bluuebunny/crossref_metadata_2025 huggingface dataset:
Luteimonas

huabeiensis sp. nov., isolated from stratum water
Authors: Wu Gang , Liu Yang , Li Qing , Du Huijing , You Jing , Li Hong , Ke Congyu , Zhang Xin , Yu Jiliang , Zhao Ting
Published: March 2013

A yellow-coloured bacterial strain, designated HB2T, isolated from stratum water was investigated using a polyphasic taxonomic approach. Cells were Gram-stain-negative, aerobic, non-spore-forming, non-flagellated and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain was a member of the genus

Luteimonas

, its three closest neighbours being

Luteimonas aquatica

BCRC 17731T (97.5 % similarity),

Luteimonas marina

JCM 12488T (97.3 %) and

Luteimonas aestuarii

DSM 19680T (96.9 %). Strain HB2T could clearly be distinguished from these type strains based on phylogenetic analysis, DNA–DNA hybridization, fatty acid composition and a range of physiological and biochemical characteristics. It is evident from the genotypic and phenotypic data that strain HB2T represents a novel species of the genus

Luteimonas

, for which the name

Luteimonas

huabeiensis sp. nov. is proposed. The type strain is HB2T ( = DSM 26429T = CICC 11005sT).
Patterns of bird functional diversity on land‐bridge island fragments
Authors: Ding Zhifeng , Feeley Kenneth J. , Wang Yanping , Pakeman Robin J. , Ding Ping
Published: March 2013

The loss of species diversity due to habitat fragmentation has been extensively studied. In contrast, the impacts of habitat fragmentation on functional diversity remains relatively poorly understood. We conducted bird functional diversity studies on a set of 41 recently isolated land‐bridge islands in the Thousand Island Lake, China.

We analysed differences in bird species richness and a recently developed suite of complementary functional diversity indices (FRic, volume of functional space occupied;FEve, evenness of abundance distribution in the functional trait space;FDiv, divergence in the distribution of abundance in the trait volume) across different gradients (island area and isolation).

We found no correlations betweenFRic andFEve orFEve andFDiv, but negative correlations betweenFRic andFDiv. As predicted, island area accounted for most of the variation in bird species richness, whereas isolation explained most of the variation in species evenness (decreasing species evenness with increasing isolation). Functional diversity appears to be more strongly influenced by habitat filtering as opposed to limiting similarity. More specifically, across all islands, bothFRic andFEve were significantly lower than expected for randomly assembled communities, butFDiv showed no clear patterns.FRic increased with island area,FEve decreased with island area andFDiv showed no clear patterns.

Our finding thatFEve decreases with island area atTILmay indicate low functional stability on such islands, and as such large islands and habitat patches may deserve extra attention and/or protection. These results help to demonstrate the importance of considering the effects of fragmentation on functional diversity in habitat management and reserve design plans.
Are ‘Good’ Citizens ‘Good’ Participants? Testing Citizenship Norms and Political Participation across 25 Nations
Authors: Bolzendahl Catherine , Coffé Hilde
Published: March 2013

Whereas research on political participation typically investigates a variety of socio-economic and attitudinal characteristics, this cross-national study focuses on the relevance of norms when explaining political participation. We examine respondents' normative beliefs about the importance of various measures of ‘good citizenship’, and their relationship to three modes of political engagement (activism, party membership and voting). We find assigning higher importance to paying taxes/obeying the law is negatively linked to all forms of participation, whereas the opposite is true for norms about the importance of voting and being active in associations. Greater emphasis on norms about understanding others and shopping politically is positively associated with political activism but not with more institutional forms of participation. The relationship between norms and participation differs somewhat across nations, with the most differences between Eastern European respondents and those from Western European and Western non-European respondents. In line with theories on democratic learning, we find that the relationship between citizenship norms and participation is often weakest among Eastern Europeans. Conclusions about the subjective and variable nature of democratic citizenship are discussed.
Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets
Authors: NIELSEN T. H. , OLSEN N. V. , TOFT P. , NORDSTRÖM C. H.
Published: March 2013

Background

Mitochondrial dysfunction is an important factor contributing to tissue damage in both severe traumatic brain injury and ischemic stroke. This experimental study explores the possibility to diagnose the condition bedside by utilising intracerebral microdialysis and analysis of chemical variables related to energy metabolism.

Methods

Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis and immediate enzymatic analysis. Mitochondrial function was blocked by unilateral infusion of NaCN/KCN (0.5 mol/L) through the microdialysis catheter (N = 5). As a reference, NaCl (0.5 mol/L) was infused by intracerebral microdialysis in one group of animals (N = 3).

Results

PbtO2 increased during cyanide infusion and returned to baseline afterwards. The lactate/pyruvate (LP) ratio increased significantly following cyanide infusion because of a marked increase in lactate level while pyruvate remained within normal limits. Glutamate and glycerol increased after cyanide infusion indicating insufficient energy metabolism and degradation of cellular membranes, respectively.

