bluuebunny/crossref_metadata_2025 huggingface dataset:
Swarming motility: a multicellular behaviour conferring antimicrobial resistance
Authors: Lai Sandra , Tremblay Julien , Déziel Eric
Published: September 2008

Swarming is a type of social motility allowing the migration of highly differentiated bacterial cells. Swarming shares many similarities with biofilm communities, which are notable for their high resistance to antimicrobial agents. We investigate here if the swarming behaviour could also be associated with a widespread antimicrobial resistant phenotype. Challenged with 13 antibiotics from various classes, swarm cells of Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Burkholderia thailandensis and Bacillus subtilis showed higher resistance than their planktonic counterparts to all the antibiotics tested, except for the antimicrobial peptides. Using P. aeruginosa as a model, this multiresistant phenotype was shown to be transient and intrinsically linked to the swarming state. Resistance of swarm cells towards other antimicrobial agents, such as triclosan and a heavy metal (arsenite), was also observed. Neither RND‐type efflux pumps, including MexAB‐OprM, MexCD‐OprJ, MexEF‐OprN and MexXY‐OprM, nor a biofilm‐associated resistance mechanism involving periplasmic glucans, appear to account for the resistance of swarm cells. Together with the high resistance of biofilms, these results support the hypothesis that antimicrobial resistance is a general feature of bacterial multicellularity. Swarming motility might thus represent a form of social behaviour useful as a model to investigate biofilm antibiotic resistance.
Ion transport and osmotic adjustment in Escherichia coli in response to ionic and non‐ionic osmotica
Authors: Shabala Lana , Bowman John , Brown Janelle , Ross Tom , McMeekin Tom , Shabala Sergey
Published: September 2008

Bacteria respond to osmotic stress by a substantial increase in the intracellular osmolality, adjusting their cell turgor for altered growth conditions. Using Escherichia coli as a model organism we demonstrate here that bacterial responses to hyperosmotic stress specifically depend on the nature of osmoticum used. We show that increasing acute hyperosmotic NaCl stress above ∼1.0 Os kg−1 causes a dose‐dependent K+ leak from the cell, resulting in a substantial decrease in cytosolic K+ content and a concurrent accumulation of Na+ in the cell. At the same time, isotonic sucrose or mannitol treatment (non‐ionic osmotica) results in a gradual increase of the net K+ uptake. Ion flux data are consistent with growth experiments showing that bacterial growth is impaired by NaCl at the concentration resulting in a switch from net K+ uptake to efflux. Microarray experiments reveal that about 40% of upregulated genes shared no similarity in their responses to NaCl and sucrose treatment, further suggesting specificity of osmotic adjustment in E. coli to ionic and non‐ionic osmotica. The observed differences are explained by the specificity of the stress‐induced changes in the membrane potential of bacterial cells highlighting the importance of voltage‐gated K+ transporters for bacterial adaptation to hyperosmotic stress.
Novel Chlamydiales strains isolated from a water treatment plant
Authors: Corsaro Daniele , Feroldi Veronica , Saucedo Gemma , Ribas Ferran , Loret Jean‐François , Greub Gilbert
Published: September 2008

Chlamydiae are obligate intracellular bacteria infecting free‐living amoebae, vertebrates and some invertebrates. Novel members are regularly discovered, and there is accumulating evidence supporting a very important diversity of chlamydiae in the environment. In this study, we investigated the presence of chlamydiae in a drinking water treatment plant. Samples were used to inoculate Acanthamoeba monolayers (Acanthamoeba co‐culture), and to recover autochthonous amoebae onto non‐nutritive agar. Chlamydiae were searched for by a pan‐chlamydia 16S rRNA gene PCR from both Acanthamoeba co‐cultures and autochthonous amoebae, and phylotypes determined by 16S rRNA gene sequencing. Autochthonous amoebae also were identified by 18S rRNA gene amplification and sequencing. From a total of 79 samples, we recovered eight chlamydial strains by Acanthamoeba co‐culture, but only one of 28 amoebae harboured a chlamydia. Sequencing results and phylogenetic analysis showed our strains belonging to four distinct chlamydial lineages. Four strains, including the strain recovered within its natural host, belonged to the Parachlamydiaceae; two closely related strains belonged to the Criblamydiaceae; two distinct strains clustered with Rhabdochlamydia spp.; one strain clustered only with uncultured environmental clones. Our results confirmed the usefulness of amoeba co‐culture to recover novel chlamydial strains from complex samples and demonstrated the huge diversity of chlamydiae in the environment, by identifying several new species including one representing the first strain of a new family.
Positive urine cytology but negative white‐light cystoscopy: an indication for fluorescence cystoscopy?
Authors: Karl Alexander , Tritschler Stefan , Stanislaus Peter , Gratzke Christian , Tilki Derya , Strittmatter Frank , Knüchel Ruth , Stief Christian G. , Zaak Dirk
Published: September 2008

OBJECTIVE

To evaluate the possible benefit of fluorescence cystoscopy (FC) in detecting cytologically ‘confirmed’ lesions when assessing urothelial carcinoma of the bladder, as negative white‐light cystoscopy in cases of a positive cytological finding represents a diagnostic dilemma.

