The published results of available treatment options are reviewed, with recommendation by the authors for appropriate nonsurgical management of PD. There are no available validated questionnaires for PD, but a thorough history and focused physical examination, including measurement of erect penile deformity, will help the clinician make the diagnosis and guide treatment options. Although there are many published reports that show efficacy of nonsurgical therapies for PD, there is a lack of large-scale, multicenter, controlled clinical trials, which makes treatment recommendations difficult. Careful review of the literature does suggest that there are treatment options that make scientific sense and appear to stabilize the disease process, reduce deformity, and improve function. Offering no treatment at all will encourage our patients to pursue alternative treatments that may do harm, and misses the opportunity to do some good. Clearly, further work is necessary to develop safe and effective nonsurgical treatments for PD.
A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression
Authors: Yu Min , Smolen Gromoslaw A. , Zhang Jianmin , Wittner Ben , Schott Benjamin J. , Brachtel Elena , Ramaswamy Sridhar , Maheswaran Shyamala , Haber Daniel A.
Published: August 2009

Epithelial-to-mesenchymal transition (EMT) plays an important role during normal embryogenesis, and it has been implicated in cancer invasion and metastasis. Here, we report that Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor β2 (TGFB2). In mammary epithelial cells, overexpression of LBX1 leads to morphological transformation, expression of mesenchymal markers, enhanced cell migration, increased CD44high/CD24low progenitor cell population, and tumorigenic cooperation with known oncogenes. In human breast cancer, LBX1 is up-regulated in the unfavorable estrogen receptor (ER)/progesterone (PR)/HER2 triple-negative basal-like subtype. Thus, aberrant expression of LBX1 may lead to the activation of a developmentally regulated EMT pathway in human breast cancer.
Specific phosphorylation and activation of ERK1c by MEK1b: a unique route in the ERK cascade
Authors: Shaul Yoav D. , Gibor Gilad , Plotnikov Alexander , Seger Rony
Published: August 2009

Extracellular signal-regulated kinases (ERKs) are key signaling molecules that regulate a large number of cellular processes, including mitosis. We showed previously that ERK1c, an alternatively spliced form of ERK1, facilitates mitotic Golgi fragmentation without the involvement of ERK1 and ERK2. Here we demonstrate that activation of ERK1c is mainly mediated by mitogen-activated protein kinase (MAPK)/ERK kinase 1b (MEK1b), which is an alternatively spliced form of MEK1 that was previously considered an inactive kinase. MEK1b phosphorylation and activity are preferentially stimulated by nocodazole, to induce its specific activity toward ERK1c. MEK1/2, on the other hand, preferentially target ERK1/2 in response to growth factors, such as EGF. As previously demonstrated for ERK1c, also MEK1b expression and activity are elevated during mitosis, and thereby enhance Golgi fragmentation and mitotic rate. MEK1 activity is also increased during mitosis, but this isoform facilitates mitotic progression without affecting the Golgi architecture. These results illustrate that the ERK cascade is divided into two routes: the classic MEK1/2–ERK1/2 and the splice-variant MEK1b–ERK1c, each of which regulates distinct cellular processes and thus extends the cascade specificity.
Strategies for Cloning PCR Products
Authors: D’Arpa Peter
Published: August 2009

INTRODUCTION

Cloning polymerase chain reaction (PCR)-amplified fragments into plasmids offers several advantages. Bacteria containing plasmids can be frozen, providing a ready supply of amplified material. Because of the variety of available plasmids with different promoters and selectable markers, cloning is also useful when mutations are to be introduced into the fragment before expression, or when sequence tags encoded in the vector are to be added in-frame. The ease with which nucleotide sequences can be added to the ends of PCR products has led to the development of a variety of cloning strategies. Because such cloning is typically the first step for generating a reagent that will be used to achieve a specific experimental goal, the efficiency of the cloning procedure is an important consideration: Cloning strategies should be simple in design and execution, requiring a minimum of enzymatic steps. Toward this goal, many companies market and continue to develop reagent kits that improve the ease and rapidity of cloning PCR products. This article focuses on some common and efficient cloning strategies, such as those that use DNA ligase or vaccinia virus topoisomerase I (TOPO), as well as techniques for in vitro and in vivo recombination of PCR products and vectors having homologous duplex ends. Also covered is the production of linear PCR products with defined 5′ and 3′ functional elements, which enable direct mammalian cell expression or in vitro transcription/translation. We present an overview of these strategies, their molecular basis, and their advantages and disadvantages for specific applications.
Single and Double Whole-Mount In Situ Hybridization in Red Flour Beetle (Tribolium) Embryos
Authors: Schinko Johannes , Posnien Nico , Kittelmann Sebastian , Koniszewski Nikolaus , Bucher Gregor
Published: August 2009

