bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RELATIONSHIP BETWEEN CONVERGENCE‐DIVERGENCE AND THE FREE RECALL OF DISCOURSE
Authors: CORNISH IAN M.
Published: May 2011

Summary. The literature on convergence‐divergence (C‐D) suggests that convergers are characterised by a greater preference for, and superior performance with, structured experience. Twenty‐seven university undergraduates were given an IQ test and the Alternate Uses test, and asked to recall a short story. The hypothesis that increasing convergence would be positively correlated with the amount of information recalled was confirmed, implying that convergers were at an advantage with highly structured material. However, divergent test performance alone showed a similar but inverse relationship with recall, casting doubt on the validity of C‐D as a cognitive style dimension, and suggesting the need for a measure of convergence‐divergence independent of performance on separate convergent and divergent tasks.
VARIETIES OF CURRICULAR EXPERIENCE: BACKMARKERS AND FRONTRUNNERS IN THE PRIMARY CLASSROOM
Authors: INGRAM JOHN , WORRALL NORMAN
Published: May 2011

Summary. In the first study a class of 10‐year‐olds was observed for the first and last five weeks of the autumn term. On both a class and individual child basis there was considerable difference between teacher‐believed and child‐actual timetables, and this increased over the term. In the second study, 53 children were classified into “frontrunners” or “backmarkers”, depending on success in pacing the taught curriculum. For backmarkers, strategies for maintaining contact were mainly child‐determined, though for frontrunners mainly teacher‐determined. Although the teachers, who proved to be traditionally directive, believed their paper timetable closely represented children's true classroom experience, a picture emerged of most children correctly perceiving themselves as backmarkers, and as having responsibility for instigating their own, largely passive, coping strategies with subsequent negative feelings about themselves and their situation.
READING ILLUSTRATED SCIENCE TEXTS: A MICRO‐COMPUTER BASED INVESTIGATION OF CHILDREN'S STRATEGIES
Authors: REID D. J. , BEVERIDGE M.
Published: May 2011

Summary. Research has shown that the effect of illustrations on children's learning of science is related to ability. This study examines the hypothesis that children who show different levels of success in a learning task will employ different strategies in their picture‐text processing. One hundred and eighty 14 year‐old children were required to learn three illustrated science topics of different levels of difficulty which were presented to them on a BBC micro‐computer. The computer was programmed to record the time spent on each sentence and each picture, as well as the point in the text at which the picture was accessed. Post hoc testing enabled the children to be divided into six groups according to their success rates on the learning tasks. Significantly longer times were spent looking at the pictures as the topics increased in difficulty; also the amount of time spent looking at pictures increased as the learning of the children decreased. For every second the least successful children spent accessing pictures, they spent about four seconds reading the text; for the most successful children this ratio was about one‐to‐six. The least successful children also accessed the pictures significantly more frequently than the most successful. The different strategies used by the children are discussed in terms of what is known about their differential learning gains from illustrated texts.
RESPONSE FEEDBACK, CERTITUDE AND LEARNING FROM TEXT
Authors: Kulhavy Raymond W. , Stock William A. , Thornton Nancy E. , Winston Kristen S. , Behrens John T.
Published: May 2011

Summary. Based upon the premise that persons modify their study behaviours in order to maintain their certainty of responding correctly, a study was conducted with 40 undergraduate volunteers examining the effects of different presentation rates and feedback context on response confidence and correct responding. Significant effects in the anticipated direction were found for presentation rate but not for the context of feedback.
PERCEPTUAL DYSFUNCTION IN POOR READERS: EVIDENCE FOR VISUAL AND AUDITORY SEGMENTATION PROBLEMS IN A SUB‐GROUP OF POOR READERS
Authors: Johnston Rhona S. , Anderson Marjorie , Perrett David I. , Holligan Christopher
Published: May 2011

Summary. The purpose of this study was to consider reading disorders in children within the context of their general perceptual development. A review of the literature suggested that visual and auditory perceptual skills advance from a holistic to an analytical approach, and that reading skills also show this progression. It was proposed that poor readers might show impairments in visual and auditory segmentation tasks, if these skills are important factors in reading development. This hypothesis was tested on a sample (N = 20) of poor readers in the primary age range who were assessed against reading age and chronological age control groups. The hypothesis was partially borne out, a quarter of the sample performing very poorly on both types of tasks. It was argued that segmentation problems in perceptual tasks may underlie reading failure in some children, although the direction of the causation has yet to be determined.
TEACHING THINKING IN EUROPE
Authors: MCGUINNESS CAROL , NISBET JOHN
Published: May 2011

Summary. This review of European research in cognition and instruction aims to categorise current trends in the teaching of thinking and problem solving. A diversity of theoretical orientations sustains research and practice in this field: Vygotskian, neo‐Piagetian, phenomenographic, information‐processing. Research‐driven intervention studies and across‐the‐curriculum reforms are reviewed. Promising lines of development include the concepts of metacognition (or self‐regulation), mediation by peers and adults, and computer tutoring. Cognitive psychology now has a sharper focus on classroom learning; and the boundaries between cognitive, affective and social aspects of learning are being eroded.
PATTERNS OF READING DEVELOPMENT IN THE FIRST SCHOOL
Authors: FRANCIS HAZEL
Published: May 2011

