bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic analyses ofPseudomonas aeruginosaisolated from healthy captive snakes: evidence of high inter‐ and intrasite dissemination and occurrence of antibiotic resistance genes
Authors: Colinon Céline , Jocktane Dominique , Brothier Elisabeth , Rossolini Gian Maria , Cournoyer Benoit , Nazaret Sylvie
Published: November 2009

Faecal carriage ofPseudomonas aeruginosawas investigated by selective plating and PCR identification test, among healthy captive snakes from zoological and private collections from France as well as from wild snakes from Guinea.P. aeruginosafaecal carriage among captive snakes was high (72 out of 83 individuals), but low among wild specimen (3 out of 23 individuals). Genetic diversity analyses of the isolates, based on SpeI‐PFGE profiles, evidenced five dominant clones or clonal complexes spreading among snakes within a site and between sites and persisting over time. Similar clones or clonal complexes were detected from mouth swabs of the owners and from water and preys used to feed the snakes, evidencing various sources of snake colonization and the first cases ofP. aeruginosacross‐contamination between snakes and owners. These observations led to the conclusion thatP. aeruginosabehaves as an opportunistic species within snakes in captivity and that colonization and dissemination occurs consecutively to processes similar to those identified within the hospital. Antibiotic susceptibility testing showed that most isolates had a wild‐type resistance profile except for one persistent clone isolated from both snakes and preys that harboured multiple antimicrobial resistance genes mediated by an integron carrying theqacH,aadB,aadA2 andcmlA10cassettes, and atetA(C)‐carrying transposon. Biocides or antibiotics used in the zoological garden could have led to the acquisition of this integron.
Understanding the inter‐relationship between improved glycaemic control, hypoglycaemia and weight change within a long‐term economic model
Authors: McEwan P. , Evans M. , Kan H. , Bergenheim K.
Published: November 2009

Background: Current guidelines for the management of type 2 diabetes advocate the attainment of sustained near normal glycaemia levels. Metformin is widely accepted as the treatment of choice for the initiation of pharmacotherapy; however, secondary failure of oral monotherapy occurs in 60% of patients resulting in the need for multiple pharmacotherapies. Therapy‐related consequences of treatment, such as weight gain and hypoglycaemia impact on the cost‐effectiveness profile of various agents. We therefore sought to ascertain the respective contribution of hypoglycaemia, weight change and improved blood glucose control on second‐line therapy options added to metformin.

Methods: This study uses a simulation model designed to evaluate the cost utility of new therapies in a population of patients with type 2 diabetes mellitus. Standard model outputs include incidence of micro‐ and macrovascular complications and diabetes‐specific and all‐cause mortality.

Results: The mean discounted quality‐adjusted life year (QALY) predicted by the model was 12.31 years. Reducing Glycosylated haemoglobin (HbA1c) by 1% gave a predicted gain of 0.413 QALYs per patient. A 3‐kg weight loss and 30% reduction in hypoglycaemia frequency produced a combined QALY gain of 0.355, whereas the reverse gave a QALY decrement of 0.356.

Conclusions: The results of this analysis quantify the QALY decrement that may result from adverse therapy effects. The beneficial effects of improved glycaemic control on QALYs may be offset by characteristic treatment‐specific adverse effects, such as weight gain and hypoglycaemia frequency.
Selective glucocorticoid receptor (type II) antagonist prevents and reverses olanzapine‐induced weight gain
Authors: Belanoff J. K. , Blasey C. M. , Clark R. D. , Roe R. L.
Published: November 2009

Use of antipsychotic medications has been associated consistently with weight gain and metabolic disturbances, and a subsequent increased risk for diabetes and cardiovascular disease. Two experiments tested whether CORT 108297, a newly identified selective glucocorticoid antagonist could (i) reduce and (ii) prevent olanzapine‐induced weight gain in rats. In the first experiment, rats dosed only with olanzapine gained a statistically significant amount of weight. When vehicle was added to their olanzapine dose, they continued to gain weight; when CORT 108297 was added to their regimen, they lost a significant amount of weight. Rats administered CORT 108297 plus olanzapine had significantly less abdominal fat than those who received olanzapine alone. In the second experiment, rats receiving olanzapine plus CORT 108297 gained significantly less weight than rats receiving only olanzapine. Increasing doses of CORT 108297 were associated with less weight gain.
Increased all‐cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene
Authors: Steele A. M. , Shields B. M. , Shepherd M. , Ellard S. , Hattersley A. T. , Pearson E. R.
Published: November 2009

Diabet. Med. 27, 157–161 (2010)

Aims  To investigate all‐cause and cardiovascular mortality in subjects with diabetes caused by a mutation in the hepatocyte nuclear factor 1α gene (HNF1A).

Methods  We identified 39 British families with HNF1A mutations. Consenting individuals were asked details of age and cause of death of parents and siblings. Copies of death certificates were requested from the family or were obtained via the Offices for National Statistics.

Results  Data were collated on 241 control subjects and 153 mutation carriers. Of those who died, 66% of mutation carriers died from a cardiovascular‐related illness compared with 43% of control subjects (P = 0.02). Family members with HNF1A mutations died at a younger age than familial control subjects [all‐cause hazard ratio, adjusting for sex and smoking status: 1.9 (95% confidence interval 1.2, 2.9, P = 0.006; cardiovascular hazard ratio: 2.3, confidence interval 1.3, 4.2, P = 0.006)].

