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THE MOLECULAR FUTURE IN CYTOLOGY

CYTOPATHOLOGY, Issue 2006
M. Salto-Tellez
Molecular diagnosis is the application of molecular biology techniques and knowledge of the molecular mechanisms of disease to diagnosis, prognostication and treatment of diseases. Molecular Diagnosis is, arguably, the fastest growing area of diagnostic medicine. The US market for molecular testing generated $1.3 billion in 2000, which was predicted to increase to about $4.2 billion by 2007.1 We proposed the term Diagnostic Molecular Cytopathology to define the application of molecular diagnosis to cytopathology2. Diagnostic Molecular Cytopathology is essential for the following reasons: (i) Molecular testing is sometimes indispensable to establish an unequivocal diagnosis on cell preparations; (ii) Molecular testing provides extra information on the prognosis or therapy of diseases diagnosed by conventional cytology; (iii) Molecular testing provides genetic information on the inherited nature of diseases that can be directly investigated in cytology samples, by either exfoliation or by fine needle aspiration; (iv) Sometimes the cytopathology sample is the most convenient (or the only available) source of material for molecular testing; (v). Direct molecular interrogation of cells allows for a diagnostic correlation that would otherwise not be possible. Parallel to this direct diagnostic implication, cytopathology is increasing important in the validation of biomarkers for specific diseases, and in therefore of significant importance in the overall translational research strategies. We illustrate its application in some of the main areas of oncology molecular testing, such as molecular fingerprinting of neoplasms,3 lymphoreticular diseases,2 sarcomas4 and lung cancer,5 as well as translational research using diagnostic cytopathology techniques. The next years will see the consolidation of Diagnostic Molecular Cytopathology, a process that will lead to a change of many paradigms. In general, diagnostic pathology departments will have to reorganize molecular testing to pursue a cost-efficient operation. Sample preparation will have to take into account optimal preservation of nuclear acids. The training of technical staff and the level of laboratory quality control and quality assurance would have to follow strict clinical (not research) laboratory parameters. And, most importantly, those pathologists undertaking molecular diagnosis as a discipline would have to develop their professional expertise within the same framework of fellowships and professional credentials that is offered in other sub-specialties. The price to pay if this effort is not undertaken is too important for the future of diagnostic pathology in general. The increasing characterization of molecular biomarkers with diagnostic, prognostic or therapeutic value is making the analysis of tissue and cell samples prior to treatment a more complex exercise. If cytopathologists and histopathologists allow others to take charge of molecular diagnosis, our overall contribution to the diagnostic process will be diminished. We may not become less important, but we may become less relevant. However, those within the discipline of diagnostic pathology who can combine the clinical background of diseases with the morphological, immunocytochemical and molecular diagnostic interpretation will represent bona fide diagnostic specialists. Such ,molecular cytopathologists' would place themselves at the centre of clinical decision-making. Reference:, 1. Liz Fletcher. Roche leads molecular diagnostics charge. Nature Biotechnol 20, 6,7; 2002 2. Salto-Tellez M and Koay ESC. Molecular Diagnostic Cytopathology - Definitions, Scope and Clinical Utility. Cytopathology 2004; 15:252,255 3. Salto-Tellez M, Zhang D, Chiu LL, Wang SC, Nilsson B, and Koay ESC. Immunocytochemistry Versus Molecular Fingerprinting of Metastases. Cytopathology, 2003 Aug; 14(4):186,90. 4. Chiu LL, Koay SCE, Chan NL and Salto-Tellez M. Molecular Cytopathology: Sequencing of the EWS-WT1 Gene Fusion Transcript in the Peritoneal Effusion of a Patient with Desmoplastic Small Round Cell Tumour. Diagnostic Cytopathology, 2003 Dec; 29(6): 341,3. 5. TM Chin, D Anuar, R Soo, M Salto-Tellez, WQ Li, B Ahmad, SC Lee, BC Goh, K Kawakami, A Segal, B Iacopetta, R Soong. Sensitive and Cost-Effective deptection of epidermal growth factor Receptor Mutations in Small Biopsies by denaturing High Performance Liquid Chromatography. (In press). [source]


Role of Parasternal Data Acquisition During Contrast Enhanced Real-Time Three-Dimensional Echocardiography

