bluuebunny/crossref_metadata_2025 huggingface dataset:
World Health Organization 2006 Child Growth Standards and 2007 Growth Reference Charts
Authors: Turck Dominique , Michaelsen Kim F. , Shamir Raanan , Braegger Christian , Campoy Cristina , Colomb Virginie , Decsi Tamás , Domellöf Magnus , Fewtrell Mary , Kolacek Sanja , Mihatsch Walter , Moreno Luis A. , van Goudoever Johannes
Published: May 2013

Growth charts are essential for evaluating children's health including their nutrition; however, the evaluation of child growth trajectories and consequently the decision to intervene are highly dependent on the growth charts used. The aim of this discussion paper of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition is to provide information on the background and rationale of the World Health Organization (WHO) 2006 child growth standards and WHO 2007 growth reference charts, describe their development, outline their main innovative aspects, discuss potential limitations, and make recommendations. WHO 2006 child growth standards (0–5 years) are based on prospectively collected data describing the growth of healthy infants who were breast‐fed according to WHO recommendations, showing a pattern of linear growth, which is remarkably consistent between different countries and ethnic groups. WHO 2007 growth reference charts (5–19 years) are based mainly on a re‐analysis of National Centre for Health Statistics data from 1977, without information on feeding. European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recommends that WHO child growth standards should be used to monitor growth in all children in the age range 0 to 2 years in Europe, whether breast‐ or formula‐fed, and that they should be considered to be used in the age range 2 to 5 years. Implementation of the WHO child growth standards should be preceded by evaluation of the implication of their use on national healthcare policies. Health professionals should be guided on their use and interpretation and an adequate communication strategy should be available locally to ensure that parents receive clear and consistent advice. The decision on whether to implement the WHO growth references (5–19 years) should be made by national bodies because the growth pattern during the 5‐ to 19‐year period differs between populations.
Endoscopic and Histologic Analysis of Gastric Mucosa‐Associated Lymphoid Tissue in Children With Helicobacter pylori Infection
Authors: Yang Hye Ran , Choi Hyoung Soo , Paik Jin Ho , Lee Hye Seung
Published: May 2013

Objectives:

Nodular gastritis (NG) associated with Helicobacter pylori infection can occur commonly in childhood and is regarded to be benign without clinical significance. This study includes endoscopic and histologic analysis of gastric mucosa‐associated lymphoid tissue (MALT) to clarify the significance of NG on endoscopy in H pylori–infected children.

Methods:

Of the 758 children who underwent endoscopy, 80 were identified as having H pylori infection. These patients were divided into 3 groups based on endoscopic severity of gastric nodularity. Histopathologic grading of MALT and immunohistochemistry of CD3, CD20, cytokeratin, and Ki‐67 were evaluated.

Results:

On endoscopy, severe NG was observed in the antrum of 38 of the 80 subjects, mild NG in 27, and an absence of NG in 15. Density of H pylori and lymphocyte infiltration differed among the 3 groups (P = 0.022 and P = 0.025, respectively). Histological grading for gastric lymphoid infiltrates was compatible with grade 1 in 47 (58.8%), grade 2 in 21 (26.3%), grade 3 in 7 (8.8%), and grade 4–5 in 4 (5.1%) in the antrum. Degree of NG, density of H pylori, neutrophil activity, and gastritis score in the antrum varied with MALT grades (P = 0.003, P = 0.042, P = 0.028, and P = 0.006, respectively).

Conclusions:

Our study suggests NG may present as a significant gastric manifestation of childhood H pylori infection that indicates gastric MALT. Thorough histologic investigation may be useful in the evaluation of gastric MALT in children infected with H pylori that manifests as severe NG in the antrum.
Stranded dolphin stomach contents represent the free-ranging population's diet
Authors: Dunshea Glenn , Barros Nélio B. , Berens McCabe Elizabeth J. , Gales Nicholas J. , Hindell Mark A. , Jarman Simon N. , Wells Randall S.
Published: May 2013

Diet is a fundamental aspect of animal ecology. Cetacean prey species are generally identified by examining stomach contents of stranded individuals. Critical uncertainty in these studies is whether samples from stranded animals are representative of the diet of free-ranging animals. Over two summers, we collected faecal and gastric samples from healthy free-ranging individuals of an extensively studied bottlenose dolphin population. These samples were analysed by molecular prey detection and these data compared with stomach contents data derived from stranded dolphins from the same population collected over 22 years. There was a remarkable consistency in the prey species composition and relative amounts between the two datasets. The conclusions of past stomach contents studies regarding dolphin habitat associations, prey selection and proposed foraging mechanisms are supported by molecular data from live animals and the combined dataset. This is the first explicit test of the validity of stomach contents analysis for accurate population-scale diet determination of an inshore cetacean.
How does tooth cusp radius of curvature affect brittle food item processing?
Authors: Berthaume Michael A. , Dumont Elizabeth R. , Godfrey Laurie R. , Grosse Ian R.
Published: May 2013

