bluuebunny/crossref_metadata_2025 huggingface dataset:
Geoengineering Knowledge: Interdisciplinarity and the Shaping of Climate Engineering Research
Authors: Szerszynski Bronislaw , Galarraga Maialen
Published: December 2013

In this paper we highlight the need to attend to the structuring power of knowledge production in geoengineering research, because of the way that problem definitions are shaped by disciplinary ways of thinking and describing the world. We also draw attention to a number of problematic assumptions about how interdisciplinary research should be approached and organised in this area. We first look at the logic of ‘subordination’, in which certain disciplines are given the task of problem definition and others—typically the social sciences—are allocated the task of filling in gaps within that given frame. We then examine the more fundamental ‘integrative imaginary’ which, we argue, mistakenly assumes that disciplines can be combined in a straightforward way to reveal different aspects of the same underlying world. We conclude by proposing a more reflexive imaginary for interdisciplinarity, one that challenges the idea of integration and subordination, that promotes and benefits from the multiplicity and heterogeneity of ways of seeing that different disciplines offer, and that can thereby contribute to greater ‘epistemological responsibility’ in geoengineering research.
Why Solar Radiation Management Geoengineering and Democracy Won't Mix
Authors: Szerszynski Bronislaw , Kearnes Matthew , Macnaghten Phil , Owen Richard , Stilgoe Jack
Published: December 2013

In this paper we argue that recent policy treatments of solar radiation management (SRM) have insufficiently addressed its potential implications for contemporary political systems. Exploring the emerging ‘social constitution’ of SRM, we outline four reasons why this is likely to pose immense challenges to liberal democratic politics: That the unequal distribution of and uncertainties about SRM impacts will cause conflicts within existing institutions; that SRM will act at the planetary level and necessitate autocratic governance; that the motivations for SRM will always be plural and unstable; and that SRM will become conditioned by economic forces.
Lessons for the Australian healthcare system from the Berwick report
Authors: Russell Lesley , Dawda Paresh
Published: December 2013

There are common key recommendations in the raft of recent reports from inquiries into hospital quality and safety issues, both in Australia and in the United Kingdom. Prime among these is that governments, bureaucrats, clinicians and administrators must work together to place the quality and safety of patient care above all other aims in the healthcare system. Performance targets and enforcement, although needed, are not the route to improvement; what is required is a change in culture to drive a system of care that is open to learning, capable of identifying and admitting its problems and acting to correct them, and where the patient’s voice is always heard.
Home range areas of koalas in an urban area of north-east New South Wales
Authors: Goldingay Ross L. , Dobner Barbara
Published: December 2013

Conserving wildlife within urban areas requires knowledge of habitat requirements and population processes, and the management of threatening factors. The koala (Phascolarctos cinereus) is one species that is adversely affected by urban development. Sick and injured koalas in the Lismore urban area are regularly taken into care. We radio-tracked koalas released from care in order to estimate home-range areas and to determine their fate. Koalas were tracked for periods of 90–742 days; 7 of 10 survived for a period of at least one year. Home ranges defined by the minimum convex polygon (MCP100%) were large (mean ± s.e. = 37.4 ± 8.2 ha). Analysis using the 95% Fixed Kernel revealed home-range areas of 8.0 ± 1.7 ha. Analysis of the habitat composition of each MCP home range showed that they included 4.3 ± 0.9 ha of primary habitat (dominated by their primary food trees). These home ranges contained 27.6 ± 6.8 ha of non-habitat (cleared or developed land). Koalas crossed roads within their home ranges at least 5–53 times; one crossed the Bruxner Highway near a roundabout at least 32 times over his 2-year tracking period. Future management should include strategic food tree planting that enhances habitat connectivity and minimises the risk of car strike or dog attack.
The Kauffman bracket skein module of two-bridge links
Authors: Le Thang , Tran Anh
Published: December 2013

We calculate the Kauffman bracket skein module (KBSM) of the complement of all two-bridge links. For a two-bridge link, we show that the KBSM of its complement is free over the ring

C

[

t

±
1

]

\mathbb {C}[t^{\pm 1}]

and when reducing

t
=
−
1

t=-1

, it is isomorphic to the ring of regular functions on the character variety of the link group.
An inverse theorem: When the measure of the sumset is the sum of the measures in a locally compact abelian group
Authors: Griesmer John
Published: December 2013

We classify the pairs of subsetsAA,BBof a locally compact abelian groupGGsatisfyingm∗(A+B)=m(A)+m(B)m_*(A+B)=m(A)+m(B), wheremmis the Haar measure forGGandm∗m_*is inner Haar measure. This generalizes M. Kneser’s classification of such pairs whenGGis assumed to be connected. Recently, D. Grynkiewicz classified the pairs of setsAA,BBsatisfying|A+B|=|A|+|B||A+B|=|A|+|B|in an abelian group, and our result is complementary to that classification. Our proofs combine arguments of Kneser and Grynkiewicz.
slaMEM: efficient retrieval of maximal exact matches using a sampled LCP array
Authors: Fernandes Francisco , Freitas Ana T.
Published: December 2013

Motivation: Maximal exact matches, or just MEMs, are a powerful tool in the context of multiple sequence alignment and approximate string matching. The most efficient algorithms to collect them are based on compressed indexes that rely on longest common prefix array-centered data structures. However, their space-efficient representations make use of encoding techniques that are expensive from a computational point of view. With the deluge of data generated by high-throughput sequencing, new approaches need to be developed to deal with larger genomic sequences.