ECHOCARDIOGRAPHY, Issue 10 2007
Attila Nemes M.D., Ph.D.
Background: Recent technical developments have resulted in high-resolution real time three-dimensional echocardiography (RT3DE). The purpose of this study was to investigate the beneficial role of parasternal-acquired images in addition to apical-acquired images during contrast stress RT3DE. Methods: The study comprised 30 consecutive patients (52 ± 11 years, 18 males) with chest pain referred for routine stress testing. The contrast RT3DE images were acquired from the apical and parasternal window with a Sonos 7500 echo system attached to a X4 matrix array transducer. Results: From the apical and parasternal acquisition, 464 segments (91%) and 267 segments (52%) could be analyzed, respectively (P < 0.001). From the apical window, more basal segments were not analyzable (22 of 180, 12% vs. 24 of 330, 7%; P = 0.06). From the parasternal window, more apical segments were not analyzable (117 of 150, 78% vs. 126 of 360, 35%; P < 0.01). The mean image quality index of the 464 analyzable segments from the apical-acquired images was 2.43. Fourteen of 180 basal segments (8%), 12 of 180 midventricular segments (7%) and 2 of 150 apical segment (1%) were only available with parasternal data acquisition. In addition to these 28 segments, 79 segments (15%) already visualized from the apical window improved in quality. The overall mean image quality index, now assessed from 492 (96%) of all segments, using both the apical and parasternal acquired data, improved to 2.74 (P < 0.05). Conclusions: Addition of parasternal to apical acquisition of contrast RT3DE data can decrease the number of nonvisualized segments and improve mean image quality. [source]


Mismatch between the timing of oviposition and the seasonal optimum.

ECOLOGICAL ENTOMOLOGY, Issue 3 2010
The stochastic phenology of Mediterranean acorn weevils
1. The timing of reproduction is predicted to match the period of maximum food availability. In this sense, the case of many phytophagous insects in temperate regions is very illustrative, as their larvae usually depend on a resource only available for a limited period of time each year. 2. For 3 years the interactions between the weevil Curculio elephas and the Mediterranean Holm oak Quercus ilex were studied. Weevil larvae grow within the acorns, feeding on the cotyledons. The timing of oviposition will determine food availability for the larvae, as acorns stop growing once they are attacked. 3. Acorn temporal growing patterns did not change between years and food availability for larvae was at its highest in October, when temperature was still suitable for larval development. However, oviposition phenology did change between years. In 2002 females oviposited later, larvae grew within larger acorns, and their body mass was significantly higher than in 2003 or 2004, when females oviposited into early acorns. 4. Thus, weevils do not always adjust oviposition to the best possible feeding conditions for their offspring. Rather, they seem to maximise their own lifetime fitness, ovipositing as soon as they emerge in late summer. Emergence, in turn, depends strongly on stochastic events such as summer storms in the Mediterranean region. 5. Under a climate change perspective, the trend towards higher August rainfall recorded in our study area may alter oviposition phenology, with the subsequent cascade effects on weevil body size and fitness [source]


Molecular Neuropathology of Temporal Lobe Epilepsy: Complementary Approaches in Animal Models and Human Disease Tissue

EPILEPSIA, Issue 2007
Michael Majores
Summary:, Patients with temporal lobe epilepsies (TLE) frequently develop pharmacoresistance to antiepileptic treatment. In individuals with drug-refractory TLE, neurosurgical removal of the epileptogenic focus provides a therapy option with high potential for seizure control. Biopsy specimens from TLE patients constitute unique tissue resources to gain insights in neuropathological and molecular alterations involved in human TLE. Compared to human tissue specimens in most neurological diseases, where only autopsy material is available, the bioptic tissue samples from pharmacoresistant TLE patients open rather exceptional preconditions for molecular biological, electrophysiological as well as biochemical experimental approaches in human brain tissue, which cannot be carried out in postmortem material. Pathological changes in human TLE tissue are multiple and relate to structural and cellular reorganization of the hippocampal formation, selective neurodegeneration, and acquired changes of expression and distribution of neurotransmitter receptors and ion channels, underlying modified neuronal excitability. Nevertheless, human TLE tissue specimens have some limitations. For obvious reasons, human TLE tissue samples are only available from advanced, drug-resistant stages of the disease. However, in many patients, a transient episode of status epilepticus (SE) or febrile seizures in childhood can induce multiple structural and functional alterations that after a latency period result in a chronic epileptic condition. This latency period, also referred to as epileptogenesis, cannot be studied in human TLE specimens. TLE animal models may be particularly helpful in order to shed characterize new molecular pathomechanisms related to epileptogenesis and open novel therapeutic strategies for TLE. Here, we will discuss experimental approaches to unravel molecular,neuropathological aspects of TLE and highlight characteristics and potential of molecular studies in human and/or experimental TLE. [source]


Foraging tactics in alternative heterochronic salamander morphs: trophic quality of ponds matters more than water permanency

FRESHWATER BIOLOGY, Issue 9 2007
MATHIEU DENOEL
Summary 1. In lentic freshwater habitats, the composition of animal assemblages shifts along a gradient from temporary to permanent basins. When habitats with different degrees of permanence are at the scale of the home range of species, they constitute alternatives in terms of energy acquisition through feeding. 2. In this context, previous studies showed an advantage of metamorphic over paedomorphic tiger salamanders (Ambystoma tigrinum) in temporary ponds which are only available to metamorphs. The aim of this study was to establish whether salamanders obtain similar benefits in ponds that do not differ in water permanence and whether salamanders shifted from detrimental to advantageous ponds. To this end, we determined the feeding habits, body condition and movement patterns of the two morphs in a complex of four permanent and four temporary ponds. 3. Consistent with previous studies, metamorphs consumed higher-quality diets than paedomorphs in term of energy intake. However, these differences occurred because metamorphs consumed fairy shrimp in a single temporary pond. Individual movement patterns confirmed that most of the metamorphs used different aquatic habitats both within and between years and that most of them moved from permanent ponds for breeding towards the most profitable temporary pond in terms of foraging. 4. These results indicate that habitat selection by salamanders is optimal in term of energy intake in metamorphs that use high quality ponds independently of hydroperiod. It seems that both spatial and temporal variation can influence the relative foraging success of each morph. [source]