PATIENTS AND METHODS

From January 1996 to December 2006, 348 patients, who had cystoscopy for surveillance or due to suspicion of urothelial carcinoma, presented with an entirely negative white‐light cystoscopy at our hospital. However, 77 of the 348 patients (22.2%) were diagnosed with a positive cytological finding. All patients had white‐light cystoscopy first and a bladder‐wash cytological specimen was obtained, then FC, followed by cold‐cup biopsies and/or transurethral resection of the bladder tumour.

RESULTS

In the 77 patients with a positive cytological specimen FC enabled the detection of the precise site of malignancy within the bladder in 63 (82%). As malignant or premalignant lesions, there were 18 moderate dysplasias, 27 carcinoma in situ (CIS), and 18 pTa‐1/G1‐3 tumours. Moreover using FC, malignant or premalignant lesions were detected in 43 of 271 patients (15.9%) who had a negative cytological specimen (15 moderate dysplasias, six CIS, 22 pTa‐1/G1‐3).

CONCLUSION

This study shows that FC is beneficial in the detection of malignant and premalignant lesions, if there is negative white‐light cystoscopy but positive urine cytology. The immediate identification of the exact site of a malignant lesion during FC enables the physician to diagnose and treat these patients more accurately and with no delay.
The Premature Ejaculation Profile: validation of self‐reported outcome measures for research and practice
Authors: Patrick Donald L. , Giuliano François , Ho Kai Fai , Gagnon Dennis D. , McNulty Pauline , Rothman Margaret
Published: September 2008

OBJECTIVE

To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self‐reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single‐item measures, a profile, and an index score.

SUBJECTS AND METHODS

Data were from men participating in observational studies in the USA (PE, 207 men; non‐PE, 1380) and Europe (PE, 201; non‐PE, 914) and from men with PE (1238) participating in a phase III randomized, placebo‐controlled clinical trial of dapoxetine. The PEP contains four measures: perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse, and interpersonal difficulty related to ejaculation, each assessed on five‐point response scales. Test‐retest reliability, known‐groups validity, and ability to detect a patient‐reported global impression of change (PGI) in condition were evaluated for the individual PEP measures and a PEP index score (the mean of all four measures). Profile analysis was conducted using multivariate analysis of variance.

RESULTS

All PEP measures showed acceptable reliability (intraclass correlation coefficients ranged from 0.66 to 0.83) and mean scores for all measures differed significantly between PE and non‐PE groups (P < 0.001). Men who reported a reduction in PE with treatment in the phase III trial had significantly greater scores on each of the four measures. The PEP profiles of men with and without PE differed significantly (P < 0.001) in both observational studies; higher levels of PGI were associated with higher PEP profiles (P < 0.001). The PEP index score also showed acceptable reliability and was significantly different between the PE and non‐PE groups (P < 0.001). Men who reported an improvement in PE with treatment in the phase III trial had significantly greater PEP index scores. In the phase III trial, nausea was the most common adverse event with dapoxetine.

CONCLUSION

The PEP provides a reliable, valid, and interpretable measure for use in monitoring outcomes of men with PE.
Clinical and laboratory characteristics of calcium stone‐formers with and without primary hyperparathyroidism
Authors: Parks Joan H. , Coe Fredric L. , Evan Andrew P. , Worcester Elaine M.
Published: September 2008

OBJECTIVE

To compare the clinical presentation, laboratory features and outcome of treatment in stone formers (SF) with primary hyperparathyroidism (HPT) to those without systemic disease.

PATIENTS, SUBJECTS AND METHODS

We compared 105 (54 female) stone‐formers (SF) with primary hyperparathyroidism (HPT) to 2416 (835 female) common SF with no systemic disease, and 260 normal subjects (NS, 106 female) using pre‐treatment and treatment data from our kidney‐stone programme. All were assessed before treatment, with three 24‐h urine samples, for stone risk factors, each with a corresponding fasting blood sample. Records were reviewed for stone rates and urological stone‐related procedures.

RESULTS

The hypercalcaemia of HPT was modest, but hypercalciuria was far more marked than in SF because the fractional calcium excretion of HPT exceeded that of SF. Surgical cure of HPT did not completely eradicate either hypercalciuria or hypophosphataemia, suggesting that these patients have some additional mineral disorder. Serum calcium and phosphate, and fractional excretion of calcium, combined into a discriminant function provided the best separation between HPT and SF. However, we present 49 patients for whom the diagnosis (HPT vs SF) has never been resolved, despite years of observation and successful reduction of stone recurrence. Stones in HPT have slightly more phosphate than SF but the difference is not large enough to be of clinical interest. The stone frequency in HPT is about that for SF, and treatment reduces stones in HPT and SF by about the same amount, 10 times.

