bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-guided inhibitor design for human FAAH by interspecies active site conversion
Authors: Mileni Mauro , Johnson Douglas S. , Wang Zhigang , Everdeen Daniel S. , Liimatta Marya , Pabst Brandon , Bhattacharya Keshab , Nugent Richard A. , Kamtekar Satwik , Cravatt Benjamin F. , Ahn Kay , Stevens Raymond C.
Published: August 2008

The integral membrane enzyme fatty acid amide hydrolase (FAAH) hydrolyzes the endocannabinoid anandamide and related amidated signaling lipids. Genetic or pharmacological inactivation of FAAH produces analgesic, anxiolytic, and antiinflammatory phenotypes but not the undesirable side effects of direct cannabinoid receptor agonists, indicating that FAAH may be a promising therapeutic target. Structure-based inhibitor design has, however, been hampered by difficulties in expressing the human FAAH enzyme. Here, we address this problem by interconverting the active sites of rat and human FAAH using site-directed mutagenesis. The resulting humanized rat (h/r) FAAH protein exhibits the inhibitor sensitivity profiles of human FAAH but maintains the high-expression yield of the rat enzyme. We report a 2.75-Å crystal structure of h/rFAAH complexed with an inhibitor,
N
-phenyl-4-(quinolin-3-ylmethyl)piperidine-1-carboxamide (PF-750), that shows strong preference for human FAAH. This structure offers compelling insights to explain the species selectivity of FAAH inhibitors, which should guide future drug design programs.
In vivo
imaging of pyrrole-imidazole polyamides with positron emission tomography
Authors: Harki Daniel A. , Satyamurthy Nagichettiar , Stout David B. , Phelps Michael E. , Dervan Peter B.
Published: August 2008

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The
18
F-radiolabeled polyamides were prepared by oxime ligation between 4-[
18
F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring β-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability.
In vivo
imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies.
StatAlign: an extendable software package for joint Bayesian estimation of alignments and evolutionary trees
Authors: Novák Ádám , Miklós István , Lyngsø Rune , Hein Jotun
Published: August 2008

Motivation: Bayesian analysis is one of the most popular methods in phylogenetic inference. The most commonly used methods fix a single multiple alignment and consider only substitutions as phylogenetically informative mutations, though alignments and phylogenies should be inferred jointly as insertions and deletions also carry informative signals. Methods addressing these issues have been developed only recently and there has not been so far a user-friendly program with a graphical interface that implements these methods.

Results: We have developed an extendable software package in the Java programming language that samples from the joint posterior distribution of phylogenies, alignments and evolutionary parameters by applying the Markov chain Monte Carlo method. The package also offers tools for efficient on-the-fly summarization of the results. It has a graphical interface to configure, start and supervise the analysis, to track the status of the Markov chain and to save the results. The background model for insertions and deletions can be combined with any substitution model. It is easy to add new substitution models to the software package as plugins. The samples from the Markov chain can be summarized in several ways, and new postprocessing plugins may also be installed.

Availability: The code is available from http://phylogeny-cafe.elte.hu/StatAlign/

Contact:  miklosi@ramet.elte.hu
Modelling the occurrence and abundance of a colonial species, the arctic tern Sterna paradisaea in the archipelago of SW Finland
Authors: Heinänen Stefan , Rönkä Mia , Von Numers Mikael
Published: August 2008

Knowledge of the habitat requirements and suitable breeding areas of sea birds is crucial for their management and conservation. However, there are still few studies that have modelled the breeding distribution and abundance of colonial sea birds. In this study, we created predictive distribution models for a colonial species, the arctic tern Sterna paradisaea, using 14 environmental variables calculated for 525 islands in the Archipelago Sea in SW Finland. We modelled the occurrence (presence‐absence) using generalised additive models (GAMs) and abundance (pair numbers/colony size) using hurdle models fitted with GAM. We tested for spatial autocorrelation in model residuals and evaluated the models on independent data. Critical factors influencing the occurrence of the arctic tern were the proportions of boulder or gravel and forest of island area, as well as island maximum elevation and area, such that the species seemed to prefer large and low islands with sparse vegetation. Abundance was influenced by the proportions of boulder or gravel and bare rock of island area, as well as exposure and island area. To some extent, different factors influenced the occurrence and the abundance. The evaluation results of the models were good, with an AUC value of 0.91 for the most accurate presence‐absence model and a Pearson's correlation coefficient of 0.60 for the most accurate hurdle model. The predictive ability of the models increased when we removed islands with single or few breeding pairs from the data set. Although the hurdle models did not produce accurate pair number estimates, they indicated which islands are suitable for larger colonies. Abundance is a crucial factor for colonial species. This modelling technique can therefore be of great value for the conservation and management of the arctic tern and similar colonial species.
Efficacy of fractionated gemtuzumab ozogamicin combined with cytarabine in advanced childhood myeloid leukaemia
Authors: Brethon Benoit , Yakouben Karima , Oudot Caroline , Boutard Patrick , Bruno Bénédicte , Jérome Cécile , Nelken Brigitte , De Lumley Lionel , Bertrand Yves , Dalle Jean‐Hugues , Chevret Sylvie , Leblanc Thierry , Baruchel André
Published: August 2008

Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20–30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33+ AML. Seventeen children received GO 3 mg/m2 on days 1, 4 and 7 plus cytarabine 100 mg/m2/d for 7 d on a compassionate‐use basis. Seven patients then received GO‐based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy‐related AML (t‐AML)] had not yet been treated. Mean follow‐up was 17 months (8–33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3–4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut‐off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.
GH replacement in patients with non‐functioning pituitary adenoma (NFA) treated solely by surgery is not associated with increased risk of tumour recurrence
Authors: Arnold J. R. , Arnold D. F. , Marland A. , Karavitaki N. , Wass J. A. H.
Published: August 2008

Background  Subjects with non‐functioning pituitary adenomas (NFAs) frequently develop GH deficiency due to tumour expansion or as a consequence of tumour therapy. The safety of GH replacement (GHR) in these individuals remains unclear.

Objective  To assess the effect of GHR on tumour recurrence in patients with NFAs solely treated by surgical removal.

Patients and methods  The study involved all patients with NFA who presented to the Department of Endocrinology in Oxford between January 1989 and July 2005 and were treated solely by surgical removal of the tumour. Patients with follow up < 1 year were excluded. Recurrence was diagnosed on the basis of radiological appearances (detectable tumour after gross total removal or regrowth of pre‐existing residue) on regular imaging surveillance.

Results  One hundred and thirty patients were included in the study, and were followed up for a mean period of 6·8 ± 4·2 years (median 5·7, range 1·2–17·6). Twenty‐three patients received GHR [16 male, 7 female, mean age at tumour diagnosis 53·7 ± 14·6 years (range 20–80)]. The mean duration of GHR was 4·6 ± 2·5 years (median 5·3, range 0·4–8·7). One hundred and seven subjects did not receive GH therapy [61 male, 46 female, mean age at tumour diagnosis 56·2 ± 14·0 years (range 20–87)]. Tumour regrowth occurred in 38 non‐GH treated subjects (36%) and 8 GHR subjects (35%). Regrowth was detected at a mean of 4·8 ± 2·8 years (range 1–11 years) in the non‐GH treated group, and at 6·5 ± 2·3 years in the GHR group. In the GHR group, recurrence occurred after a mean of 2·9 ± 2·2 years (range 0·4–5·9 years) following commencement of GH treatment. The Cox regression analysis showed that after adjusting for sex, age at tumour diagnosis, cavernous sinus invasion at diagnosis and type of tumour removal (partial or complete based on postoperative scan), GH treatment was not a significant independent predictor of recurrence (P = 0·09; hazard ratio = 0·51; 95% CI, 0·24–1·12).

Conclusion   GH replacement in patients with NFA treated by surgery alone is not associated with an increased risk of tumour recurrence.
Microstructure and mechanical properties related to particle size distribution and composition in dark chocolate
Authors: Afoakwa Emmanuel Ohene , Paterson Alistair , Fowler Mark , Vieira Joselio
Published: August 2008

Composition in dark chocolate was varied and the effects determined on microstructure, using light microscopy, and mechanical properties of molten and tempered chocolates, using a TA.HD Plus Texture Analyser. Compositional parameters were particle size distribution (PSD) (D90 of 18, 25, 35 and 50 μm), fat (25%, 30% and 35%) and lecithin (0.3% and 0.5%) contents. Micrographs revealed wide variations in sugar crystalline network structure and inter‐particle interaction strengths related to PSD and fat level. Samples containing 25% fat had more crystal agglomerates, well flocculated with greater particle‐to‐particle interaction strengths than those with higher (30% and 35%) fat contents. Increasing the D90 to 35–50 μm caused broadening of the PSD, with particles becoming coarser, which were similar at all fat levels. Mechanical analysis showed that PSD, fat and lecithin content significantly influenced firmness of molten chocolate and hardness of solid (tempered) chocolate with significant interactions among factors. Particle size was inversely correlated with firmness (1235–173 g) and hardness (7062–5546 g). Greatest effect of PSD was with 25% fat and 0.3% lecithin. With higher fat and lecithin contents, the PSD influence was reduced. It was concluded that PSD, fat and lecithin contents and their interactions were central to mechanical properties of dark chocolates.
Application of failure mode and effect analysis and cause and effect analysis on processing of ready to eat vegetables – part II
Authors: Varzakas Theodoros H. , Arvanitoyannis Ioannis S.
Published: August 2008