Applying climatically associated species pools to the modelling of compositional change in tropical montane forests

GLOBAL ECOLOGY, Issue 2 2008
Duncan J. Golicher
ABSTRACT Aim, Predictive species distribution modelling is a useful tool for extracting the maximum amount of information from biological collections and floristic inventories. However, in many tropical regions records are only available from a small number of sites. This can limit the application of predictive modelling, particularly in the case of rare and endangered species. We aim to address this problem by developing a methodology for defining and mapping species pools associated with climatic variables in order to investigate potential species turnover and regional species loss under climate change scenarios combined with anthropogenic disturbance. Location, The study covered an area of 6800 km2 in the highlands of Chiapas, southern Mexico. Methods, We derived climatically associated species pools from floristic inventory data using multivariate analysis combined with spatially explicit discriminant analysis. We then produced predictive maps of the distribution of tree species pools using data derived from 451 inventory plots. After validating the predictive power of potential distributions against an independent historical data set consisting of 3105 botanical collections, we investigated potential changes in the distribution of tree species resulting from forest disturbance and climate change. Results, Two species pools, associated with moist and cool climatic conditions, were identified as being particularly threatened by both climate change and ongoing anthropogenic disturbance. A change in climate consistent with low-emission scenarios of general circulation models was shown to be sufficient to cause major changes in equilibrium forest composition within 50 years. The same species pools were also found to be suffering the fastest current rates of deforestation and internal forest disturbance. Disturbance and deforestation, in combination with climate change, threaten the regional distributions of five tree species listed as endangered by the IUCN. These include the endemic species Magnolia sharpii Miranda and Wimmeria montana Lundell. Eleven vulnerable species and 34 species requiring late successional conditions for their regeneration could also be threatened. Main conclusions, Climatically associated species pools can be derived from floristic inventory data available for tropical regions using methods based on multivariate analysis even when data limitations prevent effective application of individual species modelling. Potential consequences of climate change and anthropogenic disturbance on the species diversity of montane tropical forests in our study region are clearly demonstrated by the method. [source]


A mid-shelf, mean wave direction climatology for southeastern Australia, and its relationship to the El Niño,Southern Oscillation since 1878 A.D.

INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 13 2005
Ian D. Goodwin
Abstract Coastal systems behave on timescales from days to centuries. Shelf and coastal wave climatological data from the Tasman Sea are only available for the past few decades. Hence, the records are too short to investigate inter- and multidecadal variability and their impact on coastal systems. A method is presented to hindcast monthly mid-shelf mean wave direction (MWD) for southeastern Australia, based on the monthly, trans-Tasman mean sea-level pressure (MSLP) difference between northern NSW (Yamba) and the north island of New Zealand (Auckland). The MSLP index is calibrated to instrumental (Waverider buoy) MWD data for the Sydney shelf and coast. Positive/negative trans-Tasman MSLP difference is significantly correlated to southerly/easterly Sydney MWD, and to long/short mean wave periods. The 124-year Sydney annual (MWD) time series displays multidecadal variability, and identifies a significant period of more southerly annual MWD during 1884 to 1914 than in the period since 1915. The Sydney MWD is significantly correlated to the Southern Oscillation Index (SOI). The correlation with the SOI is enhanced during periods when the Interdecadal Pacific Oscillation (IPO) is in its negative state and warm SST anomalies occur in the southwest Pacific region. The Sydney MWD was found to be associated with Pacific basin-wide climate fluctuations associated with the El Niño-Southern Oscillation (ENSO). Southerly/easterly Sydney MWD is correlated with low/high MSLP anomalies over New Zealand and the central Pacific Ocean. Southerly/easterly Sydney MWD is also correlated with cool/warm SST anomalies in the southwest Pacific, particularly in the eastern Coral Sea and Tasman Sea. Copyright © 2005 Royal Meteorological Society. [source]


Qualities and antioxidant properties of bread as affected by the incorporation of yam flour in the formulation

INTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2004
Chin-Lin Hsu
Summary Yams (the tubers of Dioscorea spp.) are widely consumed but are also regarded as a medicinal food in China. Traditional Chinese herbal medicines using yams are only available on a seasonal basis, as yams quickly deteriorate during winter storage. Yam (Dioscorea purpurea, a major variety of yams in Taiwan) was freeze-dried and ground to obtain yam flour. Bread was made by replacing up to 25% of wheat flour with yam flour. Although the loaf volume decreased with the addition of yam flour, the results showed that up to 20% of yam flour could be included in bread formulation without altering the sensory acceptance of the blended bread. The incorporation of yam flour in bread markedly increased the antioxidant capacity of the bread as tested by both DPPH free radical scavenging and total antioxidation tests. Breads containing yam flour can broaden the utilization of yams and may be regarded as possible health-promoting foods. [source]


