bluuebunny/crossref_metadata_2025 huggingface dataset:
Biophysical mechanisms of phase contrast in gradient echo MRI
Authors: He Xiang , Yablonskiy Dmitriy A.
Published: July 2009

Recently reported contrast in phase images of human and animal brains obtained with gradient-recalled echo MRI holds great promise for the in vivo study of biological tissue structure with substantially improved resolution. Herein we investigate the origins of this contrast and demonstrate that it depends on the tissue “magnetic architecture” at the subcellular and cellular levels. This architecture is mostly determined by the structural arrangements of proteins, lipids, non-heme tissue iron, deoxyhemoglobin, and their magnetic susceptibilities. Such magnetic environment affects/shifts magnetic resonance (MR) frequencies of the water molecules moving/diffusing in the tissue. A theoretical framework allowing quantitative evaluation of the corresponding frequency shifts is developed based on the introduced concept of a generalized Lorentzian approximation. It takes into account both tissue architecture and its orientation with respect to the external magnetic field. Theoretical results quantitatively explain frequency contrast between GM, WM, and CSF previously reported in motor cortex area, including the absence of the contrast between WM and CSF. Comparison of theory and experiment also suggests that in a normal human brain, proteins, lipids, and non-heme iron provide comparable contributions to tissue phase contrast; however, the sign of iron and lipid contributions is opposite to the sign of contribution from proteins. These effects of cellular composition and architecture are important for quantification of tissue microstructure based on MRI phase measurements. Also theory predicts the dependence of the signal phase on the orientation of WM fibers, holding promise as additional information for fiber tracking applications.
Benefits of omega‐3 supplementation for schoolchildren: Review of the current evidence
Authors: Kirby Amanda , Woodward Amelia , Jackson Sarah
Published: July 2009

Despite the potential impact nutrition may have on learning, there have been surprisingly few papers published directed towards the educational research community. In contrast, omega‐3 supplementation studies are being frequently cited in the media, leading to parents asking for advice and guidance. The purpose of this article is to review the evidence to date for any effect of using omega‐3 supplementation in school‐aged children. This article focuses on the research that has been undertaken, particularly in relation to behaviour, education and cognitive development, in both typically developing populations as well as in children with specific learning difficulties and developmental disorders. Recommendations for future studies in this area have been highlighted in view of current knowledge. In conclusion, it was found that there is a shortage of properly controlled omega‐3 supplementation trials, particularly with typically developing children, to advocate the supplementation of all children with omega‐3 fatty acids, but due to the known importance of omega‐3 fatty acids in the brain and early development, further research is required.
IKO: A Five Actuated DoF Upper Limb Exoskeleton Oriented to Workplace Assistance
Authors: Martinez Felix , Pujana-Arrese Aron , Retolaza Iban , Sacristan Irantzu , Basurko Jon , Landaluze Joseba
Published: July 2009

IKerlan’s Orthosis (IKO) is an upper limb exoskeleton oriented to increasing human force during routine activity at the workplace. Therefore, it can be considered as a force‐amplification device conceived to work in collaboration with the human arm and implementing biomimetic principles. The aim of the proposed design is to find the best compromise between maximum reachable workspace and minimum moving mass, which are the key factors for obtaining an ergonomic, wearable exoskeleton. It consists of five actuated degree of freedom (DoF) to move the human arm and three non‐actuated DoF between the back and shoulder to allow relative displacement of the sterno‐clavicular joint. Conventional electrical motors are used for most of the DoF and pneumatic muscles for one of them (forearm rotation). Power transmission is based on Bowden cables. This paper presents the IKO design, the mechanical structure of a first prototype and the redesign process from an aesthetic point of view. Controller set‐up and control strategies are also shown, together with dynamic performance from experimental results.
Analysis of the Human Interaction with a Wearable Lower‐Limb Exoskeleton
Authors: Moreno Juan C. , Brunetti Fernando , Navarro Enrique , Forner-Cordero Arturo , Pons José L.
Published: July 2009

The design of a wearable robotic exoskeleton needs to consider the interaction, either physical or cognitive, between the human user and the robotic device. This paper presents a method to analyse the interaction between the human user and a unilateral, wearable lower‐limb exoskeleton. The lower‐limb exoskeleton function was to compensate for muscle weakness around the knee joint. It is shown that the cognitive interaction is bidirectional; on the one hand, the robot gathered information from the sensors in order to detect human actions, such as the gait phases, but the subjects also modified their gait patterns to obtain the desired responses from the exoskeleton. The results of the two‐phase evaluation of learning with healthy subjects and experiments with a patient case are presented, regarding the analysis of the interaction, assessed in terms of kinematics, kinetics and/or muscle recruitment. Human‐driven response of the exoskeleton after training revealed the improvements in the use of the device, while particular modifications of motion patterns were observed in healthy subjects. Also, endurance (mechanical) tests provided criteria to perform experiments with one post‐polio patient. The results with the post‐polio patient demonstrate the feasibility of providing gait compensation by means of the presented wearable exoskeleton, designed with a testing procedure that involves the human users to assess the human‐robot interaction.
A modified LOESS normalization applied to microRNA arrays: a comparative evaluation
Authors: Risso Davide , Massa Maria Sofia , Chiogna Monica , Romualdi Chiara
Published: July 2009

Motivation: Microarray normalization is a fundamental step in removing systematic bias and noise variability caused by technical and experimental artefacts. Several approaches, suitable for large-scale genome arrays, have been proposed and shown to be effective in the reduction of systematic errors. Most of these methodologies are based on specific assumptions that are reasonable for whole-genome arrays, but possibly unsuitable for small microRNA (miRNA) platforms. In this work, we propose a novel normalization (loessM), and we investigate, through simulated and real datasets, the influence that normalizations for two-colour miRNA arrays have on the identification of differentially expressed genes.