CONCLUSION

No study to date has compared HPT with SF and NS, as done here. SF with even slight hypercalcaemia and brisk hypercalciuria probably have this curable disease, and after cure clinicians must be wary of residual hypercalciuria that requires medical treatment. Some patients will never be fully diagnosed and remain, like ours, an enigma, albeit responsive to usual medical treatments. Although stones are modestly enriched with phosphate, most are mainly calcium oxalate, so the stone analysis is not clinically a guide to diagnosis.
Rare and unusual histological variants of prostatic carcinoma: clinical significance
Authors: Mazzucchelli Roberta , Lopez‐Beltran Antonio , Cheng Liang , Scarpelli Marina , Kirkali Ziya , Montironi Rodolfo
Published: September 2008

We review the clinicopathological features of the following unusual histological variants of prostatic carcinoma: small cell carcinoma, ductal adenocarcinoma, sarcomatoid (carcinosarcoma), basal cell, squamous cell and adenosquamous, and urothelial carcinoma. These variants are rare and account for 5–10% of carcinomas that originate in the prostate. Some develop from acinar adenocarcinoma after hormonal or radiation therapy. They are usually aggressive tumours that often present with secondary deposits. The outcome is generally poor. Only basal cell carcinoma is seen as a low‐grade carcinoma.
An association between ethnicity and cardiovascular outcomes for people with Type 2 diabetes in New Zealand
Authors: Kenealy T. , Elley C. R. , Robinson E. , Bramley D. , Drury P. L. , Kerse N. M. , Moyes S. A. , Arroll B.
Published: September 2008

Aims To investigate the association between ethnicity and risk of first cardiovascular (CV) event for people with Type 2 diabetes in New Zealand.

Methods A prospective cohort study using routinely collected data from a national primary health care diabetes annual review programme linked to national hospital admission and mortality data. Ethnicity was recorded as European, Maori, Pacific, Indo‐Asian, East‐Asian or Other. A Cox proportional hazards model was used to investigate factors associated with first CV event. Data was collected from 48 444 patients with Type 2 diabetes, with first data collected between 1 January 2000 and 20 December 2005, no previous cardiovascular event at entry and with complete measurements. Risk factors included ethnicity, gender, socio‐economic status, body mass index, smoking, age at diagnosis, duration of diabetes, systolic blood pressure, serum lipids, glycated haemoglobin and urine albumin : creatinine ratio. The main outcome measures were time to first fatal or non‐fatal CV event.

Results Median follow‐up was 2.4 years. Using combined European and Other ethnicities as a reference, hazard ratios for first CV event were 1.30 for Maori (95% confidence interval 1.19–1.41), 1.04 for Pacific (0.95–1.13), 1.06 for Indo‐Asian (0.91–1.24) and 0.73 for East‐Asian (0.62–0.85) after controlling for all other risk factors.

Conclusions Ethnicity was independently associated with time to first CV event in people with Type 2 diabetes. Maori were at 30% higher risk of first CV event and East‐Asian 27% lower risk compared with European/Other, with no significant difference in risk for Pacific and Indo‐Asian peoples.
What and How Long Does It Take to Get Tenure? The Case of Economics and Business Administration in Austria, Germany and Switzerland
Authors: Schulze Günther G. , Wiermann Christian , Warning Susanne
Published: September 2008

This paper investigates the determinants of tenure decisions in Germany, Austria and the German-speaking part of Switzerland for professorships in economics, business administration and related fields. Our dataset comprises candidates who were awarded tenure as well as those who were eligible but were not tenured. We show that business candidates have a higher probability of being tenured than economists. Youth, marital status and publications matter; gender and children do not. The market for first appointments in economics relies much more on publication performance than the market for business administration.
Livestock predation by lions, leopards, spotted hyenas, and their vulnerability to retaliatory killing in the Maasai steppe, Tanzania
Authors: Kissui B. M.
Published: September 2008

The African lion Panthera leo, spotted hyena Crocuta crocuta and leopard Panthera pardus are all killed in retaliation for livestock predation, but each species suffers differently from these impacts due to differences in predatory behavior and cultural attitudes of pastoralists. Using detailed data on livestock predation in the Maasai steppe landscape in Northern Tanzania, I investigated how prey preference, location and timing of livestock attacks contributed to the vulnerability of lions, leopards and spotted hyenas to retaliatory killing. Lions mostly preyed upon adult cattle and donkeys. In contrast, hyenas and leopards primarily killed small stock (goat, sheep and calves) and dogs. Hyenas and leopards mostly attacked livestock at night, whereas lions often attacked grazing livestock during the daytime. These behaviors made lions the most vulnerable to direct retaliatory killing, although some villages specifically targeted hyenas with poison, and the cultural traditions of pastoralists also exacerbate the retaliatory killing of lions. I highlight the complex interactions of social (human) and ecological dimensions of livestock predation and retaliation against predators. Any conservation intervention should strive to address human–carnivore conflicts at the appropriate social scale.
Extinction risk scales better to generations than to years
Authors: O'Grady J. J. , Reed D. H. , Brook B. W. , Frankham R.
Published: September 2008