Digitization and geo-referencing of botanical distribution maps

JOURNAL OF BIOGEOGRAPHY, Issue 7 2002
Christian A. Schölzel
Aim In many fields of research, valuable information is stored in atlases and maps which are only available as printed media. Scientists who are interested in computational analysis often seek to digitize the data to make it accessible for numerical calculations. In this paper, an approach using the example of digitizing distribution maps taken from plant-taxonomic atlases is described. For this purpose, a software tool has been built for application in the Sonderforschungsbereich 350 `Interactions between and Modelling of Continental Geosystems' at the University of Bonn. Its functionality has to be simple in use and capable of transforming fields drawn on geographical maps into grid data even where the type of map projection is unknown. Location As an example, plant distributions over Europe and Asia have been digitized. Methods To achieve this aim through an objective statistical analysis, the local deterministic approximation has been used for geo-referencing. Results For this reason the development of a new software tool was required. Although there is a large market for related software from Geographical Information Systems (GIS), none of the available GIS-programs appeared to be capable of geo-referencing maps with unidentified projections. Rather than to give a product comparison, this paper aims on the methodology and mathematical formalism. Main conclusions The developed algorithm is a handy tool to capture data from maps based on obscure projections. Valuable historical maps, which are problematic for standard GIS-programs, can be made accessible for modern research work. [source]


Clients' perceptions of support received from health visitors during home visits

JOURNAL OF CLINICAL NURSING, Issue 7 2005
Caroline Plews BA
Aims and objectives., The current study sought to identify how many mothers from 149 visits carried out by seven health visitors identified support as a feature of the visit, whether this type of support was unique to the health visitor and what support meant to them. These responses were then compared with the taxonomies of social support from the social support literature. Background., Some studies of client perceptions describe support as an element of home visits by health visitors. However, the importance, relevance and impact on the client of this support are not described in detail. Social support theory suggests that there are tangible benefits to people's well-being and their ability to cope with various challenges that may arise from individuals' perceptions of receiving support. Design., Qualitative study using semistructured interviews. Methods., Seven volunteer health visitors recruited 149 women into the study. These clients were interviewed by the researcher, usually within one week of the home visit by their health visitor. The discussions were audio-taped and the resulting transcripts analysed using content analysis. Findings., Thirty-seven women identified receiving support which they said was only available from the health visitor. The relevance of this support to the mother and the impact on her well-being varied within the group suggesting differing perceptions of support by clients according to their personal situation. There was a correspondence between the descriptions of support given by the women and the taxonomies of social support from the social support literature. Conclusion., For some interactions between clients and their health visitors the existing theory of social support may provide an explanation of how health visitors contribute to clients' perceived ability to cope and well-being. Relevance to clinical practice., Social support may be defined as a possible outcome of health visiting. This concept will have use within educational programmes to demonstrate to students how health visiting can have an impact on clients' well-being. Similarly, the concept could be used to investigate and record health visiting practice. [source]


An ecologist's guide to ecogenomics

JOURNAL OF ECOLOGY, Issue 1 2007
N. J. OUBORG
Summary 1Currently, plant ecologists are increasingly adopting approaches and techniques from molecular biology. The new field of ecogenomics aims at understanding the mechanistic basis for adaptation and phenotypic variation by using genomic techniques to investigate the mechanistic and evolutionary basis of species interactions, and focuses on identifying the genes affected by evolution. 2While the entire toolbox of genomics is only available for model species such as Arabidopsis thaliana, we describe the options open to ecologists interested in pursuing an ecogenomics research program on ecologically relevant traits or phenomena in non-model species, for which part of the genomic toolbox may be currently unavailable. In these non-model species, a viable ecogenomics research program is possible with relatively modest effort. 3Four challenges to further development of ecogenomics are described and discussed: (i) the ecogenomic study of non-model species; (ii) reconciliation of experimental languages of ecology and evolutionary biology with molecular biology; (iii) development of specific ecogenomic data analysis tool; and (iv) adoption of a multidisciplinary cooperative research culture. 4An important task for ecologists is to provide the necessary ecological input (the ,eco' part) to ecogenomics. [source]