Results: We show that normalizations usually applied to large-scale arrays, in several cases, modify the actual structure of miRNA data, leading to large portions of false positives and false negatives. Nevertheless, loessM is able to outperform other techniques in most experimental scenarios. Moreover, when usual assumptions on differential expression distribution are missed, channel effect has a strikingly negative influence on small arrays, bias that cannot be removed by normalizations but rather by an appropriate experimental design. We find that the combination of loessM with eCADS, an experimental design based on biological replicates dye-swap recently proposed for channel-effect reduction, gives better results in most of the experimental conditions in terms of specificity/sensitivity both on simulated and real data.

Availability: LoessM R function is freely available at http://gefu.cribi.unipd.it/papers/miRNA-simulation/

Contact:  chiara.romualdi@unipd.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
Modified variational Bayes EM estimation of hidden Markov tree model of cell lineages
Authors: Olariu Victor , Coca Daniel , Billings Stephen A. , Tonge Peter , Gokhale Paul , Andrews Peter W. , Kadirkamanathan Visakan
Published: July 2009

Motivation: Human pluripotent stem cell lines persist in culture as a heterogeneous population of SSEA3 positive and SSEA3 negative cells. Tracking individual stem cells in real time can elucidate the kinetics of cells switching between the SSEA3 positive and negative substates. However, identifying a cell's substate at all time points within a cell lineage tree is technically difficult.

Results: A variational Bayesian Expectation Maximization (EM) with smoothed probabilities (VBEMS) algorithm for hidden Markov trees (HMT) is proposed for incomplete tree structured data. The full posterior of the HMT parameters is determined and the underflow problems associated with previous algorithms are eliminated. Example results for the prediction of the types of cells in synthetic and real stem cell lineage trees are presented.

Availability:The Matlab code for the VBEMS algorithm is freely available at http://www.acse.dept.shef.ac.uk/repository/vbems_lineage_tree/VBEMS.ZIP

Contact:  visakan@sheffield.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Do Congressional Candidates Have Reverse Coattails? Evidence from a Regression Discontinuity Design
Authors: Broockman David E.
Published: July 2009

Although the presidential coattail effect has been an object of frequent study, the question of whether popular congressional candidates boost vote shares in return for their parties' presidential candidates remains unexplored. This article investigates whether so-called “reverse coattails” exist using a regression discontinuity design with congressional district-level data from presidential elections between 1952 and 2004. Taking incumbency to be near-randomly distributed in cases where congressional candidates have just won or lost their previous elections, I find that the numerous substantial advantages of congressional incumbency have no effect on presidential returns for these incumbents' parties. This null finding underscores my claim that the existing coattail literature deserves greater scrutiny. My results also prompt a rethinking of the nature of the advantages that incumbents bring to their campaigns and may help deepen our understanding of partisanship in the United States.
Influence through ignorance
Authors: Brocas Isabelle , Carrillo Juan D.
Published: July 2009

An individual (the leader) with free access to information decides how much public evidence to collect. Conditional on this information, another individual with conflicting preferences (the follower) undertakes an action that affects the payoff of both players. In this game of incomplete but symmetric information, we characterize the rents obtained by the leader as a result of his control of the generation of public information. These rents capture the degree of influence exerted by a chairman on a committee from his capacity to keep discussions alive or call a vote. Similar insights are obtained if the leader decides first how much private information he collects, and then how much verifiable information he transmits to the follower.
Downstream mergers and producer's capacity choice: why bake a larger pie when getting a smaller slice?
Authors: Montez João V.
Published: July 2009

In this article, the effect of downstream horizontal mergers on the upstream producer's capacity choice was studied. Contrary to conventional wisdom, I find a nonmonotonic relationship: horizontal mergers induce a higher upstream capacity if the cost of capacity is low, and a lower upstream capacity if this cost is high. This result is explained by decomposing the total effect into two competing effects: a change in holdup and a change in bargaining erosion.
Tacit collusion and capacity withholding in repeated uniform price auctions
Authors: Dechenaux Emmanuel , Kovenock Dan
Published: July 2009

This article analyzes tacit collusion in infinitely repeated multiunit uniform price auctions in a symmetric oligopoly with capacity‐constrained firms. Under two popular definitions of the uniform price, when each firm sets a price‐quantity pair, perfect collusion with equal sharing of profit is easier to sustain in the uniform price auction than in the corresponding discriminatory auction. Moreover, capacity withholding may be necessary to sustain this outcome. Even when firms may set bids that are arbitrary finite step functions of price‐quantity pairs, in repeated uniform price auctions maximal collusion is attained with simple price‐quantity strategies exhibiting capacity withholding.
Market effects of environmental regulation: coal, railroads, and the 1990 Clean Air Act
Authors: Busse Meghan R. , Keohane Nathaniel O.
Published: July 2009