It is critical to search for, and to apply, robust generalizations in conservation biology as species‐specific data on endangered species are often limited. While generalizations are common in conservation genetics, where processes are treated on the scale of generations, the unique population dynamics of species are often stressed in ecology and conservation management. Is the apparent uniqueness of population attributes partly an artefact of measurement scale? One facet of this debate is the question of whether extinction risk scales better to years or to generations. To resolve this issue, the extinction risk of 100 well‐studied vertebrate taxa was estimated using stochastic computer projections and analyses conducted to determine whether risk related better to years or generations. Relative strengths of evidence for alternative hypotheses were assessed using information theory. Extinction risk, assessed as the population size required for a 90% probability of persistence for 100 years, was strongly related to generation length. Conversely, when extinction risk was assessed for a fixed number of generations, there was no support for a relationship between risk and years. This finding has ramifications for assessing and reporting extinction risk because it shows that (1) crucial signals for the effective management of threatened species may not be detected when risk is measured on a scale of years alone; (2) correcting for generation length will allow data from a wider range of species to be used as defaults for species with limited data; (3) generational‐scale tests of factors affecting extinction risk are more powerful than year‐based ones. We recommend that extinction risk be routinely reported on a generational scale, with results on a year scale added where warranted.
Social determinants of songbird vocal activity and implications for the persistence of small populations
Authors: Laiolo P. , Tella J. L.
Published: September 2008

Conspecific attraction is an important aspect of animal behaviour and several avian studies have shown that vocalizations may be used as an inadvertent cue to locate areas of suitable habitat. By studying the metapopulation system of a territorial passerine, the Dupont's lark Chersophilus duponti, we analysed the demographic correlates of population vocal activity, and the relationships between the occurrence of immigration and the availability of social information (e.g. vocal activity, population size, density and productivity) in 22 local populations. We found that the proportion of active singing days in spring and territorial call advertisement after breeding were positively related to the number of males within local populations. In turn, the intensity of vocal activity was associated with the likelihood of receiving immigrants, better explaining immigration than other kinds of social or public information. Because of depressed signalling, small local populations could experience reduced rescuing from others, thus compromising population persistence. In such cases, habitat management alone may not be enough to overcome this behavioural constraint. Because we found that the occurrence of inter‐patch movements also depended on the size of nearby local populations, understanding regional processes may be as important as controlling social and environmental factors for the maintenance of small populations.
OCCURRENCE AND CHARACTERIZATION OF ARABINOGALACTAN‐LIKE PROTEINS AND HEMICELLULOSES IN MICRASTERIAS (STREPTOPHYTA)1
Authors: Eder Magdalena , Tenhaken Raimund , Driouich Azeddine , Lütz‐Meindl Ursula
Published: September 2008

The cell wall of the green alga Micrasterias denticulata Bréb. ex Ralfs (Desmidiaceae, Zygnematophyceae, Streptophyta) was investigated to obtain information on the composition of component polysaccharides and proteoglycans to allow comparison with higher plants and to understand cell wall functions during development. Various epitopes currently assigned to arabinogalactan‐proteins (AGPs) of higher plants could be detected in Micrasterias by immuno TEM and immunofluorescence methods, but the walls did not bind the β‐d‐glycosyl‐Yariv (β‐GlcY) reagent. Secretory vesicles and the primary wall were labeled by antibodies against AGPs (JIM8, JIM13, JIM14). Dot and Western blot experiments indicated a proteoglycan nature of the epitopes recognized, which consisted of galactose and xylose as major sugars by high performance anion exchange chromatography with pulsed amperometric detection (HPAEC‐PAD). Epitopes of alkali‐soluble polysaccharides assigned to noncellulosic polysaccharides in higher plants could be detected and located in the wall during its formation. The polyclonal anti‐xyloglucan (anti‐XG) antibody labeled primary and secondary wall of Micrasterias, whereas the monoclonal antibody CCRC‐M1, directed against the fucose/galactose side chain of xyloglucan (XyG), did not recognize any structures. Labeling by anti‐XG antibody at the trans‐sites of the dictyosomes and at wall material containing vesicles indicated that secretion of the epitopes occurred similar to higher plants. The presence of (1→3, 1→4)‐β‐glucan (mixed linked glucan) in the secondary cell wall but not in the primary cell wall of Micrasterias could be demonstrated by an antibody recognizing this glucan type, whereas (1→3)‐β‐glucan (callose) could not be detected. The analytical results revealed that alkali‐soluble polysaccharides in the secondary wall of Micrasterias consist mostly of (1→3, 1→4)‐β‐d‐glucan.
Issues in Evaluating Fish Consumption Rates for Native American Tribes
Authors: Donatuto Jamie , Harper Barbara L.
Published: September 2008

The environmental health goals of many Native American tribes are to restore natural resources and ensure that they are safe to harvest and consume in traditional subsistence quantities. Therefore, it is important to tribes to accurately estimate risks incurred through the consumption of subsistence foods. This article explores problems in conventional fish consumption survey methods used in widely cited tribal fish consumption reports. The problems arise because of the following: (1) widely cited reports do not clearly state what they intend to do with the data supporting these reports, (2) data collection methods are incongruent with community norms and protocols, (3) data analysis methods omit or obscure the highest consumer subset of the population, (4) lack of understanding or recognition of tribal health co‐risk factors, and (5) restrictive policies that do not allow inclusion of tribal values within state or federal actions. In particular, the data collection and analysis methods in current tribal fish consumption surveys result in the misunderstanding that tribal members are satisfied with eating lower contemporary amounts of fish and shellfish, rather than the subsistence amounts that their cultural heritage and aboriginal rights indicate. A community‐based interview method developed in collaboration with and used by the Swinomish Tribe is suggested as a way to gather more accurate information on contemporary consumption rates. For traditional subsistence rates, a multidisciplinary reconstruction method is recommended.
Measures of Societal Risk and Their Potential Use in Civil Aviation
Authors: Horn Mark E. T. , Fulton Neale , Westcott Mark
Published: September 2008