INTRODUCTION

The red flour beetle, Tribolium castaneum, has emerged as an important model system for studying the evolution of development. Studies with Tribolium complement the vast amount of research done with Drosophila. Developmental features that are conserved between Drosophila and Tribolium, such as body segmentation, are achieved by quite different means, and thus comparison of developmental mechanisms between these two insects can address many interesting questions concerning the evolution of morphology and other characters. Most in situ protocols used for Tribolium have been adapted from Drosophila studies. Whole-mount in situ hybridization is a standard technique to visualize the activity of genes in embryos. The single and double staining protocol presented here uses two nonfluorescent stains to reveal gene activity. The development of both stains can be monitored visually, allowing the strength of the signal to be adjusted as needed. Cells that express both of the genes under investigation are readily detected using a microscope. The use of EGTA during fixation increases the proportion of embryos that devitellinize upon methanol treatment.
Red Flour Beetle (Tribolium) Germline Transformation and Insertional Mutagenesis
Authors: Berghammer Andreas J. , Weber Markus , Trauner Jochen , Klingler Martin
Published: August 2009

INTRODUCTION

The procedure for introducing transgenes into the Tribolium genome is similar to that for Drosophila and is of comparable efficiency. Purified transposon vector and helper plasmids are injected through the posterior pole of precellular embryos. The injected eggs are incubated under humidified conditions until they hatch. Adults resulting from injected eggs are mated inter se, and transformants are identified among their offspring with the help of visible genetic markers. The helper plasmids express the respective transposase under control of the Drosophila hsp70 promoter, but no heat shock is required. Transgenic animals are identified by fluorescent proteins that are expressed in the eye (and several other tissues including the central nervous system [CNS]) under the control of the artificial 3xP3 promoter. Among the fluorescent proteins enhanced green fluorescent protein (EGFP), enhanced yellow fluorescent protein (EYFP), enhanced cyan fluorescent protein (ECFP), and dsRed, it is EGFP and EYFP that provide the strongest signals. An alternative marker system based on rescue of the white-eye mutation in the eye pigmentation gene vermilion makes scoring transgenic animals even easier. Using these dominant markers, transgenic lines tagged with different markers can be crossbred, and offspring carrying both constructs can be easily identified, which is useful for remobilization experiments and misexpression experiments using the Gal4/UAS system. This protocol provides a detailed method for the generation of transgenic lines, which also can be applied toward the generation of improved mutator and helper strains.
Dissection and Fixation of Large Milkweed Bug (Oncopeltus) Embryos
Authors: Liu Paul , Kaufman Thomas C.
Published: August 2009

INTRODUCTION

In this protocol, blastoderm- or germband-stage large milkweed bug (Oncopeltus) embryos are collected, fixed in paraformaldehyde, and dissected from the yolk mass. Germband-stage embryos are stained with SYTOX Green, a fluorescent DNA stain, to facilitate dissection.
Use of the Sleeping Beauty Transposon System for Stable Gene Expression in Mouse Embryonic Stem Cells
Authors: Davidson Ann E. , Gratsch Theresa E. , Morell Maria H. , O’Shea K. Sue , Krull Catherine E.
Published: August 2009

INTRODUCTION

Sleeping Beauty (SB) transposon-based transfection is a two-component system consisting of a transposase and a transposon containing inverted repeat/direct repeat (IR/DR) sequences that result in precise integration into a TA dinucleotide. The transposon is designed with an expression cassette of interest flanked by IR/DRs, and SB transposase mediates stable integration and reliable long-term expression of the gene of interest. It has recently been demonstrated that SB efficiently mediates gene transfer and stable gene expression in human embryonic stem (ES) cells. Here, we describe a method for transfecting and establishing stable cell lines in mouse embryonic stem (mES) cells with the SB system.
Dissection, Plating, and Maintenance of Dorsal Horn Neuron Cultures: Figure 1.
Authors: Albuquerque Cristóvão , Joseph Donald J. , Choudhury Papiya , MacDermott Amy B.
Published: August 2009