Many environmental regulations encourage the use of “clean” inputs. When the suppliers of such an input have market power, environmental regulation will affect not only the quantity of the input used but also its price. We investigate the effect of the Title IV emissions trading program for sulfur dioxide on the market for low‐sulfur coal. We find that the two railroads transporting coal were able to price discriminate on the basis of environmental regulation and geographic location. Delivered prices rose for plants in the trading program relative to other plants, and by more at plants near a low‐sulfur coal source.
Variation in large‐bodied fish‐community structure and abundance in relation to water‐management regime in a large regulated river
Authors: Haxton T. J. , Findlay C. S.
Published: July 2009

Variation in life‐history traits (growth, condition, mortality and recruitment) and relative abundance of 11 large‐bodied fish species was investigated among three water‐management regimes (unimpounded, run‐of‐the‐river and winter reservoirs) in the large regulated Ottawa River, Canada. If waterpower management had an effect on fishes, then (1) would be expected community structuring among water‐management regimes and (2) species with similar life‐history traits should be affected in a similar manner. Large‐bodied fish communities were assessed using two different standard index‐netting techniques, one using trap nets and the other gillnets. Community structure could be discriminated based on species caught in nets using holographic neural networks (78·8% correct overall classification rate using trap nets and 76·0% using gillnets); therefore, water‐management regimes affected community structure in the Ottawa River. Littoral zone benthivores were significantly lower in abundance (P< 0·001) or absent in winter reservoirs, whereas the abundance of planktivores or species that were planktivorous at young ages were significantly greater than in unimpounded river reaches. Growth, condition and mortality did not vary among reach types except smallmouth bassMicropterus dolomieuwere in better condition in winter reservoirs than unimpounded reaches. Lake sturgeonAcipenser fulvescensrecruitment was impaired in run‐of‐the‐river reaches, whereas recruitment for other species that spawn in fast water was not affected.
Seasonal variability in growth of larval Japanese anchovy Engraulis japonicus driven by fluctuations in sea temperature in the Kii Channel, Japan
Authors: Yasue N. , Takasuka A.
Published: July 2009

Seasonal variability in the growth of larval Japanese anchovy Engraulis japonicus was examined through otolith microstructure analysis based on the samples collected from the northern side (inner area, IA) and the southern side (outer area, OA) of the Kii Channel from April 2006 to March 2007. Growth trajectories (otolith backcalculated mean standard length of 5 day intervals from 5 days after hatch to 24 days) as well as the most recent 5 day mean growth rate of larvae before capture (G5) differed among months. Growth trajectories showed the same pattern as G5. In IA, mean ±s.d.G5 ranged from 0·31 ± 0·04 mm day−1 (January) to 0·73 ± 0·06 mm day−1 (October). In OA, mean ±s.d.G5 ranged from 0·36 ± 0·05 mm day−1 (January) to 0·79 ± 0·11 mm day−1 (August). G5 values declined from November to January and then started to increase. In general, the seasonal patterns of growth were similar between IA and OA, and a clear seasonal pattern in growth was identified. When the relationships among larval growth rate, sea temperature, zooplankton density and larval density were examined, growth rate was positively related with sea temperature in both areas and not related with the other factors. The similar pattern in growth observed between IA and OA was probably due to the low spatial variability in sea temperature compared to its seasonal variability.
Latitudinal and altitudinal growth patterns of brown troutSalmo truttaat different spatial scales
Authors: Parra I. , Almodóvar A. , Nicola G. G. , Elvira B.
Published: July 2009

Spatial variation in growth of stream‐dwelling brown troutSalmo truttawas explored in 13 populations using a long‐term study (1993–2004) in the Bay of Biscay drainage, northern Spain. The high variability in fork length (LF) ofS. truttain the study area was similar to the body‐size range found in the entire European distribution of the species. MeanLFat age varied: 0+ years, 57·4–100·7 mm; 1+ years, 111·6–176·0 mm; 2+ years, 155·6–248·4 mm and 3+ years, 194·3–290·9 mm. AverageLFat age was higher in main courses and lower reaches compared with small tributaries and upper reaches. Annual specific growth rates (GL) were: 0+ to 1+ years, 0·634–0·825 mm mm−1year−1; 1+ to 2+ years, 0·243–0·342 mm mm−1year−1; 2+ to 3+ years, 0·166–0·222 mm mm−1year−1, showing a great homogeneity. Regression models showed that water temperature and altitude were the major determinants ofLFat age variability within the study area. A broader spatial analysis using available data from stream‐dwellingS. truttapopulations throughout Europe indicated a negative relationship between latitude andLFof individuals and a negative interaction between latitude and altitude. These findings support previous evidence of the pervasive role of water temperature on theLFof this species. Altitude appeared as the overall factor that includes the local variation of other variables, such as water temperature or food availability. At a larger scale, latitude was the factor that encompassed these environmental gradients and explained the differences inLFofS. trutta. In summary,LFat age in stream‐dwellingS. truttadecreases with latitude in Europe, the converse of Bergmann's rule.
Short‐term dominance: stability and consequences for subsequent growth
Authors: Tiira K. , Laurila A. , Enberg K. , Piironen J.
Published: July 2009