This article seeks to clarify the conceptual foundations of measures of societal risk, to investigate how such measures may be used validly in commonly encountered policy contexts, and to explore the application of these measures in the field of civil aviation. The article begins by examining standard measures of societal and individual risk (SR and IR), with attention given to ethical as well as analytical considerations. A comprehensive technical analysis of SR is provided, encompassing scalar risk measures, barrier functions, and a utility‐based formulation, and clarifications are offered with respect to the treatment of SR in recent publications. The policy context for SR measures is shown to be critically important, and an extension to a hierarchical setting is developed. The prospects for applying SR to civil aviation are then considered, and some technical and conceptual issues are identified. SR appears to be a useful analytical tool in this context, provided that careful attention is given to these issues.
Bayesian Methodology for Model Uncertainty Using Model Performance Data
Authors: Droguett Enrique López , Mosleh Ali
Published: September 2008

A simple and useful characterization of many predictive models is in terms of model structure and model parameters. Accordingly, uncertainties in model predictions arise from uncertainties in the values assumed by the model parameters (parameter uncertainty) and the uncertainties and errors associated with the structure of the model (model uncertainty). When assessing uncertainty one is interested in identifying, at some level of confidence, the range of possible and then probable values of the unknown of interest. All sources of uncertainty and variability need to be considered. Although parameter uncertainty assessment has been extensively discussed in the literature, model uncertainty is a relatively new topic of discussion by the scientific community, despite being often the major contributor to the overall uncertainty. This article describes a Bayesian methodology for the assessment of model uncertainties, where models are treated as sources of information on the unknown of interest. The general framework is then specialized for the case where models provide point estimates about a single‐valued unknown, and where information about models are available in form of homogeneous and nonhomogeneous performance data (pairs of experimental observations and model predictions). Several example applications for physical models used in fire risk analysis are also provided.
Evaluating Efficiency‐Equality Tradeoffs for Mobile Source Control Strategies in an Urban Area
Authors: Levy Jonathan I. , Greco Susan L. , Melly Steven J. , Mukhi Neha
Published: September 2008

In environmental risk management, there are often interests in maximizing public health benefits (efficiency) and addressing inequality in the distribution of health outcomes. However, both dimensions are not generally considered within a single analytical framework. In this study, we estimate both total population health benefits and changes in quantitative indicators of health inequality for a number of alternative spatial distributions of diesel particulate filter retrofits across half of an urban bus fleet in Boston, Massachusetts. We focus on the impact of emissions controls on primary fine particulate matter (PM2.5) emissions, modeling the effect on PM2.5 concentrations and premature mortality. Given spatial heterogeneity in baseline mortality rates, we apply the Atkinson index and other inequality indicators to quantify changes in the distribution of mortality risk. Across the different spatial distributions of control strategies, the public health benefits varied by more than a factor of two, related to factors such as mileage driven per day, population density near roadways, and baseline mortality rates in exposed populations. Changes in health inequality indicators varied across control strategies, with the subset of optimal strategies considering both efficiency and equality generally robust across different parametric assumptions and inequality indicators. Our analysis demonstrates the viability of formal analytical approaches to jointly address both efficiency and equality in risk assessment, providing a tool for decisionmakers who wish to consider both issues.
Is Epidemiology the Key to Cumulative Risk Assessment?
Authors: Levy Jonathan I.
Published: September 2008

Although cumulative risk assessment by definition evaluates the joint effects of chemical and nonchemical stressors, studies to date have not considered both dimensions, in part because toxicological studies cannot capture many stressors of interest. Epidemiology can potentially include all relevant stressors, but developing and extracting the necessary information is challenging given some of the inherent limitations of epidemiology. In this article, I propose a conceptual framework within which epidemiological studies could be evaluated for their inclusion into cumulative risk assessment, including a problem formulation/planning and scoping step that focuses on stressors meaningful for risk management decisions, extension of the chemical mixtures framework to include nonchemical stressors, and formal consideration of vulnerability characteristics of the population. In the long term, broadening the applicability and informativeness of cumulative risk assessment will require enhanced communication and collaboration between epidemiologists and risk assessors, in which the structure of social and environmental epidemiological analyses may be informed in part by the needs of cumulative risk assessment.
Overcoming Confirmation Bias in Causal Attribution: A Case Study of Antibiotic Resistance Risks
Authors: Cox, Jr Louis Anthony (Tony) , Popken Douglas A.
Published: September 2008