Ethnic variation in lower oesophageal sphincter pressure and length

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008
K. J. VEGA
Summary Background, Oesophageal manometry (OM) is used to diagnose oesophageal motor disorders. Normal values of OM among United States ethnic groups are only available for Hispanic Americans (HA). Aim, To obtain normal values of OM in adult African American (AA) volunteers, compare these with those obtained in HA and non-Hispanic white (nHw) volunteers to determine if ethnic variation in normal oesophageal motor function exists. Methods, Healthy AA, HA and nHw were recruited from the Jacksonville metropolitan area. Ethnicity was self-reported. Exclusion criteria were symptoms suggestive of oesophageal disease, medication use or concurrent illness affecting OM. All underwent OM using a solid-state system with wet swallows. Resting lower oesophageal sphincter (LOS) pressure and LOS length were measured at mid-expiration, while per cent peristaltic contractions, distal oesophageal contraction velocity, amplitude and duration were measured after 5 cc water swallows. Results, Fifty-six AA, 20 HA and 48 nHw were enrolled. All completed OM. AA had significantly higher resting LOS pressure, LOS length and distal oesophageal contraction duration than nHw (P < 0.05). Conclusions, Significant ethnic exist in OM findings between AA and nHw. These underscore the need for ethnic specific reference values for OM to allow for correct diagnosis of oesophageal motor disorders in AA. [source]


Regional daily maximum rainfall estimation for Cekerek Watershed by L-moments

METEOROLOGICAL APPLICATIONS, Issue 4 2009
Kadri Yurekli
Abstract The estimation of maximum daily rainfall (PDmax) is usually required for the estimation of design flood (the maximum flood that any hydraulic structure can safely pass). However, PDmax estimation is usually required for watersheds where rainfall data are either not available or only available in short periods from various sites and so are unsuitable for maximum daily rainfall estimation. In this study, the regional PDmax of the Cekerek watershed in Turkey is estimated using the method of l-moments using 17 rainfall stations in the region. The discordant test for outlier stations showed no discordant station in the region. Applying the homogeneity measure, Hi, the homogeneous region was identified. To find the best regional distribution, the ZDIST goodness-of-fit test was applied. This test introduced two distributions as the candidates for regional parent distributions; Generalized Extreme Values (GEV) and 3-parameter Log Normal (LOGN3) distributions. The LOGN3 distribution was selected as the best regional distribution as it has the smaller absolute value of the statistics (ZDIST) based on the goodness-of-fit-test. Copyright © 2009 Royal Meteorological Society [source]


A microarray's view of life in the desert: adding a powerful evolutionary genomics tool to the packrat's midden

MOLECULAR ECOLOGY, Issue 11 2009
MARJORIE D MATOCQ
Identifying the genetic architecture of adaptive traits is fundamental to understanding how organisms respond to their environment, over both ecological and evolutionary timeframes. Microarray technology that allows us to capture the simultaneous expression of thousands of genes provides unparalleled insight into how organisms cope with their environment at the transcriptional level. Recent studies in Molecular Ecology demonstrate how microarrays can rapidly identify which genes and pathways allow organisms to face some of the most fundamental physiological challenges posed by the environment, including compensation for the hypoxic and thermal stress of high-altitudes (Cheviron et al. 2008) and, in this issue, the biotransformation of toxic plant secondary compounds by mammals (Magnanou et al. 2009). Microarrays (Ekins et al. 1989; Fodor et al. 1991) are glass slides affixed with hundreds to thousands of oligonucleotide or cDNA sequences (probes). Messenger RNA transcripts (typically reverse transcribed to cDNA) are isolated from a tissue/sample of interest and hybridized to the array. Binding to specific probes indicates that a particular gene was transcriptionally active at or near the time of sampling and thus provides a potentially comprehensive measure of gene expression. Although a tremendously powerful tool, commercially produced oligonucleotide arrays are only available for a handful of model organisms. Nonetheless, evolutionary ecologists have exploited this resource by using a cross-species hybridization approach (e.g. Saetre et al. 2004), that is, hybridizing a model organism array with a nonmodel sample (Bar-Or et al. 2007). Magnanou et al. (2009) present a novel example of using a model muroid microarray (Agilent Technologies, Rattus) to study physiological response in a wild, nonmodel muroid, Neotoma. [source]


Supermassive black hole merger rates: uncertainties from halo merger theory

MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2006
Adrienne L. Erickcek
ABSTRACT The merger of two supermassive black holes is expected to produce a gravitational-wave signal detectable by the Laser Interferometer Space Antenna(LISA). The rate of supermassive-black-hole mergers is intimately connected to the halo merger rate, and the extended Press-Schechter (EPS) formalism is often employed when calculating the rate at which these events will be observed by LISA. This merger theory is flawed and provides two rates for the merging of the same pair of haloes. We show that the two predictions for the LISA supermassive-black-hole-merger event rate from EPS merger theory are nearly equal because mergers between haloes of similar masses dominate the event rate. An alternative merger rate may be obtained by inverting the Smoluchowski coagulation equation to find the merger rate that preserves the Press,Schechter halo abundance, but these rates are only available for power-law power spectra. We compare the LISA event rates derived from the EPS merger formalism to those derived from the merger rates obtained from the coagulation equation and find that the EPS LISA event rates are 30 per cent higher for a power spectrum spectral index that approximates the full , cold dark matter result of the EPS theory. [source]