Conclusion

Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2. The condition is biochemically characterised by a marked increase in cerebral lactate with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2. The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated at the bedside by utilising intracerebral microdialysis.
Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine
Authors: Hauser Sheketha R. , Bracken Amy L. , Deehan Gerald A. , Toalston Jamie E. , Ding Zheng‐Ming , Truitt William A. , Bell Richard L. , McBride William J. , Rodd Zachary A.
Published: March 2013

The rate of codependency for alcohol and nicotine is extremely high. Numerous studies have indicated that there is a common genetic association for alcoholism and nicotine dependency. The current experiments examined whether selective breeding for high alcohol preference in rats may be associated with increased sensitivity of the posterior ventral tegmental area (pVTA) to the reinforcing properties of nicotine. In addition, nicotine can directly bind to the serotonin‐3 (5‐HT3) receptor, which has been shown to mediate the reinforcing properties of other drugs of abuse within the pVTA Wistar rats were assigned to groups that were allowed to self‐infuse 0, 10, 50, 100, 200, 400 or 800 μM nicotine in two‐lever (active and inactive) operant chambers. P rats were allowed to self‐infuse 0, 1, 10, 50 or 100 μM nicotine. Co‐infusion of 5‐HT3 receptor antagonists with nicotine into the pVTA was also determined. P rats self‐infused nicotine at lower concentrations than required to support self‐administration in Wistar rats. In addition, P rats received more self‐infusions of 50 and 100 μM nicotine than Wistar rats; including a 5HT3 receptor antagonist (LY‐278,584 or zacopride) with nicotine reduced responding on the active lever. Overall, the data support an association between selective breeding for high alcohol preference and increased sensitivity of the pVTA to the reinforcing properties of nicotine. In addition, the data suggest that activation of 5HT3 receptors may be required to maintain the local reinforcing actions of nicotine within the pVTA.
Age‐related differences in working memory deficits during nicotine withdrawal
Authors: Falcone Mary , Wileyto E. Paul , Ruparel Kosha , Gerraty Raphael T. , LaPrate Leah , Detre John A. , Gur Ruben , Loughead James , Lerman Caryn
Published: March 2013

Nicotine withdrawal is associated with subtle working memory deficits that predict subsequent relapse. We examined the neural substrates underlying these processes in treatment‐seeking smokers, and explored the moderating influence of age on abstinence‐induced alterations in brain activity and performance. Sixty‐three smokers participated in two blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging scans while performing a visual N‐back task on two separate occasions: smoking as usual and after 24 hours of biochemically confirmed abstinence (order counterbalanced). Abstinence (versus smoking) led to reduced accuracy, slower median correct response time and reduced BOLD signal change in the three a priori regions of interest: medial frontal/cingulate gyrus and right and left dorsolateral prefrontal cortex. Significant age × session effects were found for BOLD signal change in all three regions, as well as for withdrawal and craving; for all measures, abstinence effects were attenuated in smokers aged ≥50 years compared with those <50 years old. These results suggest that abstinence effects on neurocognitive function may be more pronounced for younger smokers, and may indicate a new avenue for research exploring mechanisms underlying age differences in smoking cessation success.
Beneficial or Harmful Effect of Antipaternal Human Leukocyte Antibodies on Pregnancy Outcome? A Systematic Review and Meta‐Analysis
Authors: Lashley Eileen E.L.O. , Meuleman Tess , Claas Frans H.J.
Published: March 2013

Problem

During pregnancy, antibodies are induced that target the paternal human leukocyte antigens of the semi‐allogeneic fetus. The level and presence of these antibodies have been reported increased as well as decreased for a variety of pregnancy complications; the clinical relevance and consequences of these antibodies are not very clear. Therefore, the objective of this review is to determine whether the presence of antipaternal antibodies influences pregnancy outcome.

Method

We performed a systematic search of studies that described the effect of antipaternal antibodies on pregnancy complications. The primary outcome was the risk ratio for HLA class I and class II antibodies on pregnancy complications. Furthermore, we calculated the risk for first‐ and third‐trimester complications.

Results

The seventeen studies that were selected for meta‐analysis showed high level of statistical and clinical heterogeneity. In the meta‐analysis, we found no significant effect of HLA class I or class II antibodies on pregnancy outcome.

Conclusion

No consistent conclusions can be drawn from the meta‐analysis. Discrepancies in the meta‐analysis are the result of different screening techniques, varying time points of screening, and use of incorrect control groups. Furthermore, more detailed analyses of the characteristics and specificity of the antibodies involved are essential.
Semiautomated quantification of β‐zone parapapillary atrophy using blue light fundus autofluorescence
Authors: Mansouri Kaweh , Tung Jonathan D. , Medeiros Felipe A. , Tafreshi Ali , Dorairaj Syril , Zangwill Linda , He Feng , Jain Sonia , Weinreb Robert N.
Published: March 2013

Purpose:  To evaluate the reproducibility of measurements of area of β‐zone parapapillary atrophy (β‐PPA) using blue laser fundus autofluorescence (FAF) and confocal scanning laser ophthalmoscopy reflectance (CSLO) measurements and to assess agreement between the two imaging modalities.