Results: In this work, we have developed a new longest common prefix array-sampled representation, optimized to work with the backward search method inherently used by the FM-Index. Unlike previous implementations that sacrifice running time to have smaller space, ours lead to both a fast and a space-efficient approach. This implementation was used by the new software slaMEM, developed to efficiently retrieve MEMs. The results show that the new algorithm is competitive against existing state-of-the-art approaches.

Availability and implementation: The software is implemented in C and is operating system independent. The source code is freely available for download at http://github.com/fjdf/slaMEM/ under the GPLv3 license.

Contact:  atf@inesc-id.pt

Supplementary information:  Supplementary data are available at Bioinformatics online.
BEAMS: backbone extraction and merge strategy for the global many-to-many alignment of multiple PPI networks
Authors: Alkan Ferhat , Erten Cesim
Published: December 2013

Motivation: Global many-to-many alignment of biological networks has been a central problem in comparative biological network studies. Given a set of biological interaction networks, the informal goal is to group together related nodes. For the case of protein–protein interaction networks, such groups are expected to form clusters of functionally orthologous proteins. Construction of such clusters for networks from different species may prove useful in determining evolutionary relationships, in predicting the functions of proteins with unknown functions and in verifying those with estimated functions.

Results: A central informal objective in constructing clusters of orthologous proteins is to guarantee that each cluster is composed of members with high homological similarity, usually determined via sequence similarities, and that the interactions of the proteins involved in the same cluster are conserved across the input networks. We provide a formal definition of the global many-to-many alignment of multiple protein–protein interaction networks that captures this informal objective. We show the computational intractability of the suggested definition. We provide a heuristic method based on backbone extraction and merge strategy (BEAMS) for the problem. We finally show, through experiments based on biological significance tests, that the proposed BEAMS algorithm performs better than the state-of-the-art approaches. Furthermore, the computational burden of the BEAMS algorithm in terms of execution speed and memory requirements is more reasonable than the competing algorithms.

Availability and implementation: Supplementary material including code implementations in LEDA C++, experimental data and the results are available at http://webprs.khas.edu.tr/∼cesim/BEAMS.tar.gz.

Contacts:  ferhat.alkan@stu.khas.edu.tr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Structure and sequence elements of the CR4/5 domain of medaka telomerase RNA important for telomerase function
Authors: Kim Nak-Kyoon , Zhang Qi , Feigon Juli
Published: December 2013

Telomerase is a unique reverse transcriptase that maintains the 3′ ends of eukaryotic chromosomes by adding tandem telomeric repeats. The RNA subunit (TR) of vertebrate telomerase provides a template for reverse transcription, contained within the conserved template/pseudoknot domain, and a conserved regions 4 and 5 (CR4/5) domain, all essential for catalytic activity. We report the nuclear magnetic resonance (NMR) solution structure of the full-length CR4/5 domain from the teleost fish medaka (Oryzias latipes). Three helices emanate from a structured internal loop, forming a Y-shaped structure, where helix P6 stacks on P5 and helix P6.1 points away from P6. The relative orientations of the three helices are Mg2+ dependent and dynamic. Although the three-way junction is structured and has unexpected base pairs, telomerase activity assays with nucleotide substitutions and deletions in CR4/5 indicate that none of these are essential for activity. The results suggest that the junction is likely to change conformation in complex with telomerase reverse transcriptase and that it provides a flexible scaffold that allows P6 and P6.1 to correctly fold and interact with telomerase reverse transcriptase.
libRoadRunner: A High Performance SBML Compliant Simulator
Authors: Somogyi E. T. , Karlsson M. T. , Swat M. , Galdzicki M. , Sauro H. M
Published: December 2013

We describe libRoadRunner, a cross-platform, open-source, high performance C++ library for running and analyzing SBML-compliant models. libRoadRunner was created primarily to achieve high performance, ease of use, portability and an extensible architecture. libRoadRunner includes a comprehensive API, Plugin support, Python scripting and additional functionality such as stoichio-metric and metabolic control analysis.

Accessibility and Implementation

To maximize collaboration, we made libRoadRunner open source and released it under the Apache License, Version 2.0. To facilitate reuse, we have developed comprehensive Python bindings using SWIG (swig.org) and a C API. Li-bRoadRunner uses a number of statically linked third party libraries including: LLVM [4], libSBML [1], CVODE, NLEQ2, LAPACK and Poco. LibRoadRunner is supported on Windows, Mac OS X and Linux.