Conclusions  We have shown that individuals known to have diabetes caused by a mutation in the HNF1A gene have an increased risk of cardiovascular mortality compared with their unaffected family members. As with other forms of diabetes, consideration should be given to early statin therapy despite a seemingly protective lipid profile.
Lower‐limb risk factors for falls in people with diabetes mellitus
Authors: MacGilchrist C. , Paul L. , Ellis B. M. , Howe T. E. , Kennon B. , Godwin J.
Published: November 2009

Diabet. Med. 27, 162–168 (2010)

Background  Older people with diabetes mellitus (DM) may be at high risk of falling because of general risk factors for falls as well as disease‐specific factors.

Aims  To determine the prevalence of falls and to investigate lower‐limb factors for falls in older people with DM.

Methods  Sixty patients with DM over 55 years of age were recruited. ‘Fallers’ were those who self‐reported at least one fall in the previous year. In addition to diabetes status and demographic information, the following were assessed: neuropathy symptom score (NSS), neuropathy disability score (NDS), foot deformity score (FDS), Tinetti performance‐oriented assessment of mobility (POMA), ankle muscle strength and gait parameters. Data from ‘fallers’ and ‘non‐fallers’ were compared and logistic regression analysis performed to identify variables predictive of falls.

Results  Thirty‐five per cent (n = 21) of participants had fallen in the preceding year. Compared with ‘non‐fallers’, there was a greater incidence of peripheral neuropathy among ‘fallers’ (86% of ‘fallers’ and 56% of ‘non‐fallers’), higher vibration perception threshold (P = 0.04), slower gait velocity (P < 0.001), lower muscle strength for dorsiflexion, plantarflexion, inversion and eversion (all P < 0.001) and higher incidence of bony prominences and prominent metatarsal heads (both P < 0.001). There was a strong and significant correlation between dorsiflexion muscle strength and gait velocity. Logistic regression analysis determined that walking velocity, strength of ankle dorsiflexors and NSS accurately predicted 75% of ‘fallers’.

Conclusions  Simple clinical measures of gait velocity and ankle muscle strength may be used to identify people with DM at risk of falling, allowing preventative strategies to be implemented.
Effect of targeting normal fasting glucose levels with basal insulin glargine on glycaemic variability and risk of hypoglycaemia: a randomized, controlled study in patients with early Type 2 diabetes
Authors: Hanefeld M. , Koehler C. , Hoffmann C. , Wilhelm K. , Kamke W. , Gerstein H.
Published: November 2009

Diabet. Med. 27, 175–180 (2010)

Aims  The purpose of this sub‐study of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial was to determine efficacy and safety of targeting normal fasting plasma glucose (FPG) levels in patients with early Type 2 diabetes treated with insulin glargine in comparison with standard care.

Methods  Participants were randomly allocated to insulin or standard care. Insulin was titrated to reach FPG ≤ 5.3 mmol/l. Two years after randomization in a small subset (43 glargine, 32 standard care), continuous glucose measurement (CGMS® System Gold™), including a test meal, was performed. Sixteen volunteers with normal oral glucose tolerance test (OGTT) served as control subjects. Objectives were glycaemic variability, standard deviation (sd), mean amplitude of glucose excursion (MAGE) with postprandial glucose excursion after the test meal, time spent < 3.0 mmol/l interstitial glucose.

Results  Participants allocated to insulin and standard care had FPG levels of 5.3 and 6.1 mmol/l (P = 0.019) and glycated haemoglobin (HbA1c) 5.7% and 5.9%, respectively (P < 0.025). Time (min/24 h) spent at low glucose levels was not significantly different between groups (30.6 ± 83.8 min control subjects, 33.7 ± 75.1 min insulin, 10.6 ± 50.6 min standard care). Standard deviation and MAGE were similar for glargine and standard care, but significantly higher than in control subjects. If FPG was < 5.3 mmol/l, the postprandial glucose excursion was in the range seen in control subjects.

Conclusions  Treatment to target of FPG < 5.3 mmol/l with insulin glargine was not associated with significantly increased risk of hypoglycaemia. Strict control of FPG with insulin glargine was effective to control postprandial glucose excursion, but had no significant effect on sd and MAGE.
Polymorphisms of the macrophage migration inhibitory factor gene in a UK population with Type 1 diabetes mellitus
Authors: Martin R. J. L. , Savage D. A. , Carson D. J. , McKnight A. J. , Maxwell A. P. , Patterson C. C.
Published: November 2009

Diabet. Med. 27, 143–149 (2010)

Aims  Macrophage migration inhibitory factor (MIF) is a potent pro‐inflammatory cytokine whose production is transcriptionally regulated by glucose. Experimental data from both Type 1 diabetes mellitus (T1D) patients and animal models suggests a role for MIF in the development of T1D. The aim of this study was to employ gene resequencing to identify common DNA polymorphisms in the MIF gene and subsequently assess haplotype tagged single nucleotide polymorphisms (htSNPs) using a combination of case–control and family‐based association analyses in order to assess the association of MIF htSNPs with the development of T1D in a white population.