Schumpeter 1911: Farsighted Visions on Economic Development

AMERICAN JOURNAL OF ECONOMICS AND SOCIOLOGY, Issue 2 2002
Markus C. Becker
This paper presents to the English-speaking reader a sample of material contained only in Schumpeter's first German edition (1911) of Theorie der wirtschaftlichen Entwicklung, material subsequently omitted from later German editions and from the English translation. The newly-translated material, presented here for the first time in English, comprises a substantial part of the second chapter, only available in a completely rewritten version, and fully half of the famous seventh chapter, which has not been previously available at all in English. This material merits attention today because it contains remarkable and farsighted visions on economic theory that may inspire current efforts to devise models of economic and social evolution. In order to better appreciate the original text, we briefly introduce the "background" to Theorie and its revisions, briefly describing the social and intellectual environment of the time. We then discuss how the entrepreneur evolved over the three editions of Theorie (from 1911 to 1934) in view of the shift in Schumpeter's personal and intellectual life and outline the most important implications raised by the first German edition of 1911. Finally, we use Schumpeter's own statements to settle the obstinate confusion on the publication year of Theorie in favour of the year 1911. [source]


Firm characteristics and location: The case of the institutional investment advisory industry in the United States, 1983,1996

PAPERS IN REGIONAL SCIENCE, Issue 1 2000
John E. Bodenman
Institutional investment advisors; financial services; location Abstract. This article examines the locational dynamics of the institutional investment advisory industry in the United States, 1983,1996, focusing on the factors and firm characteristics that account for institutional investment management firms' location. The institutional investment advisory industry, one of the fastest growing industries in the financial services sector, includes firms that manage the securities portfolios of institutional clients (e.g., corporate pension funds) for a fee. Descriptive and logit analyses are used to identify, compare and contrast those factors and firm characteristics associated with firm location outside (versus inside) the traditional investment management core. The findings presented in this article diminish the notion that access to a skilled financial services labor pool and a high-quality and diversified transportation and communications infrastructure is only available in the traditional core. [source]


Attitudes to prenatal and preimplantation diagnosis in Saudi parents at genetic risk

PRENATAL DIAGNOSIS, Issue 11 2006
Ayman Alsulaiman
Abstract Background Prenatal diagnosis (PND) is only available for severe abnormality in Saudi Arabia, and preimplantation genetic diagnosis (PGD) has been proposed as a valuable alternative. The acceptability of PGD is unexplored, and may ultimately determine the value of this technology in Saudi Arabia. This study reports attitudes towards PND and PGD of Saudi couples offered genetic counselling following the birth of a child with a single gene or chromosomal condition. Methods Thirty couples attending the King Faisal Specialist Hospital and Research Centre in Riyadh were interviewed using a semi-structured questionnaire. One couple had previous experience of PND and none had experience of PGD or IVF. Results Eight of the 30 couples (27%) would only accept PGD; four (13%) only PND; three (10%) either technology; the remainder would accept neither test, or were unsure. The main concerns of those who would accept neither technology were related to personal religious views. Specific concerns about PGD related to the IVF procedure, the risk of multiple pregnancies, the chance of mistakes and the chance of not getting pregnant. A high proportion of couples (six out of seven; 86%) who had a child with thalassaemia expressed interest in PGD, and all would be prepared to use technology to avoid having an affected child. Views were more mixed for the other conditions. Conclusion PGD is acceptable to many couples and for some, it represents a valuable alternative to PND. However, parents' concerns are complex, and the acceptability of different reproductive technologies must be established on an individual basis. Copyright © 2006 John Wiley & Sons, Ltd. [source]


A comprehensive dictionary of protein accession codes for complete protein accession identifier alias resolving

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2006
Andreas M. Boehm
Abstract In mass spectrometry-based proteomics, protein identification results usually consist of peptide sequences and database-dependent accession identifiers of the matching proteins. Often certain annotations are only available in particular databases that in turn must be queried by a certain identifier. In order to simplify and unify the tracing of identified proteins back to their original annotation information, a system capable of set-oriented mapping the different accession identifiers of proteins derived from multiple sequence database sources has been developed. This allows unification of the access to protein information and tracing to other online resources providing additional information as well as resolving cross-references of protein identifications. The interface of seqDB is available via http://www.protein-ms.de following the link to seqDB. [source]