Supplementary information

Online documentation, build instructions and git source repository are available athttp://www.libroadrunner.org
Three one-dimensional coordination polymers based on 1,1′-bis(pyridin-4-ylmethyl)-2,2′-bi-1H-benzimidazole and HgX2(X= Cl, Br and I)
Authors: Li Ai-Guo , Liu Qi-Kui , Li Yan-An , Liu Zhi-Xian , Dong Yu-Bin
Published: December 2013

A new 2,2′-bi-1H-benzimidazole bridging organic ligand, namely 1,1′-bis(pyridin-4-ylmethyl)-2,2′-bi-1H-benzimidazole, C26H20N6,Lor (I), has been synthesized and used to create three new one-dimensional coordination polymers,viz.catena-poly[[dichloridomercury(II)]-μ-1,1′-bis(pyridin-4-ylmethyl)-2,2′-bi-1H-benzimidazole], [HgCl2(C26H20N6)]n, (II), and the bromido, [HgBr2(C26H20N6)]n, (III), and iodido, [HgI2(C26H20N6)]n, (IV), analogues. Free ligandLcrystallizes with two symmetry-independent half-molecules in the asymmetric unit and eachLmolecule resides on a crytallographic inversion centre. In structures (II)–(IV), theLligand is also positioned on a crystallographic inversion centre, whereas the Hg centre resides on a crystallographic twofold axis. Compound (I) adopts ananticonformation in the solid state and forms a two-dimensional network in the crystallographicbcplaneviaπ–π and C—H...π interactions. The three HgIIcoordination complexes, (II)–(IV), have one-dimensional zigzag chains composed ofLand HgX2(X= Cl, Br and I), and the HgIIcentres are in a distorted tetrahedral [HgX2N2] coordination geometry. Complexes (III) and (IV) are isomorphous, whereas complex (II) displays an interesting conformational difference from the others,i.e.a twist in the flexible bridging ligand.
(5RS)-5-(4-Methoxyphenyl)-2-(methylsulfanyl)benzo[g]pyrimido[4,5-b]quinoline-4,6,11(3H,5H,12H)-trione, withZ′ = 3, forms a three-dimensional hydrogen-bonded framework containing five types of hydrogen bond
Authors: Castillo Yelder A. , Zapata Luis F. , Trilleras Jorge , Cobo Justo , Glidewell Christopher
Published: December 2013

The title compound, C23H17N3O4S, crystallizes withZ′ = 3 in the space groupP\overline{1}. Two of the three independent molecules are broadly similar in terms of both their molecular conformations and their participation in hydrogen bonds, but the third molecule differs from the other two in both of these respects. The molecules are linked by a combination of N—H...O, N—H...N, C—H...O, C—H...N and C—H...π(arene) hydrogen bonds to form a continuous three-dimensional framework structure within which a centrosymmetric six-molecule aggregate can be identified as a key structural element.
A fivefold interpenetrating diamondoid three-dimensional metal–organic framework constructed from benzene-1,4-diacetic acid and flexible triazole derivatives: poly[[(μ2-benzene-1,4-diacetato-κ2O:O){μ2-1,4-bis[(1H-1,2,4-triazol-1-yl)methyl]benzene-κ2N4:N4′}zinc(II)] monohydrate]
Authors: Shen Hong
Published: December 2013

In the title mixed-ligand metal–organic polymeric compound, {[Zn(C10H8O4)(C12H14N6)]·H2O}n, the asymmetric unit contains a divalent ZnIIcation lying on a twofold axis, one half of a fully deprotonated benzene-1,4-diacetate (PBEA) ligand, one half of a 1,4-bis[(1H-1,2,4-triazol-1-yl)methyl]benzene (BTX) ligand and a water molecule, also lying on a twofold axis. Each ZnIIcentre is surrounded by two O-donor atoms from monodentate carboxylate groups belonging to two different PBEA2−ligands and by two triazole N-donor atoms from two different BTX ligands. Single-crystal X-ray diffraction analysis revealed that the compound has a fivefold interpenetrating diamondoid three-dimensional metal–organic framework.
Taxonomic relatedness shapes bacterial assembly in activated sludge of globally distributed wastewater treatment plants
Authors: Ju Feng , Xia Yu , Guo Feng , Wang Zhiping , Zhang Tong
Published: December 2013

Activated sludge (AS), which has been in use for 100 years, has been the most popular biological process in various wastewater treatment plants (WWTPs), in which bacteria plays central roles in pollutant removal. However, the potential relationship between bacteria taxa and the niches occupied by specific functional bacteria in AS are largely unknown. Here, correlation‐based network analysis was applied to a 16S rRNA gene pyrosequencing dataset containing > 760 000 sequences of 50 AS samples from globally distributed full‐scale WWTPs. The results showed that (i) bacterial assembly in AS was nonrandomly arranged by taxonomic relatedness and (ii) intra‐ and inter‐phylum/class co‐occurrence higher than expected by chance was induced by multiple deterministic processes, such as habitat filtering and competition. Moreover, based on bacterial occupancy, a prevalent core set of cosmopolitan functional bacteria (e.g. multiple nitrogen‐cycling‐related bacteria) was widely distributed in the AS of different WWTPs, showing strong ecological associations among them. Additionally, the AS network has statistical and structural characteristics similar to those of previously reported ecological networks, such as power‐law connectivity distribution and nonrandomly connected properties. Overall, this work provides novel insights into the bacterial associations within AS and sheds light on the ecological rules guiding bacterial assembly in WWTPs.
Generation of Intra‐oral‐like Images from Cone Beam Computed Tomography Volumes for Dental Forensic Image Comparison
Authors: Trochesset Denise A. , Serchuk Richard B. , Colosi Dan C.
Published: December 2013