When they do not use formal quantitative risk assessment methods, many scientists (like other people) make mistakes and exhibit biases in reasoning about causation, if‐then relations, and evidence. Decision‐related conclusions or causal explanations are reached prematurely based on narrative plausibility rather than adequate factual evidence. Then, confirming evidence is sought and emphasized, but disconfirming evidence is ignored or discounted. This tendency has serious implications for health‐related public policy discussions and decisions. We provide examples occurring in antimicrobial health risk assessments, including a case study of a recently reported positive relation between virginiamycin (VM) use in poultry and risk of resistance to VM‐like (streptogramin) antibiotics in humans. This finding has been used to argue that poultry consumption causes increased resistance risks, that serious health impacts may result, and therefore use of VM in poultry should be restricted. However, the original study compared healthy vegetarians to hospitalized poultry consumers. Our examination of the same data using conditional independence tests for potential causality reveals that poultry consumption acted as a surrogate for hospitalization in this study. After accounting for current hospitalization status, no evidence remains supporting a causal relationship between poultry consumption and increased streptogramin resistance. This example emphasizes both the importance and the practical possibility of analyzing and presenting quantitative risk information using data analysis techniques (such as Bayesian model averaging (BMA) and conditional independence tests) that are as free as possible from potential selection, confirmation, and modeling biases.
Effect of endophytic Beauveria bassiana on populations of the banana weevil, Cosmopolites sordidus, and their damage in tissue‐cultured banana plants
Authors: Akello Juliet , Dubois Thomas , Coyne Daniel , Kyamanywa Samuel
Published: September 2008

The entomopathogen Beauveria bassiana (Balsamo) Vuillemin (Ascomycota: Hypocreales) survives as an endophyte in a wide range of plants, offering substantial protection against tunneling insect pests. Although current research indicates that the fungus can live as an endophyte in tissue‐cultured banana plants, there is no information on the efficacy of endophytic B. bassiana against the banana weevil, Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae). Our study aimed at determining the effects of endophytic B. bassiana on oviposition rate and populations of the banana weevil, and their plant damage. Screenhouse studies were undertaken in which 8‐week‐old B. bassiana‐inoculated tissue‐cultured banana plants [cultivar Kibuzi, Musa spec. (Musaceae), genome group AAA‐EA] were infested with female banana weevils. Five days after plant infestation with the banana weevil, there was no effect of B. bassiana on oviposition rate and egg hatchability. However, after 15 weeks, the presence of B. bassiana as an endophyte in banana tissues greatly reduced banana weevil populations and their damage to plants. Between 53.4 and 57.7% of the banana weevil adults died because of B. bassiana infection, resulting in a reduction of plant damage by 29.1–62.7% depending on plant part. Beauveria bassiana was re‐isolated from different plant parts, but to a greater extent from the roots and rhizomes than from pseudostem bases. Artificial inoculation of B. bassiana in banana plants caused no negative impact on banana growth. Our study demonstrated for the first time that endophytic B. bassiana reduced populations of C. sordidus and the plant damage they cause, and can thus be an alternative method for effective delivery of this fungus to banana plants for the management of C. sordidus.
Establishing causality in the assessment of safety of medicines for children
Authors: Ashby Deborah
Published: September 2008

Background: Data on safety of medicines in children typically arises from various sources, rendering assessment of causality challenging.

Methods: We outline these sources, together with their strengths and weaknesses. Bradford Hill proposed criteria for assessment of causality of observed associations; we explore their utility in this context.

Conclusion: Collaborations between clinicians, epidemiologists and clinical pharmacologists, making intelligent use of both older and newer methodologies, can help make the use of medicines in children safer.
Metabolic fate of l‐lactaldehyde derived from an alternative l‐rhamnose pathway
Authors: Watanabe Seiya , Piyanart Sommani , Makino Keisuke
Published: September 2008

Fungal Pichia stipitis and bacterial Azotobacter vinelandii possess an alternative pathway of l‐rhamnose metabolism, which is different from the known bacterial pathway. In a previous study (Watanabe S, Saimura M & Makino K (2008) Eukaryotic and bacterial gene clusters related to an alternative pathway of non‐phosphorylated l‐rhamnose metabolism. J Biol Chem283, 20372–20382), we identified and characterized the gene clusters encoding the four metabolic enzymes [l‐rhamnose 1‐dehydrogenase (LRA1), l‐rhamnono‐γ‐lactonase (LRA2), l‐rhamnonate dehydratase (LRA3) and l‐2‐keto‐3‐deoxyrhamnonate aldolase (LRA4)]. In the known and alternative l‐rhamnose pathways, l‐lactaldehyde is commonly produced from l‐2‐keto‐3‐deoxyrhamnonate and l‐rhamnulose 1‐phosphate by each specific aldolase, respectively. To estimate the metabolic fate of l‐lactaldehyde in fungi, we purified l‐lactaldehyde dehydrogenase (LADH) from P. stipitis cells l‐rhamnose‐grown to homogeneity, and identified the gene encoding this enzyme (PsLADH) by matrix‐assisted laser desorption ionization‐quadruple ion trap‐time of flight mass spectrometry. In contrast, LADH of A. vinelandii (AvLADH) was clustered with the LRA1–4 gene on the genome. Physiological characterization using recombinant enzymes revealed that, of the tested aldehyde substrates, l‐lactaldehyde is the best substrate for both PsLADH and AvLADH, and that PsLADH shows broad substrate specificity and relaxed coenzyme specificity compared with AvLADH. In the phylogenetic tree of the aldehyde dehydrogenase superfamily, PsLADH is poorly related to the known bacterial LADHs, including that of Escherichia coli (EcLADH). However, despite its involvement in different l‐rhamnose metabolism, AvLADH belongs to the same subfamily as EcLADH. This suggests that the substrate specificities for l‐lactaldehyde between fungal and bacterial LADHs have been acquired independently.
In vivo Skin Irritation Potential of a Castanea sativa (Chestnut) Leaf Extract, a Putative Natural Antioxidant for Topical Application
Authors: Almeida Isabel F. , Valentão Patrícia , Andrade Paula B. , Seabra Rosa M. , Pereira Teresa M. , Amaral M. Helena , Costa Paulo C. , Bahia M. Fernanda
Published: September 2008