Failure mode and effect analysis (FMEA) model has been applied for the risk assessment of ready to eat vegetables manufacturing. A tentative approach of FMEA application to the ready to eat vegetables industry was attempted in conjunction with cause and effect diagrams. critical control points have been identified and implemented in the cause and effect diagram (also known as Ishikawa, tree diagram and fishbone diagram). The main emphasis was put on the quantification of risk assessment by determining the risk priority number (RPN) per identified processing hazard. Receiving, storage and distribution, packaging and cooling were the processes identified as the ones with the highest RPN (225, 225, 180 and 144 respectively) and corrective actions were undertaken. Following the application of corrective actions, a second calculation of RPN values was carried out leading to considerably lower values (below the upper acceptable limit of 130). It is noteworthy that the application of Ishikawa (cause and effect or tree diagram) led to converging results thus corroborating the validity of conclusions derived from risk assessment and FMEA. Therefore, the incorporation of FMEA and cause and effect analysis within the ISO22000 system of a ready to eat vegetables processing industry is considered imperative.
Identifying health‐related quality of life (HRQL) domains for multiple chronic conditions (diabetes, hypertension and dyslipidemia): patient and provider perspectives
Authors: Bounthavong Mark , Law Anandi V.
Published: August 2008

Objective  To examine patient and provider perspectives about the impact of having diabetes, hypertension and/or dyslipidemia (DHD) on health‐related quality of life (HRQL) in order to identify domains for an HRQL instrument focusing on specific chronic diseases (DHD).

Study design  Exploratory qualitative design was used to elicit patient and provider responses. Patient survey contained 11 demographic and nine content questions inquiring how the disease(s) affected patient HRQL. Provider survey examined how the disease(s) affected their patient's HRQL and crucial factors for improvement. Patients were included if they had DHD and spoke English. Providers working with DHD patients were identified among university faculty and community practitioners.

Results  Thirty‐eight patients (24.7%) completed the interviews. Three judges content analysed patient responses and proposed seven categories (patients ranked physical functioning first followed by diet, emotional well‐being (E), general well‐being, social functioning (S), ‘no change in HRQL’ and medications). One question about medications had four categories (medication inconvenience, medication side effects, forgetfulness and general well‐being). Index for reliability was greater than 80% for all categories. Providers ranked lifestyle modification (LM), first followed by complications, medication, self‐care, E, education, S, physical activity and resources (ability to pay) as components that impact HRQL.

Conclusions  Patient and provider perspectives were similar in four areas (E, S, medication and diet); however, the differences were in how these impacted HRQL – patients focused on activities relevant to daily life that were affected, while providers based it on processes of therapy management and self‐care (education and implementation of LM).
The use of d‐dimer testing and Wells score in patients with high probability for acute pulmonary embolism
Authors: Söderberg Mårten , Brohult Johan , Jorfeldt Lennart , Lärfars Gerd
Published: August 2008

Rationale, aims and objective  To investigate if a combination of Wells pre‐test probability score and D‐dimer testing could be used as a safe base for making clinical decisions on further investigations for patients with intermediate to high risks of pulmonary embolism (PE).

Methods  One hundred and twenty patients with signs or symptoms of acute PE were investigated with pulmonary angiography (PA) or contrast enhanced computed tomography of the pulmonary arteries (CTPA), D‐dimer testing (Tinaquant®) and clinical scoring using the Wells pre‐test probability score during their first 48 hours at the hospital. Patients were recruited consecutively from emergency departments at two teaching hospitals.

Results  The cut‐off value of 0.5 mg L−1 in D‐dimer analysis is proved adequate with a negative predictive value (NPV) of 92% in this group of patients with intermediate to high risks. The combination of D‐dimer testing and Wells score increases the NPV to 94%. The specificities of both tests were low.

Conclusion  D‐dimer and Wells pre‐test probability scores are safe to rule out acute PE even in patients with at least an intermediate risk of PE, but the specificity is low. D‐dimer testing had a higher NPV than Wells score and the combination improved the algorithm further. The cut‐off level for a high risk of PE measured with the Wells score was four and it seems reasonable to use that cut‐off level in future algorithms. In addition, both PA and CTPA can present false positive and negative results difficult to interpret.
Electronic health records: Use, barriers and satisfaction among physicians who care for black and Hispanic patients
Authors: Jha Ashish K. , Bates David W. , Jenter Chelsea , Orav E. John , Zheng Jie , Cleary Paul , Simon Steven R.
Published: August 2008

Objectives  Electronic health records (EHRs) are a promising tool to improve the quality of health care, although it remains unclear who will benefit from this new technology. Given that a small group of providers care for most racial/ethnic minorities, we sought to determine whether minority‐serving providers adopt EHR systems at comparable rates to other providers.

Methods  We used survey data from stratified random sample of all medical practices in Massachusetts in 2005. We determined rates of EHR adoption, perceived barriers to adoption, and satisfaction with EHR systems.

