bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactory transduction pathways in the Senegalese sole Solea senegalensis
Authors: Velez Z. , Hubbard P. C. , Barata E. N. , Canário A. V. M.
Published: August 2013

This study tested whether differences in sensitivity between the upper and lower olfactory epithelia of Solea senegalensis are associated with different odorant receptors and transduction pathways, using the electro‐olfactogram. Receptor mechanisms were assessed by cross‐adaptation with amino acids (L‐cysteine, L‐phenylalanine and 1‐methyl‐L‐tryptophan) and bile acids (taurocholic acid and cholic acid). This suggested that relatively specific receptors exist for 1‐methyl‐L‐tryptophan and L‐phenylalanine (food‐related odorants) in the lower epithelium, and for taurocholic acid (conspecific‐derived odorant) in the upper. Inhibition by U73122 [a phospholipase C (PLC) inhibitor] suggested that olfactory responses to amino acids were mediated mostly, but not entirely, by PLC‐mediated transduction (IC50; 15–55 nM), whereas bile acid responses were mediated by both PLC and adenylate cyclase–cyclic adenosine monophosphate (AC–cAMP) (using SQ‐22536; an AC inhibitor). Simultaneous application of both drugs rarely inhibited responses completely, suggesting possible involvement of non‐PLC and non‐AC mediated mechanisms. For aromatic amino acids and bile acids, there were differences in the contribution of each transduction pathway (PLC, AC and non‐PLC and non‐AC) between the two epithelia. These results suggest that differences in sensitivity of the two epithelia are associated with differences in odorant receptors and transduction mechanisms.
Differences between juvenile offenders with and without intellectual disabilities in the importance of static and dynamic risk factors for recidivism
Authors: van der Put C. E. , Asscher J. J. , Stams G. J. J. M. , Moonen X. M. H.
Published: August 2013

Background

Juvenile offenders with intellectual disability (ID) have been largely ignored in the literature of risk assessment, while they are overrepresented in the criminal justice system, and ID is a risk factor for juvenile delinquency and recidivism. The aim of this study was to examine whether there are differences between juvenile offenders with and without ID in the impact of risk factors for recidivism. Both the impact of static and dynamic risk factors were examined. Static risk factors were examined in the criminal history domain and dynamic risk factors were examined in the domains of family, school, use of free time, friends, alcohol/drugs, attitude, aggression and skills. This knowledge is important for both assessment and treatment of juvenile offenders with ID.

Method

The sample consisted of adolescents who appeared before the courts for a criminal act and for whom the Washington State Juvenile Court Assessment (WSJCA) was completed. The group of ID juvenile offenders (n = 102) consisted of juvenile offenders with a formal diagnosis of ID, which means a full scale IQ of less than 70, coupled with significant deficits in adaptive behaviour, with childhood onset. The juveniles of this group are special education students or they have a formal diagnosis of a special education need. The group without ID (n = 526), was a random sample of all juvenile offenders without a formal diagnosis of ID.

Results

No differences were found between juvenile offenders with and without ID in the impact of risk factors on recidivism in most domains. However, in the skills domain, the relations between all risk factors and recidivism were significantly stronger in adolescents without ID than in adolescents with ID. Although not or only borderline statistically significant, these risk factors were all negatively related to recidivism in adolescents with ID, whereas these risk factors were significantly and positively related to recidivism in adolescents without ID.

Conclusions

There are few differences between juvenile offenders with and without ID in the impact of risk factors for recidivism, suggesting that the same assessment methods can be used for juvenile offenders with and without ID. There were, however, differences between juvenile offenders with and without ID in the skills domain. What these differences mean for the treatment of juvenile offenders is yet to be determined. For now it is important to be aware of potential negative (side) effects on recidivism when skills training is offered to juvenile offenders with ID.
Mechanism of cholesterol‐assisted oligomeric channel formation by a short Alzheimer β‐amyloid peptide
Authors: Di Scala Coralie , Troadec Jean‐Denis , Lelièvre Clément , Garmy Nicolas , Fantini Jacques , Chahinian Henri
Published: August 2013

Alzheimer β‐amyloid (Aβ) peptides can self‐organize into oligomeric ion channels with high neurotoxicity potential. Cholesterol is believed to play a key role in this process, but the molecular mechanisms linking cholesterol and amyloid channel formation have so far remained elusive. Here, we show that the short Aβ22‐35 peptide, which encompasses the cholesterol‐binding domain of Aβ, induces a specific increase of Ca2+ levels in neural cells. This effect is neither observed in calcium‐free medium nor in cholesterol‐depleted cells, and is inhibited by zinc, a blocker of amyloid channel activity. Double mutations V24G/K28G and N27R/K28R in Aβ22‐35 modify cholesterol binding and abrogate channel formation. Molecular dynamic simulations suggest that cholesterol induces a tilted α‐helical topology of Aβ22‐35. This facilitates the establishment of an inter‐peptide hydrogen bond network involving Asn‐27 and Lys‐28, a key step in the octamerization of Aβ22‐35 which proceeds gradually until the formation of a perfect annular channel in a phosphatidylcholine membrane. Overall, these data give mechanistic insights into the role of cholesterol in amyloid channel formation, opening up new therapeutic options for Alzheimer's disease.