Methods:  Sixty‐five eyes of 45 patients (mean age, 68.2 ± 11.3 years) with established or suspected glaucoma from the Diagnostic Innovations in Glaucoma Study (DIGS) were prospectively included. FAF scans were obtained with the Spectralis HRA+OCT and CSLO reflectance images with the HRTII (both from Heidelberg Engineering, Heidelberg, Germany). Two masked graders independently measured β‐PPA area on 3 consecutive scans using the semi‐automated BluePeak RegionFinder software (BPRF) and on CSLO reflectance images using the optic disc contour line. Reproducibility of β‐PPA area measurements was assessed using intraclass correlation coefficients (ICC).

Results:  Intragrader reproducibility was 0.997 (95% CI, 0.996–0.998) and 0.995 (95% CI, 0.992–0.996) for grader 1 and 2, respectively, using FAF‐BPRF, and by CSLO, it was 0.991 (95% CI, 0.986–0.994) and 0.988 (95% CI, 0.982–0.992). Intergrader agreement (ICC) was 0.53 (95% CI, 0.331–0.685) for FAF‐BPRF and 0.404 (95% CI, 0.149–0.601) for CSLO (comparison between ICC, p = 0.368). Agreement (ICC) between the two devices was worse for grader 1 (0.356; 95% CI, 0.129–0.549) than grader 2 (0.856; 95% CI, 0.774–0.910) (p < 0.001).

Conclusions:  Despite excellent intragrader reproducibility for β‐PPA measurements with FAF‐BPRF and CSLO, intergrader reproducibility is low to moderate. Measurements of β‐PPA area obtained with the two instruments are of moderate agreement and, therefore, are not interchangeable.
Changing forest recovery dynamics in the northeastern United States
Authors: Klepeis Peter , Scull Peter , LaLonde Tara , Svajlenka Nicole , Gill Nicholas
Published: March 2013

Historical deforestation and forest recovery in the northeastern United States holds important implications for ecosystem services and social conditions. Bridging natural and social sciences perspectives, and incorporating both quantitative and qualitative analysis, we contribute to a rich, multidisciplinary literature on US forest change by documenting at a fine scale changing land‐cover patterns, identifying their key geophysical and social driving forces, and evaluating the strength and character of the on‐going forest transition. The interpretation of five sets of aerial photographs – spanning the period 1936–2008 for a town in central New York State – shows that 25.8 per cent of the land area reforested. Two approaches explain the trend: (1) spatial analysis of landscape features (e.g. soil type, distance to road) and (2) a land‐use history analysis based on secondary and grey literature as well as interviews with longtime landowners. Findings underscore the importance of cross‐scalar analysis, with key explanatory variables ranging from local topography to national development patterns. Twentieth‐century forest recovery is linked primarily to well‐established inter‐decadal processes: a decline in the farming sector, changing life and livelihood goals within farming families and associated land abandonment on areas marginal for agriculture. In contrast to historical trends, recent forest recovery is occurring on high‐quality soils; in 2008 approximately 15 per cent of all forest occurred on such soils, which may hold implications for biodiversity. In addition, landowners are increasingly engaged in a mix of new land uses, including energy development, and there is a steady rise in the number of amenity‐oriented rural residents. The Eaton study contributes detailed mapping of forest‐cover change in an understudied part of the northeastern USA. It also informs debates about forest transition theory and the prospects for a ‘regressive tertiary stage’ for the study region.
Enhancing Bayesian Estimators for Removing Camera Shake
Authors: Wang C. , Yue Y. , Dong F. , Tao Y. , Ma X. , Clapworthy G. , Ye X.
Published: March 2013

The aim of removing camera shake is to estimate a sharp version x from a shaken image y when the blur kernel k is unknown. Recent research on this topic evolved through two paradigms called and . only solves for k by marginalizing the image prior, while recovers both x and k by selecting the mode of the posterior distribution. This paper first systematically analyses the latent limitations of these two estimators through Bayesian analysis. We explain the reason why it is so difficult for image statistics to solve the previously reported failure. Then we show that the leading methods, which depend on efficient prediction of large step edges, are not robust to natural images due to the diversity of edges. , although much more robust to diverse edges, is constrained by two factors: the prior variation over different images, and the ratio between image size and kernel size. To overcome these limitations, we introduce an inter‐scale prior prediction scheme and a principled mechanism for integrating the sharpening filter into . Both qualitative results and extensive quantitative comparisons demonstrate that our algorithm outperforms state‐of‐the‐art methods.
Distinctive histopathologic findings in linear morphea (en coup de sabre) alopecia
Authors: Pierre‐Louis Margareth , Sperling Leonard C. , Wilke Mark S. , Hordinsky Maria K.
Published: March 2013