Results  Physicians who reported patient panels of more than 40% black or Hispanic had comparable levels of EHR adoption than other physicians (27.9% and 21.8%, respectively, P = 0.46). Physicians from minority‐serving practices identified financial and other barriers to implementing EHR systems at similar rates, although these physicians were less likely to be concerned with privacy and security concerns of EHRs (47.1% vs. 64.4%, P = 0.01). Finally, physicians from high‐minority practices had similar perceptions about the positive impact of EHRs on quality (73.7% vs. 76.6%, P = 0.43) and costs (46.9% vs. 51.5%, P = 0.17) of care.

Conclusions  In a state with a diverse minority population, we found no evidence that minority‐serving providers had lower EHR adoption rates, faced different barriers to adoption or were less satisfied with EHRs. Given the importance of ensuring that minority‐serving providers have equal access to EHR systems, we failed to find evidence of a new digital divide.
Polarized light field microscopy: an analytical method using a microlens array to simultaneously capture both conoscopic and orthoscopic views of birefringent objects
Authors: OLDENBOURG R.
Published: August 2008

For the comprehensive analysis of anisotropic materials, a new approach, called ‘polarized light field microscopy’ is introduced. It uses an LC‐PolScope to which a microlens array was added at the image plane of the objective lens. The system is patterned after the ‘light field microscope’ that achieves both lateral and axial resolution in thick specimens in a single camera exposure. In polarized light field microscopy, the microlens array generates a hybrid image consisting of an array of small conoscopic images, each sampling a different object area. Analysis of the conoscopic images reveals the birefringence of each object area as a function of the propagation direction of transmitted light rays. The principles and utility of the instrument that we are calling ‘light field LC‐PolScope’ are demonstrated with images of a thin, polycrystalline calcite film, revealing the azimuth and inclination angle of the optic axis for many crystals simultaneously, including crystals with diameters as small as 2 μm. Compared to traditional conoscopy and related methods, the vastly improved throughput and quantitative analysis afforded by the light field LC‐PolScope make it the instrument of choice for measuring 3D birefringence parameters of complex structures.
Motion‐enhanced, differential interference contrast (MEDIC) microscopy of moving vesicles in live cells: VE‐DIC updated
Authors: HILL D. B. , MACOSKO J. C. , HOLZWARTH G. M.
Published: August 2008

Video‐enhanced differential interference contrast microscopy with background subtraction has made visible many structures and processes in living cells. In video‐enhanced differential interference contrast, the background image is stored manually by defocusing the microscope before images are acquired. We have updated and improved video‐enhanced differential interference contrast by adding automatic generation of the background image as a rolling average of the incoming image stream. Subtraction of this continuously updated 12‐bit background image from the incoming 12‐bit image stream provides a flat background which allows the contrast of moving objects, such as vesicles, to be strongly enhanced while suppressing stationary features such as the overall cell shape. We call our method MEDIC, for motion‐enhanced differential interference contrast. By carrying out background subtraction with 12‐bit images, the number of grey levels in the moving vesicles can be maximized and a single look‐up table can be applied to the entire image, enhancing the contrast of all vesicles simultaneously. Contrast is increased by as much as a factor of 13. The method is illustrated with raw, background and motion‐enhanced differential interference contrast images of moving vesicles within a neurite of a live PC12 cell and a live chick motorneuron.
A comparison between the force of infection estimates for blood‐borne viruses in injecting drug user populations across the European Union: a modelling study
Authors: Sutton A. J. , Hope V. D. , Mathei C. , Mravcik V. , Sebakova H. , Vallejo F. , Suligoi B. , Brugal M.T. , Ncube F. , Wiessing L. , Kretzschmar M.
Published: August 2008

Summary.  A number of studies have been conducted in injecting drug user (IDU) populations in Europe, in which the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) was measured together with demographic and epidemiological information such as age and the age at first injection. A measure of the risk of becoming infected is the force of infection (FOI), defined as the per capita rate at which susceptible individuals acquire infection. The objective of this study was to estimate the FOI and its heterogeneity for HBV, HCV and HIV (where available) for IDU populations in a number of countries in Europe. Data were obtained from five countries: Belgium, the United Kingdom, Spain and Italy, and the Czech Republic, which provided two data sets. The model describes the prevalence of infection as a function of the FOI that may vary over time or duration of IDU. In addition to this, if two or more infections were being considered then a parameter describing the potential heterogeneity of the FOI within the IDU population was also estimated. The results here add to the growing evidence that new initiates to injecting are at an increased risk of blood‐borne viral infection compared with more experienced IDUs. In addition, there is evidence of individual heterogeneity of FOI estimates within the overall IDU populations. This suggests that different proportions of individuals in each population are at increased risk of infection compared with the rest of the population. Future interventions should identify and target these individuals. Moreover, changes over time in individual heterogeneity estimates of IDU populations may provide an indicator for measuring intervention impacts.
The advantages of topical combination therapy in the treatment of inflammatory dermatomycoses
Authors: Havlickova Blanka , Friedrich Markus
Published: August 2008