Summary. This study identified different reading progress patterns in children in the early primary years, extending the findings of other studies conducted with older children. Analysis of both standardised and teacher assessments suggested that the best readers at 7 had exhibited steady progress over two years on a linear gradient established during or before the first few months in school. Others, however, exhibited curvilinear progress patterns, characterised by a gentle gradient over some months followed by a steeper incline which matched or exceeded the rate of progress of the better readers, in some cases catching up. The poorest readers at 7 had not reached this point of “take‐off”, though some were showing signs of being near to it. The findings are examined in the light of the nature of the assessments adopted. Their significance for teachers' identification of pupils' support needs both before and after they move towards independent reading, and for the use and interpretation of standardised test scores, are discussed.
Assessing emotional and behavioural problems in reception class school‐children: factor structure, convergence and prevalence using the PBCL
Authors: James‐Roberts Ian St , Singh Gurmeet , Lynn Richard , Jackson Shirley
Published: May 2011

The Preschool Behaviour Checklist was designed to help nursery staff to identify and work with children who may have emotional and behavioural problems. The aim here was to consider its suitability for use as a screening instrument in primary school reception classes, which provide the first setting in which all United Kingdom children come under repeated daily scrutiny by professional staff. A partial‐replication design was used, employing 23 teachers and 516 children in a first, and 35 teachers and 350 children in a second, study. The two studies showed similar factor structures, including both internalising and externalising factors in each case. Assessed in relation to the teachers' judgments, the PBCL produced sensitivity and specificity rates of 85 percent and 91 per cent respectively. Depending on the criterion score used, 15–21 per cent of reception class schoolchildren were found to have emotional and behavioural problems. A correlation of 0.83 was obtained between PBCL and Child Behavior Checklist Teacher Report Form measures over a two‐week period. The need to compare the teachers' measures with external assessments and to evaluate how they inform practice is discussed.
Cheating and achievement‐avoidance at school: components and assessment
Authors: Rost Detlef H. , Wild Klaus Peter
Published: May 2011

The development and psychometric properties of a general school cheating scale are reported. German grammar school students (grades 10–12, N=197) responded to 44 five‐point scaled items concerning different facets of cheating and achievement avoidance at school. Based on an explorative principal component analysis, a 14‐item general scale ‘Cheating and Effort Avoidance at School’ was developed, covering the use of forbidden aids, unrealistic hopes and defensive tactics, and avoidance of test situations. The satisfying psychometric properties of the sale (a=.83 to a=.86, test‐retest reliability after four to six weeks, r=.75) was confirmed with a second (N=487 and third (N=902) sample of grammar school students (grades 10–13). Some validity data are reported: positive relations to the factors ‘worry’ and ‘emotionality’ of test anxiety as well as to the fear of failure aspect of achievement motivation; negative relation to school achievement (grade in maths and German), to satisfaction with own academic achievement, to academic self‐concept and to the hope for success component of achievement motivation.
Is being smart everything? The influence of student achievement on teachers' perceptions
Authors: Carr Martha , Kurtz‐Costes Beth E.
Published: May 2011

The purpose of this project was to explore the accuracy and predictors of teachers' perceptions of their students' metacognition, self‐concept, and attributional beliefs. Nineteen third grade teachers each nominated six children from their classrooms based on the children's maths abilities (high, medium, low). The children were tested on metacognitive knowledge, self‐concept, and attributional beliefs. Teachers completed questionnaires estimating each child's metacognitive abilities, academic self‐concept, and attributional beliefs about the reasons underlying academic success and failure. Analyses indicated that teachers' perceptions were biased by children's abilities, as higher ability children were portrayed more favourably on all variables. Regressions of teachers' perceptions on children's scores revealed that teachers were moderately accurate in their ratings of children's metacognitive abilities, but not of their attributional beliefs or self‐concepts. Implications for metacognitive and motivational models of the learner are discussed.
The classroom competence and attitudes towards pedagogical principles of beginning teachers
Authors: Preece Peter F. W.
Published: May 2011

The relationship between preservice education students' (N=135) attitudes towards general pedagogical principles and the quality of their classroom teaching was investigated. A weak negative relationship was obtained between students' attitudes and the assessment category ‘relationships with children’. This suggests that fostering positive attitudes in preservice students towards general pedagogical principles, based on practices in themselves directly associated with enhancing pupil achievement, may result in lower quality teaching because of an adverse effect this has on pupil‐teacher relationships.
Locus of control in behaviourally disordered children
Authors: Elliott Julian
Published: May 2011

It is widely held that behaviourally disordered children have greater difficulty than their peers in recognising a contingent relationship between their actions and subsequent outcomes (i.e., they have a relatively external locus of control) yet studies have not examined intra‐group differences within this population. For this reason, this study explored the relationship between a number of specific behaviours and locus of control in 237 children with emotional and behavioural difficulties. Cluster analysis and nonmetric multidimensional scaling were employed to group locus of control items and behaviours in ways which might assist prediction. The findings indicated very little relationship between locus of control and behaviour. It is suggested that clinicians working with behaviourally disordered children should treat the claims for the construct's therapeutic importance with a degree of caution.
Season of birth and gender effects in children attending moderate learning difficulty schools
Authors: Bibby Peter A. , Lamb Susannah J. , Leyden Gervase , Wood David
Published: May 2011