Tooth cusp sharpness, measured by radius of curvature (RoC), has been predicted to play a significant role in brittle/hard food item fracture. Here, we set out to test three existing hypotheses about this relationship: namely, the Blunt and Strong Cusp hypotheses, which predict that dull cusps will be most efficient at brittle food item fracture, and the Pointed Cusp hypothesis, which predicts that sharp cusps will be most efficient at brittle food item fracture using a four cusp bunodont molar. We also put forth and test the newly constructed Complex Cusp hypothesis, which predicts that a mixture of dull and sharp cusps will be most efficient at brittle food item fracture. We tested the four hypotheses using finite-element models of four cusped, bunodont molars. When testing the three existing hypotheses, we assumed all cusps had the same level of sharpness (RoC), and gained partial support for the Blunt Cusp hypotheses. We found no support for the Pointed Cusp or Strong Cusp hypotheses. We used the Taguchi sampling method to test the Complex Cusps hypothesis with a morphospace created by independently varying the radii of curvature of the four cusps in the buccolingual and mesiodistal directions. The optimal occlusal morphology for fracturing brittle food items consists of a combination of sharp and dull cusps, which creates high stress concentrations in the food item while stabilizing the food item and keeping the stress concentrations in the enamel low. This model performed better than the Blunt Cusp hypothesis, suggesting a role for optimality in the evolution of cusp form.
The interplay between relatedness and horizontal gene transfer drives the evolution of plasmid-carried public goods
Authors: Mc Ginty Sorcha É. , Lehmann Laurent , Brown Sam P. , Rankin Daniel J.
Published: May 2013

Plasmids carry a wide range of genes that are often involved in bacterial social behaviour. The question of why such genes are frequently mobile has received increasing attention. Here, we use an explicit population genetic approach to model the evolution of plasmid-borne bacterial public goods production. Our findings highlight the importance of both transmission and relatedness as factors driving the evolution of plasmid-borne public goods production. We partition the effects of plasmid transfer of social traits into those of infectivity and the effect of increased relatedness. Our results demonstrate that, owing to its effect on relatedness, plasmid mobility increases the invasion and stability of public goods, in a way not seen in individually beneficial traits. In addition, we show that plasmid transfer increases relatedness when public goods production is rare but this effect declines when production is common, with both scenarios leading to an increase in the frequency of plasmid-borne public goods. Plasmids remain important vectors for the spread of social genes involved in bacterial virulence thus an understanding of their dynamics is highly relevant from a public health perspective.
How to get into bones: proton pump and carbonic anhydrase inOsedaxboneworms
Authors: Tresguerres Martin , Katz Sigrid , Rouse Greg W.
Published: May 2013

Osedaxare gutless siboglinid worms that thrive on vertebrate bones lying on the ocean floor, mainly those of whales. The posterior body of femaleOsedaxpenetrates into the bone forming extensions known as ‘roots’, which host heterotrophic symbiotic bacteria in bacteriocytes beneath the epidermis. TheOsedaxroot epithelium presumably absorbs bone collagen and/or lipids, which are metabolized by the symbiotic bacteria that in turn serve forOsedax's nutrition. Here, we show thatOsedaxroots express extremely high amounts of vacuolar-H+-ATPase (VHA), which is located in the apical membrane and in cytoplasmic vesicles of root and ovisac epithelial cells. The enzyme carbonic anhydrase (CA), which catalyses the hydration of CO2into H+and HCO3−, is also expressed in roots and throughoutOsedaxbody. These results suggestOsedaxroots have massive acid-secreting capacityviaVHA, fuelled by H+derived from the CA-catalysed hydration of CO2produced by aerobic metabolism. We propose the secreted acid dissolves the bone carbonate matrix to then allow the absorption of bone-derived nutrients across the skin. In an exciting example of convergent evolution, this model for acid secretion is remarkably similar to mammalian osteoclast cells. However, while osteoclasts dissolve bone for repairing and remodelling, theOsedaxroot epithelium secretes acid to dissolve foreign bone to access nutrients.
Imaging Sodium in Axons and Dendrites
Authors: Ross William , Fleidervish Ilya , Lasser-Ross Nechama
Published: May 2013

This protocol describes a one-photon method to detect the time course and the spatial distribution of intracellular sodium ion concentrations [Na+]i, which result from action potentials and synaptic activity in different regions of neurons in brain slices. The one-photon technique has been applied to several different cell types and can likely be applied to other neurons in brain slices, particularly those that are relatively flat. Imaging of [Na+]i changes is much less common than imaging of [Ca2+]i changes, in part because typical signals are much smaller and more difficult to detect. However, with careful experiments, accurate and interesting results can be obtained. In this protocol, a cell is loaded with an indicator that responds to Na+, the cell is stimulated, and the spatial and temporal characteristics of the fluorescence changes are recorded with an appropriate detector or camera.
Digital Micromirror Devices: Principles and Applications in Imaging
Authors: Bansal Vivek , Saggau Peter
Published: May 2013

A digital micromirror device (DMD) is an array of individually switchable mirrors that can be used in many advanced optical systems as a rapid spatial light modulator. With a DMD, several implementations of confocal microscopy, hyperspectral imaging, and fluorescence lifetime imaging can be realized. The DMD can also be used as a real-time optical processor for applications such as the programmable array microscope and compressive sensing. Advantages and disadvantages of the DMD for these applications as well as methods to overcome some of the limitations will be discussed in this article. Practical considerations when designing with the DMD and sample optical layouts of a completely DMD-based imaging system and one in which acousto-optic deflectors (AODs) are used in the illumination pathway are also provided.
Negative Feedback Control of Jasmonate Signaling by an Alternative Splice Variant of JAZ10
Authors: Moreno Javier E. , Shyu Christine , Campos Marcelo L. , Patel Lalita C. , Chung Hoo Sun , Yao Jian , He Sheng Yang , Howe Gregg A.
Published: May 2013