INTRODUCTION

Primary cultures of embryonic dorsal horn (DH) neurons can be prepared using mass cultures, microisland cultures, or macroisland cultures. In all cases, long-term survival of neurons is enhanced by the presence of astrocytes. After the feeder layer of astrocytes has become nearly or fully confluent, it is ready to receive freshly dissociated neurons. Embryonic dorsal root ganglion (DRG) neurons can also be added to the cultures if DRG/DH neuron cocultures are desired. These cultures are suitable for electrophysiological, molecular, and immunocytochemical studies. DH neurons, including both excitatory and inhibitory neurons, form synapses with themselves (autapses) and with each other. DRG neurons form synapses onto DH neurons. Finding synaptically connected pairs of neurons is most readily achieved when the cells are grown on microislands. This protocol describes the dissociation, plating, and maintenance of DH neuron cultures using a feeder layer of astrocytes.
Hematopoietic Stem Cell Targeting with Surface-Engineered Lentiviral Vectors
Authors: Verhoeyen Els , Cosset François-Loïc
Published: August 2009

INTRODUCTION

In the protocol presented here, hematopoietic stem cells (HSCs) are specifically transduced with a vector displaying the HSC-activating polypeptides, stem cell factor (SCF) and thrombopoietin (TPO). Targeted HSC transduction is evaluated in the non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model.
Engineering the Surface Glycoproteins of Lentiviral Vectors for Targeted Gene Transfer
Authors: Verhoeyen Els , Cosset François-Loïc
Published: August 2009

INTRODUCTION

Vectors derived from retroviruses such as lentiviruses and oncoretroviruses are especially suitable tools for long-term gene transfer, because they allow stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors are preferred over vectors derived from oncoretroviruses such as murine leukemia virus (MLV) vectors, because they can transduce nonproliferating target cells. Moreover, lentiviral vectors that can target tissues specifically will be valuable for various gene-transfer approaches in vivo. To achieve targeted gene transfer, two types of surface modifications have been made to lentiviral vectors: (1) heterologous viral glycoproteins have been incorporated to exploit the tropism of other viruses (this is called pseudotyping), and (2) heterologous polypeptides have been fused to viral glycoproteins to retarget the lentiviral particles to a cell of interest. This article provides an overview of innovative approaches to upgrade lentiviral vectors for tissue targeting.
Functional in vivo optical imaging of tumor angiogenesis, growth, and metastasis prevented by administration of anti‐human VEGF antibody in xenograft model of human fibrosarcoma HT1080 cells
Authors: Hanyu Aki , Kojima Kiyotsugu , Hatake Kiyohiko , Nomura Kimie , Murayama Hironori , Ishikawa Yuichi , Miyata Satoshi , Ushijima Masaru , Matsuura Masaaki , Ogata Etsuro , Miyazawa Keiji , Imamura Takeshi
Published: August 2009

Angiogenesis plays a crucial role in cancer progression and metastasis. Thus, blocking tumor angiogenesis is potentially a universal approach to prevent tumor establishment and metastasis. In this study, we used in vivo and ex vivo fluorescence imaging to show that an antihuman vascular endothelial growth factor (VEGF) antibody represses angiogenesis and the growth of primary tumors of human fibrosarcoma HT1080 cells in implanted nude mice. Interestingly, administering the antihuman VEGF antibody reduced the development of new blood vessels and normalized pre‐existing tumor vasculature in HT1080 cell tumors. In addition, antihuman VEGF antibody treatment decreased lung metastasis from the primary tumor, whereas it failed to block lung metastasis in a lung colonization experiment in which tumor cells were injected into the tail vein. These results suggest that VEGF produced by primary HT1080 cell tumors has a crucial effect on lung metastasis. The present study indicates that the in vivo fluorescent microscopy system will be useful to investigate the biology of angiogenesis and test the effectiveness of angiogenesis inhibitors. (Cancer Sci 2009)
Timing of first alcohol use and alcohol dependence: evidence of common genetic influences
Authors: Sartor Carolyn E. , Lynskey Michael T. , Bucholz Kathleen K. , Madden Pamela A. F. , Martin Nicholas G. , Heath Andrew C.
Published: August 2009

Aims  To estimate the magnitude of genetic and environmental influences on timing of first alcohol use and alcohol dependence (AD) and to quantify the overlap in these influences across the two alcohol‐related outcomes.

Participants   The sample consisted of 5382 twins (2691 complete pairs), aged 24–36 years, from the Australian Twin Registry.

Measurements  History of alcohol use and DSM‐IV alcohol dependence were assessed by structured telephone interview.