This paper examines the effects of season of birth and gender on academic achievement and cognitive abilities in children attending moderate learning difficulty schools. Given the high preponderance of both boys and children born in summer attending special schools it is important to consider how well these children perform in relation to their peers. A multivariate analysis reveals that both boys and summer born children perform better on tests of intelligence, mathematical ability, and reading comprehension. Summer born children also perform better on a test of communication skills. Discriminant functions analysis reveals that for both gender and season of birth IQ is the major predictor variable followed by reading comprehension, mathematical ability and communication skill. For gender, IQ discriminates more successfully than the other variables, whereas with season of birth the relative sizes of the effects are more comparable. The results of the analysis are discussed in terms of the implications for the identification of children for placement in moderate learning difficulty schools.
Strategy‐training related to children's text production
Authors: Søvik Nils , Heggberget Mette , Samuelstuen Marit
Published: May 2011

The study dealt with the problem whether the effects of an experimental training programme would improve (1) children's strategies in writing and (2) the quality of their related text production. The study was organised as a pretest‐posttest control‐group design with an equal number of fourth grade students in the experimental and control group. Students in the experimental group were trained on a programme with writing‐related strategies during six sessions in a laboratory equipped with required instrumentation for data collection. The results indicated that some across‐domain strategies and most of the domain‐specific strategies were improved by the programme. Also a positive transfer effect was observed concerning students' writing attainments, particularly with regard to writing tasks based on series of pictures.
The effects of a problem‐solving based Logo environment on children's information processing components
Authors: Mevarech Zemira R. , Kapa Ester
Published: May 2011

The present study investigated the simultaneous effects of a problem‐solving based Logo environment on children's metacomponents, knowledge acquisition components regarding graphing skills, and figural creativity. Participants were 108 fifth‐grade children who studied in four classrooms. Intact classrooms were randomly assigned to one of two conditions: a problem‐solving based Logo environment called Logo‐Stat, or a comparison. The duration of the study was one semester. Results showed significant multivariate effects on metacomponents, knowledge acquisition components, and creativity, in favour of the Logo‐Stat group. Univariate analyses indicated that knowledge acquisition components and certain aspects of figural creativity (e.g., originality) and metacomponents (e.g., correctness) were more strongly affected by Logo‐Stat than others (e.g., fluency, flexibility, and utilisation). The theoretical and practical implications are discussed.
Maladaptive motivational style: the role of domain specific task demand in English and mathematics
Authors: Galloway David , Leo Elizabeth L. , Rogers Colin , Armstrong Derrick
Published: May 2011

This study is concerned with the differences in the prevalence of maladaptive motivational styles in a school population in aspects of two National Curriculum core subjects: English and mathematics. Using a curriculum‐based adaptation of procedures devised by Craske (1988), all pupils in Years 7,9 and 11 of two secondary schools, and all pupils in Year 6 of 11 of their feeder primary schools, were categorised into one of three motivational styles: learned helplessness, self‐worth motivation and mastery orientation. These three motivational styles are concerned with the ways in which pupils respond in the face of a perceived threat of failure on an educational task. Mastery orientation is considered adaptive while learned helplessness and self‐worth motivation are considered maladaptive. This study compares the prevalence of each motivational style in English comprehension with that of mathematics and provides empirical evidence of a higher prevalence of maladaptive motivational styles in English comprehension than in mathematics irrespective of age, gender, ethnic origin and non‐verbal reasoning ability. The findings support the view that motivational style is more a product of situational than individual variables. Implications for the development of domain‐specific motivational style are discussed.
Professional and personal development for teachers: the application of learning following a counselling module
Authors: Hall Eric , Hall Carol , Sirin Ahmet
Published: May 2011

A group of 82 teachers from a wide range of educational settings attended a one‐term, 30‐hour counselling module which was embedded in a Master's Degree programme in Human Relations. This article reports an evaluation of the extent to which the participants applied this learning in their professional and personal lives. The use of a self‐report inventory demonstrated no significant changes in the use of the counselling strategies immediately after the training, but significant changes one year later. This implies a substantial sleeper effect, where the positive effects of the training were appearing well after the module had ended. The study provides information on the general effectiveness of counselling training and in relation to specific counselling strategies. Differences according to age, gender, length of work experience and previous experience of counselling courses were identified. Qualitative reports including interviews, diary reports and goal setting, indicate substantial applications of counselling strategies in both professional and personal life.
Writing style and the narrative essay
Authors: Lavelle Ellen
Published: May 2011

Background. Writing styles reflect the ways that writers think about themselves and about writing, as well as the pattern of strategies that writers consistently use to achieve their goals (Lavelle, 1993). Generally, writing styles may be considered along the deep/surface continuum with deep styles geared toward making a complex meaning beyond the given words, and surface writing reflecting a listing approach based on the reproduction of information. However, some students have adopted an Elaborative style reflecting a high degree of personal expression in writing. The Elaborative style employs a self‐referencing strategy — ‘Writing makes me feel good’, ‘I put a lot of myself in writing’ represents an affective dimension in writing — one geared toward personal meaning. Unfortunately, Elaborative writing is usually encouraged only in the composition class where it is considered a precursor to academic or objective composition.