Identification of unknown individuals using dental comparison is well established in the forensic setting. The identification technique can be time and resource consuming if many individuals need to be identified at once. Medical CT (MDCT) for dental profiling has had limited success, mostly due to artifact from metal‐containing dental restorations and implants. Description: The authors describe a CBCT reformatting technique that creates images, which closely approximate conventional dental images. Method: Using a i‐CAT Platinum CBCT unit and standard issue i‐CAT Vision software, a protocol is developed to reproducibly and reliably reformat CBCT volumes. The reformatted images are presented with conventional digital images from the same anatomic area for comparison. Conclusion: The authors conclude that images derived from CBCT volumes following this protocol are similar enough to conventional dental radiographs to allow for dental forensic comparison/identification and that CBCT offers a superior option over MDCT for this purpose.
Delirium Due to Intoxication from the Novel Synthetic Tryptamine 5‐MeO‐DALT
Authors: Jovel Andres , Felthous Alan , Bhattacharyya Anjan
Published: December 2013

Synthetic tryptamines have gained popularity for their hallucinogenic properties, unscheduled status, and availability from “head shops” and through the internet. Here, we present a case of synthetic tryptamine‐induced delirium secondary to 5‐MeO‐DALT ingestion in a previously healthy young male. 5‐MeO‐DALT led to the hospitalization of our patient after ingestion of a standard dose, presenting with extreme agitation, tachycardia, diaphoresis, and combativeness leading to physical restraint and intravenous sedation. A search of PubMed, Ovid, and Google Scholar for keywords of “5‐MeO‐DALT,” “5‐methoxy‐N,N‐diallyltryptamine,” or “Lucy‐N‐Nate” found no case reports or clinical articles in the literature. Rapid emergence and commercialization of this novel synthetic tryptamine 5‐MeO‐DALT points to the importance of health care and forensic professionals keeping abreast of the latest drugs of abuse and their clinical features. The authors hope this report leads the way in disseminating the potential risks associated with unscheduled and unregulated substances, synthetic tryptamines such as 5‐MeO‐DALT in particular.
Comparison of sexual compatibility in crosses between the southern and northern populations of the cabbage beetle Colaphellus bowringi
Authors: Liu Xing‐Ping , Tu Xiao‐Yun , He Hai‐Min , Chen Chao , Xue Fang‐Sen
Published: December 2013

It is widely accepted that the genetic divergence and reproductive incompatibility between closely related species and/or populations is often viewed as an important step toward speciation. In this study, sexual compatibility in crosses between the southern XS population and the northern TA population of the polyandrous cabbage beetle Colaphellus bowringi was investigated by testing their mating preferences, mating latency, copulation duration, and reproductive performances of post‐mating. In choice mating experiments, the percentages of matings were significantly higher in intra‐population crosses than in inter‐population crosses. Both isolation index (I) and index of pair sexual isolation (IPSI) indicated partial mating incompatibility or assortative mating in crosses between the two different geographical populations. In single pair mating experiments, XS females in inter‐population crosses mated significantly later and copulated significantly shorter than those in intra‐population crosses. However, TA females in inter‐population crosses mated significantly earlier and copulated longer than those in intra‐population crosses, suggesting that larger XS males may enhance heterotypic mating. The lifetime fecundity was highest in XS homotypic matings, lowest in TA homotypic matings, and intermediate in heterotypic matings between their parents. The inter‐population crosses resulted in significantly lower egg hatching rate and shorter female longevity than intra‐population crosses. These results demonstrated that there exist some incompatibilities in premating, postmating‑prezygotic, and postzygotic stages between the southern XS population and northern TA population of the cabbage beetle Colaphellus bowringi.
Overview of Regular Dialysis Treatment in Japan (as of 31 December 2011)
Authors: Nakai Shigeru , Watanabe Yuzo , Masakane Ikuto , Wada Atsushi , Shoji Tetsuo , Hasegawa Takeshi , Nakamoto Hidetomo , Yamagata Kunihiro , Kazama Junichiro James , Fujii Naohiko , Itami Noritomo , Shinoda Toshio , Shigematsu Takashi , Marubayashi Seiji , Morita Osamu , Hashimoto Seiji , Suzuki Kazuyuki , Kimata Naoki , Hanafusa Norio , Wakai Kenji , Hamano Takayuki , Ogata Satoshi , Tsuchida Kenji , Taniguchi Masatomo , Nishi Hiroshi , Iseki Kunitoshi , Tsubakihara Yoshiharu
Published: December 2013