Dermatomycoses are contagious superficial fungal infections, which are highly prevalent in developed and developing countries. Caused by a range of Epidermophyton, Microsporum and Trichophyton species, dermatomycoses manifest on glabrous skin as ‘ringworm’, an annular scaly lesion with a variable inflammatory component. Itch is the chief subjective symptom, particularly in tinea cruris. Unless lesions are extensive or resistant to local therapy, dermatomycoses of glabrous skin are treated with topical antifungal agents, such as imidazoles and allylamines. Studies show, however, that the addition of a topical corticosteroid to imidazole therapy increases the bioavailability and prolongs the activity of the antimycotic, while rapidly reducing inflammatory symptoms. Travocort® is a combination of 1% isoconazole nitrate (ISN), a broad‐spectrum imidazole with established antimicrobial activity and antimycotic efficacy, and 0.1% diflucortolone valerate (DFV), a potent topical corticosteroid with low systemic absorption and therefore a low risk of systemic glucocorticoid side‐effects. In randomised, double‐blind controlled clinical trials, Travocort® therapy showed a more rapid onset of action, faster relief of itch and other inflammatory symptoms, improved overall therapeutic benefits and better mycological cure rate during the first 2 weeks of treatment compared with ISN monotherapy. Travocort® is well tolerated and, because of prolonged ISN retention in the skin, provides antifungal protection against reinfection for some weeks after therapy.
SIMULTANEOUS MODELLING OF THE MICHAELIS‐MENTEN KINETICS OF PARACETAMOL SULPHATION AND GLUCURONIDATION
Authors: Reith David , Medlicott Natalie J , Kumara De Silva Rohana , Yang Lin , Hickling Jeremy , Zacharias Mathew
Published: August 2008

The aim of the present study was to perform anin vivoestimation of the Michaelis‐Menten constants of the major metabolic pathways of paracetamol (APAP).

A two‐occasion, single‐dose cross‐over trial was performed using 60 and 90 mg/kg doses of APAP in healthy patients undergoing third molar dental extraction. Plasma samples were collected over 24 h and urine was collected for 8 h after dosing. Twenty patients were enrolled in the study and complete data for plasma and urine were available for both doses for 13 volunteers who were included in the analysis; seven of the volunteers were men, the median age (range) was 22 years (19–31) and the median weight (range) was 68 kg (50–86).

The mean (95% CI) kmfor APAP glucuronidation was 6.89 mmol/L (3.57–10.22) and the Vmaxwas 0.97 mmol/h per kg (0.65–1.28). The kmfor APAP sulphation was 0.097 mmol/L (0.041–0.152) and the Vmaxwas 0.011 mmol/h per kg (0.009–0.013). For the combined excretion of APAP‐cysteine and APAP‐mercapturate, the kmwas 0.303 mmol/L (0.131–0.475) and the Vmaxwas 0.004 mmol/h per kg (0.002–0.005).

The estimates forin vivoMichaelis‐Menten constants for APAP glucuronidation and sulphation were in the order of those reported previously usingin vitromethods.
Are traditional risk factors valid for assessing cardiovascular risk in end‐stage renal failure patients?
Authors: SHAH DIBYA S , POLKINGHORNE KEVAN R , PELLICANO REBECCA , KERR PETER G
Published: August 2008

Aim:  Cardiovascular diseases (CVD) are the major cause of morbidity and mortality in end‐stage renal failure (ESRF). Establishing whether traditional risk factors are valid predictors of CVD in ESRF is important in order to devise preventive and interventional strategies for the ESRF populations.

Methods:  In this retrospective cohort study, a cohort of patients on dialysis were examined between September 2000 and February 2001. Only those without previous CVD events at baseline were included. For each individual, 5 year CVD risk was calculated using the New Zealand 5 year CVD risk prediction charts based on the Framingham Heart Study prognostic algorithm. The subsequent 5 year CVD outcome for each patient was determined and the observed rate of first CVD events was compared to the predicted risk. Relation of individual risk factors with the CVD outcome was also assessed.

Results:  Of the patients, 274 were without previous CVD events at baseline and 27% experienced CVD events during the subsequent 5 years. Observed CVD risk was more than twofold that of predicted risk although there was a linear correlation between the two. Among individual risk factors, increasing age, diabetes and smoking were significantly related to the incidence of the CVD events but, unlike in the general population, systolic blood pressure, total cholesterol/high‐density lipoprotein ratio and body mass index were not significantly related to CVD events.