Aims. The purpose of this study was to examine the relationships among writing styles as measured by the Inventory of Processes in College Composition (Lavelle, 1993), writing apprehension, and writing performance on a personal narrative writing task. Given the self‐referencing strategy associated with the Elaborative style, it was hypothesised that Elaborative scale scores would predict narrative essay outcomes in terms of the degree of personal investment and complexity.

Sample. The sample consisted of 74 college students enrolled in freshman composition, a general studies course at a medium size midwestem university in the United States.

Methods. The Inventory of Processes in College Composition and the Daly Miller Writing Apprehension Test were administered to students during a regular, 50‐minute class period. Students also responded in essay format to a personal writing prompt: ‘My Most Unforgettable Character’.

Results. Results support the Elaborative writing style as predictive of the degree of personal involvement in writing a narrative essay but not as predictive of the complexity of writing outcome. Writing apprehension in conjunction with Procedural scale score were predictive of the complexity of essay outcomes and Elaborative and Low self‐efficacy writing styles were predictive of writing apprehension.

Conclusions. The Elaborative construct represents a highly personal and emotive approach to writing and learning and is useful in understanding writers' strengths and deficits. Elaborative writers were confident and highly invested in writing a brief narrative essay, but might be encouraged to be more planful in order to achieve a greater level of complexity. Writing apprehension has been supported as a multidimensional construct related to writing self‐efficacy. Implications for instruction include offering a wide range of writing assignments, emphasis on reflection and planning, and consideration of narrative writing as an educational tool in content areas.
Educational implications of field dependence‐independence: in answer to Bagley and Mallick
Authors: Tinajero Carolina , Páramo M. Fernanda
Published: May 2011

Background. This article replies to some of the comments made by Bagley & Mallick (1998) about our investigation (Tinajero & Páramo, 1997).

Aims. To clarify some of Bagley and Mallick's comments about our investigation, and to defend alternative interpretations about some aspects which refer to field dependent‐independent cognitive style (FDI) mentioned by the authors, such as the overlapping between measures of cognitive style and ability, and the implications the latter has in an educational context.

Methods. A revision of theoretical arguments and empirical evidence about the questions which are dealt with.

Conclusion. The generalisation of the results of our study about the relationship between FDI and academic achievement seems to be feasible in the light of data from previous studies carried out with samples of very different origin. Investigation into FDI takes place alongside theoretical debates about aspects such as its adaptive value or its overlapping with intelligence. These debates remain open.
Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature
Authors: Haddock Rebecca E. , Hill Caryl E.
Published: May 2011

Non‐technical summary  The maintenance of healthy blood pressure is influenced by the activity of the sympathetic perivascular nerves which surround small arteries and arterioles. Increases in sympathetic neurovascular control may play a role in the genesis and progression of cardiovascular disease during obesity. Our data show that sympathetic nerve‐mediated vasoconstriction is augmented during diet‐induced obesity and that ATP and purinergic mechanisms play a significant role. Changes occur due to an increase in sympathetic nerve density and release of ATP, with a potential contribution from a decreased sensitivity to sensory vasodilatory neurotransmitters. Improving control of sympathetic function through the identification of potential therapeutic targets is likely to lead to increased cardiovascular health benefits for overweight and obese individuals.
Renal defects in KCNE1 knockout mice are mimicked by chromanol 293B in vivo: identification of a KCNE1‐regulated K+ conductance in the proximal tubule
Authors: Neal A. M. , Taylor H. C. , Millar I. D. , Kibble J. D. , White S. J. , Robson L.
Published: May 2011

Non‐technical summary  The kidney plays a critical role in regulating body fluid volume and blood pressure by conserving ions, solutes and water. Knowing the processes that underpin the handling of ions, solutes and water by the kidney is essential to our understanding of fluid and blood pressure regulation. Movement of ions is mediated by specific transport proteins found in the membranes of kidney cells. These proteins are regulated by additional proteins, called accessory proteins. In the current study, we have examined the role of the accessory protein KCNE1 in regulating a channel, KCNQ1, which is important in kidney function. We have observed that in the absence of KCNE1 the kidney has difficulty conserving sodium, chloride and water. However, by using specific inhibitors of these proteins we have also determined that although KCNE1 has a role in kidney function, the mechanism of its action is unlikely to be by regulating the protein KCNQ1.
Metabotropic glutamate receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave‐dependent activation of SK and TRPC channels
Authors: El‐Hassar Lynda , Hagenston Anna M. , D’Angelo Lisa Bertetto , Yeckel Mark F.
Published: May 2011