Findings  In both sexes, the relationship between age at first alcohol use and risk for AD followed a linear trend, such that the highest rates of AD were observed in individuals who began drinking at an earlier than average age (14 years or younger). Heritability estimates for timing of first alcohol use and AD were 36% and 53%, respectively. Shared environmental factors accounted for 15% of variance in initiation. There was no evidence of shared environmental influences on AD. The genetic correlation between timing of first alcohol use and AD was 0.59.

Conclusions  Findings highlight the substantial role of genetics in the development of AD and the early manifestation of that genetic risk in the timing of alcohol use initiation which, unlike AD, is also influenced to a modest degree by shared environmental factors. The considerable overlap in heritable influences—and the virtual absence of overlap in individual‐specific environmental influences—on initiation of alcohol use and AD indicates that the association between age at first drink and AD is attributable in large part to common genetic sources of variance.
Brief motivational interventions for college student problem gamblers
Authors: Petry Nancy M. , Weinstock Jeremiah , Morasco Benjamin J. , Ledgerwood David M.
Published: August 2009

Aims  College students experience high rates of problem and pathological gambling, yet little research has investigated methods for reducing gambling in this population. This study sought to examine the efficacy of brief intervention strategies.

Design  Randomized trial.

Setting  College campuses.

Participants  A total of 117 college student problem and pathological gamblers.

Interventions  Students were assigned randomly to: an assessment‐only control, 10 minutes of brief advice, one session of motivational enhancement therapy (MET) or one session of MET, plus three sessions of cognitive–behavioral therapy (CBT). The three interventions were designed to reduce gambling.

Measurements  Gambling was assessed at baseline, week 6 and month 9 using the Addiction Severity Index–gambling (ASI‐G) module, which also assesses days and dollars wagered.

Findings  Compared to the assessment‐only condition, those receiving any intervention had significant decreases in ASI‐G scores and days and dollars wagered over time. The MET condition decreased significantly ASI‐G scores and dollars wagered over time, and increased the odds of a clinically significant reduction in gambling at the 9‐month follow‐up relative to the assessment‐only condition, even after controlling for baseline indices that could impact outcomes. The Brief Advice and MET+CBT conditions had benefits on some, but not all, indices of gambling. None of the interventions differed significantly from one another.

Conclusions  These results suggest the efficacy of brief interventions for reducing gambling problems in college students.
A double‐blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow‐release oral morphine versus methadone in opioid‐dependent in‐patients willing to undergo detoxification
Authors: Madlung‐Kratzer Ekkehard , Spitzer Berhard , Brosch Renate , Dunkel Dirk , Haring Christian
Published: August 2009

Aims  Evaluation of the efficacy and safety of slow‐release oral morphine (SROM) compared with methadone for detoxification from methadone and SROM maintenance treatment.

Design  Randomized, double‐blind, double‐dummy, comparative multi‐centre study with parallel groups.

Setting  Three psychiatric hospitals in Austria specializing in in‐patient detoxification.

Participants  Male and female opioid dependents (age > 18 years) willing to undergo detoxification from maintenance therapy in order to reach abstinence.

Interventions  Abstinence was reached from maintenance treatment by tapered dose reduction of either SROM or methadone over a period of 16 days.

Measurements  Efficacy analyses were based on the number of patients per treatment group completing the study, as well as on the control of signs and symptoms of withdrawal [measured using Short Opioid Withdrawal Scale (SOWS)] and suppression of opiate craving. In addition, self‐reported somatic and psychic symptoms (measured using Symptom Checklist SCL‐90‐R) were monitored.

Findings  Of the 208 patients enrolled into the study, 202 were eligible for analysis (SROM: n = 102, methadone: n = 100). Completion rates were 51% in the SROM group and 49% in the methadone group [difference between groups: 2%; 95% confidence interval (CI): −12% to 16%]. The rate of discontinuation in the study was high mainly because of patients voluntarily withdrawing from treatment. No statistically significant differences between treatment groups were found in terms of signs and symptoms of opiate withdrawal, craving for opiates or self‐reported symptoms. SROM and methadone were both well tolerated.

Conclusions  Detoxification from maintenance treatment with tapered dose reduction of SROM is non‐inferior to methadone.
Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilities
Authors: Lobo Daniela S. S. , Kennedy James L.
Published: August 2009

Aims  To summarize and discuss findings from genetic studies conducted on pathological gambling (PG).

Methods  Searches were conducted on PubMed and PsychInfo databases using the keywords: ‘gambling and genes’, ‘gambling and family’ and ‘gambling and genetics’, yielding 18 original research articles investigating the genetics of PG.