Dominance status was determined among groups of four fish by using individuals from eight brown trout Salmo trutta populations. Subsequent growth of the fish was later recorded in larger groups. Seven months after the first set of trials, an additional set of dominance trials was performed by using the same fish. Social status affected subsequent growth; individuals having the lowest ranks grew less when compared to the higher ranking fish. Furthermore, the short term dominance hierarchy was rather stable between the two trials. This was especially the case with the lowest ranking fish, which tended to remain in the lowest position also in the second trial. The results suggest that the short term dominance trials done among few conspecifics reflect relatively well not only the subordinates' relative but also absolute social status.
Investigational piscivory of some juvenile Australian freshwater fishes by the introduced Mozambique tilapia Oreochromis mossambicus
Authors: Doupé R. G. , Knott M. J. , Schaffer J. , Burrows D. W.
Published: July 2009

Experimental tanks were used to observe predatory effects in three different size classes of Mozambique tilapia Oreochromis mossambicus (one of the world's most widespread exotic species and generally regarded to be a herbivore or both herbivore and detritivore) when tested against 10 juvenile Australian freshwater fish species, and significant levels of predation against all were recorded. There was a general trend for larger O. mossambicus to kill more prey and this was also reflected in a separate series of experiments using juvenile barramundi Lates calcarifer over a range of size classes. Predatory effects by O. mossambicus broadly reflected the accepted models of predator–prey interactions, being that mortality (and survival) was closely related to relative body size and mouth gape limitation. Experimental evidence for piscivory in O. mossambicus was supported by field sampling that detected prey fish remains in 16% of all fish surveyed (n = 176). The recognition of active piscivory by O. mossambicus in laboratory and field situations is the first such evidence, and suggests a need to re‐evaluate the nature of their effects in introduced environments.
Lunar periodicity and the timing of river entry in Atlantic salmon Salmo salar
Authors: Kuparinen A. , O'Hara R. B. , Merilä J.
Published: July 2009

Historical catch records of Atlantic salmon Salmo salar from three rivers discharging to the Baltic Sea in an area free from tides and from strong effects of the moon on illumination were analysed to investigate whether timing of S. salar river entry was associated with lunar cycles directly. Although a significant effect of lunar phase on river entry was detected, with more fish entering rivers around the full moon than other phases, the effect of the lunar cycle was very small compared with other sources of variation. Hence, the biological role of lunar cycle as a determinant of the timing of S. salar runs in the investigated populations was negligible, suggesting that lunar cycle per se does not play a role in the timing of S. salar river entry.
Plasma soluble tumour necrosis factor‐α receptor 2 is elevated in obesity: specific contribution of visceral adiposity
Authors: Cartier Amélie , Côté Mélanie , Bergeron Jean , Alméras Natalie , Tremblay Angelo , Lemieux Isabelle , Després Jean‐Pierre
Published: July 2009

Objective  We examined the obesity phenotype most strongly associated with increased plasma concentrations of sTNFR2, and compared which of the two markers, TNF‐α or sTNFR2, better predicts indices of plasma glucose‐insulin homeostasis.

Design, patients and measurements  Plasma sTNFR2 levels were measured in a sample of 287 healthy nondiabetic men [age: 43·9 ± 8·0 years (mean ± SD)], covering a wide range of adiposity values (BMI: 29·0 ± 4·4 kg/m2; waist girth: 100·0 ± 11·7 cm).

Results  Plasma sTNFR2 levels correlated positively and significantly with BMI (r = 0·36; P < 0·0001), fat mass (r = 0·42; P < 0·0001), waist girth (r = 0·38; P < 0·0001) as well as with visceral (r = 0·37; P < 0·0001) and subcutaneous adipose tissue (AT) (r = 0·40; P < 0·0001) areas measured by computed tomography. Two subgroups (n = 27 in each group) of overweight men (BMI ≥25 kg/m2) were individually matched for similar BMI values, but with markedly different levels of visceral AT (< or ≥130 cm2) and then compared with a control group of 46 lean subjects (with both BMI <25 kg/m2 and visceral AT <130 cm2). This analysis revealed that men characterized by high levels of visceral AT had significantly higher concentrations of sTNFR2 compared with obese men with low visceral AT (1861 ± 457 pg/ml vs. 1722 ± 400; P < 0·05) and with lean controls (1570 ± 291 pg/ml; P < 0·001). Whereas subjects classified across tertiles of TNF‐α levels showed no difference in glucose tolerance and insulin levels, subjects in the upper tertile of plasma sTNFR2 levels were characterized with the highest plasma insulin concentrations during the OGTT and had the highest area under the curve of insulin concentrations.

Conclusions  These results indicate that sTNFR2 levels are more closely related to abdominal AT accumulation than to total adiposity. Furthermore, plasma concentrations of sTNFR2 are independently related to plasma glucose‐insulin homeostasis beyond the known contribution of visceral adiposity.
Targeting energy expenditure in muscle as a means of combating obesity
Authors: Clarke Iain J , Henry Belinda A
Published: July 2009

1. To date, an effective therapeutic agent that induces weight loss in obese subjects remains elusive. In order to establish a successful means to combat obesity, it is imperative that we identify novel targets that regulate energy balance.

