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Substantial Progress (substantial + progress)
Selected AbstractsProtein Biochips: Oriented Surface Immobilization of Proteins,MACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 2 2010Po-Chiao Lin Abstract Substantial progress in biochip technologies has established an efficient and reliable platform for advanced biological and biomedical applications. In particular, the use of protein biochips in high-throughput screens provides high content information. We briefly introduce here recent developments in protein biochip preparation with a special focus on our own work on new methods for protein immobilization and protein microarray fabrication, including the application of the Diels-Alder reaction, Staudinger ligation, ,click' sulfonamide formation, and the photochemical thiol-ene reaction. These chemical methods allow for oriented, site-specific protein conjugation on solid surfaces with high sensitivity and specificity under mild, aqueous conditions. [source] ,Protective premedication': an option with gabapentin and related drugs?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2004A review of gabapentin, pregabalin in the treatment of post-operative pain Substantial progress has been made during the last decades in our understanding of acute pain mechanisms, and this knowledge has encouraged the search for novel treatments. Of particular interest has been the observation that tissue injury initiates a number of modulations of both the peripheral and the central pain pathways, which convert the system from a ,physiological' to a ,pathological' mode of processing afferent information. Gabapentin, which binds to the ,2, subunit of the voltage-dependent calcium channel, is active in animal models of ,pathological' but not in models of ,physiological' pain. Consequently, attention has so far been focused on neuropathic pain as a target for the clinical use of gabapentin and analogues. Recently, several reports have indicated that gabapentin may have a place in the treatment of post-operative pain. This article presents a brief summary of the potential mechanisms of post-operative pain, and a systematic review of the available data of gabapentin and pregabalin for post-operative analgesia. It is concluded that the results with gabapentin and pregabalin in post-operative pain treatment published so far are promising. It is suggested that future studies should explore the effects of ,protective premedication' with combinations of various antihyperalgesic and analgesic drugs for post-operative analgesia. [source] Molecular, ecological and evolutionary approaches to understanding Alternaria diseases of citrusMOLECULAR PLANT PATHOLOGY, Issue 6 2003Kazuya Akimitsu SUMMARY Alternaria fungi cause four different diseases of citrus: Alternaria brown spot of tangerines, Alternaria leaf spot of rough lemon, Alternaria black rot of several citrus fruits and Mancha foliar of Mexican lime. The first three diseases are caused by the small-spored species, Alternaria alternata and the causal agents can only be differentiated using pathogenicity tests, toxin assays or genetic markers. Mancha foliar is caused by the morphologically distinct, large-spored species A. limicola. Substantial progress has been made in understanding the biology, ecology, population biology, systematics, molecular biology and biochemistry of the interactions between these pathogens and citrus. Epidemiological studies have focused on brown spot of tangerines and their hybrids and have contributed to the development of a model of disease development which has improved control and reduced fungicide use. Studies of the population genetics, host specificity and ecology of A. alternata from different ecological niches on citrus have revealed host specific forms of the pathogen which cause disease on different citrus species, the existence of three phylogenetic lineages of the fungus which cause brown spot world-wide, and closely related non-pathogenic isolates which colonize healthy citrus tissue. The role of host-specific toxins in Alternaria diseases of citrus has been extensively studied for over 20 years, and these pathosystems have become model systems for host-pathogen interactions. Recent molecular research has started to unravel the genetic basis of toxin production and the host susceptibility to toxin, and the role of extracellular, degradative enzymes in disease. [source] Review of current treatment of sacral chordomaORTHOPAEDIC SURGERY, Issue 3 2009Kang-wu Chen MD Chordoma is a relatively rare, locally aggressive tumor which is known to arise from embryonic remnants of the notochord and to occur exclusively along the spinal axis, with a predilection for the sacrum. Although chordoma typically presents as a single lesion, a few cases of metastasis have been reported and the prognosis of such patients may be poor. Chordomas are slowly growing tumors with insidious onset of symptoms, making early diagnosis difficult. Recent improvements in imaging have provided valuable information for early diagnosis. The optimal treatment for sacral chordoma is en bloc sacral resection with wide surgical margins. Improvement in surgical techniques has widened the opportunities to provide effective treatment. However, the effects of adjuvant treatment options are still both unclear and controversial. Substantial progress has been made in the study of molecular-targeted therapy. The authors review the current surgical and adjuvant treatment modalities, including molecular-targeted therapy, available for management of sacral chordoma. [source] Mesoscopic Modelling of Polymer-Based Optoelectronic DevicesPLASMA PROCESSES AND POLYMERS, Issue S1 2007Hélder M. C. Barbosa Abstract Substantial progress has been made in fabricating optoelectronic devices using polymers as an active material. In polymer light emitting diodes (PLEDs), a balanced injection of electrons and holes from the electrodes is fundamental to increase