Results  Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50–60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life‐events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems.

Conclusions  Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies.
Tetraplegia following parathyroidectomy in two long‐term haemodialysis patients
Authors: Mercieri M. , Paolini S. , Mercieri A. , De Blasi R. A. , Palmisani S. , Pinto G. , Arcioni R.
Published: August 2009

We report two cases of postoperative iatrogenic tetraparesis, which occurred in different hospitals after surgery for parathyroidectomy. Both patients were on long‐term haemodialysis. The prolonged neck extension usually required by this procedure was probably the main factor involved in the genesis of the spinal cord injury. Spinal abnormalities associated with chronic renal failure may have made these patients more vulnerable. In our opinion, it is advisable to investigate thoroughly any sign of spinal stenosis in patients who undergo any procedure requiring significant neck extension, particularly if on long‐term haemodialysis.
Thrombotic thrombocytopenic purpura following transurethral resection of the prostate
Authors: Benington S. R. , McKillop A. , Macartney I. , Burns S.
Published: August 2009

A 65‐year old man developed anaemia, profound thrombocytopenia and acute renal failure 2 days after transurethral resection of the prostate. Based on the clinical picture and blood film evidence of microangiopathic haemolysis, thrombotic thrombocytopenic purpura was diagnosed. The patient was treated with a course of plasma exchange, renal replacement therapy and methylprednisolone and made a good recovery. Thrombotic thrombocytopenic purpura is an uncommon cause of haematological and renal abnormalities in the postoperative period. It has a high mortality if untreated, and should be considered in the differential diagnosis of any postoperative patient with a low platelet count and anaemia, since prompt investigation and treatment is life‐saving.
Simulation as a tool to improve the safety of pre‐hospital anaesthesia – a pilot study*
Authors: Batchelder A. J. , Steel A. , Mackenzie R. , Hormis A. P. , Daniels T. S. , Holding N.
Published: August 2009

We conducted a pilot study of the effects of simulation as a tool for teaching doctor‐paramedic teams to deliver pre‐hospital anaesthesia safely. Participants undertook a course including 43 full immersion, high‐fidelity simulations. Twenty videos taken from day 4 and days 9/10 of the course were reviewed by a panel of experienced pre‐hospital practitioners. Participants’ performance at the beginning and the end of the course was compared. The total time from arrival to inflation of the tracheal tube cuff was longer on days 9/10 than on day 4 (mean (SD) 14 min 52 s (2 min 6 s) vs 11 min 28 s (1 min 54 s), respectively; p = 0.005), while the number of safety critical events per simulation were fewer (median (IQR [range]) 1.0 (0–1.8 [0–2]) vs 3.5 (1.5–4.8 [0–8], respectively; p = 0.011). Crew resource management behaviours also improved in later simulations. On a personal training needs analysis, participants reported increased confidence after the course.
The effect of the European Clinical Trials Directive on published drug research in anaesthesia
Authors: Walker E. , Hankins M. C. , White S. M.
Published: August 2009

The clinical indications for anaesthetic drugs are developed through peer‐reviewed publication of clinical trials. We performed a bibliometric analysis of all human research papers reported in nine general anaesthesia journals over 6 years (n = 6489), to determine any effects of the 2004 European Clinical Trials Directive on reported drug research in anaesthesia originating from Europe and the United Kingdom. We found 89% studies involved patients and 11% volunteers. Of 3234 (50%) drug studies, 96% were phase IV (post‐marketing) trials. Worldwide, the number of research papers fell by 3.6% (p < 0.004) in the 3 years following introduction of the European Clinical Trials Directive (5% Europe, 18% United Kingdom), and drug research papers fell by 12% (p < 0.001; 15% Europe, 29% United Kingdom). The introduction of the Clinical Trials Directive has therefore coincided with a decline in European drug research, particularly that originating from the United Kingdom. We suggest a number of measures researchers could take in response, and we propose a simplification of the application process for phase IV clinical trials, emphasising patient risk assessment.
Kinematical characteristics of the factorized velocity model
Authors: Stovas Alexey
Published: August 2009

The factorized velocity model that incorporates both vertical heterogeneity and constant anisotropy is one of the complicated analytical models used in seismic data processing and interpretation. In this paper, I derive the analytic equations for offset, traveltime and relative geometrical spreading for the quasi‐compressional (qP‐) waves that can be used for modelling and inversion of the traveltime parameters. I show that the presence of anelliptic anisotropy usually dominates over the vertical heterogeneity with respect to the non‐hyperbolicity of the factorized velocity model.
Behavioural disturbance in people with Down's syndrome and dementia
Authors: Prasher V. P. , Filer A.
Published: August 2009