2. Exciting new data have created resurgence in interest in the role of thermogenesis in energy balance. Recently, it has been demonstrated that functional brown adipocytes are present in adult humans and that brown adipocytes and myocytes are derived from a similar cell lineage and are thus likely to have similar physiological functions.

3. Recent work in the sheep has demonstrated that diffuse fat beds and skeletal muscle exhibit thermogenic properties. Furthermore, in sheep, central administration of leptin markedly increases postprandial thermogenesis in both fat and muscle tissues. This demonstrates that thermogenic processes in skeletal muscle can be manipulated in a similar way to thermogenesis in brown fat.

4. Given that skeletal muscle comprises a significant portion of bodyweight, approximately 30–40% of total body mass, we predict that energy expended by this tissue is likely to have significant ramifications for the regulation of bodyweight.

5. We propose that manipulation of skeletal muscle thermogenesis may provide a novel avenue for the development of anti‐obesity therapies.
Urinary uric acid : creatinine ratios in healthy Turkish children
Authors: Poyrazoğlu Hakan M. , Düşünsel Ruhan , Yazici Cevat , Durmaz Halil , Dursun İsmail , Şahin Habibe , Gündüz Zübeyde , Gürgöze Metin K.
Published: July 2009

Background:  Determining uric acid : creatinine ratios in random urine samples may be useful to assess the excretion of uric acid in children. Because it was shown that urinary uric acid excretion varies with age and geographic area, it is important to have accurate reference values of uric acid excretion. The aim of the present study was therefore to obtain regional reference values for urinary uric acid : creatinine ratios in healthy Turkish children.

Methods:  A total of 1306 children aged 1 month–15 years were analyzed for uric acid and creatinine, and urinary uric acid : creatinine ratios were determined from each sample. The second non‐fasting morning urine samples were taken from all the children. Urine samples were analyzed for uric acid using the uricase method, and for creatinine with the Jaffe reaction.

Results:  The mean ± SD and 5th–95th percentiles of urinary uric acid : creatinine ratios (mg/mg) were 1.09 ± 0.48 and 0.27–1.87 at 1–6 months, 0.86 ± 0.41 and 0.19–1.64 at 7–12 months, 0.76 ± 0.32 and 0.32–1.43 at 1–3 years, 0.63 ± 0.29 and 0.20–1.23 at 4–6 years, 0.44 ± 0.24 and 0.14–0.93 at 7–11 years, and 0.30 ± 0.14 and 0.12–0.62 at 12–15 years. Uric acid : creatinine ratios were not significantly different between boys and the girls except at 12–15 years. Girls aged 12–15 years had higher urinary uric acid : creatinine ratio when compared with boys (P < 0.05). There was no correlation between urinary uric acid : creatinine ratio and protein intake.

Conclusions:  Urinary uric acid : creatinine ratio changes with age. When assessing urinary uric acid : creatinine ratio, the clinician should consider the age of the child.
Reliability of family history of lifestyle‐related diseases on questionnaire
Authors: Saito Tomohiro , Nanri Seiichiro , Saito Ikuo
Published: July 2009

Background:  Family history of lifestyle‐related diseases is an important risk factor and is widely used in epidemiologic studies. To justify its use the validity of the family history needs to be assessed. The aim of the present study was therefore to examine reliability, that is, consistency in repeated measurements, of the family history obtained on questionnaire.

Methods:  A questionnaire survey on the family history of lifestyle‐related diseases was conducted for 438 high school students about students' parents, grandparents, uncles and aunts, twice with a 1 year interval. The questionnaire was filled in by their parents. Discordance between the two questionnaires in age, age at death and a positive history of lifestyle‐related diseases expressed by age at onset by decade age among the family members was examined. Kappa was used as a measure of agreement.

Results:  The kappas for relatives were high, mostly >0.7 for hypertension and >0.5 for myocardial infarction, angina pectoris, stroke, diabetes mellitus and hypercholesterolemia. The discordance tended to be higher among grandparents than parents, uncles and aunts. The discordance with regard to relatives was mostly <4% for angina pectoris, myocardial infarction, stroke and diabetes mellitus; for hypertension and hypercholesterolemia the discordance was <6%.

Conclusions:  The questionnaire provides a reliable and valid method of collecting family history on relatives of high school students. Thus, family history obtained through questionnaires can be used justifiably as a risk factor for lifestyle‐related diseases among children and youths.
Neutropenia in the acute phase of Kawasaki disease and prevention of coronary artery aneurysm
Authors: Onouchi Zenshiro , Hamaoka Kenji , Ozawa Seiichiro , Sakata Koichi , Kiyosawa Nobuyuki , Ito Hisato
Published: July 2009

Background:  The significance of neutropenia in Kawasaki disease (KD) has not been fully elucidated as yet.