their performance. Using a mesoscopic model based on a generalized Monte-Carlo method, we studied the influence of changing zero-field barrier heights at both electrode,polymer interfaces in the performance of a PLED with an active layer of poly(para -phenylenevinylene) (PPV). Our results show that by controlling the electrodes work functions it is possible to tune the region inside the device where charge recombination preferentially takes place. [source] Overview of retinoid metabolism and functionDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2006Rune Blomhoff Abstract Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all- trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all- trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11- cis -retinal is isomerized to all- trans -retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all- trans retinol to all- trans retinal and all- trans retinoic acid, and esterification of all- trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all- trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 606,630, 2006 [source] Prevention and treatment of hepatitis C in injection drug usersHEPATOLOGY, Issue 5B 2002Brian R. Edlin 3180 18th St. Injection drug users constitute the largest group of persons infected with the hepatitis C virus (HCV) in the United States, and most new infections occur in drug users. Controlling hepatitis C in the U.S. population, therefore, will require developing, testing, and implementing effective prevention and treatment strategies for persons who inject drugs. Fortunately, a substantial body of research and clinical experience exists on the prevention and management of chronic viral diseases among injection drug users. The need to implement interventions to stop the spread of HCV among drug users is critical. The capacity of substance-use treatment programs need to be expanded to accommodate all who want and need treatment. Physicians and pharmacists should be educated in how to provide access to sterile syringes and to teach safe injection techniques, both of which are lifesaving interventions. The treatment of hepatitis C in drug users requires an interdisciplinary approach that brings together expertise in treating hepatitis and caring for drug users. Treatment decisions should be made individually by patients with their physicians, based on a balanced assessment of risks and benefits and the patient's personal values. Physicians should carefully assess, monitor, and support adherence and mental health in all patients, regardless of whether drug use is known or suspected. Research is needed to better understand how best to prevent and treat hepatitis C in substance users. In the meantime, substantial progress can be made if existing knowledge and resources are brought to bear. [source] Regulation of T-cell receptor signalling by membrane microdomainsIMMUNOLOGY, Issue 4 2004Tahir M. Razzaq Summary There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms. [source] Rational Functionalization of Carbon Nanotubes Leading to Electrochemical Devices with Striking Applications,ADVANCED MATERIALS, Issue 15 2008Jie Yan Abstract As one-dimensional carbon nanostructures, carbon nanotubes (CNTs) are a member of the carbon family but they possess very different structural and electronic properties from other kinds of carbon materials frequently used in electrochemistry, such as glassy carbon, graphite, and diamond. Although the past decade has witnessed rapid and substantial progress in both the fundamental understanding of CNT-oriented electrochemistry and the development of various kinds of electrochemical devices with carbon nanotubes, the increasing demand from both academia and industry requires CNT-based electrochemical devices with vastly improved properties, such as good reliability and durability, and high performance. As we outline here, the smart functionalization of CNTs and effective methods for the preparation of devices would pave the way to CNT-based electronic devices with striking applications. [source] SOFCo Planar Solid Oxide Fuel CellINTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, Issue 1 2004Liang A. Xue SOFCo-EFS Holdings LLC has developed a multi-layer, planar solid oxide fuel cell (SOFC) stack that has the potential to provide superior performance and reliability at reduced costs. Our approach combines state-of-the-art SOFC materials with the manufacturing technology and infrastructure established for multi-layer ceramic (MLC) packages for the microelectronics industry. With the proper selection of SOFC materials, implementation of MLC fabrication methods offers unique designs for stacks. Over the past two years, substantial progress has been made in the design and manufacturing development of our second-generation stack. Effective stack and manifold seals have been developed. Cell performance has been improved and relatively low non-cell contributions to stack resistance have been achieved. Stack development has been facilitated through the implementation of two key test methods: (1) a 10-cm single-cell test to bridge the gap in performance data obtained from button cell tests (used for cell R&D) and stack tests; and (2) a novel instrumented short stack (<5 cells) that allows for effective isolation of individual contributions to stack resistance. As a result of progress made to date, a clear pathway for improving stack performance has been established, thereby building confidence that commercial stack performance targets will be reached. [source] The International Petroleum Industry Environmental Conservation Association social responsibility working group and human rightsINTERNATIONAL SOCIAL SCIENCE JOURNAL, Issue 2005Jenny Owens This chapter describes how the oil and gas industry is responding to one specific challenge to sustainable development , the promotion of human rights. The human rights activities and practices of the industry fall into three categories: direct responsibility, shared responsibility