Non‐technical summary  The hippocampus is a neural structure that is critical for some forms of memory function. It performs this function through the ability of its neurons to fire patterns of activity that encode information and the ability of the synaptic connections between neurons to strengthen or weaken. Glutamate, an important synaptic neurotransmitter, can activate different types of receptors, including metabotropic glutamate receptors (mGluRs). mGluRs have been shown to be important for learning and memory. It has also been shown that changes in mGluR type 5 might contribute to mental retardation and autism, suggesting that manipulation of mGluR5 might reduce their symptoms. In this study we examined how mGluR activation can activate neuron membrane channels (SK and TRPC) in hippocampal neurons that regulate their activity. Our findings suggest that mGluR activation of SK and TRPC channels are likely to be important for sculpting patterns of activity that encode information by the hippocampus.
Failure Bending Moment for Pipes With an Arbitrary-Shaped Circumferential Flaw
Authors: Li Yinsheng , Hasegawa Kunio , Shibuya Akira , Cofie Nathaniel G.
Published: May 2011

When a flaw is detected in a stainless steel piping system, an evaluation has to be performed to determine its suitability for continued operation. The failure bending moment of the flawed pipe can be predicted by limit load criterion in accordance with Appendix E-8 in the JSME S NA-1-2008 and/or Appendix C in the ASME Code Section XI. However, in these current codes, the limit load criterion is only calculated for the case of pipes containing a single flaw with constant depth, although the actual flaw depth is variable along the circumferential direction. Particularly, geometrical shapes of stress corrosion cracks are generally complex. The objective of this paper is to propose a method by formula for predicting the load-carrying capacity of pipes containing a circumferential surface flaw with any arbitrary shape. The failure bending moment is obtained by dividing the surface flaw into several subflaw segments. Using this method, good agreement is observed between the numerical solution and the reported experimental results. Several numerical examples are also presented to show the validity of the proposed methodology. Finally, it is demonstrated that three subflaw segments are sufficient to determine the collapse bending moment of a semi-elliptical surface flaw using the proposed methodology.
Stomatal Closure by Fast Abscisic Acid Signaling Is Mediated by the Guard Cell Anion Channel SLAH3 and the Receptor RCAR1
Authors: Geiger Dietmar , Maierhofer Tobias , AL-Rasheid Khaled A. S. , Scherzer Sönke , Mumm Patrick , Liese Anja , Ache Peter , Wellmann Christian , Marten Irene , Grill Erwin , Romeis Tina , Hedrich Rainer
Published: May 2011

Plant survival during periods of drought may involve SLAH3, a nitrate-conducting anion channel activated by abscisic acid.
Snips and Tales of Planarian Tails
Authors: VanHook Annalisa M.
Published: May 2011

The hydrolase Notum inhibits Wnt signaling to specify regeneration of head structures in planaria.
Adapting to a Hot Meal
Authors: Gough Nancy R.
Published: May 2011

Mosquitoes that feed on warm-blooded animals exhibit a heat shock response in the gut that promotes digestion and fecundity.
Lipids for a Long Life
Authors: Wong Wei
Published: May 2011

Lipids that bind to mammalian cannabinoid receptors mediate the longevity-promoting effects of dietary restriction in
Caenorhabditis elegans
.
Structure-Analysis of the HIV-1 Integrase Y143C/R Raltegravir Resistance Mutation in Association with the Secondary Mutation T97A
Authors: Reigadas S. , Masquelier B. , Calmels C. , Laguerre M. , Lazaro E. , Vandenhende M. , Neau D. , Fleury H. , Andréola M. L.
Published: May 2011

The HIV-1 integrase (IN) mutations Y143C/R are known as raltegravir (RAL) primary resistance mutations. In a previous study (S. Reigadas et al., PLoS One 5:e10311, 2010), we investigated the genetic pathway and the dynamics of emergence of the Y143C/R mutations in three patients failing RAL-containing regimens. In these patients, the Y143C/R mutation was associated with the T97A mutation. The aim of the present biochemical and molecular studies
in vitro
was to evaluate whether the secondary mutation, T97A, associated with the Y143C/R mutation could increase the level of resistance to RAL and impact IN activities. Site-directed mutagenesis experiments were performed with expression vectors harboring the region of the
pol
gene coding for IN. With a 3′-end processing assay, the 50% inhibitory concentrations (IC
50
) were 1.2 μM, 1.2 μM, 2.4 μM (fold change [FC], 2), and 20 μM (FC, 16.7) for IN wild type (WT), the IN T97A mutation, the IN Y143C/T97A mutation, and the IN Y143R/T97A mutation, respectively. FCs of 18 and 100 were observed with the strand transfer assay for IN Y143C/T97A and Y143R/T97A mutations, with IC
50
of 0.625 μM and 2.5 μM, respectively. In the strand transfer assay, the IN Y143C or R mutation combined with the secondary mutation T97A severely impaired susceptibility to RAL compared to results with the IN Y143C or R mutation alone. Assays without RAL suggested that the T97A mutation could rescue the catalytic activity which was impaired by the presence of the Y143C/R mutation. The combination of the T97A mutation with the primary RAL resistance mutations Y143C/R strongly reduces the susceptibility to RAL and rescues the catalytic defect due to the Y143C/R mutation. This result indicates that the emergence of the Y143C/R/T97A double-mutation pattern in patients is a signature of a high resistance level.
Applying New Diagnostic Criteria for Acute Kidney Injury To Facilitate Early Identification of Nephrotoxicity in Vancomycin-Treated Patients
Authors: Minejima Emi , Choi Joyce , Beringer Paul , Lou Mimi , Tse Edmund , Wong-Beringer Annie
Published: May 2011