Methods  All exons, introns and approximately 3 kb upstream and downstream of the MIF gene were screened for DNA polymorphisms in 46 individuals using DNA sequencing. Genotyping of the htSNPs was performed in 432 cases, 407 control subjects and 290 T1D parent–offspring trios, using Taqman, Sequenom, Pyrosequencing and fluorescence‐based microsatellite technologies.

Results  Twenty‐three polymorphisms (two novel) with a minor allele frequency > 10% were identified. Four MIF htSNPs (rs875643 G>A, rs7388067 C>T, rs5844572 −/CATT, rs6003941 T>G) were identified. Allele and haplotype frequencies were similar between case and control groups (P > 0.6 by permutation test) and assessment of allele transmission distortion from informative parents to affected offspring also failed to find an association. Stratification of these analyses for age‐at‐onset and human leukocyte antigen (HLA)‐DR risk group (DR3/DR4) did not reveal any significant associations.

Conclusions  It is unlikely that common polymorphisms in the MIF gene strongly influence susceptibility to T1D in the UK population.
A method of identifying and correcting miscoding, misclassification and misdiagnosis in diabetes: a pilot and validation study of routinely collected data
Authors: De Lusignan S. , Khunti K. , Belsey J. , Hattersley A. , Van Vlymen J. , Gallagher H. , Millett C. , Hague N. J. , Tomson C. , Harris K. , Majeed A.
Published: November 2009

Diabet. Med. 27, 203–209 (2010)

Aims  Incorrect classification, diagnosis and coding of the type of diabetes may have implications for patient management and limit our ability to measure quality. The aim of the study was to measure the accuracy of diabetes diagnostic data and explore the scope for identifying errors.

Method  We used two sets of anonymized routinely collected computer data: the pilot used Cutting out Needless Deaths Using Information Technology (CONDUIT) study data (n = 221 958), which we then validated using 100 practices from the Quality Improvement in Chronic Kidney Disease (QICKD) study (n = 760 588). We searched for contradictory diagnostic codes and also compatibility with prescription, demographic and laboratory test data. We classified errors as: misclassified—incorrect type of diabetes; misdiagnosed—where there was no evidence of diabetes; or miscoded—cases where it was difficult to infer the type of diabetes.

Results  The standardized prevalence of diabetes was 5.0 and 4.0% in the CONDUIT and the QICKD data, respectively: 13.1% (n = 930) of CONDUIT and 14.8% (n = 4363) QICKD are incorrectly coded; 10.3% (n = 96) in CONDUIT and 26.2% (n = 1143) in QICKD are misclassified; nearly all of these cases are people classified with Type 1 diabetes who should be classified as Type 2. Approximately 5% of T2DM in both samples have no objective evidence to support a diagnosis of diabetes. Miscoding was present in approximately 7.8% of the CONDUIT and 6.1% of QICKD diabetes records.

Conclusions  The prevalence of miscoding, misclassification and misdiagnosis of diabetes is high and there is substantial scope for further improvement in diagnosis and data quality. Algorithms which identify likely misdiagnosis, misclassification and miscoding could be used to flag cases for review.
An Analysis of Thai Financial Reporting Practices and the Impact of the 1997 Economic Crisis
Authors: SUTTHACHAI SIRILUCK , COOKE TERENCE E.
Published: November 2009

We focus on listed Thai companies between 1993 and 2002 to ascertain whether the 1997 economic crisis, which we refer to as an economic disturbance, had an impact on financial reporting practices. Both changes in measurement and disclosure practices are considered and the period of study is divided into three sub‐periods: the pre‐economic crisis period (1993–96), the economic crisis period (1996–98) and the post‐economic crisis period (1998–2002). The results show that there were significant increases in disclosure levels over the ten years but no substantial changes in measurement methods. This work takes on added relevance in the light of the recent (2007–08) economic bubble and subsequent financial crisis worldwide.
Aligning Performance Measurement Systems With Strategy: The Case of Environmental Strategy
Authors: PEREGO PAOLO , HARTMANN FRANK
Published: November 2009

Alignment of an organization's performance measurement system with its strategy is widely advocated as a guiding principle in management control system design. Despite its importance, it is far from clear what strategic alignment of performance measures entails, whether and how organizations achieve it. In this article we explore the alignment of performance measures focusing on firms' use of environmental performance indicators as the consequence of pursuing an environmental strategy. Based on the economic and contingency literatures on management control system design and performance measurement, we propose that the use of such performance measures is a consequence of changing the design of the performance measurement system to accommodate the strategy, and by increasing the informativeness of performance metrics. We test these propositions in a sample of financial managers in manufacturing firms in The Netherlands. We find that alignment to environmental strategy is mostly achieved through the increased quantification of environmental performance measures and via their increased sensitivity to managerial actions.
Incentives for Non‐Disclosure by Corporate Groups
Authors: BRADBURY MICHAEL , DEAN GRAEME , CLARKE FRANK L.
Published: November 2009