The plant hormone jasmonate (JA) activates gene expression by promoting ubiquitin-dependent degradation of jasmonate ZIM domain (JAZ) transcriptional repressor proteins. A key feature of all JAZ proteins is the highly conserved Jas motif, which mediates both JAZ degradation and JAZ binding to the transcription factor MYC2. Rapid expression of JAZ genes in response to JA is thought to attenuate JA responses, but little is known about the mechanisms by which newly synthesized JAZ proteins exert repression in the presence of the hormone. Here, we show in Arabidopsis (Arabidopsis thaliana) that desensitization to JA is mediated by an alternative splice variant (JAZ10.4) of JAZ10 that lacks the Jas motif. Unbiased protein-protein interaction screens identified three related basic helix-loop-helix transcription factors (MYC2, MYC3, and MYC4) and the corepressor NINJA as JAZ10.4-binding partners. We show that the amino-terminal region of JAZ10.4 contains a cryptic MYC2-binding site that resembles the Jas motif and that the ZIM motif of JAZ10.4 functions as a transferable repressor domain whose activity is associated with the recruitment of NINJA. Functional studies showed that the expression of JAZ10.4 from the native JAZ10 promoter complemented the JA-hypersensitive phenotype of a jaz10 mutant. Moreover, treatment of these complemented lines with JA resulted in the rapid accumulation of JAZ10.4 protein. Our results provide an explanation for how the unique domain architecture of JAZ10.4 links transcription factors to a corepressor complex and suggest how JA-induced transcription and alternative splicing of JAZ10 premessenger RNA creates a regulatory circuit to attenuate JA responses.
A Chloroplast ABC1-like Kinase Regulates Vitamin E Metabolism in Arabidopsis
Authors: Martinis Jacopo , Glauser Gaétan , Valimareanu Sergiu , Kessler Felix
Published: May 2013

In bacteria and mitochondria, ABC1 (for Activity of bc1 complex)-like kinases regulate ubiquinone synthesis, mutations causing severe respiration defects, including neurological disorders in humans. Little is known about plant ABC1-like kinases; in Arabidopsis (Arabidopsis thaliana), five are predicted in mitochondria but, surprisingly, six are located at lipid droplets in chloroplasts. These are a known site of prenylquinone (including tocopherol [vitamin E], phylloquinone [vitamin K] and plastoquinone) metabolism and contain a large proportion of the tocopherol cyclase (VTE1) required for vitamin E synthesis and recycling. Therefore, ABC1-like kinases may be involved in the regulation of chloroplast prenylquinone metabolism. Using a nontargeted lipidomics approach, we demonstrate that plants lacking the plastoglobule ABC1-like kinase ABC1K3 are defective both for the production of plastochromanol-8 (a plastoquinone-derived lipid antioxidant) and the redox recycling of α-tocopherol, whereas tocopherol production is not affected. All of these pathways require VTE1 activity. However, in the abc1k3 mutant, VTE1 levels are strongly reduced posttranscriptionally. We provide evidence that the ABC1-like kinase ABC1K3 phosphorylates VTE1, possibly stabilizing it at plastoglobules. However, ABC1K3 may also have other targets and be involved in a wider chloroplast regulatory network.
Crystal structure and thermal properties of a square-planar NiIIcomplex of cyanide and a tricyclic bis-amidine ligand formedin situunder solvothermal conditions
Authors: Stolárová Monika , Černák Juraj , Tomás Milagros , Falvello Larry R.
Published: May 2013

The reaction ofN1,N1′-(ethane-1,2-diyl)bis(propane-1,3-diamine) (bapen), K2[Ni(CN)4]·H2O and dimethylformamide in the presence of Gd(NO3)3·6H2O under solvothermal conditions yielded yellow crystals of dicyanido(2,3,4,6,7,9,10,11-octahydropyrimido[2′,1′:3,4]pyrazino[1,2-a]pyrimidine)nickel(II) hemihydrate, [Ni(CN)2(C10H16N4)]·0.5H2O, (I), the crystal structure of which is composed of [Ni(CN)2(pdpm)] molecules (pdpm is 2,3,4,6,7,9,10,11-octahydropyrimido[2′,1′:3,4]pyrazino[1,2-a]pyrimidine) on general positions linked by O—H...N hydrogen bonds to water molecules located on twofold axes. This structural unit is further linked by nonclassical C—H...N interactions to form a warped two-dimensional net perpendicular to the unit-cellbaxis. The nets are stacked, with C—H...O contacts joining successive units. The NiIIcation is coordinated with square-planar geometry by a chelating pdpm ligand and two cyanide ligands in mutuallycispositions. Complex (I) is stable up to 360 K, at which point dehydration takes place; the ligands start to decompose at 558 K.
A comparison of 3,4,6a,7,10,10a-hexahydro-7,10-epoxypyrimido[2,1-a]isoindol-6(2H)-one and 2-(2-aminoethyl)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione: structural and reactivity differences of two homologous tricyclic imides
Authors: Mitchell Lauren A. , Stanley Julie M. , Espinosa De Hoyos Liliana , Holliday Bradley J.
Published: May 2013