and indirect influence. Specific responses to human rights issues are illustrated through case studies from some of the member companies of the International Petroleum Industry Environmental Conservation Association. The chapter demonstrates that the oil and gas industry has achieved substantial progress in establishing and implementing human rights policies and practices. However, the debate between industry, representatives of civil society and governments over the roles, responsibilities and accountability for human rights of transnational corporations in general, and of the oil and gas industry in particular, continues. While under international law the responsibility to protect human rights rests primarily with governments, companies and others, including non-governmental organisations and multilateral organisations, can support human rights. The industry recognises the need to develop measures to help address human rights challenges and that this effort will require co-operation and shared responsibility among all relevant actors. [source] Innovations in United States genetics nursing: Practice and researchJAPAN JOURNAL OF NURSING SCIENCE, Issue 2 2005Dale H. LEA Abstract Aim:, Clinical and research applications from human genome discoveries are growing and creating both opportunities and challenges to the integration of genetic concepts into practice and research. Nurses have a long history of caring for individuals, families, and groups with genetic conditions. In the past two decades, a small group of nurses in the USA have used a variety of strategies to further develop the field of genetics nursing. In this paper we identify innovative approaches to identifying genetics-related nursing roles and opportunities, as well as successful collaborative efforts beyond nursing to address the emerging health and societal challenges related to human genetics discoveries. Methods:, The information presented here comes from a variety of sources where the authors or genetics nurses directly participated, including: (i) a systematic literature review of genetics nursing; (ii) a comprehensive research study of models of delivering clinical genetics services and the roles of health professionals; and (iii) participation in numerous national research, planning, programmatic, and advisory groups involved with clinical genetics-related health services, research, education, and public policy. Results:, Genetics nurses in the US have developed innovative responses to genetics-related challenges within and beyond the profession of nursing. These include: (i) establishing an organization for nurses in genetics and gaining formal recognition of genetics as a specialty of nursing; (ii) defining the scope of genetics nursing practice and developing a new genetics nursing credential; (iii) establishing a multiprofessional genetics education coalition and defining genetic competency for health-care practice; (iv) creating new clinical practice roles for nurses that integrate emerging genetics concepts and skills into diverse clinical practice areas; (v) expanding nursing involvement in genetics-related research; and (vi) participation in high-level genetics advisory groups. Conclusions:, The US experience shows that nurses have made substantial progress in expanding their involvement in genetic services through visionary leadership, innovative approaches to challenges, establishing support with nurse colleagues, and engaging in multiprofessional efforts. The most important first step is developing a supportive environment for nurse advancement. In the US, the genetics nurses' organization known as the International Society of Nurses in Genetics (ISONG) has provided this base. [source] Dynamic spatial cognition: Components, functions, and modifiability of body schema1JAPANESE PSYCHOLOGICAL RESEARCH, Issue 3 2006KAORU SEKIYAMA Abstract:, There has been substantial progress towards the understanding of the classical notion of "body schema," with recent advances in experimental methodology and techniques. Mental rotation of the hands can be used as a tool to investigate body schema. Research has shown that implicit motor imagery (i.e., mental simulated movements) can be generated based on the body schema, by combining both stored and incoming sensory information. Multimodal stimulation of peripersonal space has also served as an experimental paradigm for the study of body schema. Perception of peripersonal space is based on body-part-centered space coding that is considered as a manifestation of the body schema, its function being to integrate visual, tactile, and proprioceptive information, and perhaps motor plans as well. By combining such experimental paradigms with neuroimaging and neurophysiological techniques, research has converged to show that the parietal association cortex and premotor cortex are important for the body schema. Multimodal perception of body parts and peripersonal space have been also studied in relation to prism adaptation and tool use effects, indicating a clear modifiability of the body schema. Following prolonged adaptation to reversed vision, a reversed hand representation can be added to the body schema like a tool. The stored component of the body schema may not be established well in young children. But once established it may not be deleted even after an arm is amputated, although it may be weakened. All of these findings help to specify properties of the body schema, its components, functions, and modifiabilities. [source] Caring for Older Americans: The Future of Geriatric MedicineJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue S6 2005American Geriatrics Society Core Writing Group of the Task Force on the Future of Geriatric Medicine In response to the needs and demands of an aging population, geriatric medicine has grown rapidly during the past 3 decades. The discipline has defined its core values as well as the knowledge base and clinical skills needed to improve the health, functioning, and