Conclusion:  The very high incidence of CVD in ESRF patients suggest that non‐traditional risk factors present in the uraemic state are independent risk factors for CVD in ESRF patients. Nevertheless, the application of traditional cardiovascular risk profiles does allow risk stratification of the ESRF population.
Long‐term safety, tolerability, and efficacy of the novel anti‐muscarinic agent imidafenacin in Japanese patients with overactive bladder
Authors: Homma Yukio , Yamaguchi Osamu
Published: August 2008

Objectives:  To evaluate the long‐term safety, tolerability, and efficacy of imidafenacin, a novel anti‐muscarinic agent, in Japanese patients with overactive bladder.

Methods:  Men and women who had overactive bladder symptoms were enrolled for open‐label treatment with 0.1 mg of imidafenacin twice daily for 52 weeks; the safety and efficacy of the treatment regimen were assessed.

Results:  A total of 478 patients received the treatment and 376 patients completed the 52‐week program. Imidafenacin was well tolerated, the most common adverse event being a dry mouth (40.2% of the patients). Compared with short‐term treatment, long‐term treatment did not produce an increase in the frequency of adverse events. Imidafenacin had no significant effects on the corrected QT interval, vital signs, results from laboratory tests, or post‐void residual volume. A significant efficacy of imidafenacin was observed from week 4 through week 52. After 52 weeks, imidafenacin produced mean changes from baseline in the number of incontinence episodes (−83.51%), urgency incontinence episodes (−84.21%), voiding frequency (−2.35 micturitions/day), urgency episodes (−70.53%), and volume voided per micturition (28.99 mL). There were also significant reductions from baseline in all domains of the King's Health Questionnaire.

Conclusions:  Favorable safety, tolerability, and efficacy profiles for 0.1 mg of imidafenacin administered twice daily were maintained over 52 weeks in Japanese patients with overactive bladder.
Corporate and Divisional Manager Involvement in Divestitures – a Contingent Analysis*
Authors: Brauer Matthias
Published: August 2008

In prior research, insights into the degree and type of corporate and divisional level manager involvement in divestiture processes have remained sparse. Based on extant empirical research on managerial processes in divestitures and a review of literature on the antecedents of divestitures, this paper identifies a set of internal and external contingencies which potentially influence the degree of corporate and divisional level manager involvement in divestitures. Findings from an in‐depth case study of four parallel divestitures by a major European technology company (TechCo) in the late 1990s indicate which of these contingencies seem to have a relevant influence on the involvement of the different managerial levels in divestiture processes. The contingent approach contributes to theory by providing explanations for existing, conflicting empirical evidence concerning the degree and type of corporate and divisional level manager involvement in divestiture processes. The second major theoretical contribution of the paper lies in the identification and description of the type of managerial actions these different contingencies bring about.
The Life Course as Developmental Theory
Authors: Elder Glen H.
Published: August 2008

The pioneering longitudinal studies of child development (all launched in the 1920s and 1930s) were extended well beyond childhood. Indeed, they eventually followed their young study members up to the middle years and later life. In doing so, they generated issues that could not be addressed satisfactorily by available theories. These include the recognition that individual lives are influenced by their ever‐changing historical context, that the study of human lives calls for new ways of thinking about their pattern and dynamic, and that concepts of human development should apply to processes across the life span. Life course theory has evolved since the 1960s through programmatic efforts to address such issues.
Exploring the Genetic and Environmental Etiology of High General Cognitive Ability in Fourteen‐ to Thirty‐Six‐Month‐Old Twins
Authors: Petrill Stephen A. , Saudino Kimberly , Cherny Stacey S. , Emde Robert N. , Fulker David W. , Hewitt John K. , Plomin Robert
Published: August 2008

Although numerous theories have attempted to explain the origins of high general cognitive ability (g), the genetic and environmental etiology of high g during infancy and early childhood has not previously been investigated. We report results of a twin study of high cognitive ability at 14, 20, 24, and 36 months using twins from the more than 600 children participating in the MacArthur Longitudinal Twin Study. High g groups were formed from the ninetieth percentile and above at each age, with IQ equivalent means at or above 126 across the ages. Results suggest increasing genetic influence and increasing genetic stability from 14 to 36 months using DeFries‐Fulker multiple regression analyses. However, genetic influences are substantial when examining individuals who possess high g scores averaged across all 4 ages. These results suggest that, although high cognitive ability may be genetically influenced in early childhood, these influences differ in magnitude from 14 to 36 months.
The Relation of Change in Maternal Interactive Styles to the Developing Social Competence of Full‐Term and Preterm Children
Authors: Landry Susan H. , Smith Karen E. , Miller‐Loncar Cynthia L. , Swank Paul R.
Published: August 2008