A nationwide statistical survey of 4255 dialysis facilities was conducted at the end of 2011. Responses were submitted by 4213 facilities (99.0%). The number of new patients started on dialysis was 38 613 in 2011. Although the number of new patients decreased in 2009 and 2010, it increased in 2011. The number of patients who died each year has been increasing; it was 30 743 in 2011, which exceeded 30 000 for the first time. The number of patients undergoing dialysis has also been increasing every year; it was 304 856 at the end of 2011, which exceeded 300 000 for the first time. The number of dialysis patients per million at the end of 2011 was 2385.4. The crude death rate of dialysis patients in 2011 was 10.2%, which exceeded 10% for the first time in the last 20 years. The mean age of new dialysis patients was 67.84 years and the mean age of the entire dialysis patient population was 66.55 years. The most common primary cause of renal failure among new dialysis patients was diabetic nephropathy (44.3%). Diabetic nephropathy was also the most common primary disease among the entire dialysis patient population (36.7%), exceeding chronic glomerulonephritis (34.8%) which had been the highest until last year. The survey included questions related to the Great East Japan Earthquake, which occurred on 11 March 2011. The results on items associated with the Great East Japan Earthquake were reported separately from this report. The mean uric acid levels of the male and female patients were 7.30 and 7.19 mg/dL, respectively. Certain drugs for hyperuricemia were prescribed for approximately 17% of patients. From the results of the facility survey, the number of patients who underwent peritoneal dialysis (PD) was 9642 and the number of patients who did not undergo PD despite having a peritoneal dialysis catheter was 369. A basic summary of the results on the survey items associated with PD is included in this report and the details were reported separately.
The Effect of Feed Solids Concentration and Inlet Temperature on the Flavor of Spray Dried Whey Protein Concentrate
Authors: Park Curtis W. , Bastian Eric , Farkas Brian , Drake MaryAnne
Published: December 2013

Previous research has demonstrated that unit operations in whey protein manufacture promote off‐flavor production in whey protein. The objective of this study was to determine the effects of feed solids concentration in liquid retentate and spray drier inlet temperature on the flavor of dried whey protein concentrate (WPC). Cheddar cheese whey was manufactured, fat‐separated, pasteurized, bleached (250 ppm hydrogen peroxide), and ultrafiltered (UF) to obtain WPC80 retentate (25% solids, wt/wt). The liquid retentate was then diluted with deionized water to the following solids concentrations: 25%, 18%, and 10%. Each of the treatments was then spray dried at the following temperatures: 180 °C, 200 °C, and 220 °C. The experiment was replicated 3 times. Flavor of the WPC80 was evaluated by sensory and instrumental analyses. Particle size and surface free fat were also analyzed. Both main effects (solids concentration and inlet temperature) and interactions were investigated. WPC80 spray dried at 10% feed solids concentration had increased surface free fat, increased intensities of overall aroma, cabbage and cardboard flavors and increased concentrations of pentanal, hexanal, heptanal, decanal, (E)2‐decenal, DMTS, DMDS, and 2,4‐decadienal (P < 0.05) compared to WPC80 spray dried at 25% feed solids. Product spray dried at lower inlet temperature also had increased surface free fat and increased intensity of cardboard flavor and increased concentrations of pentanal, (Z)4‐heptenal, nonanal, decanal, 2,4‐nonadienal, 2,4‐decadienal, and 2‐ and 3‐methyl butanal (P < 0.05) compared to product spray dried at higher inlet temperature. Particle size was higher for powders from increased feed solids concentration and increased inlet temperature (P < 0.05). An increase in feed solids concentration in the liquid retentate and inlet temperature within the parameters evaluated decreased off‐flavor intensity in the resulting WPC80.
Chronic CRF1 receptor blockade reduces heroin intake escalation and dependence‐induced hyperalgesia
Authors: Park Paula E. , Schlosburg Joel E. , Vendruscolo Leandro F. , Schulteis Gery , Edwards Scott , Koob George F.
Published: December 2013

Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain‐related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro‐adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin‐releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia‐like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self‐administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal‐induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self‐administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence‐associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid‐induced hyperalgesia and eventually intake escalation.
Identification of novel genetic markers and evaluation of genetic structure in a population of Japanese crested ibis
Authors: Tsubono Kanako , Taniguchi Yukio , Matsuda Hirokazu , Yamada Takahisa , Sugiyama Toshie , Homma Kosuke , Kaneko Yoshinori , Yamagishi Satoshi , Iwaisaki Hiroaki
Published: December 2013

Japanese population of the Japanese crested ibis Nipponia nippon was founded by five individuals gifted from the People's Republic of China. In order to exactly evaluate genetic structure, we first performed development of novel genetic makers using 89 microsatellite primer pairs of related species for cross‐amplification. Of these, only three primer pairs were useful for the genetic markers. Additionally, we sequenced allelic PCR products of these three markers together with 10 markers previously identified. Most markers showed typical microsatellite repeat units, but two markers were not simple microsatellites. Moreover, over half of the markers did not have the same repeat units as those of the original species. These results suggested that development of novel genetic markers in this population by cross‐amplification is not efficient, partly because of low genetic diversity. Furthermore, the cluster analysis by STRUCTURE program using 17 markers showed that the five founders were divided into two clusters. However, the genetic relationships among the founders indicated by the clustering seemed to be questionable, because the analysis relied largely on a small number of triallelic markers, in spite of the addition of the three useful markers. Therefore, more efficient methods for identifying large numbers of single nucleotide polymorphisms are desirable.
Characterizing variability in warfarin dose requirements in children using modelling and simulation
Authors: Hamberg Anna‐Karin , Wadelius Mia , Friberg Lena E. , Biss Tina T. , Kamali Farhad , Jonsson E. Niclas
Published: December 2013

Aims

Although genetic, clinical and demographic factors have been shown to explain approximately half of the inter‐individual variability in warfarin dose requirement in adults, less is known about causes of dose variability in children. This study aimed to identify and quantify major genetic, clinical and demographic sources of warfarin dose variability in children using modelling and simulation.