well-being of older persons and to provide appropriate palliative care. Geriatric medicine has developed new models of care, advanced the treatment of common geriatric conditions, and advocated for the health and health care of older persons. Nevertheless, at the beginning of the 21st century, the health care of older persons is at a crossroads. Despite the substantial progress that geriatric medicine has made, much more remains to be done to meet the healthcare needs of our aging population. The clinical, educational, and research approaches of the 20th century are unable to keep pace and require major revisions. Maintaining the status quo will mean falling further and further behind. The healthcare delivery and financing systems need fundamental redesign to improve quality and eliminate waste. The American Geriatrics Society (AGS) Task Force on the Future of Geriatric Medicine has identified five goals aimed at optimizing the health of older persons: ,,To ensure that every older person receives high-quality, patient-centered health care ,,To expand the geriatrics knowledge base ,,To increase the number of healthcare professionals who employ the principles of geriatric medicine in caring for older persons ,,To recruit physicians and other healthcare professionals into careers in geriatric medicine ,,To unite professional and lay groups in the effort to influence public policy to continually improve the health and health care of seniors Geriatric medicine cannot accomplish these goals alone. Accordingly, the Task Force has articulated a set of recommendations primarily aimed at the government, organizations, agencies, foundations, and other partners whose collaboration will be essential in accomplishing these goals. The vision described in this document and the accompanying recommendations are only the broad outline of an agenda for the future. Geriatric medicine, through its professional organizations and its partners, will need to mobilize resources to identify and implement the specific steps that will make the vision a reality. Doing so will require broad participation, consensus building, creativity, and perseverance. The consequences of inaction will be profound. The combination of a burgeoning number of older persons and an inadequately prepared, poorly organized physician workforce is a recipe for expensive, fragmented health care that does not meet the needs of our older population. By virtue of their unique skills and advocacy for the health of older persons, geriatricians can be key leaders of change to achieve the goals of geriatric medicine and optimize the health of our aging population. Nevertheless, the goals of geriatric medicine will be accomplished only if geriatricians and their partners work in a system that is designed to provide high-quality, efficient care and recognizes the value of geriatrics. [source] FGF and FGFR signaling in chondrodysplasias and craniosynostosisJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2005P.J. Marie Abstract The first experimental mouse model for FGF2 in bone dysplasia was made serendipitously by overexpression of FGF from a constitutive promoter. The results were not widely accepted, rightfully drew skepticism, and were difficult to publish; because of over 2,000 studies published on FGF-2 at the time (1993), only a few reported a role of FGF-2 in bone growth and differentiation. However, mapping of human dwarfisms to mutations of the FGFRs shortly, thereafter, made the case that bone growth and remodeling was a major physiological function for FGF. Subsequent production of numerous transgenic and targeted null mice for several genes in the bone growth and remodeling pathways have marvelously elucidated the role of FGFs and their interactions with other genes. Indeed, studies of the FGF pathway present one of the best success stories for use of experimental genetics in functionally parsing morphogenetic regulatory pathways. What remains largely unresolved is the pleiotropic nature of FGF-2. How does it accelerate growth in one cell then stimulate apoptosis or retard growth for another cell in the same type of tissue? Some of the answers may come through distinguishing the FGF-2 protein isoforms, made from alternative translation start sites, these appear to have substantially different functions. Although we have made substantial progress, there is still much to be learned regarding FGF-2 as a most complex, enigmatic protein. Studies of genetic models in mice and human FGFR mutations have provided strong evidence that FGFRs are important modulators of osteoblast function during membranous bone formation. However, there is some controversy regarding the effects of FGFR signaling in human and murine genetic models. Although significant progress has been made in our understanding of FGFR signaling, several questions remain concerning the signaling pathways involved in osteoblast regulation by activated FGFR. Additionally, little is known about the specific role of FGFR target genes involved in cranial bone formation. These issues need to be addressed in future in in vitro and in vivo approaches to better understand the molecular mechanisms of action of FGFR signaling in osteoblasts that result in anabolic effects in bone formation. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] Facilitation in the conceptual melting potJOURNAL OF ECOLOGY, Issue 6 2009Rob W. Brooker Summary 1. Here we present an introduction to this issue's Special Feature arising from the British Ecological Society Symposium: Facilitation in Plant Communities (20,22 April 2009). 2. Papers in the Special Feature demonstrate the benefits that arise from cross-system application of general concepts, for example, the well-known stress gradient hypothesis. Such comparisons challenge our definition of facilitation, as well as our pre-conceptions on the nature of intermediary organisms. 