Acute kidney injury (AKI) associated with high-dose vancomycin (VAN) therapy is a clinical concern, but no uniform diagnostic criteria exist. The AKI Network (AKIN) proposed new criteria to diagnose AKI based on abrupt changes in serum creatinine or urine output. We conducted a prospective observational study to determine the incidence and severity of AKI and associated outcomes using the AKIN criteria versus traditional definitions. Eligible patients (
n
= 227) were elderly (median, 70 years) and received VAN therapy for 8 days (median). AKI occurred in 43 patients (19%) using AKIN criteria at an onset of 6 days. AKI incidence was similar for patients with a trough level of ≥15 (24%; 17/72) versus <15 (17%; 26/155) μg/ml. Compared to non-AKI patients, more AKI patients resided in the intensive care unit (ICU) (47% [20/43] versus 27% [50/184];
P
= 0.017), had a prior AKI episode (19% [8/43] versus 7% [5/184];
P
= 0.001), and received vasopressor (28% [12/43] versus 14% [25/184];
P
= 0.04) and/or nephrotoxins (84% [36/43] versus 67% [123/184];
P
= 0.04). Seventeen of the AKI patients met traditional criteria, of whom more patients had stage 2 and 3 AKI (76% versus 8%;
P
= 0.0001), dosage adjustment (41% versus 15%) and renal consultation (35% versus 12%), prolonged length of stay after AKI (11 versus 7.5 days) and died (29% versus 12%) than those diagnosed by AKIN criteria (
P
value not significant). Use of AKIN criteria for AKI has the potential to improve care of VAN-treated patients by facilitating early detection of AKI and warrants confirmation in large prospective trials.
Penetration of Ertapenem into Muscle Measured by In Vivo Microdialysis in Mechanically Ventilated Patients
Authors: Boyadjiev I. , Boulamery A. , Simon N. , Martin C. , Bruguerolle B. , Leone M.
Published: May 2011

Ertapenem at 1 g once daily has been suggested to be underdosed in intensive care unit (ICU) patients to attain optimal concentrations in target tissues. Therefore, our study aimed to assess the kinetics of ertapenem in plasma and skeletal muscle in ICU patients using microdialysis. Average muscle free-ertapenem concentrations were above the MIC values of targeted pathogens. In a few patients, the concentrations were below the MIC values. The clinical efficiency of ertapenem at 1 g once daily should be evaluated in a large population of ICU patients.
Synergistic Drug Combinations for Tuberculosis Therapy Identified by a Novel High-Throughput Screen
Authors: Ramón-García Santiago , Ng Carol , Anderson Hilary , Chao Joseph D. , Zheng Xingji , Pfeifer Tom , Av-Gay Yossef , Roberge Michel , Thompson Charles J.
Published: May 2011

Therapeutic options for tuberculosis (TB) are limited and notoriously ineffective despite the wide variety of potent antibiotics available for treating other bacterial infections. We investigated an approach that enables an expansion of TB therapeutic strategies by using synergistic combinations of drugs. To achieve this, we devised a high-throughput synergy screen (HTSS) of chemical libraries having known pharmaceutical properties, including thousands that are clinically approved. Spectinomycin was used to test the concept that clinically available antibiotics with limited efficacy against
Mycobacterium tuberculosis
might be used for TB treatment when coadministered with a synergistic partner compound used as a sensitizer. Screens using
Mycobacterium smegmatis
revealed many compounds in our libraries that acted synergistically with spectinomycin. Among them, several families of antimicrobial compounds, including macrolides and azoles, were also synergistic against
M. tuberculosis in vitro
and in a macrophage model of
M. tuberculosis
infection. Strikingly, each sensitizer identified for synergy with spectinomycin uniquely enhanced the activities of other clinically used antibiotics, revealing a remarkable number of unexplored synergistic drug combinations. HTSS also revealed a novel activity for bromperidol, a butyrophenone used as an antipsychotic drug, which was discovered to be bactericidal and greatly enhanced the activities of several antibiotics and drug combinations against
M. tuberculosis
. Our results suggest that many compounds in the currently available pharmacopoeia could be readily mobilized for TB treatment, including disease caused by multi- and extensively drug-resistant strains for which there are no effective therapies.
Valacyclovir for Herpes Simplex Encephalitis
Authors: Pouplin Thomas , Pouplin Julie Nguyen , Van Toi Pham , Lindegardh Niklas , Rogier van Doorn H. , Hien Tran Tinh , Farrar Jeremy , Török M. Estée , Chau Tran Thi Hong
Published: May 2011