Linear morphea en coup de sabre is a localized form of morphea that presents as paramedian face or frontal scalp depression. The histopathology of alopecia in linear morphea is typically characterized by sclerosis and a reduction in the number of follicular units. We present a 26‐year‐old Caucasian female with a 1.5‐year history of linear morphea and alopecia with unique atrophic follicular remnants on scalp biopsy. Transverse and vertical sections of biopsy specimens showed dense, dermal sclerosis with marked eccrine gland atrophy and replacement of much of the adipose by collagenous tissue. All sebaceous glands had disappeared, but erector pili muscles persisted. Numerous vertical, columnar and epithelial structures were present at the sites of formerly viable hair follicles. Transverse sections of these atrophic follicular remnants had a resemblance to telogen follicles but were microscopically different. The morphology of these follicular remnants indicates an end‐stage process or permanent alopecia. Similar follicular remnants have been reported in chemotherapy‐induced permanent alopecia but not in alopecia secondary to morphea or other cicatricial alopecias. We discuss the significance of these findings and their relationship to other forms of cicatricial or permanent alopecia based on the literature and case review.
Non‐linear association between 25‐hydroxyvitamin D and the incidence of Type 2 diabetes: a community‐based nested case–control study
Authors: Tohidi M. , Bozorgmanesh M. , Mohebi R. , Khalili D. , Saadat N. , Khorrami N. , Azizi F. , Hadaegh F.
Published: March 2013

Aims

To examine the nature of the association between 25‐hydroxyvitamin D [25(OH)D] and newly diagnosed type 2 diabetes.

Methods

Serum 25(OH)D concentrations were measured for 761 participants (aged 20–83 years) in the Tehran Lipid and Glucose Study, selected for a 1‐to‐3 nested case–control study. Cases were 191 cases of Type 2 diabetes diagnosed during a median follow‐up of 3.6 years. A total of 570 participants were matched with these cases with regard to age, sex, BMI, and month of entering the study. Diabetes was defined according to the American Diabetes Association criteria, 2003. Serum 25(OH)D was measured using the enzyme immunoassay method. Odds ratios for Type 2 diabetes were obtained from conditional logistic regression models for tertiles of serum 25(OH)D concentrations [tertile‐1: 2.82–11.02 (reference), tertile‐2: 11.03–21.80, and tertile‐3: ≥ 21.82 ng/ml]. The multivariate model was adjusted for age, sex, family history of diabetes, systolic blood pressure, triglyceride‐to‐ HDL cholesterol ratio, waist‐to‐height ratio, lifestyle modification intervention, leisure time physical activity, and fasting plasma glucose at baseline. Non‐linearity in the associations between baseline 25(OH)D and Type 2 diabetes, was examined by using restricted cubic splines.

Results

Unadjusted odds ratios (95% confidence intervals) of diabetes were 0.73 (0.74–1.13), 0.54 (0.34–0.85) for the second and third tertiles, respectively. Multivariate adjusted odds ratios were 0.47 (0.25–0.90) and 0.43 (0.23–0.82), respectively. Below the cutoff of ~ 10 ng/ml the risk of newly diagnosed Type 2 diabetes increased dramatically.

Discussion

It was found that 25(OH)D concentrations contributed to the Type 2 diabetes incidence rate in a non‐linear fashion, with the risk beginning to increase sharply for values < 10 ng/ml.
Do resource value and ownership status affect intensity and resolution of contests in a parasitoid wasp?
Authors: Mohamad Rihab , Monge Jean‐Paul , Goubault Marlène
Published: March 2013

Biological control of bruchid beetles, Callosobruchus maculatus (Fabricius) (Coleoptera: Bruchidae), infesting cowpea seeds, Vigna unguiculata (L.) Walpers (Fabaceae), can be performed via augmentative releases of Dinarmus basalis Rondani (Hymenoptera: Pteromalidae) parasitoid wasps. Females of the latter species are therefore likely to experience intense intraspecific competition: they should encounter numerous previously parasitized hosts but also conspecific competitors, with which they may fight to secure hosts on which to lay their eggs. Such contests might therefore disrupt biological control programs. Here, we studied aggressive behavior that D. basalis females show toward conspecific competitors and subsequent host exploitation strategies. We further investigated factors that classically affect contest intensity and outcomes in animals, such as the effect of ownership status, by manipulating the residency period before the intruder's arrival. In addition, we tested the effect of the size of female reproductive tissue (measured in terms of egg load) and the quality of the habitat previously experienced by females (either rich or poor in hosts). These two factors are expected to influence the value that females place on the host and therefore the costs they are willing to pay to win it. Finally, we discussed the consequences of agonistic behaviors on females' host exploitation strategies. Our results suggest that contest competition may actually enhance host control by favoring parasitoid dispersion, rather than disrupting it.
Female beetles facilitate leaf feeding for males on toxic plants
Authors: GONTIJO LESSANDO M.
Published: March 2013

Milkweed plants produce latex, which works as a defence against some herbivorous insects. The cerambycid beetles Tetraopes femoratus (LeConte) puncture the leaf midrib vein to extravasate the latex, and thus render the leaf edible. Nonetheless, it has not yet been investigated whether there is any further implication beyond food acquisition regarding this behaviour.

The present study examined the hypothesis that leaf latex drainage is done mainly by females of T. femoratus, and that the males opportunistically prefer to feed on those ‘disarmed’ leaves.