3. We suggest that under some circumstances a clear definition of the two-way nature of interactions is essential, e.g. when considering the evolutionary implications of facilitation. In other cases, however, we can perhaps be more relaxed, e.g. when facilitation is a component of conservation ecology. 4.Synthesis. Overall we believe that establishing facilitation as an independent concept has driven substantial progress towards a clearer understanding of how ecological systems work. Through the links established by work such as that presented in this Special Feature, we believe this field will continue to make rapid progress and aid ecological understanding in general. [source] REVIEW: Vitamin transport and homeostasis in mammalian brain: focus on Vitamins B and EJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Reynold Spector Abstract With the application of genetic and molecular biology techniques, there has been substantial progress in understanding how vitamins are transferred across the mammalian blood,brain barrier and choroid plexus into brain and CSF and how vitamin homeostasis in brain is achieved. In most cases (with the exception of the sodium-dependent multivitamin transporter for biotin, pantothenic acid, and lipoic acid), the vitamins are transported by separate carriers through the blood,brain barrier or choroid plexus. Then the vitamins are accumulated by brain cells by separate, specialized systems. This review focuses on six vitamins (B1, B3, B6, pantothenic acid, biotin, and E) and the newer genetic information including relevant ,knockdown' or ,knockout' models in mice and humans. The overall objective is to integrate this newer information with previous physiological and biochemical observations to achieve a better understanding of vitamin transport and homeostasis in brain. This is especially important in view of the newly described non-cofactor vitamin roles in brain (e.g. of B1, B3, B6, and E) and the potential roles of vitamins in the therapy of brain disorders. [source] Psychosocial Well-Being and Quality of Life Among Women Newly Diagnosed With Genital HerpesJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 3 2009Hayley Mark ABSTRACT Objective: To assess the psychosocial well-being and quality of life among women with a new genital herpes simplex virus diagnosis. Design: Data were collected by a cross-sectional survey. Participants: Eighty-three women diagnosed with genital herpes simplex virus by culture, visual exam and/or a description of symptoms within the last 3 months were recruited from primary health care clinics by their provider. Measures: Participants completed the Hospital Anxiety and Depression Scale and the Recurrent Genital Herpes Quality of Life scale. Results: Thirty-four percent of the women qualified as "clinical cases" for depression, and 64% were designated as "anxiety cases" based on Hospital Anxiety and Depression Scale scoring methods. A majority of participants reported feeling ashamed about having herpes and worried about having an outbreak or giving herpes to someone else. Conclusions: Despite substantial progress toward understanding genital herpes simplex virus epidemiology and transmission, a diagnosis of genital herpes continues to cause considerable psychosocial morbidity and to impact quality of life. There is a dearth of good evidence on how best to intervene to minimize the psychological impact of a diagnosis. Experts recommend addressing both the medical and psychological aspects of infection by providing antiviral therapy, written material, and resources. [source] Apoptosis and necrosis in liver diseaseLIVER INTERNATIONAL, Issue 2 2004Hartmut Jaeschke Abstract: Liver cell injury and cell death is a prominent feature in all liver disease processes. During the last 5,10 years, most research activities focused almost exclusively on evaluating apoptotic cell death and the corresponding intracellular signaling pathways. Although this effort led to substantial progress in our understanding of the mechanisms of apoptosis, it also created substantial confusion regarding the predominant mode of cell death and the relevance of apoptosis in a variety of liver disease models, as discussed in this review for acetaminophen and troglitazone hepatotoxicity, obstructive cholestasis and viral hepatitis. Part of the problem is related to the fact that there is no specific assay or parameter, with the exception of morphological changes in vivo, which allows the unequivocal distinction between apoptosis and oncotic necrosis. In addition, some aspects of the signaling pathways are similar. Therefore, to make progress in identifying relevant pharmacological intervention strategies to prevent or attenuate human liver disease processes, it is of critical importance to apply several different experimental approaches and analyze as many parameters as possible. In addition, positive controls for the assumed process should be used whenever possible and mechanisms of cell injury should only be investigated in model systems relevant for the human pathophysiology. [source] Experimental design and taxonomic scope of fragmentation studies on European mammals: current status and future prioritiesMAMMAL REVIEW, Issue 2 2010Alessio MORTELLITI ABSTRACT 1Habitat loss, habitat fragmentation and habitat degradation are the greatest threats to mammals in Europe and the rest of the world. Despite the fact that extensive literature exists, no comprehensive review or synthesis is available to date and this may slow down scientific progress and hamper conservation efforts. 2The goal of this study is to understand if and in what direction progress has been made in the study of the effects of habitat loss and fragmentation on the spatial distribution of European terrestrial mammals. Firstly, we carry out a general synthesis which is structured around 11 key points. The aim of this point-by-point analysis is to identify trends, knowledge gaps and any significant bias in the available literature, and to highlight strengths and shortfalls of the different approaches which have to date been applied. Secondly, we follow a species-specific systematic approach: for each species, we synthesise key results. 