Methods

Clinical, demographic and genetic data from 163 children with a median age of 6.3 years (range 0.06–18.9 years), covering over 183 years of warfarin therapy and 6445 INR observations were used to update and optimize a published adult pharmacometric warfarin model for use in children.

Results

Genotype effects in children were found to be comparable with what has been reported for adults, with CYP2C9 explaining up to a four‐fold difference in dose (CYP2C9 *1/*1 vs. *3/*3) and VKORC1 explaining up to a two‐fold difference in dose (VKORC1 G/G vs. A/A), respectively. The relationship between bodyweight and warfarin dose was non‐linear, with a three‐fold difference in dose for a four‐fold difference in bodyweight. In addition, age, baseline and target INR, and time since initiation of therapy, but not CYP4F2 genotype, had a significant impact on typical warfarin dose requirements in children.

Conclusions

The updated model provides quantitative estimates of major clinical, demographic and genetic factors impacting on warfarin dose variability in children. With this new knowledge more individualized dosing regimens can be developed and prospectively evaluated in the pursuit of improving both efficacy and safety of warfarin therapy in children.
Urinary diversion after radical cystectomy for bladder cancer: options, patient selection, and outcomes
Authors: Lee Richard K. , Abol‐Enein Hassan , Artibani Walter , Bochner Bernard , Dalbagni Guido , Daneshmand Siamak , Fradet Yves , Hautmann Richard E. , Lee Cheryl T. , Lerner Seth P. , Pycha Armin , Sievert Karl‐Dietrich , Stenzl Arnulf , Thalmann Georg , Shariat Shahrokh F.
Published: December 2013

Context

The urinary reconstructive options available after radical cystectomy (RC) for bladder cancer are discussed, as are the criteria for selection of the most appropriate diversion, and the outcomes and complications associated with different diversion options.

Objective

To critically review the peer‐reviewed literature on the function and oncological outcomes, complications, and factors influencing choice of procedure with urinary diversion after RC for bladder carcinoma.

Evidence Acquisition

A Medline search was conducted to identify original articles, review articles, and editorials on urinary diversion in patients treated with RC. Searches were limited to the English language.

Keywords included: ‘bladder cancer’, ‘cystectomy’, ‘diversion’, ‘neobladder’, and ‘conduit’.

The articles with the highest level of evidence were selected and reviewed, with the consensus of all of the authors of this paper.

Evidence Synthesis

Both continent and incontinent diversions are available for urinary reconstruction after RC. In appropriately selected patients, an orthotopic neobladder permits the elimination of an external stoma and preservation of body image without compromising cancer control. However, the patient must be fully educated and committed to the labour‐intensive rehabilitation process. He must also be able to perform self‐catheterisation if necessary.

When involvement of the urinary outflow tract by tumour prevents the use of an orthotopic neobladder, a continent cutaneous reservoir may still offer the opportunity for continence albeit one that requires obligate self‐catheterisation.

For patients who are not candidates for continent diversion, the ileal loop remains an acceptable and reliable option.

Conclusions

Both continent and incontinent diversions are available for urinary reconstruction after RC.

Orthotopic neobladders optimally preserve body image, while continent cutaneous diversions represent a reasonable alternative.

Ileal conduits represent the fastest, easiest, least complication‐prone, and most commonly performed urinary diversion.
Mitochondrial fusion and fission proteins: novel therapeutic targets for combating cardiovascular disease
Authors: Hall A R , Burke N , Dongworth R K , Hausenloy D J
Published: December 2013

Mitochondria are no longer considered to be solely the static powerhouses of the cell. While they are undoubtedly essential to sustaining life and meeting the energy requirements of the cell through oxidative phosphorylation, they are now regarded as highly dynamic organelles with multiple functions, playing key roles in cell survival and death. In this review, we discuss the emerging role of mitochondrial fusion and fission proteins, as novel therapeutic targets for treating a wide range of cardiovascular diseases.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
Fine‐tuning somatostatin receptor signalling by agonist‐selective phosphorylation and dephosphorylation: IUPHAR Review 5
Authors: Schulz Stefan , Lehmann Andreas , Kliewer Andrea , Nagel Falko
Published: December 2013

The biological actions of somatostatin are mediated by a family of five GPCRs, named sst1 to sst5. Somatostatin receptors exhibit equally high‐binding affinities to their natural ligand somatostatin‐14 and largely overlapping distributions. The overexpression of somatostatin receptors in human tumours is the molecular basis for diagnostic and therapeutic application of the stable somatostatin analogues octreotide, lanreotide and pasireotide. The efficiency of somatostatin receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation and dephosphorylation of intracellular carboxyl‐terminal serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite‐specific antibodies for human sst2 and sst5 receptors. These phosphosite‐specific antibodies are unique tools to monitor the spatial and temporal dynamics of receptors phosphorylation and dephosphorylation. Using a combined approach of phosphosite‐specific antibodies and siRNA knock‐down screening, relevant kinases and phosphatases were identified. Emerging evidence suggests distinct mechanisms of agonist‐selective fine‐tuning for individual somatostatin receptors. The recently uncovered differences in phosphorylation and dephosphorylation of these receptors may hence be of physiological significance in mediating responses to acute, persistent or repeated stimuli in a variety of target tissues.
Quantile Regression in the Study of Developmental Sciences
Authors: Petscher Yaacov , Logan Jessica A. R.
Published: December 2013