The recommended treatment for herpes simplex encephalitis (HSE) remains intravenous acyclovir. In resource-poor countries, however, intravenous formulations are usually unavailable or unaffordable. We report the penetration of acyclovir into the cerebrospinal fluid (CSF) in patients with HSE, treated with the oral prodrug valacyclovir at 1,000 mg three times daily. The oral therapy achieved adequate acyclovir concentrations in the CSF and may be an acceptable early treatment for suspected HSE in resource-limited settings.
In Vitro
Interaction between Fluconazole and Triclosan against Clinical Isolates of Fluconazole-Resistant Candida albicans Determined by Different Methods
Authors: Yu Lu , Ling Guanghui , Deng Xuming , Jin Jing , Jin Qi , Guo Na
Published: May 2011

The
in vitro
interaction between triclosan and fluconazole against 24 azole-resistant clinical isolates of
Candida albicans
was evaluated by the microdilution checkerboard technique. The synergisms were verified by time-killing curves and agar diffusion tests in selected strains. Antagonistic activity was not detected.
Meropenem Penetration into Epithelial Lining Fluid in Mice and Humans and Delineation of Exposure Targets
Authors: Drusano G. L. , Lodise T. P. , Melnick D. , Liu W. , Oliver A. , Mena A. , VanScoy B. , Louie A.
Published: May 2011

Pseudomonas aeruginosa
pneumonia remains a most-difficult-to-treat nosocomial bacterial infection. We used mathematical modeling to identify drug exposure targets for meropenem in the epithelial lining fluid (ELF) of mice with
Pseudomonas
pneumonia driving substantial [2 to 3 log
10
(CFU/g)] killing and which suppressed resistant subpopulation amplification. We bridged to humans to estimate the frequency with which the largest licensed meropenem dose would achieve these exposure targets. Cell kills of 2 and 3 log
10
(CFU/g) and resistant subpopulation suppression were mediated by achieving time > MIC in ELF of 32%, 50%, and 50%. Substantial variability in meropenem's ability to penetrate into ELF of both mice and humans was observed. Penetration variability and high exposure targets combined to prevent even the largest licensed meropenem dose from achieving the targets at an acceptable frequency. Even a highly potent agent such as meropenem does not adequately suppress resistant subpopulation amplification as single-agent therapy administered at maximal dose and optimal schedule. Combination chemotherapy is likely required in humans if we are to minimize resistance emergence in
Pseudomonas aeruginosa
pneumonia. This combination needs evaluation both in the murine pneumonia model and in humans.
Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults
Authors: Cook Aaron M. , Martin Craig , Adams Val R. , Morehead R. Scott
Published: May 2011

The physiochemical properties of levofloxacin suggest that it is an agent which may exhibit altered pharmacokinetics in obese individuals. The purpose of this study was to describe the pharmacokinetics of a single 750-mg intravenous dose of levofloxacin in both hospitalized and ambulatory obese individuals. The hypothesis was that a standard dose of levofloxacin in obese individuals would achieve serum concentrations likely to be therapeutic. A single levofloxacin dose of 750 mg was infused over 90 min, and seven serial serum samples were subsequently obtained to evaluate the pharmacokinetics after the first dose. The peak concentrations of levofloxacin were comparable to those seen with normal-weight individuals. However, the area under the concentration-time curve and clearance were quite variable. Accelerated clearance was evident in the ambulatory obese individuals. Further investigation of the effects of obesity on the pharmacokinetics of levofloxacin is necessary to ensure optimal dosing.
Ceftaroline versus Ceftriaxone in a Highly Penicillin-Resistant Pneumococcal Pneumonia Rabbit Model Using Simulated Human Dosing
Authors: Croisier-Bertin Delphine , Piroth Lionel , Charles Pierre-Emmanuel , Larribeau Aurélie , Biek Donald , Ge Yigong , Chavanet Pascal
Published: May 2011