image

Aβ22‐35 peptide, which encompasses the cholesterol binding domain of Aβ, induces a specific increase of Ca2+ level in neural cells. Double mutations V24G/K28G and N27R/K28R modify cholesterol binding and abrogate channels formation. Molecular dynamic simulations suggest that cholesterol induces a tilted α‐helical peptide topology facilitating the formation of annular octameric channels, as schematically shown in the graphic (with a hydrogen bond shown in green for two vicinal peptides). Overall, the data give insights into the role of cholesterol in amyloid channel formation and open up new therapeutic options for Alzheimer's disease.
Vesicular GABA transporter (VGAT) transports β‐alanine
Authors: Juge Narinobu , Omote Hiroshi , Moriyama Yoshinori
Published: August 2013

Vesicular GABA transporter (VGAT) is expressed in GABAergic and glycinergic neurons, and is responsible for vesicular storage and subsequent exocytosis of these inhibitory amino acids. In this study, we show that VGAT recognizes β‐alanine as a substrate. Proteoliposomes containing purified VGAT transport β‐alanine using Δψ but not ΔpH as a driving force. The Δψ‐driven β‐alanine uptake requires Cl−. VGAT also facilitates Cl− uptake in the presence of β‐alanine. A previously described VGAT mutant (Glu213Ala) that disrupts GABA and glycine transport similarly abrogates β‐alanine uptake. These findings indicated that VGAT transports β‐alanine through a mechanism similar to those for GABA and glycine, and functions as a vesicular β‐alanine transporter.

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Vesicular GABA transporter (VGAT) is expressed in GABAergic and glycinergic neurons, and is responsible for vesicular storage and subsequent exocytosis of these inhibitory amino acids. In the present study, we showed that proteoliposomes containing purified VGAT transport β‐alanine using Δψ as a driving force. VGAT also facilitates Cl− uptake. Our findings indicated that VGAT functions as a vesicular β‐alanine transporter.
JosephLanner,JohannStraussSr and ‘The Future of Rhythm’
Authors: McKee Eric
Published: August 2013

In his 1837 article ‘Strauss: His Orchestra, His Waltzes – the Future of Rhythm’,Berlioz advocates treating rhythm as an independent dimension just as fundamental to music as melody and harmony. He observes that ‘the combinations in the realm of rhythm must certainly be as numerous as melodic ones, and the links between them could be made as interesting as for melody.Nothing can be more obvious than that there are rhythmic dissonances, rhythmic consonances, and rhythmic modulations.’ The true pioneers in the field of rhythm, he continues, are Beethoven and Weber – andJohannStraussSr.IcontinueBerlioz's line of thought by examining the use of two‐beat melodic grouping patterns within a notated 3/4 metre byStrauss and his near‐contemporary,JosephLanner, to create rhythmic dissonances, which often (but not necessarily) take the form of melodic hemiola, metrical modulation, and extended anacrusis. My article concludes with some general considerations on the expressive, formal and choreographical implications of metrical dissonance as it relates to the dancers on the Viennese ballroom floor.
What do patients with glaucoma think about personal health records?
Authors: Somner John EA , Sii Freda , Bourne Rupert , Cross Vinette , Shah Peter
Published: August 2013

Purpose

Putting patients in control of their records is one way of promoting patient centred care and patients with chronic health problems may benefit most from personal health records (PHRs). Glaucoma management is often complicated by incomplete understanding and poor adherence to treatment, two areas which a PHR may help to address. This study aimed to discover what patients with glaucoma think about PHRs and what type of information a glaucoma PHR should contain.

Methods

A consultation exercise using a focus group approach involving 71 participants was undertaken to discuss if a PHR would be useful and what it would be like. Narrative data were collected through written notes and an online forum in addition to transcripts of the focus group feedback session and individual interviews. Recordings were transcribed and analysed with simple thematic analysis facilitated by NVivo software (www.qsrinternational.com).

Results

The consultation exercise indicated enthusiasm for PHRs. Views varied on the best format, some participants strongly favoured electronic records and others preferred a low‐tech, paper based format. A comprehensive dataset of 24 items was developed which highlighted areas which are not covered by existing guidance to developers. A model for how PHRs may be useful as an education tool in clinical practice was devised.