Visual acuity in the cathemeral strepsirrhine Eulemur macaco flavifrons

AMERICAN JOURNAL OF PRIMATOLOGY, Issue 4 2009
Carrie C. Veilleux
Abstract Studies of visual acuity in primates have shown that diurnal haplorhines have higher acuity (30,75 cycles per degree (c/deg)) than most other mammals. However, relatively little is known about visual acuity in non-haplorhine primates, and published estimates are only available for four strepsirrhine genera (Microcebus, Otolemur, Galago, and Lemur). We present here the first measurements of visual acuity in a cathemeral strepsirrhine species, the blue-eyed black lemur (Eulemur macaco flavifrons). Acuity in two subjects, a 3-year-old male and a 16-year-old female, was assessed behaviorally using a two-alternative forced choice discrimination task. Visual stimuli consisted of high contrast square wave gratings of seven spatial frequencies. Acuity threshold was determined using a 70% correct response criterion. Results indicate a maximum visual acuity of 5.1,c/deg for the female (1718 trials) and 3.8,c/deg for the male (846 trials). These values for E. macaco are slightly lower than those reported for diurnal Lemur catta, and are generally comparable to those reported for nocturnal Microcebus murinus and Otolemur crassicaudatus. To examine ecological sources of variation in primate visual acuity, we also calculated maximum theoretical acuity for Cheirogaleus medius (2.8,c/deg) and Tarsius syrichta (8.9,c/deg) using published data on retinal ganglion cell density and eye morphology. These data suggest that visual acuity in primates may be influenced by activity pattern, diet, and phylogenetic history. In particular, the relatively high acuity of T. syrichta and Galago senegalensis suggests that visual predation may be an important selective factor favoring high visual acuity in primates. Am. J. Primatol. 71:343,352, 2009. © 2009 Wiley-Liss, Inc. [source]


REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra- and Extracellular Regulation

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010
Justine S. Fitzgerald
Citation Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. Governing the invasive trophoblast: current aspects on intra- and extracellular regulation. Am J Reprod Immunol 2010 This review summarizes several aspects especially of regulating factors governing trophoblast invasion. Those include the composition of the extracellular matrix containing a variety of matrix metalloproeinases and their inhibitors, but also intracellular signals. Furthermore, a newly described trophoblast subtype, the endoglandular trophoblast, is presented. Its presence may provide a possible mechanism for opening and connecting uterine glands into the intervillous space. Amongst others, two intracellular signalling pathways are crucial for regulation of trophoblast functions and development: Wnt- and signal transducer and activator of transcription (STAT)3 signalling. Wnt signalling promotes implantation, placentation and trophoblast differentiation. Several Wnt-dependent cascades and regulatory mechanisms display different functions in trophoblast cells. The STAT3 signalling system is fundamental for induction and regulation of invasiveness in physiological trophoblastic cells, but also in tumours. The role of galectins (Gal) in trophoblast regulation and placenta development comes increasingly into focus. The Gal- 1,4, 7,10 and 12,14 have been detected in humans. Detailed information is only available for Gal-1, -2, -3, -4, -9 and -12 in endometrium and decidua. Gal-1, -3 and -13 (-14) have been detected and studied in trophoblast cells. [source]


Structure of nanocrystalline anatase solved and refined from electron powder data

ACTA CRYSTALLOGRAPHICA SECTION A, Issue 4 2002
T. E. Weirich
Energy-filtered Debye,Scherrer electron powder data have been successfully employed to determine the structure of nanocrystalline anatase (TiO2). The performed structure analysis includes determining the unit cell, space group, solving the structure via direct methods from extracted intensities and refining the structure using the Rietveld technique. The refined structural parameters for space group I41amd are a = 3.872,(2), c = 9.616,(5),Å with titanium at 0.5,0.75,0.375 and oxygen at 0.5,0.75,0.1618,(6). The obtained structure indicates low internal stress as judged from the almost regular geometry of the TiO6 building blocks. Striking resemblance with the anatase structure determined previously by Burdett, Hughbanks, Miller, Richardson & Smith [J. Am. Chem. Soc. (1987). 109, 3639,3646] from neutron diffraction on coarse-grained material gives strong support for the correctness of the structure determined here. The result of the present study shows that the methods originally developed for determining structures from X-ray powder data work equally well with data from electron powder diffraction. This may open the window for structural investigations on the vast number of nanocrystalline materials and thin films whose structures are difficult to determine by X-ray diffraction since they are frequently only available in small quantities. [source]


Regression Analysis with a Misclassified Covariate from a Current Status Observation Scheme

BIOMETRICS, Issue 2 2010
Leilei Zeng
Summary Naive use of misclassified covariates leads to inconsistent estimators of covariate effects in regression models. A variety of methods have been proposed to address this problem including likelihood, pseudo-likelihood, estimating equation methods, and Bayesian methods, with all of these methods typically requiring either internal or external validation samples or replication studies. We consider a problem arising from a series of orthopedic studies in which interest lies in examining the effect of a short-term serological response and other covariates on the risk of developing a longer term thrombotic condition called deep vein thrombosis. The serological response is an indicator of whether the patient developed antibodies following exposure to an antithrombotic drug, but the seroconversion status of patients is only available at the time of a blood sample taken upon the discharge from hospital. The seroconversion time is therefore subject to a current status observation scheme, or Case I interval censoring, and subjects tested before seroconversion are misclassified as nonseroconverters. We develop a likelihood-based approach for fitting regression models that accounts for misclassification of the seroconversion status due to early testing using parametric and nonparametric estimates of the seroconversion time distribution. The method is shown to reduce the bias resulting from naive analyses in simulation studies and an application to the data from the orthopedic studies provides further illustration. [source]