This study evaluated the changing nature of mothers' interactive behaviors to understand alterations in children's social development across 6, 12, 24, and 40 months of age. Social skills were observed during daily activities and toy play in the home for medically high risk (HR;n= 73) and low risk (LR;n= 114) very low birthweight (VLBW) preterm and full‐term (FT;n= 112) children. Variations in mothers' responses to children's changing capabilities predicted rates of change in children's social skills. For example, mothers who showed higher levels of maintaining measured across 6 to 40 months had children who displayed greater increases in initiating, but this was more apparent in daily activities than toy play and for the VLBW children compared to the FT children. Those VLBW children at the highest degrees of biological risk displayed faster gains in initiating than the other groups when their mothers provided even greater levels of support. Results demonstrate the importance of using methodologies that test more complex models of growth when evaluating parent‐child relations.
Individual Differences in Contextual Facilitation: Evidence from Dyslexia and Poor Reading Comprehension
Authors: Nation Kate , Snowling Margaret J.
Published: August 2008

Ninety‐two 7‐ to 10‐year‐old children read words presented in isolation or following a spoken sentence context. In absolute terms, poor readers showed more contextual facilitation than good readers. However, when the relative benefit of context was assessed, this was greater for children with better reading skills, and comprehension was a better predictor of contextual facilitation than decoding. Study 2 compared the performance of dyslexics with that of reading‐age matched poor comprehenders and normal readers. The dyslexics showed greater contextual facilitation than the normal readers who, in turn, showed more priming than poor comprehenders. The results show that dyslexic children use context to compensate for poor decoding skills, whereas children with poor reading comprehension skills fail to benefit from context as much as normal readers.
A Three Year Follow‐up of Attachment and Indiscriminate Friendliness in Children Adopted from Romanian Orphanages
Authors: Chisholm Kim
Published: August 2008

Attachment and indiscriminately friendly behavior were assessed in children who had spent at least 8 months in a Romanian orphanage (RO) and two comparison groups of children: a Canadian‐born, nonadopted, never institutionalized comparison group (CB) and an early adopted comparison group adopted from Romania before the age of 4 months (EA). Attachment was assessed using 2 measures: an attachment security questionnaire based on parent report, and a Separation Reunion procedure that was coded using the Preschool Assessment of Attachment. Indiscriminately friendly behavior was examined using parents' responses to 5 questions about their children's behavior with new adults. Although RO children did not score differently from either CB or EA children on the attachment security measure based on parent report, they did display significantly more insecure attachment patterns than did children in the other 2 groups. In addition, RO children displayed significantly more indiscriminately friendly behavior than both CB and EA children, who did not differ in terms of indiscriminate friendliness. RO children's insecure attachment patterns were not associated with any aspect of their institutional environment, but were related to particular child and family characteristics. Specifically, insecure RO children had more behavior problems, scored lower on the Stanford‐Binet Intelligence Scale, and had parents who reported significantly more parenting stress than RO children classified as secure.
A Prospective Longitudinal Study of Attachment Disorganization/Disorientation
Authors: Carlson Elizabeth A.
Published: August 2008

The research explores the antecedents and consequences of attachment disorganization from a prospective longitudinal perspective. The relations of attachment disorganization/disorientation to endogenous (e.g., maternal medical history, infant temperament) and environmental (e.g., maternal caregiving quality, infant history of abuse) antecedents and to behavioral consequences from 24 months to 19 years are examined. For the 157 participants in the longitudinal study, attachment disorganization was correlated significantly with environmental antecedents (e.g., maternal relationship and risk status, caregiving quality, and infant history of maltreatment), but not with available endogenous antecedents. Infant history of attachment disorganization was correlated with consequent variables related to mother‐child relationship quality at 24 and 42 months, child behavior problems in preschool, elementary school and high school, and psychopathology and dissociation in adolescence. Structural models suggest that disorganization may mediate the relations between early experience and later psychopathology and dissociation. The findings are considered within a developmental view of psychopathology, that is, pathology defined in terms of process, as a pattern of adaptation constructed by individuals in their environments.
Peer Relationships and Self‐Esteem among Children Who Have Been Maltreated
Authors: Bolger Kerry E. , Patterson Charlotte J. , Kupersmidt Janis B.
Published: August 2008

A prospective longitudinal design was employed to assess risks associated with maltreatment in a representative community sample of 107 maltreated children and an equal number of nonmaltreated comparison children. Heightened difficulties in peer relationships and self‐esteem were associated with greater severity and chronicity of maltreatment. For example, children who experienced chronic maltreatment were less well‐liked by peers. Type of maltreatment was also related to specific aspects of children's adjustment. For instance, sexual abuse predicted low self‐esteem, but not problems in peer relationships. Emotional maltreatment, on the other hand, was related to difficulties in peer relationships, but not to low self‐esteem. Thus, the best predictions of specific aspects of children's adjustment were provided by considering timing, type, and severity of maltreatment. For some groups of maltreated children, having a good friend was associated with improvement over time in self‐esteem.
The Foundations of Literacy: Learning the Sounds of Letters
Authors: Treiman Rebecca , Tincoff Ruth , Rodriguez Kira , Mouzaki Angeliki , Francis David J.
Published: August 2008