3Our results show how substantial progress has been hampered for several reasons including: a large predominance of small-scale field studies of short duration, and a generalised lack of control of: (i) confounding variables; (ii) spatial autocorrelation; and (iii) false absences. Also, despite the relatively high number of studies, few were theoretical studies and even fewer were meta-analyses. The lack of meta-analyses is likely to be due to the small amount of crucial details included in the publications, such as model parameters or information on the landscape context (such as the amount of residual forest cover). 4We synthesise the main results for 14 species. The level of progress is highly variable: for some species, such as the red squirrel Sciurus vulgaris, a series of long-term, large-scale process-oriented studies has allowed an in-depth understanding of its ecology in fragmented landscapes. On the other hand, with other species such as the bank vole Myodes glareolus, despite a relatively large number of field studies, little progress has been made. [source] Sociolinguistic Approaches to Second Language Acquisition Research,1997,2007MODERN LANGUAGE JOURNAL, Issue 5 2007ELAINE TARONE This article discusses sociolinguistically oriented research on second language acquisition (SLA) in the decade since Firth and Wagner (1997). Over the last 10 years, substantial progress has been made in developing a model of the sociolinguistic processes that inform second language acquisition. This model is supported by empirical evidence on the relationship between social context and second language use and acquisition, which shows that learners' second language (L2) input and processing of L2 input in social settings are socially mediated, that social and linguistic context affect linguistic use, choice, and development, and that learners intentionally assert social identities through their L2 in communicating in social contexts. A strength of sociolinguistically oriented SLA research is its strong focus on linguistic outcomes, tracking the impact of contextual factors in producing those outcomes. Preston (2000, 2002) and Fasold and Preston (2006) provided a central sociolinguistic framework to integrate research on the interaction of social factors and cognitive processes in producing interlanguage, which is a variable linguistic system. [source] Sociolinguistic Approaches to Second Language Acquisition Research,1997,2007MODERN LANGUAGE JOURNAL, Issue 2007ELAINE TARONE This article discusses sociolinguistically oriented research on second language acquisition (SLA) in the decade since Firth and Wagner (1997). Over the last 10 years, substantial progress has been made in developing a model of the sociolinguistic processes that inform second language acquisition. This model is supported by empirical evidence on the relationship between social context and second language use and acquisition, which shows that learners' second language (L2) input and processing of L2 input in social settings are socially mediated, that social and linguistic context affect linguistic use, choice, and development, and that learners intentionally assert social identities through their L2 in communicating in social contexts. A strength of sociolinguistically oriented SLA research is its strong focus on linguistic outcomes, tracking the impact of contextual factors in producing those outcomes. Preston (2000, 2002) and Fasold and Preston (2006) provided a central sociolinguistic framework to integrate research on the interaction of social factors and cognitive processes in producing interlanguage, which is a variable linguistic system. [source] Photoaging of human skinPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2000M. Berneburg Chronic sun exposure causes photoaging of human skin, a process that is characterized by clinical, histological and biochemical changes which differ from alterations in chronologically aged but sun-protected skin. Within recent years, substantial progress has been made in unraveling the underlying mechanisms of photoaging. Induction of matrix metalloproteinases as a consequence of activator protein (AP)-1 and nuclear factor (NF)-,B activation as well as mutations of mitochondrial DNA have been identified recently. This has increased our understanding of photoaging significantly and has led to new prophylactic and therapeutic strategies aimed at the prevention and repair of the detrimental effects of chronic sun-exposure on the skin. [source] Diagnostic evaluation of developmental delay/mental retardation: An overviewAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2003Agatino Battaglia Abstract Mental retardation (MR) is one of the few clinically important disorders for which the etiopathogenesis is still poorly understood. It is a condition of great concern for public health and society. MR is currently defined as a significant impairment of cognitive and adaptive functions, with onset before age 18 years. It may become evident during infancy or early childhood as developmental delay (DD), but it is best diagnosed during the school years. MR is estimated to occur in 1,10% of the population, and research on its etiology has always been a challenge in medicine. The etiopathogenesis encompasses so many different entities that the attending physician can sometimes feel a "virtual panic," starting a wide-range diagnostic evaluation. The Consensus Conference of the American College of Medical Genetics has recently established guidelines regarding the evaluation of patients with MR [Curry et al., 1997], emphasizing the high diagnostic utility of cytogenetic studies and neuroimaging in certain clinical settings. However, since then there has been substantial progress in molecular cytogenetics and neuroimaging techniques, the use of which has allowed recognition and definition of new disorders, thus