The experiments revealed that puncturing the leaf midrib vein to extravasate latex is done mainly by females of T. femoratus and not only serves their purpose of food acquisition, but also mediates an opportunistic feeding behaviour among males.

Males of T. femoratus preferred to feed on milkweed leaves that had previously been fed upon by females. In addition, field observations showed that mating occurred more frequently on recently ‘disarmed’ leaves, suggesting increased copulation opportunities for females during leaf feeding.

In sum, the results reveal that the feeding defence strategy of T. femoratusfemales to toxic milkweed foliage has created an opportunity for males to feed on milkweed leaves with a reduced risk of latex exposure and entanglement. Thus, this research provides empirical evidence of plant–insect interactions contributing to the appearance of an opportunistic adaptive feeding behaviour, which has broader implications for eco‐evolutionary systems.
Monoclonal antibodies: potential new therapeutic treatment against multiple myeloma
Authors: Allegra Alessandro , Penna Giuseppa , Alonci Andrea , Russo Sabina , Greve Bruna , Innao Vanessa , Minardi Viviana , Musolino Caterina
Published: March 2013

Despite recent treatments, such as bortezomib, thalidomide, and lenalidomide, therapy of multiple myeloma (MM) is limited, and MM remains an incurable disease associated with high mortality. The outcome of patients treated with cytotoxic therapy has not been satisfactory. Therefore, new therapies are needed for relapsed MM. A new anticancer strategy is the use of monoclonal antibodies (MoAbs) that represent the best available combination of tumor cytotoxicity, environmental signal privation, and immune system redirection. Clinical results in patients with relapsed/refractory MM suggest that MoAbs are likely to operate synergistically with traditional therapies (dexamethasone), immune modulators (thalidomide, lenalidomide), and other novel therapies (bortezomib); in addition, MoAbs have shown the ability to overcome resistance to these therapies. It remains to be defined how MoAb therapy can most fruitfully be incorporated into the current therapeutic paradigms that have achieved significant survival earnings in patients with MM. This will require careful consideration of the optimal sequence of treatments and their clinical position as either short‐term induction therapy, frontline therapy in patients ineligible for ASCT, or long‐term maintenance treatment.
Ecologically functional landscapes and the role of dingoes as trophic regulators in south‐eastern Australia and other habitats
Authors: Letnic Mike , Baker Lynn , Nesbitt Brad
Published: March 2013

Large carnivores can play a pivotal role in maintaining healthy, balanced ecosystems. By suppressing the abundances and hence impacts of herbivores and smaller predators, top predators can indirectly benefit the species consumed by herbivores and smaller predators. Restoring and maintaining the ecosystem services that large carnivores provide has been identified as a critical step required to sustain biodiversity and maintain functional, resilient ecosystems. Recent research has shown that Australia's largest terrestrial predator, the Dingo (Canis lupus dingo), has strong effects on ecosystems in arid Australia and that these effects are beneficial for the conservation of small mammals and vegetation. Similarly, there is evidence from south‐eastern Australia that dingoes suppress the abundance of macropods and red Fox (Vulpes vulpes). It is likely that dingoes in south‐eastern Australia also generate strong indirect effects on the prey of foxes and macropods, as has been observed in the more arid parts of the continent. These direct and indirect effects of dingoes have the potential to be harnessed as passive tools to assist biodiversity conservation through the maintenance of ecologically functional dingo populations. However, research is required to better understand dingoes' indirect effects on ecosystems and the development of dingo management strategies that allow for both the preservation of dingoes and protection of livestock.
Intravenous topiramate: Comparison of pharmacokinetics and safety with the oral formulation in healthy volunteers
Authors: Clark Anne M. , Kriel Robert L. , Leppik Ilo E. , Marino Susan E. , Mishra Usha , Brundage Richard C. , Cloyd James C.
Published: March 2013

Purpose

Although oral topiramate (TPM) products are widely prescribed for migraines and epilepsy, injectable TPM is not available for human use. We have developed a solubilized TPM formulation using a cyclodextrin matrix, Captisol with the long‐term goal of evaluating its safety and efficacy in neonatal seizures. This study in healthy adult volunteers was performed as required by the U.S. Food and Drug Administration (FDA) to demonstrate the pharmacokinetics and safety prior to initiation of studies involving children. This study allowed investigation of absolute bioavailability, absolute clearance, and distribution volume of TPM, information that could not be obtained without using an intravenous TPM formulation.

Methods

This study was an open‐label, two‐way crossover of oral and intravenous TPM in 12 healthy adult volunteers. Initially two subjects received 50 mg, intravenously and orally. Following evidence of safety in the first two subjects, 10 individuals received 100 mg doses of intravenous and oral TPM randomly sequenced 2 weeks apart. Blood samples were taken just prior to drug administration and at intervals up to 120 h afterwards. TPM was measured using a validated liquid chromatography—mass spectrometry method. Concentration‐time data were analyzed using a noncompartmental approach with WinNonlin 5.2.