Learning the sounds of letters is an important part of learning to read and spell. To explore the factors that make some letter‐sound correspondences easier for children to learn than others, we first analyzed knowledge of letters' sounds (and names) by 660 children between 3½ and 7½ years old. A second study examined preschoolers' (M age 4 years, 11 months) ability to learn various sound‐letter mappings. Together, the results show that an important determinant of letter‐sound knowledge is whether the sound occurs in the name of the letter and, if so, whether it is at the beginning or the end. The properties of the sound itself (consonant versus vowel, sonorant versus obstruent, stop versus continuant) appear to have little or no influence on children's learning of basic letter‐sound correspondences. The findings show that children use their knowledge of letters' names when learning the letters' sounds rather than memorizing letter‐sound correspondences as arbitrary pairings.
Causal Inferences and the Positivity Bias in Children: The Role of the Covariation Principle
Authors: Schuster Beate , Ruble Diane N. , Weinert Franz E.
Published: August 2008

It is argued that developmental studies regarding Kelley's covariation principle had provided children with incomplete covariation information, and that the assessment of attributions differed conceptually from Kelley's model and pertinent adult studies. It is further proposed that younger children's tendency for positive self‐evaluations (“positivity bias”) is due to their inferences not yet being based on the mechanism described by the covariation principle. In 2 studies, conducted in the United States and Germany, participants of different ages received complete covariation information and were asked for attributions, ability estimations, and expectations of success. Children from grade 2 on selected the correct cause(s) when the effect covaried only with one cause, but only at a later age when covariation with 2 causes was presented. Ability estimations and expectation of success were more positive in younger than in older participants, replicating the “positivity bias.” However, children did not simply become more negative (“pessimistic”) with age but rather more realistic: Estimations of ability decreased when failure covaried with the person but not when there was covariation with the entity; expectation of success decreased when failure covaried with a stable cause (person or entity) but not when no covariation information was provided, and even increased when failure covaried with the circumstances (a variable cause).
Parenting and Preschooler Attachment among Low‐Income Urban African American Families
Authors: Barnett Douglas , Kidwell Shari L. , Leung Kwan Ho
Published: August 2008

This study examined the parental correlates of child attachment in a preschool‐aged, economically disadvantaged, urban, African American sample. Sixty‐nine 4‐ to 5‐year‐olds and their primary caregivers participated in the Strange Situation assessment procedure. Based on Cassidy and Marvin's classification system for preschoolers, 61% of the children were classified as securely attached, with girls being significantly more likely to be securely attached than boys (74% versus 45%). The majority of the insecure attachments were of the avoidant variety. Consistent with attachment theory, parents of securely attached children were rated as significantly more warm and accepting and less controlling with their children than were parents of insecurely attached preschoolers. Relative to parents of securely attached preschoolers, parents of children judged to be insecurely attached reported being more likely to use corporal punishment and less likely to use verbal reminders when their children misbehaved. Parenting was associated with attachment over and above the effects of child sex.
Words and Gestures: Infants' Interpretations of Different Forms of Symbolic Reference
Authors: Namy Laura L. , Waxman Sandra R.
Published: August 2008

In 3 experiments, we examine the relation between language acquisition and other symbolic abilities in the early stages of language acquisition. We introduce 18‐and 26‐month‐olds to object categories (e.g., fruit, vehicles) using a novel word or a novel symbolic gesture to name the objects. We compare the influence of these two symbolic forms on infants' object categorization. Children at both ages interpreted novel words as names for object categories. However, infants' interpretations of gestures changed over development. At 18 months, infants spontaneously interpreted gestures, like words, as names for object categories; at 26 months, infants spontaneously interpreted words but not gestures as names. The older infants succeeded in interpreting novel gestures as names only when given additional practice with the gestural medium. This clear developmental pattern supports the prediction that an initial general ability to learn symbols (both words and gestures) develops into a more focused tendency to use words as the predominant symbolic form.
Individual Differences in Emotionality in Infancy
Authors: Kochanska Grazyna , Coy Katherine C. , Tjebkes Terri L. , Husarek Susan J.
Published: August 2008

In this multimethod investigation of early emotionality, we observed 112 8‐to 10‐month‐olds' responses to standard procedures consisting of multiple brief episodes that elicited joy, fear, anger, and discomfort to aversive stimulation. We obtained parental reports about the infants' temperament and observed their emotional tone during naturalistic interactions with their mothers. Parameters of emotional response to the standard procedures (latency, discrete behaviors, and average and peak intensity across facial, vocal, and bodily channels) cohered strongly within each episode. To a lesser extent and with the exception of anger, they also cohered across episodes targeting the same emotion. The four emotions appeared orthogonal, except for the peak intensity of response, which cohered modestly across the 3 negative emotions. The emotionality measures converged to some extent: responses to the standard procedures and father‐reported temperament related meaningfully to the infant's emotional tone in mother‐child interactions. As predicted, infants' capacity for focused or effortful attention was modestly associated with better modulated negative emotionality.