A regulatory approved deed of cross guarantee (the deed) was introduced into Australia in December 1991, relieving participating companies within a group from having to prepare, have audited, and file financial statements. We examine the characteristics of firms that obtain relief from filing (and therefore disclosing) separate financial statements of closed‐group companies by adopting the deed. This is the first attempt to analyse adoption using large‐scale archival data. The results support the survey evidence in Dean and Clarke (2005), thus providing triangulation on their work. In particular they support the view that the decision to adopt the deed is a function of strategic factors as well as accounting and auditing cost savings. Those strategic factors were not in focus when regulators first introduced a deed of indemnity in 1985, nor when the original indemnity was modified to become a deed of cross guarantee in 1991 or when it was further modified in 1998. Further, evidence is provided to test the conflicting ideas arising from the analytical literature and the mixed results in the empirical, voluntary disclosure literatures. That evidence suggests that non‐disclosure arises when firms are in a more competitive industry and, in particular, when there is ability to retain non‐disclosure at the consolidated level (i.e., where the number of segments is high). Other factors supporting non‐disclosure are leverage and the proportion of foreign operations (proxying for deed complexity). The proportion of outside directors (a proxy for legal liability) and the number of shares outstanding (a proxy for agency costs of equity) are not associated with the decision to adopt the deed.
Relevance of Academic Research and Researchers' Role in the IASB's Financial Reporting Standard Setting
Authors: FÜLBIER ROLF UWE , HITZ JOERG‐MARKUS , SELLHORN THORSTEN
Published: November 2009

The International Accounting Standards Board (IASB) faces a vast number of standard‐setting issues at all levels of financial reporting. The purpose of this article is to explore the relevance of academic research for financial reporting standard setting and the role of academic researchers in the standard‐setting process. We contribute to the current debate surrounding International Financial Reporting Standards (IFRS) by drawing inferences from prior findings regarding the role of research in the IASB's standard‐setting efforts. After defining three broad categories of standard‐setting questions, we explore how the international heterogeneity of its constituency imposes constraints on the IASB's work. Then, whether and how academic research can inform policy makers is investigated from an epistemological perspective. Based on a review of extant literature, the general criteria which a piece of research should fulfil in order to be perceived as relevant and useful by standard setters are discussed. This discussion is followed by more detailed considerations regarding the suitability of different research approaches for each of the three categories of standard‐setting questions. We also touch on the subject of inferential problems inherent in most academic accounting research. Since the main objective is to contribute insights relevant to the IASB's efforts, we analyse academics' career systems and their incentives to engage in research intermediation, before discussing possible ways in which interested researchers can channel their insights into the IASB's standard‐setting process. Overall, the international dimension of IASB standard setting and its implications for relevant research are emphasized.
3‐D visualization and animation technologies in anatomical imaging
Authors: McGhee John
Published: November 2009

This paper explores a 3‐D computer artist’s approach to the creation of three‐dimensional computer‐generated imagery (CGI) derived from clinical scan data. Interpretation of scientific imagery, such as magnetic resonance imaging (MRI), is restricted to the eye of the trained medical practitioner in a clinical or scientific context. In the research work described here, MRI data are visualized and interpreted by a 3‐D computer artist using the tools of the digital animator to navigate image complexity and widen interaction. In this process, the artefact moves across disciplines; it is no longer tethered to its diagnostic origins. It becomes an object that has visual attributes such as light, texture and composition, and a visual aesthetic of its own. The introduction of these visual attributes provides a platform for improved accessibility by a lay audience. The paper argues that this more artisan approach to clinical data visualization has a potential real‐world application as a communicative tool for clinicians and patients during consultation.
Anatomical models and wax Venuses: art masterpieces or scientific craft works?
Authors: Ballestriero R.
Published: November 2009

The art of wax modelling has an ancient origin but rose to prominence in 14th century Italy with the cult of votive artefacts. With the advent of Neoclassicism this art, now deemed repulsive, continued to survive in a scientific environment, where it flourished in the study of normal and pathological anatomy, obstetrics, zoology and botany. The achievement of having originated the creation of anatomical models in coloured wax must be ascribed to a joint effort undertaken by the Sicilian wax modeller Gaetano Giulio Zumbo and the French surgeon Guillaume Desnoues in the late 17th century. Interest in anatomical wax models spread throughout Europe during the 18th century, first in Bologna with Ercole Lelli, Giovanni Manzolini and Anna Morandi, and then in Florence with Felice Fontana and Clemente Susini. In England, the art of anatomical ceroplastics was brought to London from Florence by the sculptor Joseph Towne. Throughout the centuries many anatomical artists preferred this material due to the remarkable mimetic likeness obtained, far surpassing any other material. Independent of the material used, whether wood, wax or clay, anatomical models were always considered merely craft works confined to hospitals or faculties of medicine and have survived to this day only because of their scientific interest. Italian and English waxes are stylistically different but the remarkable results obtained by Susini and Towne, and the fact that some contemporary artists are again representing anatomical wax bodies in their works, makes the border that formerly separated art and craft indistinguishable.
Semicircular canals and agility: the influence of size and shape measures
Authors: Cox Philip G. , Jeffery Nathan
Published: November 2009