Key Findings

All subjects completed the study. The mean (±standard deviation) absolute oral bioavailability was 109% (±10.8%). For intravenous and oral TPM the mean distribution volumes were 1.06 L/kg (±0.29) and 0.94 L/kg (±0.24). Clearances were 1.33 L/h (±0.26) and 1.22 L/h (±0.26). The half‐life values were 42.3 h (±6.2) and 41.2 h (±7.5). No changes in heart rate, blood pressure, electrocardiography, or infusion site reactions were observed. Mild central nervous system cognitive adverse events and ataxia occurred between dosing and 2 h post dose with both intravenous and oral administration. With intravenous TPM, these adverse effects occurred as early as during the 15‐min intravenous infusion.

Significance

In healthy adults, oral TPM is bioequivalent to intravenous TPM, and infusion of 50–100 mg over 15 min is safe. Neurologic effects occurred during the infusion, demonstrating that TPM rapidly diffuses into the brain, which supports its evaluation for neonatal seizures. Results from this pilot study will inform the design of subsequent studies in children and newborns, including controlled clinical trials intended to assess the efficacy and safety of intravenous TPM for neonatal seizures. In addition, our results provide support for the further development of intravenous TPM as bridge therapy for older children and adults in whom oral TPM therapy is interrupted.
Standardized Computer‐based Organized Reporting of EEG: SCORE
Authors: Beniczky Sándor , Aurlien Harald , Brøgger Jan C. , Fuglsang‐Frederiksen Anders , Martins‐da‐Silva António , Trinka Eugen , Visser Gerhard , Rubboli Guido , Hjalgrim Helle , Stefan Hermann , Rosén Ingmar , Zarubova Jana , Dobesberger Judith , Alving Jørgen , Andersen Kjeld V. , Fabricius Martin , Atkins Mary D. , Neufeld Miri , Plouin Perrine , Marusic Petr , Pressler Ronit , Mameniskiene Ruta , Hopfengärtner Rüdiger , van Emde Boas Walter , Wolf Peter
Published: March 2013

The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free‐text format. The purpose of our endeavor was to create a computer‐based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video‐EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan‐European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer‐based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, “episodes” (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer‐assisted analysis into the report, it will make possible the build‐up of a multinational database, and it will help in training young neurophysiologists.
The solution of nitrogen inversion in amidases
Authors: Syrén Per‐Olof
Published: March 2013

An important mechanistic aspect of enzyme catalyzed amide bond hydrolysis is the specific orientation of the lone pair of the nitrogen of the scissile amide bond during catalysis. As discussed in the literature during the last decades, stereoelectronic effects cause the single lone pair in the formed tetrahedral intermediate to be situated in a non‐productive conformation in the enzyme active site and hence nitrogen inversion or rotation is necessary. By discussing recent mechanistic findings in the literature relevant for the conformation of the lone pair of the reacting amide nitrogen atom, it will be demonstrated that nature has evolved at least two catalytic strategies to cope with the stereoelectronic constraints inherent to amide bond hydrolysis regardless of the fold or catalytic mechanism. One solution to the inversion problem is to stabilize the transition state of inversion by hydrogen bond formation; another is to introduce a concerted proton shuttle mechanism that avoids inversion and delivers a hydrogen to the lone pair. By using molecular modeling it is demonstrated that the H‐bond strategy is general and can be expanded to include many amidases/proteases with important metabolic functions, including the proteasome. Some examples of the proton shuttle mechanism will also be mentioned. To complete the picture of efficient enzyme catalyzed amide bond hydrolysis, general interactions in the active site of these catalysts will be discussed. An expanded knowledge of the prerequisites of efficient amide bond hydrolysis beyond the oxyanion hole and the catalytic dyad/triad will be of importance for enzyme and drug design.
Diagenesis versus hydrothermalism and fluid–rock interaction within the Tuscan Nappe of the Monte Amiata CO2‐rich geothermal area (Italy)
Authors: Gasparrini M. , Ruggieri G. , Brogi A.
Published: March 2013

In southern Tuscany (central Italy), deep to shallow geothermal systems were active since the Pleistocene and comprise fluids carrying variable amounts of CO2. The Monte Amiata geothermal fields include two main reservoirs: a deep one located in the Palaeozoic metamorphic succession (1300–3000 m deep) belonging to the Tuscan metamorphic ‘basement’ and a shallow one hosted in the Mesozoic sedimentary succession (500–1000 m deep) belonging to the Tuscan Nappe. Multiple sets of calcite veins were investigated in some outcrops of the Tuscan Nappe succession exposed in the Monte Amiata area and surroundings. Two main fluid systems were characterized: the former related to combined diagenetic syn‐tectonic processes from highly saline fluids after interaction with the Late Triassic evaporites (Burano Fm) and the latter related to a fossil geothermal system, Pleistocene in age, fed by low‐salinity meteoric fluids, carrying CO2, radiogenic Sr and heavy O isotopes after interaction with the subsurface rocks. Comparison with the present‐day hydrothermal fluids allowed to sketch the thermal evolution of the system from past to present. Geochemical data proved that portions of the vein–host rocks were reset after interaction with CO2‐rich fluids circulating in the past. Consequently, textural and mineralogical changes are expected to have occurred with respect to the undisturbed rock masses. Understanding these modifications, their location and extension, is a prerequisite to construct (i) geochemical models addressed to the comprehension of the diagenesis induced in sediments after long‐term CO2 storage; and (ii) geological models applied to the prediction of rock heterogeneity distribution within the upper reservoirs, characterizing the shallow (500–1500 m) geothermal systems of southern Tuscany.
Indignation or Resignation: The Implications of Transparency for Societal Accountability
Authors: Bauhr Monika , Grimes Marcia
Published: March 2013