Linear regression analysis is one of the most common techniques applied in developmental research, but only allows for an estimate of the average relations between the predictor(s) and the outcome. This study describes quantile regression, which provides estimates of the relations between the predictor(s) and outcome, but across multiple points of the outcome's distribution. Using data from the High School and Beyond and U.S. Sustained Effects Study databases, quantile regression is demonstrated and contrasted with linear regression when considering models with: (a) one continuous predictor, (b) one dichotomous predictor, (c) a continuous and a dichotomous predictor, and (d) a longitudinal application. Results from each example exhibited the differential inferences which may be drawn using linear or quantile regression.
Robust Segmentation of Multiple Intersecting Manifolds from Unoriented Noisy Point Clouds
Authors: Kustra J. , Jalba A. , Telea A.
Published: December 2013

We present a method for extracting complex manifolds with an arbitrary number of (self‐) intersections from unoriented point clouds containing large amounts of noise. Manifolds are formed in a three‐step process. First, small flat neighbourhoods of all possible orientations are created around all points. Next, neighbourhoods are assembled into larger quasi‐flat patches, whose overlaps give the global connectivity structure of the point cloud. Finally, curved manifolds are extracted from the patch connectivity graph via a multiple‐source flood fill. The manifolds can be reconstructed into meshed surfaces using standard existing surface reconstruction methods. We demonstrate the speed and robustness of our method on several point clouds, with applications in point cloud segmentation, denoising and medial surface reconstruction.
What is the best option for failed sphincter repair?
Authors: Hong K. D. , da Silva G. , Wexner S. D.
Published: December 2013

Aim

This study aimed to evaluate the outcome of various procedures for patients with fecal incontinence following failed sphincteroplasty.

Method

Patients who underwent surgery for failed sphincteroplasty from January 2000 to June 2012 were identified. They were assessed using the Fecal Incontinence Quality of Life (FIQoL) scale and the Cleveland Clinic Florida‐Wexner Fecal Incontinence Score (CCFFIS).

Results

Fifty‐nine patients [97% females; median age 52 (25–81) years] were identified. They underwent either repeat sphincteroplasty (RS; n = 33), artificial bowel sphincter (ABS; n = 11) or sacral nerve stimulation (SNS; n = 15). The median follow‐up was 31 (3–138) months. The RS group had a significantly wider external sphincter defect and had undergone fewer previous sphincteroplasties. The most common complication was infection. The incidence of complications was significantly higher after ABS (73%) compared with RS (24%) and SNS (33%) (P = 0.01). Seventeen (29%) patients required re‐operation for complications or failure, with a lower rate in the RS group (P = 0.004). There was no difference in the rates of device removal after ABS or SNS. Ten (17%) patients underwent further surgery or re‐implantation of the device with no difference between the groups. At follow‐up, five (45%) ABS and 10 (67%) SNS patients retained a functioning device (P = 0.4). The mean postoperative CCFFIS decreased from 17.5 to 11.5 in the RS group, from 18.7 to 8.6 in the ABS group, and from 17.6 to 9.1 in the SNS group (P ≤ 0.02 for all). There were no differences in the improvement of CCFFIS or FIQoL scores among groups.

Conclusion

RS, ABS and SNS are associated with similar improvements in continence after failed sphincteroplasty. Due to increased complications and re‐operation with ABS and SNS, RS may be the first step in managing these patients.
Impending paradoxical embolism: have we lost the clot?
Authors: Ghent Finn , Bassin Levi , Keller Michael , Cranney Gregory , McKenzie David , Grant Peter W.
Published: December 2013

Impending paradoxical embolism is a rare diagnosis that requires urgent treatment. We present a case where surgical thromboembolectomy was undertaken. The thrombus vanished from view on transesophageal ultrasound and was presumed to have undergone embolisation while bypass was established. Unexpectedly, it was found tangled in the superior vena cava cannula apertures.
Tumor‐related epilepsy and epilepsy surgery
Authors: Lhatoo Samden D. , Moghimi Narges , Schuele Stephan
Published: December 2013

Tumor‐related epilepsy (TRE) is a major etiologic category of epilepsy. TRE is heterogeneous, and the epidemiology, pathology, pathophysiology, clinical features, treatment, and outcomes vary accordingly. In addition, treatment imperatives vary between almost purely epilepsy considerations and those that are primarily oncologic. Often, there is no clear separation of imperatives, and there is a relatively scant evidence base that underpins management decisions in such cases. Given a diverse molecular as well as clinical landscape and the rapid pace with which new knowledge accrues, there are relatively few recent literature resources on TRE that provide neurologists, neurosurgeons, epileptologists, and oncologists with an up‐to‐date, state‐of‐the‐art review of the field in all of its important aspects. The proceedings of the Sixth International Epilepsy Colloquium in Cleveland in Ohio, U.S.A., in May 2013 on Tumoral Epilepsy and Epilepsy Surgery address, at least in part, several TRE aspects crucial to modern epilepsy and oncology practice.
Recent aspects of classification and epidemiology of epilepsy‐associated tumors
Authors: Japp Anna , Gielen Gerrit H. , Becker Albert J.
Published: December 2013