The crystal structures of 3,4,6a,7,10,10a-hexahydro-7,10-epoxypyrimido[2,1-a]isoindol-6(2H)-one, C11H12N2O2, and 2-(2-aminoethyl)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione, C10H12N2O3, two tricyclic imides, show one and two molecules in the asymmetric unit, respectively. Intermolecular hydrogen-bonding interactions are observed in both compounds.
Synthesis and photophysical properties of 2,5,8,11-tetrakis(5-hexylthiophen-2-yl)tetrathieno[2,3-a:3′,2′-c:2′′,3′′-f:3′′′,2′′′-h]naphthalene
Authors: Gao Libin
Published: May 2013

The title compound, C58H64S8, has been prepared by Pd-catalysed direct C—H arylation of tetrathienonaphthalene (TTN) with 5-hexyl-2-iodothiophene and recrystallized by slow evaporation from dichloromethane. The crystal structure shows a completely planar geometry of the TTN core, crystallizing in the monoclinic space groupP21/c. The structure consists of slipped π-stacks and the interfacial distance between the mean planes of the TTN cores is 3.456 (5) Å, which is slightly larger than that of the comparable derivative of tetrathienoanthracene (TTA) with 2-hexylthiophene groups. The packing in the two structures is greatly influenced by both the aromatic core of the structure and the alkyl side chains.
An orthorhombic polymorph of a cyclization product of perindopril
Authors: Bojarska Joanna , Maniukiewicz Waldemar , Sieroń Lesław , Remko Milan
Published: May 2013

Low-temperature X-ray diffraction experiments were employed to investigate the crystal structures of an orthorhombic polymorph of the intramolecular cyclization product of perindopril, a popular angiotensive-converting enzyme (ACE) inhibitor, namely ethyl (2S)-2-[(3S,5aS,9aS,10aS)-3-methyl-1,4-dioxo-5a,6,7,8,9,9a,10,10a-octahydro-3H-pyrazino[1,2-a]indol-2-yl]pentanoate, C19H30N2O4, (Io), and its tetragonal equivalent, (It), which was previously reported at ambient temperature [Bojarskaet al.(2013).J. Chil. Chem. Soc.58, 1415–1417]. Polymorph (Io) crystallizes in the orthorhombic space groupP212121with two molecules in the asymmetric unit, while tetragonal form (It) crystallizes in the space groupP41212 with one molecule in the asymmetric unit. The geometric parameters of (Io) are very similar to those of (It). The six-membered rings in both polymorphs adopt a slightly deformed chair conformation and the piperazinedione rings are in a boat conformation. However, the proline rings adopt an envelope conformation in (Io), while in (It) the ring exists in a slightly deformed half-chair conformation. The most significant difference between the two structures is the orientation of the ethyl pentanoate chain. Molecules associate in pairs in a head-to-tail manner forming infinite columns. In (Io), molecules are related by a twofold screw axis forming identical columns, while in (It), molecules in successive neighbouring columns are related by alternating twofold screw axes and fourfold screw axes. In both cases, the crystal packing is stabilized by weak intermolecular C—H...O interactions only.
catena-Poly[[(tetrahydrofuran-κO)potassium]-μ-(η5:η5)-2,3,4,5-tetramethyl-1-n-pentylcyclopentadienyl]
Authors: Seidel Rüdiger W. , Ganesamoorthy Chelladurai , Loerke Sinah , Winter Manuela V. , Gemel Christian , Fischer Roland A.
Published: May 2013

The title compound, [K(C14H23)(C4H8O)]n, comprises zigzag chains of alternating bridging 2,3,4,5-tetramethyl-1-n-pentylcyclopentadienyl ligands and potassium ions, with an ancillary tetrahydrofuran ligand in the coordination environment of potassium. The coordination polymer strands so formed extend by 21screw symmetry in theb-axis direction. The chemically modified cyclopentadienyl ligand, with a tetheredn-pentyl group, was synthesized from 2,3,4,5-tetramethylcyclopent-2-enone by a Grignard reaction.
On The Outside Looking In: Reflections on the Role of Inspection in Driving Up Quality in the Criminal Justice System
Authors: Shute Stephen
Published: May 2013

This article examines the role of external inspection in enhancing the quality of a criminal justice system. It seeks to answer six foundational questions: how should we understand the nature and purposes of criminal justice inspection? what methodologies ought it to employ? who should do it? what values should it respect? how much does it cost? and does it ‘work'? The article reveals that the difference between inspection and other forms of scrutiny activity is largely a matter of emphasis; that the same is true of the difference between inspection and research; that ‘lay’ involvement in inspection can be beneficial; that independence is a core value for inspection, albeit one that is best understood as independence of judgement; that transparency is a further key value but not always honoured; and that evidence that inspection improves service delivery and hence justifies its costs is weak and further research is needed.
The Mandatory Bid Rule: Efficient, After All?
Authors: Schuster Edmund‐Philipp
Published: May 2013