increasing the diagnostic yield. This review will focus on the most appropriate investigations shown to be, at present, necessary to define the etiology of DD/MR, in the context of recommendations for the clinical evaluation of the patient with undiagnosed MR. © 2003 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 10 2007Article first published online: 13 SEP 200 Sitagliptin: novel drug for type 2 diabetes Sitagliptin (Januvia), the first dipeptidyl peptidase-4 (DPP-4) inhibitor, has been introduced for the treatment of type 2 diabetes in combination with metformin or a glitazone when either agent plus exercise and diet fail to control blood glucose. Inhibition of DPP-4 prevents the breakdown of incretin hormones that promote insulin release from pancreatic beta cells. In trials lasting up to 24 weeks, adding sitagliptin to established therapy reduced HbA1C by 0.67-0.90 per cent. It is contraindicated in patients with moderate or more severe renal impairment. At the recommended dose of 100mg per day, a month's treatment with sitagliptin costs £33.36. Guide to treating mentalillness in primary care A new guide from the Centre for Clinical and Academic Workforce Innovation aims to help health professionals and others treating people with mental illness. A Complete Guide to Primary Care Mental Health, a toolkit presented as a reference book and CD, covers aspects of treatment, the law and working with the voluntary sector and includes training materials compatible with evidence-based guidance. Copies are available from amazon.co.uk. Follow-up improves statin adherence Patients may take long holidays from statin treatment but a visit to the doctor is among the most effective ways to improve adherence, a US study shows (Arch Intern Med 2007;167:847,52). Observation of 239 911 patients who began statin treatment during a seven-year period showed that 54 per cent stopped their treatment for at least 90 days. Of these, 48 per cent restarted within one year and 60 per cent within two years. Factors associated with restarting treatment were a visit to the doctor who prescribed the statin (odds ratio, OR, 6.1) or a visit to a different doctor (OR 2.9). A cholesterol test and hospital admission for a cardiovascular event were also significant factors. Pharmacist MUR does not reduce heart failure deaths Medication review by trained community pharmacists does not reduce admissions or deaths among patients with heart failure, according to a study from East Anglia (BMJ online: 23 April 2007; doi:10.1136/bmj.39164.568183.AE). Patients admitted as emergencies with heart failure were randomised to usual care or two home visits by a community pharmacist within two and eight weeks after discharge. Pharmacists reviewed medication and advised on self-management of symptoms and lifestyle. There were no significant differences in hospital admissions over the next six months (rate ratio 1.15 for pharmacist vs control) or deaths (rate ratio 1.18); quality of life scores were similar in the two groups. The authors speculate that the interventions may have been too brief or too late (lifestyle changes having been made already), or disadvantaged by not adjusting beta-blocker doses. A Cardiff study of pharmacist medication reviews for elderly patients (BMJ online: 20 April 2007; doi:10.1136/bmj.39171. 577106.55), found that their advice had the potential to undermine patients' ,confidence, integrity and self-governanc'. The study found that pharmacists gave advice unnecessarily and uninvited. CHD targets met early The national programme to tackle heart disease has made substantial progress towards it targets, the Department of Health says in a 10-year report, and a 40 per cent cut in mortality will be achieved ahead of the deadline of 2010. Coronary Heart Disease Ten Years On: Improving Heart Care, a report by Professor Roger Boyle, National Director for Heart Disease and Stroke, states that 7 per cent of the population is now taking statins, resulting in 9700 deaths avoided annually. The prevalence of untreated hypertension fell from 32 to 24 per cent between 1998 and 2003. The report also summarises changes in service delivery, nutrition and smoking cessation. HRT: ovarian cancer risk The MHRA has not altered its advice on the use of HRT following news that five years' use increases ovarian cancer risk in women over 50. The Million Women Study revealed an approximately 20 per cent increased risk of ovarian cancer or death among women still using HRT after five or more years. There was no difference in risk between oestrogen-only and combined formulations. The MHRA says HRT is still indicated for relieving symptoms of the menopause for short-term use; as an alternative for women over 50 who cannot take other treatments to prevent osteoporosis, or when such options fail; and in women under 50 who experience a premature menopause. Poor angina treatment Over half of patients with angina continue to experience attacks despite treatment, according to a survey by the British Cardiac Patients Association. The survey of 600 patients with angina also found that twot-hirds of respondents reported that angina had a moderate to severe impact on their lives. Half said that the adverse effects of their treatment negatively affected their work, two-thirds reported an adverse impact on sex, and almost three-quarters of patients taking beta-blockers reported fatigue. A second survey of 2000 adults revealed widespread ignorance about the prevalence and symptoms of angina. The surveys were sponsored by Servier Laboratories Limited and conducted in collaboration with Research Quorum. Cabergoline restriction Indications for the dopamine agonist cabergoline (Cabaser) are being restricted to match those of pergolide (Celance), the MHRA has announced. Pergolide was recently withdrawn in the United States and its use in the EU is limited because of the risk of cardiac valvular damage. Similar toxicity has been reported with cabergolide, which is now restricted