The semicircular canals of the inner ear sense angular accelerations and decelerations of the head and enable co‐ordination of posture and body movement, as well as visual stability. Differences of agility and spatial sensitivity among species have been linked to interspecific differences in the relative size of the canals, particularly the radius of curvature (R) and the ratio of the canal plane area to streamline length (P/L). Here we investigate the scaling relationships of these two size variables and also out‐of‐plane torsion in the three semicircular canals (anterior, posterior and lateral), in order to assess which is more closely correlated with body size and locomotor agility. Measurements were computed from 3D landmarks taken from magnetic resonance images of a diverse sample of placental mammals encompassing 16 eutherian orders. Body masses were collected from the literature and an agility score was assigned to each species. The R and P/L of all three semicircular canals were found to have highly significant positive correlations with each other and no statistical difference was found between the slope of 2P/L against R and 1. This indicated that, contrary to initial hypotheses, there is little difference between 2P/L and R as measures of semicircular canal size. A measure of the in‐plane circularity of the canal was obtained by dividing 2P/L by R and out‐of‐plane torsion was measured as angular deviation from a plane of best fit. It was predicted that deviations from in‐plane and out‐of‐plane circularity would increase at small body size due to the constraints of fitting a proportionately larger canal into a smaller petrous bone. However, neither measurement was found to have a significant correlation with body mass, indicating that deviations from circularity (both in‐plane and out‐of‐plane) are not sufficient to alter P/L to an extent that would impact the sensitivity of the canals. 2P/L and R were both shown to be significantly correlated with locomotor agility. The posterior canal was the least correlated with agility, suggesting that it may be generally less closely aligned to the direction of movement than the anterior canal. Of the three canals, the lateral canal was the most highly correlated with agility. In particular, it could be used to distinguish between species that move in a largely 2D environment and those that locomote in 3D space (aerial, arboreal and aquatic species). This complements previous work suggesting that the lateral canal primarily commands navigation, whereas the vertical canals control reflex adjustments. It was also found that 2P/L is substantially better correlated with agility than is R in the lateral canal. This result is intriguing given the above finding that there is no statistical difference between 2P/L and R, and requires further investigation.
Visuospatial attention disturbance in Duchenne muscular dystrophy
Authors: DE MOURA MARIA CLARA DRUMMOND SOARES , VALLE LUIZ EDUARDO RIBEIRO DO , RESENDE MARIA BERNADETE DUTRA , REED UMBERTINA CONTI , PINTO KATIA OSTERNACK
Published: November 2009

Aim  The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to investigate attentional function in individuals with DMD.

Method  Twenty‐five males (mean age 12y; SD 2y 2mo) with DMD and 25 healthy males (mean age 12y; SD 2y) were tested in a visuospatial task (Posner computerized test). They were instructed to respond as quickly as possible to a lateralized visual target stimulus with the ipsilateral hand. Their attention was automatically orientated by a peripheral prime stimulus or, alternatively, voluntarily orientated by a central spatially informative cue.

Results  The main result obtained was that the attentional effect (sum of the benefit and the cost of attention) did not differ between the two groups in the case of automatic attention (p=0.846) but was much larger for individuals with DMD than for comparison individuals in the case of voluntary attention (p<0.001).

Interpretation  The large voluntary attentional effect exhibited by the participants with DMD seems similar to that of younger children, suggesting that the disease is associated with delayed maturation of voluntary attention mechanisms.
AAV‐mediated chronic over‐expression of SNAP‐25 in adult rat dorsal hippocampus impairs memory‐associated synaptic plasticity
Authors: McKee Alex G. , Loscher Jennifer S. , O’Sullivan Niamh C. , Chadderton Naomi , Palfi Arpad , Batti Laura , Sheridan Graham K. , O’Shea Sean , Moran Mary , McCabe Olive , Fernández Alfonso Blanco , Pangalos Menelas N. , O’Connor John J. , Regan Ciaran M. , O’Connor William T. , Humphries Peter , Farrar G. Jane , Murphy Keith J.
Published: November 2009

J. Neurochem. (2009) 112, 991–1004.

Long‐term memory is formed by alterations in glutamate‐dependent excitatory synaptic transmission, which is in turn regulated by synaptosomal protein of 25 kDa (SNAP‐25), a key component of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor complex essential for exocytosis of neurotransmitter‐filled synaptic vesicles. Both reduced and excessive SNAP‐25 activity has been implicated in various disease states that involve cognitive dysfunctions such as attention deficit hyperactivity disorder, schizophrenia and Alzheimer’s disease. Here, we over‐express SNAP‐25 in the adult rat dorsal hippocampus by infusion of a recombinant adenoassociated virus vector, to evaluate the consequence of late adolescent‐adult dysfunction of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor protein in the absence of developmental disruption. We report a specific and significant increase in the levels of extracellular glutamate detectable by microdialysis and a reduction in paired‐pulse facilitation in the hippocampus. In addition, SNAP‐25 over‐expression produced cognitive deficits, delaying acquisition of a spatial map in the water maze and impairing contextual fear conditioning, both tasks known to be dorsal hippocampal dependent. The high background transmission state and pre‐synaptic dysfunction likely result in interference with requisite synapse selection during spatial and fear memory consolidation. Together these studies provide the first evidence that excess SNAP‐25 activity, restricted to the adult period, is sufficient to mediate significant deficits in the memory formation process.
Macroecological patterns of species and genetic diversity in vascular plants of the Mediterranean basin
Authors: Fady Bruno , Conord Cyrille
Published: November 2009

Aim  We address the question of whether broad scale biogeographical structure of species diversity (SD) matches that of genetic diversity (GD) of vascular plants.