International organizations, policy experts, and nongovernmental organizations promote greater governmental transparency as a crucial reform to enhance accountability and curb corruption. Transparency is predicted to deter corruption in part by expanding the possibilities for public or societal accountability, that is, for citizens and citizens associations to monitor, scrutinize, and act to hold public office holders to account. Although the societal accountability mechanism linking transparency and good government is often implied, it builds on a number of assumptions seldom examined empirically. This article unpacks the assumptions of principal‐agent theories of accountability and suggests that the logic of collective action can be used to understand why exposure of egregious and endemic corruption may instead demobilize the demos (i.e., resignation) rather than enhance accountability (i.e., indignation). We explore these theoretical contentions and examine how transparency affects three indicators of indignations versus resignation—institutional trust, political involvement, and political interest—given different levels of corruption. The empirical analyses confirm that an increase in transparency in highly corrupt countries tends to breed resignation rather than indignation.
Carbonate concretions—explained
Authors: Marshall Jim D. , Pirrie Duncan
Published: March 2013

Carbonate concretions are common features of sedimentary rocks of all geological ages. They are most obvious in sandstones and mudstones as ovoid bodies of rock that protrude from natural outcrops: clearly harder or better cemented than their host rocks. Many people are excited by finding fossils in the centre of mudstone‐hosted concretions (Fig. 1) but spend little time wondering why the fossils are so well preserved. While the study of concretions has benefitted from the use of advanced analytical equipment, simple observations in the field can also help to answer many questions. For example, in cliff sections, original sedimentary beds and sedimentary structures can be traced right through concretions (Fig. 2): so it can be deduced that the concretion clearly formed after these depositional structures were laid down. In this article we explain how and where concretions form and discuss the evidence, ranging from outcrop data to sophisticated laboratory analyses, which can be used to determine their origins. The roles of microbes, decaying carcasses, compaction and groundwaters are highlighted. Concretions not only preserve fossils but can also subdivide oil, gas and water reservoirs into separate compartments.

An early diagenetic carbonate concretion split in half to reveal an ammonite retaining its original aragonite shell, from the Maastrichtian of Antarctica. Image courtesy of Alistair Crame (British Antarctic Survey, NERC). Lens cap is 6 cm.

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Calcite cemented concretion standing proud from the otherwise poorly cemented sandstones. Large spherical concretions commonly occur in sandstones, where the porosity and permeability are equal in all directions. Jurassic, Bencliffe Grit, Osmington Mills, Dorset. Vertical thickness is 80 cm.

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New water for old? Geology and the long view on water resources
Authors: Younger Paul
Published: March 2013

Water used to be regarded as a classic renewable resource, on the reasonable grounds that (in most places, at least) it has a tendency to keep on falling from the sky. However, in recent decades concerns have begun to mount that water is being used consumptively (in some places, at least). This article examines the concept.
Free fatty acid as a marker of energy malnutrition in liver cirrhosis
Authors: Hanai Tatsunori , Shiraki Makoto , Nishimura Kayoko , Imai Kenji , Suetsugu Atsushi , Takai Koji , Shimizu Masahito , Naiki Takafumi , Moriwaki Hisataka
Published: March 2013

Aim

Protein–energy malnutrition is frequently observed in patients with liver cirrhosis (LC). Non‐protein respiratory quotient (npRQ) measured by indirect calorimetry is a good marker to estimate energy malnutrition, and predicts the prognosis of patients with LC. However, measurement of npRQ is limited because of the high cost of indirect calorimetry. Our aim was to find out an alternative marker to npRQ that can be used in the routine clinical setting.

Methods

One hundred and fifty‐six patients with LC were enrolled in this study. Indirect calorimetry and blood examinations were conducted after overnight fasting, and anthropometry was performed by an expert dietician. The correlation between npRQ and other parameters were calculated by simple and multiple regression analysis. Receiver–operator curve (ROC) analysis was used to identify the cut‐off value that would best predict the threshold npRQ of 0.85.

Results

Plasma levels of free fatty acid (FFA) was significantly correlated with npRQ value by simple (r = −0.39, P < 0.0001) and multiple regression analysis (t = −2.96, P = 0.0052). Free fatty acid rose in parallel with the increasing disease severity as defined by Child–Pugh classification (P < 0.05). FFA was also correlated with increasing oxidation rate of fat (r = 0.38, P < 0.0001) and decreasing oxidation rate of carbohydrate (r = −0.39, P < 0.0001). The cut‐off value of FFA to predict npRQ = 0.85 was 660 μEq/L by ROC analysis.