The mandatory bid rule has its origins in the UK and now applies throughout the EU and in many other jurisdictions. Under a mandatory bid, an acquirer of a controlling stake in a listed company has to offer to the remaining shareholders a buy‐out of their minority stakes at a price equal to the consideration received by the incumbent controller. While the rule warrants that no value‐destroying control transfers take place, it is often criticised for preventing value‐increasing transactions. This paper challenges some of the claims made by critics of mandatory bids. Highlighting the effects of synergy gains in private sale‐of‐control transactions, it is shown that mandatory bids prevent inefficient control transfers, where minority shareholder protection rules provide inadequate protection. Furthermore, mandatory bids help facilitate transfers to the most efficient bidders in multi‐bidder settings. The mandatory bid is justifiable, on economic grounds, in wider circumstances than is commonly assumed by law and economics scholars.
This Time, it's for Real: The Health and Social Care Act 2012
Authors: Davies A.C.L.
Published: May 2013

This article examines the Health and Social Care Act 2012 and associated reforms to the National Health Service in England. It focuses on the Act's policy of making the NHS market more ‘real’, by both encouraging and compelling NHS bodies to act as ‘market players’. The article considers whether the reforms are compatible with the constitutional requirements of accountability for the provision of a public service such as the NHS. It argues that the reforms threaten accountability for three reasons: they make the Secretary of State for Health's relationship with the NHS more complex, they create opaque networks of non‐statutory bodies which may influence NHS decision‐making, and (especially in relation to competition) they ‘juridify’ policy choices as matters of law. Taken together, these arguments suggest that there is force in the claim that the reforms will contribute to ‘creeping’ – and thus unaccountable – privatisation of the NHS.
Assumption of Responsibility in Corporate Groups: Chandler v Cape plc
Authors: Petrin Martin
Published: May 2013

In Chandler v Cape plc, the Court of Appeal imposed for the first time liability on a company for a breach of its duty of care to an employee of its subsidiary. In doing so, the court laid out a new four‐part test for ascertaining a parent company's responsibility for the health and safety of individuals employed by group companies. Although liability of parent companies may be justified under the right circumstances, the court's approach in Chandler is problematic in a number of ways and raises more questions than it answers.
Factor Xa Inhibitor Attenuates Leukocyte Adhesion and Thrombus Formation in an Experimental Mouse Model of the Metabolic Syndrome
Authors: Iba Toshiaki , Aihara Koichiro , Watanabe Shin , Yanagawa Youichi , Yamada Atushi , Koichiro Niwa , Ohsaka Akimichi
Published: May 2013

Aims

In a model of acute inflammation, Factor Xa inhibitors have been reported not only to suppress the coagulation system but also to exert anti‐inflammatory effects. However, this has not been experimentally demonstrated in a model of chronic inflammation. Recent studies demonstrated that vascular inflammation in the metabolic syndrome plays major roles in the development of thrombotic diseases. Therefore, we examined the anti‐inflammatory effects of fondaparinux, a Factor Xa inhibitor, in a mouse model of the metabolic syndrome, looking at both leukocyte adhesion on the vascular endothelium and thrombus formation.

Methods

Following clamping of the mesenteric vein for 20 min in the KK‐Ay mouse, mice were administered by subcutaneous injection either low‐dose or high‐dose fondaparinux or placebo (n = 10 in each group. Microscopic observation of the intestinal microcirculation was carried out. In another series, blood samples were taken and measured for blood cell counts and organ damage markers (n = 6 in each).

Results

Both leukocyte adherence and thrombus formation were inhibited by treatment with fondaparinux. Red blood cell and white blood cell counts were maintained better in high‐dose group. Levels of alanine aminotransferase (ALT) were significantly reduced in both low‐dose and high‐dose groups (P < 0.05 and 0.01, compared with control, respectively).

Conclusions

Factor Xa inhibitor attenuates leukocyte adhesion and leukocyte‐platelet conjugate formation in a mouse model of the metabolic syndrome. These effects appeared to be related to both inhibition of thrombus formation and reduction in markers of organ damage.
Non‐invasive prenatal diagnosis for single gene disorders: experience of patients
Authors: Lewis C. , Hill M. , Chitty L.S.
Published: May 2013

The aim of this study is to explore women's experiences of using newly developed non‐invasive prenatal diagnosis (NIPD) for single gene disorders. Methods used in this study include qualitative one‐to‐one interviews with eight women with pregnancies at risk of achondroplasia, Apert syndrome, thanatophoric dysplasia or a neuromuscular condition. The results of the study show that the women were positive about an accurate, safe, and early test. Where the foetus was at increased risk of inheriting a genetic condition, the benefits of NIPD over invasive testing were that it reduced the period of uncertainty and worry by being conducted within the first trimester. For those women for whom there was a low recurrence risk, the period of uncertainty could be reduced and pregnancy ‘normalized’ earlier. For women who would not have risked invasive testing, NIPD enabled them to have an early diagnostic test that was more accurate than ultrasound. Where ultrasound abnormalities were detected, NIPD ended the ‘diagnostic odyssey’, enabling women to make practical and psychological preparations for the birth. NIPD conducted through specialist services was considered most appropriate. NIPD for these particular single gene disorders was appreciated by women and appears to be satisfactory. Further exploration of stakeholder views may be required to inform more widespread implementation of NIPD for a broader range of genetic conditions.
Reduced α‐synuclein levels in cerebrospinal fluid in Parkinson's disease are unrelated to clinical and imaging measures of disease severity
Authors: van Dijk K. D. , Bidinosti M. , Weiss A. , Raijmakers P. , Berendse H. W. , van de Berg W. D. J.
Published: May 2013