Location  The Mediterranean basin.

Methods  We normalized vascular plant species richness (SD) estimates per country using the Med‐Checklist taxonomic database. We used a linear regression analysis to correlate normalized country estimates with country longitudinal position. We also compiled published and geo‐referenced within‐population GD data for tree species, which had populations in the Mediterranean. We normalized GD estimates for each population across species. Again, we used a linear regression analysis to correlate GD with population longitudinal position. We then compared the populations’ geographical and bioclimatic trends for GD with Last Glacial Maximum (LGM) palaeo‐climate data and the species current ecological requirements.

Results  The eastern Mediterranean and the coast of former Yugoslavia had higher SD than other regions. There was no overall spatial structure of SD in the Mediterranean, whereas there was an east–west trend of decreasing GD. This trend for GD tended to covary with an east–west warm/wet–cold/dry trend detected during the LGM. Low elevation xerothermic pine species displayed significantly less GD than higher elevation mesothermic or mountain pine species.

Main conclusions  We suggest that LGM climate may have significantly shaped the current longitudinal and altitudinal patterns of GD we observed in woody taxa across the Mediterranean, although it did not affect comparable SD patterns. In particular, colder LGM summer temperatures in the western Mediterranean may have reduced population sizes significantly more than in the eastern Mediterranean. As plant species richness and GD did not covary, SD and GD may not be used as surrogates of one another in the Mediterranean basin. As they contain comparatively less GD, conservation priorities in the Mediterranean should focus on hot spots of endemism and Western Mediterranean populations and species.
Role of outer‐membrane cytochromes MtrC and OmcA in the biomineralization of ferrihydrite by Shewanella oneidensis MR‐1
Authors: REARDON C. L. , DOHNALKOVA A. C. , NACHIMUTHU P. , KENNEDY D. W. , SAFFARINI D. A. , AREY B. W. , SHI L. , WANG Z. , MOORE D. , MCLEAN J. S. , MOYLES D. , MARSHALL M. J. , ZACHARA J. M. , FREDRICKSON J. K. , BELIAEV A. S.
Published: November 2009

In an effort to improve the understanding of electron transfer mechanisms at the microbe–mineral interface, Shewanella oneidensis MR‐1 mutants with in‐frame deletions of outer‐membrane cytochromes (OMCs), MtrC and OmcA, were characterized for the ability to reduce ferrihydrite (FH) using a suite of microscopic, spectroscopic, and biochemical techniques. Analysis of purified recombinant proteins demonstrated that both cytochromes undergo rapid electron exchange with FH in vitro with MtrC displaying faster transfer rates than OmcA. Immunomicroscopy with cytochrome‐specific antibodies revealed that MtrC co‐localizes with iron solids on the cell surface while OmcA exhibits a more diffuse distribution over the cell surface. After 3‐day incubation of MR‐1 with FH, pronounced reductive transformation mineral products were visible by electron microscopy. Upon further incubation, the predominant phases identified were ferrous phosphates including vivianite [Fe3(PO4)2·8H2O] and a switzerite‐like phase [Mn3,Fe3(PO4)2·7H2O] that were heavily colonized by MR‐1 cells with surface‐exposed outer‐membrane cytochromes. In the absence of both MtrC and OmcA, the cells ability to reduce FH was significantly hindered and no mineral transformation products were detected. Collectively, these results highlight the importance of the outer‐membrane cytochromes in the reductive transformation of FH and support a role for direct electron transfer from the OMCs at the cell surface to the mineral.
Functioning of Older, Long‐Term Cancer Survivors: The Role of Cancer and Comorbidities
Authors: Deimling Gary T. , Arendt Jacquelyn A. , Kypriotakis George , Bowman Karen F.
Published: December 2009

OBJECTIVES: To examine the relative effect of comorbidities, noncancer symptoms, and cancer‐related factors on the functioning of older adult long‐term survivors of breast, colorectal, and prostate cancers.

DESIGN: Data from in‐person interviews with survivors of a tumor registry–based stratified random sample were used to test a multivariate model using ordinary least‐squares regression.

SETTING: Survivors were identified in the tumor registry of a National Cancer Institute–designated Comprehensive Cancer Center in Cleveland, Ohio.

PARTICIPANTS: Three hundred twenty‐one older (≥60), long‐term (≥5 years) cancer survivors.

MEASUREMENTS: The primary outcome measure, functional difficulty, was measured using Nagi's Performance Limitations Index. Predictors included a number of indicators of survivors' personal characteristics, age‐related health characteristics, and cancer‐related characteristics.

RESULTS: The model explained 44% of the variance in functional difficulties between the cancer survivors in this sample. The strongest predictors were symptoms not attributed to cancer (β=0.28) and comorbidities (β=0.22), although cancer‐related factors explained an additional 8% of the variance over that explained by demographic and noncancer health factors, with current cancer‐related symptoms being a significant predictor (β=0.14).