Methods:  Subjects were retrospectively sampled from two clinical trials. These patients treated with aspirin alone (ASA) and PolyglobinN‐Bayel (PolyN) given as i.v. immunoglobulin were categorized as ASA‐early (n = 0), ASA‐late (n = 8), PolyN‐early (n = 18), or PolyN‐late (n = 27) based on the therapy administered and the incidence of neutropenia before the 10th day of illness (DI) and after 11 DI. Data regarding the time of onset of neutropenia, and incidence of coronary artery lesion (CAL) formation were obtained. P < 0.05 was considered statistically significant.

Results:  No patients in the ASA group exhibited neutropenia within 10 DI. The time of onset of neutropenia in the PolyN‐early group was 8 ± 1.3 DI. That in the PolyN‐late group (19.8 ± 8 DI) was earlier than in the ASA‐late group (26.6 ± 14 DI; P < 0.025). PolyN‐early patients had a lower incidence of CAL formation than ASA‐non patients (patients without neutropenia in the ASA group; P = 0.00019) and ASA‐late patients (P = 0.04). That in the PolyN‐early group tended to be lower than in the PolyN‐late group (P < 0.1).

Conclusion:  Early neutropenia indicated that circulating neutrophils within 10 DI may play an indispensable role in the following sequence to CAL formation in KD.
Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia
Authors: Boo Nem‐Yun , Wong Fei‐Liang , Wang May‐Kay , Othman Ainoon
Published: July 2009

Background:  The aim of the present study was to compare, in a case–control study, the prevalence of nucleotide 211 guanine to adenine (G→A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 µmol/L during first 48 h of life or ≥300 µmol/L thereafter), and to determine whether this mutation was a significant risk factor associated with severe hyperbilirubinemia.

Methods:  Seventy‐four term infants of Chinese descent admitted with severe hyperbilirubinemia were recruited. Infants without severe hyperbilirubinemia (n = 125) were randomly selected from among healthy Chinese term infants. UGT1A1 nucleotide 211 polymorphism was assayed using the Taqman single nucleotide polymorphism genotyping method. Using gestational age, types of feeds, G6PD mutation, G6PD enzyme levels, and UGT1A1 gene mutation status as independent variables, logistic regression analysis was carried out to determine the significant risk factors associated with severe hyperbilirubinemia.

Results:  UGT1A1 gene mutation was significantly more common among hyperbilirubinemic infants (39.2%) than controls (25.6%; P = 0.04). Gestational age (adjusted odds ratio [OR], 0.7; 95% confidence intervals [CI]: 0.5–0.9; P = 0.01), G6PD mutation (adjusted OR, 7.2; 95%CI: 2.7–19.0; P < 0.0001), exclusive breast‐feeding (adjusted OR, 11.7; 95%CI: 2.7–49.9; P = 0.001), and homozygous variant of UGT1A1 gene mutation (adjusted OR, 32.2; 95%CI: 3.8–273.2; P = 0.001) were significant risk factors. Heterozygous variant of UGT1A1 gene mutation, actual levels of G6PD enzyme, and mixed feeding were not.

Conclusion:  Homozygous variant of nucleotide 211 G→A mutation of UGT1A1 gene is a significant risk factor associated with severe hyperbilirubinemia among Malaysian Chinese newborns.
Diagnostic quality of Actigraph‐based physical activity cut‐offs for children: What overweight/obesity references can tell?
Authors: Guinhouya Comlavi B. , Apété Géoffroy K. , Hubert Hervé
Published: July 2009

Background:  There is conflicting literature about Actigraph‐based cut‐off points (CoP) that define the lower limit of moderate–to–vigorous physical activity (MVPA) among children. The aim of the present study was to compare the diagnostic quality of Actigraph‐based CoP relative to different body mass index (BMI) classification systems of the weight status of children.

Methods:  One hundred and thirteen children aged 8–11 years recruited from three randomly selected elementary schools wore the Actigraph, model 7164 (Actigraph Manufacturing Technology) for 3 days. Five CoP, expressed in counts per minute (c.p.m.; CoP 1000 CoP 2000, CoP 3000, CoP 3200, and CoP 3600) were used to compute their MVPA. The area under the receiver operating characteristic curves (AUC) together with specific indices allowed assessment of the performance of these CoP in reference to overweight/obesity status as defined using BMI‐based criteria from the International Obesity Task Force (IOTF), French References (FR) and World Health Organization (WHO) standards.

Results:  Overweight/obesity frequency ranged from 30% to 42%, with no sex‐related difference. All AUC (range, 0.623–0.660) were significantly higher than 0.500 except from those of CoP 1000 and 2000 using the IOTF criteria (0.602 ± 0.058 and 0.601 ± 0.057, respectively) and the FR (0.608 ± 0.060 for CoP 1000). Furthermore, with the WHO standards, all the CoP provided non‐significant AUC (range, 0.566–0.597). According to the IOTF and the FR criteria, respectively, CoP 3600 had the highest probability of correct decision (0.62 and 0.68), the lowest misclassification errors (0.38 and 0.32), the highest validity coefficient (0.21 and 0.29), and the highest expected maximum utility (59 and 83).