Behavioural disturbance associated with dementia in people with Down's syndrome has not been fully researched. This study investigated such problems in demented Downs’ syndrome subjects and non‐demented Down's syndrome controls. Changes in mood, difficulty with communication, gait deterioration, loss of self‐care skills, sleep disturbance, day‐time wandering and urinary incontinence were found to be associated with dementia. Problems giving the greatest cause for concern to carers were restlessness, loss of communication skills, urinary incontinence and wandering. Care provision specifically focused on management of behavioural disturbance in individuals who develop dementia is recommended.
Histrionic personality disorder as pseudo‐learning disability
Authors: Cooper S.‐A. , Collacott R. A.
Published: August 2009

The case of a 20‐year‐old woman with a histrionic personality disorder is described. She claims to have a mild learning disability, and indeed, is receiving special college education for people with learning disabilities and has a specialist learning disability social worker, despite being of above average intelligence. Aetiologically, her persona is viewed as a psychological defence, rather than a deliberate attennpt at deception. A process of ‘institutionalization’ appears to have occurred and compounded the problems with further regression. Psychiatrists and professionals in allied disciplines should not accept that a person has a learning disability purely because that person tells you that he or she has one.
Transvestism in a person with learning disabilities presenting with behavioural problems
Authors: Thomas P. R. , DeAlwis K.
Published: August 2009

A case of transvestism is reported in a 47‐year‐old man with learning disabilities. He had developed encephalitis in childhood, which had resulted in moderate learning disabilities and epilepsy, and had been living in institutions from the age of six. He did not have any chance to express his sexual desire and this frustration manifested as aggressive behaviour. Recently, he moved to a community home and his deviant sexual behaviour became apparent. Management of his problems Involves organizing a behavioural programme linking his cross dressing with aggressive behaviour.
A patient with osteomalacia as single presenting symptom of gluten‐sensitive enteropathy
Authors: de BOER Lcol‐Arts W. A. , TYTGAT G. N. J.
Published: August 2009

A 59‐year‐old male patient presented with invalidating osteomalacia of 2.5 years' duration. The osteomalacia was caused by severe malabsorption due to gluten‐sensitive enteropathy (GSE). There were no other signs or symptoms of GSE in this patient. Clinical presentation with monosymptomatic osteomalacia is very unusual. It seems that patients with GSE who undergo little exposure to the sun are at particular risk of developing overt osteomalacia. Unrecognized GSE should always be considered in the differential diagnosis of osteomalacia.
Dexfenfluramine in the treatment of severe obesity: a placebo‐controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour
Authors: MATHUS‐VLIEGEN E. M. H. , VAN, de VOORDE K. , KOK A. M. E. , RES A. M. A.
Published: August 2009

Dexfenfluramine, an effective and safe serotoninergic drug with anorectic and possible food‐selection‐tuning properties, was investigated in a placebo‐controlled study of 1 year's duration in severe and refractory obesity. The aim of the study was to assess weight loss, and changes in cardiovascular risk factors, food intake and eating behaviour. Dexfenfluramine‐ and placebo‐treated patients achieved a similar weight loss (> 10% of initial weight, by 39.5 and 30.0%, > 20% of initial overweight by 42.1% and 32.5% and > 10 kg by 41.4 and 33.3%, respectively, of the initial cohorts). Furthermore, the decreases in weight (10.7 vs. 8.0 kg), in body mass index (3.9 vs. 2.9 kg m−2) and in waist/hip ratio (0.04 vs. 0.02) were not significantly different. After discontinuation of the drug, the increase in weight (2.8 vs. 1.0 kg) was significantly higher in the dexfenfluramine‐treated group. Except for a borderline better effect on glucose of dexfenfluramine, both groups showed similar beneficial changes in food intake and cardiovascular risk factors. Eating behaviour in response to emotional and external stimuli was comparable in the two groups, but placebo‐treated patients had to restrain their eating more in order to achieve the same weight loss. Notwithstanding the fact that weight losses and an associated amelioration of health‐risk factors were of similar magnitude in dexfenfluramine‐ and placebo‐treated patients, dexfenfluramine might have a useful role in promoting a less stressed adherence to prolonged restriction of energy intake in the severe and refractory obese subject.