CONCLUSION: These findings indicate the importance of monitoring cancer‐related characteristics along with comorbidities and noncancer symptoms in long‐term survivors because they jointly affect overall physical functioning. Special attention needs to be given to women and minority cancer survivors as well.
The treatment of bleeding is to stop the bleeding! Treatment of trauma‐related hemorrhage
Authors: Boffard Kenneth D. , Choong Philip Iau Tsau , Kluger Yoram , Riou Bruno , Rizoli Sandro B. , Rossaint Rolf , Warren Brian
Published: December 2009

BACKGROUND: The secret with any alternative to transfusion is to minimize the need for transfusion in the first place. This can be done by reducing the volume of blood loss. The volume of blood being lost can be reduced by direct methods where possible (i.e., hemostasis at the point of bleeding), or by improving the coagulation profile of the patient, thereby improving the extrinsic coagulation. Recombinant activated factor VII (rFVIIa) offers theoretical possibilities of improving the coagulation profile.

STUDY DESIGN AND METHODS: The efficacy and safety of rFVIIa for the treatment of bleeding in patients with severe blunt and penetrating trauma has been investigated in two double‐blind, placebo‐controlled studies within a single trial—one on patients with blunt injury and the other in similar patients with penetrating injury.

RESULTS: In patients with blunt trauma alive at 48 hours, treatment with rFVIIa effected a significant reduction in the primary endpoint of 48‐hour red blood cell (RBC) transfusion requirement (p = 0.02), and the safety of the dosing regimen was established. Similar trends were observed in patients with penetrating injuries. Across both studies and treatment arms, the 48‐hour mortality rate ranged from 16 to 19 percent. In the blunt trauma study, this equated to 13 patients from each arm who died before the benefits of treatment could be adequately assessed. Analysis of data for the 117 blunt trauma patients who survived at least 48 hours after receiving study treatment shows that, in addition to reducing RBC requirement, rFVIIa significantly reduced the need for massive transfusion over 48 hours (>20 RBC units) (relative risk reduction of 56% [95% confidence interval: 9%‐79%]; p = 0.03), and the fresh‐frozen plasma (p = 0.036), platelet (p = 0.023), and cryoprecipitate (p = 0.053) requirements within 48 hours, and was associated with a significant reduction in the 30‐day risk of acute respiratory distress syndrome (ARDS) (p = 0.05) and multiple organ failure and/or ARDS (p = 0.05).

CONCLUSION: Treatment with adjunctive rFVIIa significantly reduces transfusion requirements in the 48 hours after severe injury and these procoagulant effects may improve clinical outcome at 30 days.
The Decision of the Supply Chain Executive to Support or Impede Supply Chain Integration: A Multidisciplinary Behavioral Agency Perspective*
Authors: Villena Verónica H. , Gomez‐Mejia Luis R. , Revilla Elena
Published: November 2009

Applying the behavioral agency model developed by Wiseman and Gomez‐Mejia (1998), this article analyzes human resource factors that induce supply chain executives (SCEs) to make decisions that foster or hinder supply chain integration. We examine two internal sources (compensation and employment risk) and one external source (environmental volatility) of risk bearing that can make SCEs more reluctant to make the decision to promote supply chain integration. We argue and empirically confirm the notion that an employment and compensation system that increases SCE risk bearing reduces the SCE's willingness to make risky decisions and thus discourages supply chain integration. We also reveal that this negative relationship becomes stronger under conditions of high environmental volatility. In addressing the “so what?” question, we found empirical support for the hypothesis that supply chain integration positively influences operational performance. Even though this decision has a positive value for the firm, we showed that SCEs discourage supply chain integration when they face higher risk bearing. Hypotheses are tested using a combination of primary survey data and archival measures in a sample of 133 Spanish firms.
Supply Chain Strategy, Product Characteristics, and Performance Impact: Evidence from Chinese Manufacturers*
Authors: Qi Yinan , Boyer Kenneth K. , Zhao Xiande
Published: November 2009

Supply chain management has become one of the most popular approaches to enhance the global competitiveness of business corporations today. Firms must have clear strategic thinking in order to effectively organize such complicated activities, resources, communications, and processes. An emerging body of literature offers a framework that identifies three kinds of supply chain strategies: lean strategy, agile strategy, and lean/agile strategy based on in‐depth case studies. Extant research also suggests that supply chain strategies must be matched with product characteristics in order for firms to achieve better performance. This article investigates supply chain strategies and empirically tests the supply chain strategy model that posits lean, agile, and lean/agile approaches using data collected from 604 manufacturing firms in China. Cluster analyses of the data indicate that Chinese firms are adopting a variation of lean, agile, and lean/agile supply chain strategies identified in the western literature. However, the data reveal that some firms have a traditional strategy that does not emphasize either lean or agile principles. These firms perform worse than firms that have a strategy focused on lean, agile, or lean/agile supply chain. The strategies are examined with respect to product characteristics and financial and operational performance. The article makes significant contributions to the supply chain management literature by examining the supply chain strategies used by Chinese firms. In addition, this work empirically tests the applicability of supply chain strategy models that have not been rigorously tested empirically or in the fast‐growing Chinese economy.
The Influence of Cost and Quality Priorities on the Propensity to Outsource Production*
Authors: Gray John V. , Roth Aleda V. , Tomlin Brian
Published: November 2009