Epileptic seizures are frequent manifestations of brain tumors. However, biopsy specimens of patients who undergo neurosurgical removal of circumscribed foci to control chronic recurrent pharmacoresistant seizures often reveal tumor entities that are rare in general brain tumor series. The spectrum of these “long‐term epilepsy‐associated neoplasms” comprises highly differentiated glial and glioneuronal tumors that show a benign biologic behavior and clinical course, and that rarely relapse. Several entities are well recognizable on the basis of histopathologic and immunohistochemical characteristics. An intriguing functional aspect of these tumors, sometimes collectively referred to as “epileptomas,” is their prominent epileptogenicity, which may represent a clinical feature indicating rather than causing the generally benign biologic behavior of these tumors. A frequent feature of respective neoplasms is their coincidence with dysplastic lesions in the vicinity of the tumor itself. The recent advent of new molecular markers, including genomic alterations leading to activation of the protooncogene BRAF and impaired function of isocitrate dehydrogenase (IDH1), provides excellent new tools in the differential diagnosis of low grade brain tumors, and provides intriguing implications to further develop the pathogenetic concepts of these neoplasms. Despite this progress, a number of tumors from patients with chronic epilepsy show combinations of cytologic, histologic, and immunohistochemical characteristics that challenge the current neuropathologic classification schemes. Attempts are currently ongoing to develop further classification schemes.
Seizure characteristics and prognostic factors of gliomas
Authors: Kerkhof Melissa , Vecht Charles J.
Published: December 2013

Epilepsy in neuroepithelial tumors is highly prevalent. Neurogliomas (dysembryoplastic neuroepitheliomas [DNETs] and gangliogliomas) have a seizure incidence of 80–100%, low‐grade gliomas of 60–85%, and glioblastoma of 30–60%. With each type, the appearance of seizures is usually the presenting clinical symptom, and with neuroglial tumors often the only clinical sign. Tumor locations in the temporal and insular cortex are associated with a higher risk of developing epilepsy in both neuroglial tumors and low‐grade gliomas. Focal seizures with or without alteration of consciousness and/or secondary generalization are common. Focal seizures with altered consciousness are present in 50–70% of neuroglial tumors, and secondarily generalized seizures in 70% of low‐grade gliomas. Surgical treatment, particularly gross tumor resection, contributes strongly to seizure freedom, especially in neuroglial tumors. Refractory epilepsy is more common in low‐grade gliomas, occurring in 30–35%. Recurrence or worsening of seizures is often associated with tumor recurrence in glioblastomas. Translational studies have revealed a strong prevalence of IDH1 enzyme mutation together with the presence of seizures and long‐term survival in low‐grade gliomas. Disturbances of glutamate metabolism occur both in low‐grade tumors and glioblastomas, and provide insight into mutual cellular pathway abnormalities contributing to both seizure development and tumor growth. Likewise, the recent clinical observations on antitumor activity of the anticonvulsant valproic acid in glioblastoma now provide promising outlooks on single therapies that target both seizures and gliomas.
Tumoral epileptogenicity: How does it happen?
Authors: Pallud Johan , Capelle Laurent , Huberfeld Gilles
Published: December 2013

Gliomas are the most frequent primary brain tumors and most glioma patients have seizures. The origin and mechanisms of human glioma–related epilepsy are multifactorial and an intermix of oncologic and neuronal processes. In this brief review, we show that the infiltrated peritumoral neocortex appears to be the key structure for glioma‐related epileptic activity, which depends on the interactions between the tumor per se and the surrounding brain. We shed light on the underlying mechanisms from two different “tumorocentric” and “epileptocentric” approaches, with a special emphasis on the glioma‐related glutamatergic and γ‐aminobutyric acid (GABA)ergic changes leading to epileptogenicity. Because gliomas use the neurotransmitter glutamate as a “tumor growth factor” to enhance glioma cell proliferation and invasion with neurotoxic, proinvasive, and proliferative effects, glutamate homeostasis is impaired, with elevated extracellular glutamate concentrations. Such excitatory effects contribute to the generation of epileptic activity in the peritumoral neocortex. GABAergic signaling is also involved both in tumor growth and in paradoxical excitatory effects mediated by alterations in neuronal and tumor cell Cl− homeostasis related to cotransporter changes. Local excitability may also be affected by an increase in extracellular K+ concentration, the alkalization of peritumoral neocortex, and alterations of gap‐junction functioning. Finally, the tumor itself may mechanically affect locally neuronal behavior, connections, and networks. Better understanding of glioma‐related oncologic and epileptologic processes are crucial for development of combined therapeutic strategies, but so far, the surgical management of gliomas should comprise a maximally safe surgical resection encompassing peritumoral neocortex.
Long‐term monitoring of brain tumors: When is it necessary?
Authors: Kennedy Jeffrey , Schuele Stephan U.
Published: December 2013

Tumors, particularly low grade glioma and glioneuronal tumors, account for 25–35% of patients who are undergoing epilepsy surgery for intractable seizures. A comprehensive epilepsy evaluation including video–electroencephalography (EEG) monitoring is useful for most of these patients, to determine the optimal extent of resection for the achievement of seizure‐free outcome without causing postoperative deficits. Video‐EEG monitoring for patients with brain tumor should also be considered in specific situations, such as patients with new postoperative seizures or advanced tumors with unexplained mental status change.