Conclusion:  When children are classified using BMI‐based criteria, the threshold of 3600 c.p.m. should be more appropriate in discriminating non‐overweight from overweight/obese.
Why Doesn't Regional Integration Improve Income Convergence in Africa?*
Authors: Hammouda Hakim Ben , Karingi Stephen N. , Njuguna Angelica E. , Jallab Mustapha Sadni
Published: July 2009

Abstract:  This paper investigates why regional integration does not improve income convergence in Africa, despite the common goal of more open and freer trade. Based on empirical analysis using African countries data, the paper presents the evidence that there has been little progress in income convergence in Africa. The paper shows that despite the importance of regional integration there has been limited progress and prospects of the African integration process are not as promising as would be expected for such an important pillar in Africa's development agenda.
Mesure de l'Efficacité des Banques dans les Pays en Voie de Développement: Le Cas de l'Union Economique et Monetaire Ouest Africaine (UEMOA)*
Authors: Kablan Sandrine
Published: July 2009

Résumé:  Cette étude se propose de mesurer l'efficacité des banques de l'UEMOA et ses facteurs déterminants, après les réformes bancaires de 1993 à 1996. La méthode de l'enveloppement des données (DEA) a été utilisée pour évaluer l'efficacité technique des banques tandis que celle des frontières stochastiques (SFA) a été utilisée pour estimer l'efficacité‐coût. Les résultats indiquent des évolutions similaires pour les deux types d’efficacité pour tous les pays de l'UEMOA, sauf pour la Côte d’Ivoire et le Burkina Faso. Une analyse plus détaillée suivant le type de banque (locales privées, étrangères ou publiques) révèle que les premières sont les plus efficaces, suivies par les secondes, puis des troisièmes. L'indice de Malmquist montre que l'augmentation de l'efficacité technique est beaucoup plus le fait d’économie d’échelle que de l'incorporation des innovations technologiques. Enfin, l'efficacité des banques de l'UEMOA dépend des variables telles que la solidité financière, le ratio de créances douteuses par pays, la concentration bancaire et le PIB par habitant.
Some Benefits of Being an Activist: Measuring Activism and Its Role in Psychological Well‐Being
Authors: Klar Malte , Kasser Tim
Published: July 2009

Do activists lead happier and more fulfilled lives than the average person? Two online surveys using a sample of college students (N = 341) and a national sample of activists matched with a control group (N = 718) demonstrated that several indicators of activism were positively associated with measures of hedonic, eudaimonic, and social well‐being. Furthermore, in both studies, activists were more likely to be “flourishing” (Keyes, 2002) than were nonactivists. A third study of college students (N = 296) explored the possible causal role of activism by measuring well‐being after subjects either engaged in a brief activist behavior, a brief nonactivist behavior, or no behavior. Although well‐being did not differ substantially between these three groups, the subjects who did the brief activist behavior reported significantly higher levels of subjective vitality than did the subjects who engaged in the nonactivist behavior. Potential mediators of the relationship between activism and well‐being and the usefulness of these findings are discussed.
Cilnidipine mediates a neuroprotective effect by scavenging free radicals and activating the phosphatidylinositol 3‐kinase pathway
Authors: Lee Young Joo , Park Kee Hyung , Park Hyun‐Hee , Kim Yun Jin , Lee Kyu‐Yong , Kim Seung Hyun , Koh Seong‐Ho
Published: July 2009

We investigated the neuroprotective effect and mechanisms of action of cilnidipine, a long‐acting, second‐generation 1,4‐dihydropyridine inhibitor of L‐ and N‐type calcium channels, in PC12 cells that were neuronally differentiated by treatment with nerve growth factor (nPC12 cells). To evaluate the effect of cilnidipine on viability, nPC12 cells were treated with several concentrations of this drug before performing viability assays. Free radical levels and intracellular signaling proteins were measured with the fluorescent probe, 2′,7′‐dichlorodihydrofluorescein diacetate and western blotting, respectively. Cell viability was not affected by low concentrations of cilnidipine up to 150 μM, but it was slightly decreased at 200 μM cilnidipine. Following H2O2 exposure, the viability of nPC12 cells decreased significantly; however, treatment with cilnidipine increased the viability of H2O2‐injured nPC12 cells in a concentration‐dependent manner. Treatment with H2O2 resulted in a concentration‐dependent increase in free radical levels in nPC12 cells, and cilnidipine treatment reduced free radical levels in H2O2‐injured nPC12 cells in a dose‐dependent manner. Cilnidipine treatment increased the expression of p85aPI3K (phosphatidylinositol 3‐kinase) phosphorylated Akt, phosphorylated glycogen synthase kinase‐3 (pGSK‐3β), and heat shock transcription factor (HSTF‐1) which are proteins related to neuronal cell survival, and decreased levels of cytosolic cytochrome c, activated caspase 3, and cleaved poly (ADP‐ribose) polymerase (PARP), which are associated with neuronal cell death, in H2O2‐injured nPC12 cells. These results indicate that cilnidipine mediates its neuroprotective effects by reducing oxidative stress, enhancing survival signals (e.g., PI3K, phosphorylated Akt, pGSK‐3β, and HSTF‐1), and inhibiting death signals from cytochrome c release, caspase 3 activation, and PARP cleavage.
Botulinum neurotoxins C, E and F bind gangliosides via a conserved binding site prior to stimulation‐dependent uptake with botulinum neurotoxin F utilising the three isoforms of SV2 as second receptor
Authors: Rummel Andreas , Häfner Kirstin , Mahrhold Stefan , Darashchonak Natallia , Holt Matthew , Jahn Reinhard , Beermann Silke , Karnath Tino , Bigalke Hans , Binz Thomas
Published: July 2009