Ceftaroline (CPT) is a new cephalosporin exhibiting bactericidal activity against Gram-positive organisms, including methicillin-resistant
Staphylococcus aureus
(MRSA) and multidrug-resistant
Streptococcus pneumoniae
(MDRSP), as well as common Gram-negative pathogens. This study investigated the
in vivo
efficacy of a 48-hour simulated human dose regimen of CPT compared with ceftriaxone (CRO) against isolates of
S. pneumoniae
with different susceptibilities to penicillin in a rabbit pneumonia model. Three
S. pneumoniae
strains were used: CRO-susceptible penicillin-susceptible
S. pneumoniae
(CRO-S PSSP), CRO-susceptible penicillin-intermediate
S. pneumoniae
(CRO-S PISP), and CRO-resistant penicillin-resistant
S. pneumoniae
(CRO-R PRSP). Animals were randomized to the control group (no treatment) (
n
= 22) or to a group given intravenous (IV) CPT human equivalent (HE) dosage (600 mg/12 h;
n
= 19) or IV CRO HE dosage (1 g/24 h;
n
= 19). The total doses needed to achieve the HE dosage were 71 and 82 mg/kg of body weight/24 h for CRO and CPT, respectively. One group of rabbits infected with the CRO-R PRSP strain received intramuscular (IM) administration of CPT (5 or 20 mg/kg twice daily;
n
= 5 for each). Evaluation of efficacy was based on bacterial counts in the lungs and spleen. For IV CPT and IV CRO, the mean areas under the concentration-time curves from 0 to 24 h (AUC
0–24
s) were 155 and 938 mg · h/liter, respectively, the maximum concentrations in serum (
C
max
s) were 20 and 158 mg/liter, respectively, and the minimum concentrations in serum (
C
min
s) were 1.3 and 6 mg/liter, respectively. Both agents effectively treated pulmonary infections caused by CRO-S PSSP or CRO-S PISP with complete bacterial eradication in the lungs and spleen after 2 days of treatment. Against PRSP, CPT demonstrated excellent bactericidal activity, reducing bacterial counts in the lungs and spleen by approximately 8 and 4 log units, respectively (
P
< 0.001); CRO treatment resulted in a 2-log-unit reduction in the bacterial counts in lungs that did not reach statistical significance. Twice-daily IM CPT (5 mg/kg) reduced the bacterial burden by approximately 6 log units in the lungs and 3 log units in the spleen, and the 20-mg/kg dosage effectively eradicated PRSP infection. These findings further validate the
in vivo
bactericidal activity of CPT against pneumococci.
Dissemination of
bla
KPC-2
by the Spread of Klebsiella pneumoniae Clonal Complex 258 Clones (ST258, ST11, ST437) and Plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae Species in Brazil
Authors: Andrade Leonardo Neves , Curiao Tânia , Ferreira Joseane Cristina , Longo Juliana Mucedola , Clímaco Eduardo Carneiro , Martinez Roberto , Bellissimo-Rodrigues Fernando , Basile-Filho Aníbal , Evaristo Marco Antônio , Del Peloso Pedro F. , Ribeiro Vanessa Bley , Barth Afonso Luis , Paula Milena Cristina , Baquero Fernando , Cantón Rafael , Darini Ana Lúcia da Costa , Coque Teresa M.
Published: May 2011

This article reports the spread of
bla
KPC-2
in the Sao Paulo and Rio de Janeiro states, facilitated by globally spread
K. pneumoniae
clonal complex 258 (CC258) clones (ST258, ST11, and ST437) and a diversity of plasmids (IncFII, IncN, and IncL/M, two untypeable plasmids carrying Tn
4401
a or Tn
4401
b) successfully disseminated among species of the
Enterobacteriaceae
(
Enterobacter cloacae
,
Serratia marcescens
, and
Citrobacter freundii
). It also constitutes the first description of sequence type 258 (ST258) in Brazil, which was associated with a nosocomial hospital outbreak in Ribeirao Preto city.
Piperaquine Resistance Is Associated with a Copy Number Variation on Chromosome 5 in Drug-Pressured
Plasmodium falciparum
Parasites
Authors: Eastman Richard T. , Dharia Neekesh V. , Winzeler Elizabeth A. , Fidock David A.
Published: May 2011

The combination of piperaquine and dihydroartemisinin has recently become the official first-line therapy in several Southeast Asian countries. The pharmacokinetic mismatching of these drugs, whose plasma half-lives are ∼20 days and ∼1 h, respectively, implies that recrudescent or new infections emerging shortly after treatment cessation will encounter piperaquine as a monotherapy agent. This creates substantial selection pressure for the emergence of resistance. To elucidate potential resistance determinants, we subjected cloned
Plasmodium falciparum
Dd2 parasites to continuous piperaquine pressure
in vitro
(47 nM; ∼2-fold higher than the Dd2 50% inhibitory concentration [IC
50
]). The phenotype of outgrowth parasites was assayed in two clones, revealing an IC
50
against piperaquine of 2.1 μM and 1.7 μM, over 100-fold greater than that of the parent. To identify the genetic determinant of resistance, we employed comparative whole-genome hybridization analysis. Compared to the Dd2 parent, this analysis found (in both resistant clones) a novel single-nucleotide polymorphism in
P. falciparum crt
(
pfcrt
), deamplification of an 82-kb region of chromosome 5 (that includes
pfmdr1
), and amplification of an adjacent 63-kb region of chromosome 5. Continued propagation without piperaquine selection pressure resulted in “revertant” piperaquine-sensitive parasites. These retained the
pfcrt
polymorphism and further deamplified the chromosome 5 segment that encompasses
pfmdr1
; however, these two independently generated revertants both lost the neighboring 63-kb amplification. These results suggest that a copy number variation event on chromosome 5 (825600 to 888300) is associated with piperaquine resistance. Transgene expression studies are underway with individual genes in this segment to evaluate their contribution to piperaquine resistance.
Interleukin-10 and Immunity against Prokaryotic and Eukaryotic Intracellular Pathogens
Authors: Cyktor Joshua C. , Turner Joanne
Published: May 2011

The generation of an effective immune response against an infection while also limiting tissue damage requires a delicate balance between pro- and anti-inflammatory responses. Interleukin-10 (IL-10) has potent immunosuppressive effects and is essential for regulation of immune responses. However, the immunosuppressive properties of IL-10 can also be exploited by pathogens to facilitate their own survival. In this minireview, we discuss the role of IL-10 in modulating intracellular bacterial, fungal, and parasitic infections. Using information from several different infection models, we bring together and highlight some common pathways for IL-10 regulation and function that cannot be fully appreciated by studies of a single pathogen.