Background and purpose

The cerebrospinal fluid (CSF) concentration of α‐synuclein may reflect the aggregation of α‐synuclein in brain tissue that neuropathologically characterizes Parkinson's disease (PD). Although most studies in large cohorts report reduced CSF α‐synuclein levels in PD, the available data to date are not consistent due to variation in group sizes, pre‐analytical confounding factors and assay characteristics. Furthermore, it remains unclear whether CSF α‐synuclein concentrations correlate with measures of disease severity. Acknowledging the methodological issues that emerged from previous studies, we evaluated whether CSF α‐synuclein levels differ between patients with PD and controls, and relate to disease duration or severity.

Methods

α‐Synuclein levels were measured in CSF samples of 53 well‐characterized patients with PD and 50 healthy controls employing a recently developed time‐resolved Förster's resonance energy transfer assay. In addition, we studied the relationship of CSF α‐synuclein levels with disease duration, clinical measures of disease severity and the striatal dopaminergic deficit as measured by dopamine transporter binding and single photon emission computed tomography.

Results

In patients with PD, we observed a decrease in mean CSF α‐synuclein levels that was unrelated to disease duration or measures of disease severity. Using total protein normalized α‐synuclein, a sensitivity and specificity of 70% and 74% could be reached for distinguishing between patients with PD and controls.

Conclusion

CSF α‐synuclein levels are reduced in patients with PD compared with healthy controls. However, sensitivity and specificity indicate that α‐synuclein will not suffice as a single biomarker. CSF α‐synuclein levels do not correlate with measures of disease severity, including striatal dopaminergic deficit.
Being Penn State: The Role of Joe Paterno's Prototypicality in the Sandusky Sex-Abuse Scandal
Authors: Wiley Shaun , Dahling Jason J.
Published: May 2013

More than any other man, Mr. Paterno is Penn State – the man who brought the institution national recognition, the man who built a football program based on honor for 46 years, the winningest football coach in Division I history…Paterno is at the core of the university's sense of identity. (Guarino, 2011, November 10)

We believe that Alderfer's (2013) intergroup analysis of the Penn State scandal can be enriched by focusing on the special role that Joe Paterno played in the events leading up to the 2010 grand jury that brought the scandal to light outside the university community. On the basis of the social identity theory of leadership (Hogg, 2001), we argue that the community afforded Paterno the trust that he appears to have abused to suppress the scandal because he embodied the norms, values, and goals of Penn State in a way that made him prototypical of the university. By making the broader group category salient, Paterno was able to shape the behavior of representatives of many sub-groups described by Alderfer within the administration, athletics, and community. Coupled with a high degree of institutional ambiguity, Paterno's prototypicality likely enabled him to suppress the “constructive diversity” (p. 123) of checks and balances that should have operated at Penn State. This disruption to effective intergroup processes prohibited necessary oversight over the PSU athletic program and the Second Mile that otherwise might have uncovered Jerry Sandusky's crimes much earlier.
SIR DYNAMICS WITH ECONOMICALLY DRIVEN CONTACT RATES
Authors: MORIN BENJAMIN R. , FENICHEL ELI P. , CASTILLO‐CHAVEZ CARLOS
Published: May 2013

The susceptible‐infected‐recovered (SIR) model has greatly evidenced epidemiology despite its apparent simplicity. Most applications of the SIR framework use a form of nonlinear incidence to describe the number of new cases per instant. We adapt theorems to analyze the stability of SIR models with a generalized nonlinear incidence structure. These theorems are then applied to the case of standard incidence and incidence resulting from adaptive behavioral response based on epidemiological‐economic theory. When adaptive behavior is included in the SIR model multiple equilibria and oscillatory epidemiological dynamics can occur over a greater parameter space. Our analysis, based on the epidemiological‐economic incidence, provides new insights into epidemics as complex adaptive systems, highlights important nonlinearities that lead to complex behavior, and provides mechanistic motivation for a shift away from standard incidence, and outlines important areas of research related to the complex‐adaptive dynamics of epidemics.
Angiotensin-Converting Enzyme–Induced Activation of Local Angiotensin Signaling Is Required for Ascending Aortic Aneurysms in Fibulin-4–Deficient Mice
Authors: Huang Jianbin , Yamashiro Yoshito , Papke Christina L. , Ikeda Yuichi , Lin Yanling , Patel Miteshkumar , Inagami Tadashi , Le Victoria P. , Wagenseil Jessica E. , Yanagisawa Hiromi
Published: May 2013

Up-regulation of angiotensin-converting enzyme in the aortic wall causes aneurysms in fibulin-4–deficient mice, which can be prevented by losartan or captopril.
Probing the Brain of Comorbidity
Authors: Palotie Aarno , Kallela Mikko , Anttila Verneri
Published: May 2013

Inherited sleep disorders might provide insights for migraine pathophysiology.
Cell Host Response to Infection with Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences with SARS Coronavirus
Authors: Josset Laurence , Menachery Vineet D. , Gralinski Lisa E. , Agnihothram Sudhakar , Sova Pavel , Carter Victoria S. , Yount Boyd L. , Graham Rachel L. , Baric Ralph S. , Katze Michael G.
Published: May 2013

A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact
in vivo
pathogenesis and could orient therapeutic strategies against that emergent virus.