Improvement of the quality of lumazine synthase crystals by protein engineering

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2008
Lidia Rodríguez-Fernández
Icosahedral macromolecules have a wide spectrum of potential nanotechnological applications, the success of which relies on the level of accuracy at which the molecular structure is known. Lumazine synthase from Bacillus subtilis forms a 150,Å icosahedral capsid consisting of 60 subunits and crystallizes in space group P6322 or C2. However, the quality of these crystals is poor and structural information is only available at 2.4,Å resolution. As classical strategies for growing better diffracting crystals have so far failed, protein engineering has been employed in order to improve the overexpression and purification of the molecule as well as to obtain new crystal forms. Two cysteines were replaced to bypass misfolding problems and a charged surface residue was replaced to force different molecular packings. The mutant protein crystallizes in space group R3, with unit-cell parameters a = b = 313.02, c = 365.77,Å, , = , = 90.0, , = 120°, and diffracts to 1.6,Å resolution. [source]


Clinical and Histological Aspects of CNV Formation: Studies in an Animal Model

ACTA OPHTHALMOLOGICA, Issue thesis2 2008
Nathan Lassota MD
Abstract. The purpose of the present thesis was to develop an animal model of CNV in order to study the early formation of CNV and to test the effects of an anti-angiogenic treatment. Porcine eyes were chosen as a substrate for CNV induction, since they are similar to human eyes in terms of both macroscopic and microscopic morphology. However, a major difference is that pigs lack a fovea; instead they have a visual streak, with a relatively stable and high concentration of cones. By surgical perforation of Bruch's membrane we were able to induce formation of CNV membranes. The morphology and cellular composition of these membranes varied with the surgical technique employed. When RPE cells were locally removed at the time of perforation, the resulting CNV was thinner, contained fewer blood vessels and was less prone to leak on fluorescein angiography than when RPE cells were left intact at induction. The neuroretina overlying the perforation site was not damaged by any of the surgical techniques, thus allowing the subsequent retinal damage to be ascribed to the actual process of CNV formation. Using this animal model allowed us to directly map histological findings onto fluorescein angiograms and thereby perform meaningful correlations between histopathologic and photographic features. Such correlations have been hampered in human subjects, since human eyes are not enucleated as a consequence of CNV and are therefore only available for post-mortem studies. In such studies there often is a considerable time-gap between the death of the patient and the latest available fluorescein angiogram, thereby allowing macular pathology to evolve in the interim. Histological examination of the porcine membranes demonstrated that they were composed of RPE cells, glial cells, macrophages, endothelial cells, collagen and smooth muscle fibres, which are the same cellular and fibrillar elements that dominate human CNV membranes. The porcine model was applied to test the effects, in a randomized and masked fashion, of intravitreally injected bevacizumab. Bevacizumab, a pan VEGF A antibody, was found to reduce both the proliferation of endothelial cells in CNV membranes and the propensity to leak in fluorescein angiograms. Immunohistochemically, bevacizumab was detected in the inner limiting membrane, in retinal blood vessels and binding uniformly to the entire CNV membrane without any cellular predisposition. Based on the above findings we believe that the porcine CNV model shows a bearing to human disease and therefore might be used as a tool to obtain improved treatments for this debilitating condition. [source]


Management of severe adult atopic dermatitis

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2002
Nicholas Reynolds
In common with many units, we run a specialist atopic eczema clinic that receives both secondary and tertiary referrals. Investigation into possible provoking factors includes RAST testing and patch testing where appropriate. The mainstay of treatment for moderate to severe atopic eczema remains topical steroids and emollients. Our specialist nurses play a key role in education and in particular demonstrating topical treatments , including bandaging. It is surprising that many patients have not previously been shown how to apply the treatments prescribed. Nevertheless, despite optimizing topical treatment protocols, a proportion of patients require hospital admission or second-line therapy. Our recent double-blind, randomized, controlled trial of narrow-band UVII vs. UVA (as used in PUVA) vs. placebo has confirmed that narrow-band WB phototherapy is an effective adjunctive treatment in moderate to severe atopic eczema. This trial also highlighted the value of recording disease activity (e.g. SASSAD) in individual patients following a change of therapy. UVA1 may be useful for acute severe atopic eczema but this UV source is only available in limited centres within the UK. Selected resistant patients or patients with acute flares are considered for short-term cyclosporin therapy. Azathioprine is widely used by consultant dermatologists in the UK as a second-line agent , despite the lack of evidence of efficacy. We are currently conducting a randomized placebo-controlled trial to address this issue. The importance of checking thiopurine methyl transferase (TPMT) prior to initiating azathioprine therapy has been emphasized. Our pilot data, with a dosage regime based on the TPMT result, suggest that patients may achieve a longer-term remission after a relatively short course. Mycophenolate mofetil has been reported to be effective in an open trial and methotrexate is also used but there is a lack of published evidence. The advent of topical tacrolimus and ascomycins, which have been shown to be effective in controlled trials, appear to be a promising development in the management of patients with moderate to severe atopic eczema and may lead to reduction in the use of systemic agents. [source]