The high toxicity of clostridial neurotoxins primarily results from their specific binding and uptake into neurons. At motor neurons, the seven botulinum neurotoxin serotypes A–G (BoNT/A–G) inhibit acetylcholine release, leading to flaccid paralysis, while tetanus neurotoxin blocks neurotransmitter release in inhibitory neurons, resulting in spastic paralysis. Uptake of BoNT/A, B, E and G requires a dual interaction with gangliosides and the synaptic vesicle (SV) proteins synaptotagmin or SV2, whereas little is known about the entry mechanisms of the remaining serotypes. Here, we demonstrate that BoNT/F as wells depends on the presence of gangliosides, by employing phrenic nerve hemidiaphragm preparations derived from mice expressing GM3, GM2, GM1 and GD1a or only GM3. Subsequent site‐directed mutagenesis based on homology models identified the ganglioside binding site at a conserved location in BoNT/E and F. Using the mice phrenic nerve hemidiaphragm assay as a physiological model system, cross‐competition of full‐length neurotoxin binding by recombinant binding fragments, plus accelerated neurotoxin uptake upon increased electrical stimulation, indicate that BoNT/F employs SV2 as protein receptor, whereas BoNT/C and D utilise different SV receptor structures. The co‐precipitation of SV2A, B and C from Triton‐solubilised SVs by BoNT/F underlines this conclusion.
Relationship between phosphodiesterase type 4 inhibition and anti‐inflammatory activity of CI‐1044 in rat airways
Authors: Pruniaux Marie‐Pierre , Lagente Vincent , Ouaged Malika , Bertin Bernadette , Moreau François , Julien‐Larose Christine , Rocher Marie‐Noelle , Leportier Christelle , Martin Brigitte , Bouget Anita , Dubuit Jean‐Pierre , Burnouf Catherine , Doherty Annette M. , Bertrand Claude P.
Published: July 2009

The anti‐inflammatory effects of CI‐1044 and of the other selective PDE4 inhibitors rolipram and cilomilast were investigated in Brown‐Norway (BN) rats, against lipopolysaccharide‐induced tumor necrosis factor α (TNFα) production in whole blood and antigen‐induced lung eosinophilia. In vitro, CI‐1044 inhibited TNFα production with an IC50of 0.31 μmbeing equipotent to Cilomilast (IC50 = 0.26 μm) and rolipram (IC50 = 0.11 μm). Given orally, CI‐1044 inhibited ex vivo TNFα production with an ED50value of 0.4 mg/kg after single administration, whereas rolipram (ED50 = 1.4 mg/kg) and cilomilast (ED50 = 1.6 mg/kg) were less potent. In the same ex vivo setting, but given repeatedly, CI‐1044 led to an ED50of 0.5 mg/kg corresponding to a plasma concentration of 82.6 ng/mL (0.22 μm). In vivo, CI‐1044 prevented TNFα release with an ED50of 1 mg/kg p.o. and inhibited ovalbumin‐induced lung eosinophilia following single or repeated oral administration with an ED50of 3.25 and 4.8 mg/kg p.o., respectively, suggesting the absence of pharmacological tolerance. CI‐1044 in this model was equipotent to rolipram (81% inhibition at 10 mg/kg) but better than cilomilast (25% inhibition at 10 mg/kg). Finally, CI‐1044 (10 mg/kg) inhibited inflammatory cell recruitment with a long duration of action (up to 8 h) and was still active when given post‐challenge. Our data show that CI‐1044 is an orally active PDE4 inhibitor that may be used as an anti‐inflammatory therapy in lung inflammatory diseases.
Human liver stem cell‐derived microvesicles accelerate hepatic regeneration in hepatectomized rats
Authors: Herrera M. B. , Fonsato V. , Gatti S. , Deregibus M. C. , Sordi A. , Cantarella D. , Calogero R. , Bussolati B. , Tetta C. , Camussi G.
Published: July 2009

Several studies indicate that adult stem cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human liver stem cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an α4‐integrin‐dependent mechanism. However, MVs pre‐treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA‐dependent effect. Microarray analysis and quantitative RT‐PCR demonstrated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre‐treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.
Implant surfaces and design (Working Group 4)
Authors: Lang Niklaus P. , Jepsen Søren
Published: July 2009

Introduction: The remit of this working group (4) was to update existing knowledge on the effects of implant surface topography, composition and design on bone integration and re‐osseointegration.

Material and methods: Based on five narrative reviews that were performed following a defined search strategy, clinical implications as well as suggestions for further research have been formulated.

Results: The results and conclusions of the review processes in the following papers together with the group consensus, clinical implications and directions for future research are presented:  1. Effects of titanium surface topography on bone integration.  2. Effects of implant surface coatings and composition on bone integration (two reviews).  3. Effects of different implant surfaces and designs on marginal bone level alterations.  4. Re‐osseointegration onto previously contaminated implant surfaces.