IMPORTANCE
Identification of a novel coronavirus causing fatal respiratory infection in humans raises concerns about a possible widespread outbreak of severe respiratory infection similar to the one caused by SARS-CoV. Using a human lung epithelial cell line and global transcriptomic profiling, we identified differences in the host response between HCoV-EMC and SARS-CoV. This enables rapid assessment of viral properties and the ability to anticipate possible differences in human clinical responses to HCoV-EMC and SARS-CoV. We used this information to predict potential effective drugs against HCoV-EMC, a method that could be more generally used to identify candidate therapeutics in future disease outbreaks. These data will help to generate hypotheses and make rapid advancements in characterizing this new virus.
Anthrax Toxin-Mediated Delivery of thePseudomonasExotoxin A Enzymatic Domain to the Cytosol of Tumor Cells via Cleavable Ubiquitin Fusions
Authors: Bachran Christopher , Morley Thomas , Abdelazim Suzanne , Fattah Rasem J. , Liu Shihui , Leppla Stephen H.
Published: May 2013

Anthrax toxin proteins fromBacillus anthracisconstitute a highly efficient system for delivering cytotoxic enzymes to the cytosol of tumor cells. However, exogenous proteins delivered to the cytosol of cells are subject to ubiquitination on lysines and proteasomal degradation, which limit their potency. We created fusion proteins containing modified ubiquitins with their C-terminal regions fused to thePseudomonasexotoxin A catalytic domain (PEIII) in order to achieve delivery and release of PEIII to the cytosol. Fusion proteins in which all seven lysines of wild-type ubiquitin were retained while the site cleaved by cytosolic deubiquitinating enzymes (DUBs) was removed were nontoxic, apparently due to rapid ubiquitination and proteasomal degradation. Fusion proteins in which all lysines of wild-type ubiquitin were substituted by arginine had high potency, exceeding that of a simple fusion lacking ubiquitin. This variant was less toxic to nontumor tissues in mice than the fusion protein lacking ubiquitin and was very efficient for tumor treatment in mice. The potency of these proteins was highly dependent on the number of lysines retained in the ubiquitin domain and on retention of the C-terminal ubiquitin sequence cleaved by DUBs. It appears that rapid cytosolic release of a cytotoxic enzyme (e.g., PEIII) that is itself resistant to ubiquitination is an effective strategy for enhancing the potency of tumor-targeting toxins.

IMPORTANCEBacterial toxins typically have highly efficient mechanisms for cellular delivery of their enzymatic components. Cytosolic delivery of therapeutic enzymes and drugs is an important topic in molecular medicine. We describe anthrax toxin fusion proteins containing ubiquitin as a cytosolic cleavable linker that improves the delivery of an enzyme to mammalian cells. The ubiquitin linker allowed modulation of potency in cells and in mice. This effective strategy for enhancing the intracellular potency of an enzyme may be useful for the cytosolic delivery and release of internalized drugs.
Opposing Roles for Two Molecular Forms of Replication Protein A in Rad51-Rad54-Mediated DNA Recombination in Plasmodium falciparum
Authors: Gopalakrishnan Anusha M. , Kumar Nirbhay
Published: May 2013

The bacterial RecA protein and its eukaryotic homologue Rad51 play a central role in the homologous DNA strand exchange reaction during recombination and DNA repair. Previously, our lab has shown that PfRad51, the
Plasmodium falciparum
homologue of Rad51, exhibited ATPase activity and promoted DNA strand exchange
in vitro
. In this study, we evaluated the catalytic functions of PfRad51 in the presence of putative interacting partners, especially
P. falciparum
homologues of Rad54 and replication protein A. PfRad54 accelerated PfRad51-mediated pairing between single-stranded DNA (ssDNA) and its homologous linear double-stranded DNA (dsDNA) in the presence of 0.5 mM CaCl
2
. We also present evidence that recombinant PfRPA1L protein serves the function of the bacterial homologue single-stranded binding protein (SSB) in initiating homologous pairing and strand exchange activity. More importantly, the function of PfRPA1L was negatively regulated in a dose-dependent manner by PfRPA1S, another RPA homologue in
P. falciparum
. Finally, we present
in vivo
evidence through comet assays for methyl methane sulfonate-induced DNA damage in malaria parasites and accompanying upregulation of PfRad51, PfRad54, PfRPA1L, and PfRPA1S at the level of transcript and protein needed to repair DNA damage. This study provides new insights into the role of putative Rad51-interacting proteins involved in homologous recombination and emphasizes the physiological role of DNA damage repair during the growth of parasites.