to second-line use when a nonergot treatment for Parkinson's disease has failed. It is contraindicated in patients with valvular damage or a history of fibrotic disorders and requires patient monitoring. Sodium reduction cuts CV events Long-term reduction in dietary sodium may reduce cardiovascular events by 25 per cent, US epidemiologists say (BMJ online: 20 April 2007; doi:10.1136/bmj.39147.604896.55). Participants in the two Trials of Hypertension Prevention (TOHP I and II) reduced their sodium intake by 44 and 33mmol per 24hr. After 10,15 years' follow-up of 2415 participants, the adjusted relative risk of cardiovascular events was 0.75 compared with controls. There was a nonsignificant 20 per cent reduction in mortality. Copyright © 2007 Wiley Interface Ltd [source] Radical innovation in a small firm: a hybrid electric vehicle development project at Volvo CarsR & D MANAGEMENT, Issue 4 2010Hans Pohl The potential paradigmatic shift in technology from the internal combustion engine to electric propulsion via hybrid electric vehicles (HEVs) has been addressed by most automakers, and has produced very different outcomes. This paper uses the framework of core capabilities to discuss how the small automaker, Volvo Cars, made substantial progress in its HEV development using an approach based on limited resources and a low risk. A comparison with Toyota's successful but very resource-demanding Prius project reveals some factors contributing towards rapid development in a context of limited resources, including focused project objectives, tight collaboration with suppliers of the new technologies, reuse of existing technologies and an unaggressive, bottom-up approach to change the firm's values and norms and other core capability dimensions. This paper provides an empirical illustration of how a small company in a mature industry worked with radical innovation in a development project drawing on the combination of organizational slack, entrepreneurial employees and an extensive use of external (knowledge) suppliers. [source] Unraveling the Logic of ASEAN's Decision-Making: Theoretical Analysis and Case ExaminationASIAN POLITICS AND POLICY, Issue 3 2010Yi-hung Chiou Throughout its history, the Association of Southeast Asian Nations (ASEAN) has based decisions on consensus and consultation, producing a loosely defined, weak regional organization. The results of nonbinding and watered-down resolutions make substantial progress for ASEAN difficult. This article explores the logic of ASEAN's decision-making by applying rational choice theory. It argues that the characteristics of ASEAN's decision-making mechanism allow member states to base their actions on how individual nations perceive their interests to be best served by group resolutions. By constructing a series of hypotheses to pattern ASEAN's decision-making, this article examines four cases and how players resolved each. The findings suggest that the constraints of group decision-making and divergent interests between member states play a major role in shaping the effectiveness of resolutions. [source] Reversible acetylation of chromatin: Implication in regulation of gene expression, disease and therapeuticsBIOTECHNOLOGY JOURNAL, Issue 3 2009Ruthrotha B. Selvi Abstract The eukaryotic genome is a highly dynamic nucleoprotein complex that is comprised of DNA, histones, nonhistone proteins and RNA, and is termed as chromatin. The dynamicity of the chromatin is responsible for the regulation of all the DNA-templated phenomena in the cell. Several factors, including the nonhistone chromatin components, ATP-dependent remodeling factors and the chromatin-modifying enzymes, mediate the combinatorial post-translational modifications that control the chromatin fluidity and, thereby, the cellular functions. Among these modifications, reversible acetylation plays a central role in the highly orchestrated network. The enzymes responsible for the reversible acetylation, the histone acetyltransferases (HATs) and histone deacetylases (HDACs), not only act on histone substrates but also on nonhistone proteins. Dysfunction of the HATs/HDACs is associated with various diseases like cancer, diabetes, asthma, cardiac hypertrophy, retroviral pathogenesis and neurodegenerative disorders. Therefore, modulation of these enzymes is being considered as an important therapeutic strategy. Although substantial progress has been made in the area of HDAC inhibitors, we have focused this review on the HATs and their small-molecule modulators in the context of disease and therapeutics. Recent discoveries from different groups have established the involvement of HAT function in various diseases. Furthermore, several new classes of HAT modulators have been identified and their biological activities have also been reported. The scaffold of these small molecules can be used for the design and synthesis of better and efficient modulators with superior therapeutic efficacy. [source] Exploring the Structural Complexities of Metal,Metalloid Nanoparticles: The Case of Ni,B as CatalystCHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2009Junfeng Geng Dr. Abstract Understanding of the structural complexities of metal,metalloid nanoparticles is at the heart of several proposals for investigating the physical properties and practical applications of these bi-elemental nanomaterials. To date, the most widely studied metal,metalloid is the nickel,boron (Ni,B) system; however, the exact nature of the structure of the material itself has remained unclear. Herein we show our systematic investigations of the material in an attempt to reveal its fascinating nanostructure. The relation between its high catalytic activity and the ultrafine structure is explored, and the work has been further extended to the formation of colloidal Ni,B nanoparticles. The results presented in this work may represent a substantial progress toward a full understanding of the nickel,boron chemistry. [source] | ||||||||||||||||||||||