Abstract:  Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet‐mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1‐diphenyl‐2‐picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron‐chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40°. The IC50 found for the iron chelation and DPPH scavenging assays were 132.94 ± 9.72 and 12.58 ± 0.54 µg/ml (mean ± S.E.M.), respectively. The total phenolic content was found to be 283.8 ± 8.74 mg GAE/g extract (mean ± S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application.
Effects of salt stress on purslane (Portulaca oleracea) nutrition
Authors: Teixeira M. , Carvalho I.S.
Published: September 2008

The objective of this study was to determine the influence of saline stress on the chemical composition of purslane (Portulaca oleracea), in particular the mineral composition. Four salinity levels were investigated using irrigation solutions with electrical conductivity values of 0.8, 6.8, 12.8 and 24.2 dS m−1 and two planting dates (May and July) were tested. Samples of full‐grown leaf and stems of purslane were harvested after 7 and 15 days of the saline treatment exposure. Chemical analysis (dry matter basis) of leaves showed significant differences among the different saline treatments for all the characteristics measured. Salinity levels, planting date and harvest time significantly influenced (P < 0.05) the levels of crude protein, total lipids, ash and carbohydrate content. Salinity treatments did not significantly (P > 0.05) affect the water content of purslane leaves. The crude protein content of purslane leaves decreased with increasing salinity levels and time of exposure to treatment. However, carbohydrates and mineral residue content increased. An unusual phenomenon was noted for intermediate salinity levels, whereby an increase in total lipid content was measured in leaves of plants exposed to salinity treatments of 6.8 and 12.8 dS m−1. The highest mineral residue content was seen in leaves of purslane exposed to the highest salinity treatment. The mineral composition was also affected by salinity levels, Na and Cl uptake, and accumulation increased with increasing salinity in irrigation solution; Mg concentration was not significantly (P > 0.05) affected by salinity levels, although a slight increase was seen, and Ca, K and Zn levels significantly (P < 0.05) decreased. Ca and Zn preferentially accumulated in the leaves, while K and Na values were higher in the stems. A significant increase (P < 0.05) in relative ratio of Na/K, Mg/K, Na/Ca and Mg/Ca was observed with increasing salinity levels. A decrease in the yield of purslane was only observed for the most severe saline treatment, where the highest ratio of Mg/Ca was seen. This study reveals that purslane is relatively tolerant to conditions of moderate salinity, thus improving its potential to become a key vegetable crop for animal and human consumption.
Mapping Water Table Depth Using Geophysical and Environmental Variables
Authors: Buchanan S. , Triantafilis J.
Published: September 2008

Despite its importance, accurate representation of the spatial distribution of water table depth remains one of the greatest deficiencies in many hydrological investigations. Historically, both inverse distance weighting (IDW) and ordinary kriging (OK) have been used to interpolate depths. These methods, however, have major limitations: namely they require large numbers of measurements to represent the spatial variability of water table depth and they do not represent the variation between measurement points. We address this issue by assessing the benefits of using stepwise multiple linear regression (MLR) with three different ancillary data sets to predict the water table depth at 100‐m intervals. The ancillary data sets used are Electromagnetic (EM34 and EM38), gamma radiometric: potassium (K), uranium (eU), thorium (eTh), total count (TC), and morphometric data. Results show that MLR offers significant precision and accuracy benefits over OK and IDW. Inclusion of the morphometric data set yielded the greatest (16%) improvement in prediction accuracy compared with IDW, followed by the electromagnetic data set (5%). Use of the gamma radiometric data set showed no improvement. The greatest improvement, however, resulted when all data sets were combined (37% increase in prediction accuracy over IDW). Significantly, however, the use of MLR also allows for prediction in variations in water table depth between measurement points, which is crucial for land management.
Quantitative Structure‐Activity Relationships for PPAR‐γ Binding and Gene Transactivation of Tyrosine‐Based Agonists Using Multivariate Statistics
Authors: Giaginis Costas , Theocharis Stamatios , Tsantili‐Kakoulidou Anna
Published: September 2008