IMPORTANCE
Homologous recombination plays a major role in chromosomal rearrangement, and Rad51 protein, aided by several other proteins, plays a central role in DNA strand exchange reaction during recombination and DNA repair. This study reports on the characterization of the role of
P. falciparum
Rad51 in homologous strand exchange and DNA repair and evaluates the functional contribution of PfRad54 and PfRPA1 proteins. Data presented here provide mechanistic insights into DNA recombination and DNA damage repair mechanisms in this parasite. The importance of these research findings in future work will be to investigate if Rad51-dependent mechanisms are involved in chromosomal rearrangements during antigenic variation in
P. falciparum
. A prominent determinant of antigenic variation, the extraordinary ability of the parasite to rapidly change its surface molecules, is associated with
var
genes, and antigenic variation presents a major challenge to vaccine development.
Injury surveillance in the World Football Tournaments 1998–2012
Authors: Junge Astrid , Dvorak Jiri
Published: May 2013

Background

International sports bodies should protect the health of their athletes, and injury surveillance is an important pre-requisite for injury prevention. The Fédération International de Football Association (FIFA) has systematically surveyed all football injuries in their tournaments since 1998.

Aims

Analysis of the incidence, characteristics and changes of football injury during international top-level tournaments 1998–2012.

Methods

All newly incurred football injuries during the FIFA tournaments and the Olympic Games were reported by the team physicians on a standardised injury report form after each match. The average response rate was 92%.

Results

A total of 3944 injuries were reported from 1546 matches, equivalent to 2.6 injuries per match. The majority of injuries (80%) was caused by contact with another player, compared with 47% of contact injuries by foul play. The most frequently injured body parts were the ankle (19%), lower leg (16%) and head/neck (15%). Contusions (55%) were the most common type of injury, followed by sprains (17%) and strains (10%). On average, 1.1 injuries per match were expected to result in absence from a match or training. The incidence of time-loss injuries was highest in the FIFA World Cups and lowest in the FIFA U17 Women's World Cups. The injury rates in the various types of FIFA World Cups had different trends over the past 14 years.

Conclusions

Changes in the incidence of injuries in top-level tournaments might be influenced by the playing style, refereeing, extent and intensity of match play. Strict application of the Laws of the Games is an important means of injury prevention.
The association of alcohol drinking pattern and self-inflicted intentional injury in Korea: a cross-sectional WHO collaborative emergency room study
Authors: Chun Sungsoo , Reid Easton A , Yun Mieun
Published: May 2013

Objectives

Self-inflicted intentional injuries are increasing at an alarming rate in the Republic of Korea, yet few reports describe their relationship with alcohol consumption. The aim of this study was to characterise the association of alcohol drinking patterns and self-inflicted intentional injury in Korean emergency departments (EDs) using WHO collaborative study protocol.

Design

Cross-sectional study.

Setting

Data were collected from four general hospital EDs in four geographically diverse regions of Korea: Seoul, Suwon, Chuncheon and Gwangju.

Participants

Information was collected on 1989 patients aged 18 and above. A representative probability sample was drawn from patients admitted to each ED for the first time within 6 h of injury.

Primary and secondary outcome measures

Alcohol-related non-fatal injuries.

Results

Among 467 persons with alcohol-related injuries, 33 (7.1%), were self-inflicted intentional injuries and 137 (29.3%) were intentional injuries caused by someone else. The adjusted odds of self-inflicted intentional injury verses unintentional injury were calculated for heavy (OR 1.764; 95% CI 0.783 to 3.976), binge (OR 2.125; 95% CI 0.930 to 4.858) and moderate drinking (OR 3.039; 95% CI 1.129 to 8.178) after controlling for demographic variables. Similar odds were reported for pooled intentional injury data (self-inflicted and caused by someone else) and drinking patterns.

Conclusions

These data show a strong association between all patterns of acute alcohol consumption and self-inflicted intentional injury in the Republic of Korea.
The eye response test alone is sufficient to predict stroke outcome—reintroduction of Japan Coma Scale: a cohort study
Authors: Shigematsu Kazuo , Nakano Hiromi , Watanabe Yoshiyuki
Published: May 2013

Objectives

Prompt assessment of consciousness levels is vitally important during the emergency care of stroke patients. The Japan Coma Scale (JCS) is a one-axis coma scale published in 1974 with outstanding simplicity. The hypothesis is that JCS is sufficient to predict stroke outcome. The aim of the study was to verify the predictability of JCS, which should help JCS attain international recognition.

Design

A cohort study.

Setting

A prefectural stroke registry.

Participants

We analysed 13 788 stroke patients identified from January 1999 to December 2009 inclusive in the entire Kyoto prefecture and registered in the Kyoto Stroke Registry (KSR).

Main outcome measures

We investigated the relationship between consciousness levels, based on JCS at stroke onset and activities of daily living (ADL) at 30 days or deaths within 30 days in a large population-based stroke registry. We calculated Spearman's coefficient for the correlation between JCS and the ADL scale, generated estimated survival curves by the Kaplan-Meier method and finally compared HRs for death within 30 days after onset, comparing patients with different conscious levels based on JCS.

Results

A total of 13 406 (97.2%) patients were graded based on JCS. JCS correlated to the ADL scale with Spearman's correlation coefficient of 0.61. HRs for death within 30 days were 1 (reference) (95% CIs), 5.55 (4.19 to 7.37), 9.54 (7.16 to 12.71) and 35.21 (26.10 to 44.83) in those scored as JCS0, JCS1, JCS2 and JCS3, respectively.

Conclusions

Using a single test of eye response, JCS has outstanding merits as a coma scale, that is, simplicity and applicability. The present study adds predictability for early outcome in stroke patients. JCS is valuable, especially in an emergency setting, when a prompt assessment of consciousness levels is needed.