Outsourcing of production has escalated over the past decade due to unprecedented competition and worldwide access to low‐cost labor markets. This article examines how cost and quality priorities—two key attributes of manufacturing strategy—influence a manufacturer's propensity to outsource. By doing so, we bridge the existing gap between research on manufacturing strategy and firm boundaries. We develop a theory‐based model that links a manufacturer's cost and quality priorities to its plans to outsource production. Our empirical analyses, based on survey data obtained from 867 manufacturing business units, control for firm‐specific factors previously shown to impact outsourcing, including asset specificity, uncertainty, and current capabilities in cost and quality. We found that the competitive priority placed on cost played an integral role in sourcing decisions, while, surprisingly, conformance quality priorities did not. The cost result is consistent with our expectations and observations in practice. The significant effect of cost priority on outsourcing shows that any theory of firm boundaries that fails to consider competitive priorities is incomplete. The finding regarding quality, which was counter to our expectations, may partially explain why there is an emergence of so many nonconforming products associated with outsourcing. Taken together, our results provide theoretical insights for future research into how manufacturing managers can improve their decision making on outsourcing production.
A Competitive Model of Customization with Lead‐Time Effects
Authors: Xia Nan , Rajagopalan Sampath
Published: November 2009

In this article, we study the competitive interactions between a firm producing standard products and a firm producing custom products. Consumers with heterogeneous preferences choose between n standard products, which may not meet their preferences exactly but are available immediately, and a custom product, available only after a certain lead time l. Standard products incur a variety cost that increases with n and custom products incur a lead time cost that is decreasing in the lead time l. We consider a two‐stage game wherein at stage 1, the standard product firm chooses the variety and the custom firm chooses the lead time and then both firms set prices simultaneously. We characterize the subgame‐perfect Nash equilibrium of the game. We find that both firms can coexist in equilibrium, either sharing the market as local monopolists or in a price‐competitive mode. The standard product firm may offer significant or minimal variety depending on the equilibrium outcome. We provide several interesting insights on the variety, lead time, and prices of the products offered and on the impact of problem parameters on the equilibrium outcomes. For instance, we show that the profit margin and price of the custom product are likely to be higher than that of standard products in equilibrium under certain conditions. Also, custom firms are more likely to survive and succeed in product markets with larger potential market sizes. Another interesting insight is that increased consumer sensitivity to product fit may result in lower lead time for the custom product.
The Influence of Forward‐Looking Antecedents, Uncertainty, and Anticipatory Emotions on Project Escalation*
Authors: Harvey Paul , Victoravich Lisa M.
Published: November 2009

This study extends research on the escalation of commitment phenomenon by investigating decision makers' tendency to look forward to project completion and develop anticipatory perceptions and emotions concerning goal attainment. We examine the influence of two project‐specific predictors of escalation (level of progress and presence of an alternative project) on perceived uncertainty and the extent to which anticipatory emotions (i.e., current affective reactions to possible future events) mediate the influence of uncertainty on levels of commitment to a failing project. Results indicated that level of progress and the presence of an alternative project affected uncertainty, which influenced anticipatory emotions. Lower levels of uncertainty and higher levels of positive anticipatory emotions increased the tendency to escalate commitment.
Supply Networks as a Complex Adaptive System: Toward Simulation‐Based Theory Building on Evolutionary Decision Making
Authors: Nair Anand , Narasimhan Ram , Choi Thomas Y.
Published: November 2009

In this article, we examine how the firms embedded in supply networks engage in decision making over time. The supply networks as a complex adaptive system are simulated using cellular automata (CA) through a dynamic evolution of cooperation (i.e., “voice” decision) and defection (i.e., “exit” decision) among supply network agents (i.e., firms). Simple local rules of interaction among firms generate complex patterns of cooperation and defection decisions in the supply network. The incentive schemes underlying decision making are derived through different configurations of the payoff‐matrix based on the game theory argument. The prisoner's dilemma game allows capturing the localized decision‐making process by rational agents, and the CA model allows the self‐organizing outcome to emerge. By observing the evolution of decision making by cooperating and defecting agents, we offer testable propositions regarding relationship development and distributed nature of governance mechanisms for managing supply networks.
Seeking Closure: Competition in Complementary Markets*
Authors: Cattani Kyle , Heese Hans Sebastian
Published: November 2009

When offering a product that has a complementary product in a different market, a firm must consider the interdependence between the complementary products as well as the competition within markets. If the firm participates in both markets, the balancing act becomes even more challenging. This article provides insights about strategies in this latter setting: when should the firm seek to keep its products closed to competing complementary products, and when would the firm be better off by accepting a common standard? To address these questions, we employ standard game theoretic analysis to a simple spatial model that captures aspects of both intermarket externalities and intramarket competition. We find that if a firm participates in both markets and chooses a closed standard, it achieves lower profits compared to an open standard, but gains greater market share. Surprisingly, we find that customers are better off when standards are kept closed.