Conclusion

FFA is a useful alternative marker to represent npRQ in patients with LC.
The clinical significance of mesenchyme forkhead 1 (FoxC2) in gastric carcinoma
Authors: Zhu Jin‐Liang , Song Yong‐Xi , Wang Zhen‐Ning , Gao Peng , Wang Mei‐Xian , Dong Yu‐Lan , Xing Cheng‐Zhong , Xu Hui‐Mian
Published: March 2013

Aims

Mesenchyme forkhead 1 (FoxC2) is an epithelial–mesenchymal transition (EMT)‐inducing factor. Previous studies have demonstrated that FoxC2 binds directly to the promoter region of p120‐catenin (p120ctn). The aim of this study was to investigate the clinical significance of FoxC2 expression and the inter‐relationship between FoxC2 and p120ctn, in gastric cancer.

Methods and results

Immunohistochemistry was used to examine the expression of FoxC2 and p120ctn proteins in 325 gastric cancer samples. Staining for FoxC2 in cancer tissues was markedly stronger than in normal tissues. High FoxC2 expression was associated significantly with differentiation, invasion depth, lymph node metastasis and tumour stage. Patients with high FoxC2 expression or low p120ctn expression had a poor prognosis. In the high p120ctn expression group, the prognosis for patients with low FoxC2 expression was better than for the high FoxC2 group. Moreover, stepwise Cox regression showed that p120ctn was an independent prognostic factor, but FoxC2 in combination with p120ctn was not correlated significantly with survival.

Conclusions

We found that FoxC2 and p120ctn play important roles in the progression and prognosis of gastric cancer. Moreover, FoxC2 and p120ctn should be evaluated further as novel biomarkers and therapeutic targets for gastric cancer treatment.
Potency under pressure: the impact of hydrostatic pressure on antigenic properties of influenza virus hemagglutinin
Authors: Eichelberger Schafer L. , Sultana Ishrat , Gao Jin , Getie‐Kebtie Melkamu , Alterman Michail , Eichelberger Maryna C.
Published: March 2013

Background

Influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. The potency of influenza vaccines is measured by single radial immunodiffusion (SRID) assay that quantifies antigenic forms of hemagglutinin (HA). Hydrostatic pressure results in loss of binding of influenza virus to red blood cells, but it is not known whether this infers loss of potency.

Objectives

Our goal was to determine the impact of pressure on HA antigenic structure.

Methods

Viruses included in the 2010–2011 trivalent influenza vaccine were subjected to increasing number of cycles at 35 000 psi in a barocycler, and the impact of this treatment measured by determining hemagglutination units (HAU) and potency. Potency was assessed by SRID and immunogenicity in mice.

Results

After 25 cycles of pressure, the potency measured by SRID assay was below the limit of quantification for the H1N1 and B viruses used in our study, while the H3N2 component retained some potency that was lost after 50 pressure cycles. Pressure treatment also resulted in loss of HAU, but this did not strictly correlate with the potency value. Curiously, loss of potency was abrogated when influenza A, but not B, antigens were exposed to pressure in chicken egg allantoic fluid. Protection against pressure appeared to be mediated by specific interactions because addition of bovine serum albumin did not have the same effect.

Conclusions

Our results show that pressure‐induced loss of potency is strain dependent and suggests that pressure treatment may be useful for identifying vaccine formulations that improve HA stability.
Les divers modes de prise en charge des orphelins et les moyens d'action des pouvoirs publics: le cas du Mozambique dans le contexte de la Communauté de développement de l’Afrique australe
Authors: Shibuya Tomoko , Taylor Viviene
Published: March 2013

S’efforçant de placer la situation des orphelins du Mozambique dans son contexte régional, celui de l’Afrique australe, et s’inspirant d'études sur le terrain tant quantitatives que qualitatives, cet article examine les différents modes de prise en charge des orphelins et la politique de protection qui leur est applicable au Mozambique, en s’intéressant tout particulièrement aux enfants qui vivent dans des centres d'hébergement ou qui fréquentent les foyers d'accueil. Dans un souci de mieux faire comprendre ce que vivent ces enfants et de jeter un éclairage sur la protection sociale qui leur est fournie, cette analyse montre que les orphelins qui sont pris en charge de manière informelle par des familles d'accueil présentent davantage de risques d'être exploités, négligés ou maltraités que ceux qui vivent dans des structures d'accueil non gouvernementales. Cette étude souligne la nécessité de sélectionner avec plus d'attention les familles d'accueil dans lesquelles les enfants sont placés. Les recommandations portent notamment sur la nécessité de privilégier le renforcement des capacités et les réformes institutionnelles tendant à mettre en place des politiques de protection sociale pour les orphelins dans le cadre d'un socle général de protection sociale. Le suivi et l'évaluation des institutions qui prennent en charge les orphelins s’imposent comme une priorité.