Peroxisome proliferator‐activated receptor‐γ offers a molecular target for drugs aimed to treat type II diabetes mellitus, while its therapeutic potency against cancer disease is currently being explored in preclinical studies. Tyrosine derivatives constitute a major class of peroxisome proliferator‐activated receptor‐γ agonists attracting considerable research interest in drug discovery. Thus, the establishment of adequate QSAR models would serve as a guide for further molecular design. In the present study, multivariate data analysis was applied on a large set of tyrosine‐based peroxisome proliferator‐activated receptor‐γ agonists for modelling binding affinity, expressed as pKi and gene transactivation, expressed as pEC50. A pool of descriptors based on physicochemical and molecular properties as well as on specific structural characteristics was used and two PLS models with satisfactory statistics were produced for binding data. According to them, molecular weight, rotatable bonds and lipophilicity were found to exert a considerable positive influence, while excess negative and positive charge created by additional acidic or basic groups in the molecules was unfavourable. With gene transactivation data, an adequate model was obtained only for the highly active compounds if considered separately. The higher complexity incorporated in gene transactivation data was further investigated by establishing a PLS model, which improved the inter‐relationship between pEC50 and pKi.
Stroke Care Development in Mainland China: Past, Present and Future
Authors: Wang Chunxue , Li Jingjing , Zhao Xingquan , Wang Yilong , Wu Di , Wang Yongjun
Published: September 2008

Stroke care in China was less developed than in western countries but great headway has been made in recent years through unremitting efforts by a group of local neurologists working in this field.
Intracranial Thrombus Extent Predicts Clinical Outcome, Final Infarct Size and Hemorrhagic Transformation in Ischemic Stroke: The Clot Burden Score
Authors: Puetz Volker , Dzialowski Imanuel , Hill Michael D. , Subramaniam Suresh , Sylaja P.N. , Krol Andrea , O'Reilly Christine , Hudon Mark E. , Hu William Y. , Coutts Shelagh B. , Barber Philip A. , Watson Timothy , Roy Jayanta , Demchuk Andrew M.
Published: September 2008

Background

In ischemic stroke, functional outcomes vary depending on site of intracranial occlusion. We tested the prognostic value of a semiquantitative computed tomography angiography-based clot burden score.

Methods

Clot burden score allots major anterior circulation arteries 10 points for presence of contrast opacification on computed tomography angiography. Two points each are subtracted for thrombus preventing contrast opacification in the proximal M1, distal M1 or supraclinoid internal carotid artery and one point each for M2 branches, A1 and infraclinoid internal carotid artery. We retrospectively studied patients with disabling neurological deficits (National Institute of Health Stroke Scale score ≥ 5) and computed tomography angiography within 24-hours from symptom onset. We analyzed percentages independent functional outcome (modified Rankin Scale score ≤ 2), final infarct Alberta Stroke Program Early Computed Tomography Score and parenchymal hematoma rates across categorized clot burden score groups and performed multivariable analysis.

Results

We identified 263 patients (median age 73-years, National Institute of Health Stroke Scale score 10, onset-to-computed tomography angiography time 165 min). Clot burden score < 10 was associated with reduced odds of independent functional outcome (odds ratio 0.09 for clot burden score ≤5; odds ratio 0.22 for clot burden score 6–7; odds ratio 0.48 for clot burden score 8–9; all versus clot burden score 10; P <0.02 for all). Lower clot burden scores were associated with lower follow-up Alberta Stroke Program Early CT Scores ( P <0.001) and higher parenchymal hematoma rates ( P = 0.008). Inter-rater reliability for clot burden score was 0.87 (lower 95% confidence interval 0.71) and intra-rater reliability 0.96 (lower 95% confidence interval 0.92).

Conclusion

The quantification of intracranial thrombus extent with the clot burden score predicts functional outcome, final infarct size and parenchymal hematoma risk acutely. The score needs external validation and could be useful for patient stratification in stroke trials.
Immune and Inflammatory Responses to Stroke: Good Or Bad?
Authors: McCombe P. A. , Read S. J.
Published: September 2008

Inflammatory and immune responses play important roles following ischaemic stroke. Inflammatory responses contribute to damage and also contribute to repair. Injury to tissue triggers an immune response. This is initiated through activation of the innate immune system. In stroke there is microglial activation. This is followed by an influx of lymphocytes and macrophages into the brain, triggered by production of pro-inflammatory cytokines. This inflammatory response contributes to further tissue injury. There is also a systemic immune response to stroke, and there is a degree of immunosuppression that may contribute to the stroke patient's risk of infection. This immunosuppressive response may also be protective, with regulatory lymphocytes producing cytokines and growth factors that are neuroprotective. The specific targets of the immune response after stroke are not known, and the details of the immune and inflammatory responses are only partly understood. The role of inflammation and immune responses after stroke is twofold. The immune system may contribute to damage after stroke, but may also contribute to repair processes. The possibility that some of the immune response after stroke may be neuroprotective is exciting and suggests that deliberate enhancement of these responses may be a therapeutic option.