Conclusions

Asking patients what they thought about a glaucoma PHR raised challenging questions and adds perspective to predominantly clinician led development. Listening and responding to such viewpoints is fundamental to developing more patient centred PHRs which may act both as health record and self‐care educational tool to promote more holistic, efficient glaucoma care.
Immunogenic assessment of plant‐produced human papillomavirus type 16 L1/L2 chimaeras
Authors: Pineo Catherine B. , Hitzeroth Inga I. , Rybicki Edward P.
Published: August 2013

Cervical cancer is caused by infection with human papillomaviruses (HPV) and is a global concern, particularly in developing countries, which have ~80% of the burden. HPV L1 virus‐like particle (VLP) type–restricted vaccines prevent new infections and associated disease. However, their high cost has limited their application, and cytological screening programmes are still required to detect malignant lesions associated with the nonvaccine types. Thus, there is an urgent need for cheap second‐generation HPV vaccines that protect against multiple types. The objective of this study was to express novel HPV‐16 L1‐based chimaeras, containing cross‐protective epitopes from the L2 minor capsid protein, in tobacco plants. These L1/L2 chimaeras contained epitope sequences derived from HPV‐16 L2 amino acid 108–120, 56–81 or 17–36 substituted into the C‐terminal helix 4 (h4) region of L1 from amino acid 414. All chimaeras were expressed in Nicotiana benthamiana via an Agrobacterium‐mediated transient system and targeted to chloroplasts. The chimaeras were highly expressed with yields of ~1.2 g/kg plant tissue; however, they assembled differently, indicating that the length and nature of the L2 epitope affect VLP assembly. The chimaera containing L2 amino acids 108–120 was the most successful candidate vaccine. It assembled into small VLPs and elicited anti‐L1 and anti‐L2 responses in mice, and antisera neutralized homologous HPV‐16 and heterologous HPV‐52 pseudovirions. The other chimaeras predominantly assembled into capsomeres and other aggregates and elicited weaker humoral immune responses, demonstrating the importance of VLP assembly for the immunogenicity of candidate vaccines.
National Japanese survey of thrombolytic therapy selection for coronary aneurysm: Intracoronary thrombolysis or intravenous coronary thrombolysis in patients with Kawasaki disease
Authors: Harada Mana , Akimoto Katsumi , Ogawa Shunichi , Kato Hitoshi , Nakamura Yosikazu , Hamaoka Kenji , Saji Tsutomu , Shimizu Toshiaki , Kato Tatsuo
Published: August 2013

Background

Thrombolytic therapy for coronary aneurysm thrombosis of Kawasaki disease (KD) includes antiplatelet and anticoagulants, i.v. coronary thrombolysis (IVCT), and i.c. thrombolysis (ICT). Therapeutic methods, drugs and doses vary among medical facilities.

Methods and Results

A nationwide survey of thrombolytic therapy was conducted under the auspices of the Ministry of Health, Labour and Welfare Research Program to Intractable Diseases Research Grants. A secondary survey targeted 14 facilities conducting thrombolytic therapy during a 5 year period (2004–2009). The primary survey investigated performance of thrombolytic therapy for 23 KD patients at 14 facilities, and of these, five with acute myocardial infarction had received ICT and combined therapy. The secondary survey investigated the pre‐treatment condition of aneurysm and thrombosis and actual treatment methods. ICT was effective for small thrombi (≤10 mm), while IVCT was effective even for giant thrombi (>10 mm). ICT was also effective for thrombi within several hours after formation.

Conclusion

In the present nationwide survey, thrombolytic therapy was more effective in cases of a shorter duration between thrombus formation and the start of treatment. It was found that many facilities used only IVCT for thrombus alone. Medications given to KD children did not cause serious hemorrhagic complications, unlike in adults. Although doses exceeded recommended levels in many cases, the only complications were nasal bleeding and fever.
Aim‐then‐shoot anemotaxis involved in the hopping approach of potato tuberworm moth Phthorimaea operculella toward a sex pheromone source
Authors: TEJIMA SHIN , ONO TOMOHIRO , SAKUMA MASAYUKI
Published: August 2013

Male moths locate conspecific females by pheromone‐induced upwind flight maintained by detecting a visual flow, termed optomotor anemotaxis. Their behavioural pattern is characterized by an upwind surge in response to a pheromone stimulus and crosswind casting after odour loss, which is considered to be reset and restarted on receipt of another pheromone pulse. However, pheromone‐stimulated males of the potato tuberworm moth Phthorimaea operculella exhibit a series of short and straight intermittent flights, or hops, when moving upwind. It is unclear whether they navigate by employing the same behavioural pattern and wind detection mechanism as that used by flying moths. To analyze odour‐modulated anemotaxis in male potato tuberworm moths, a flat wind tunnel is constructed to give regular odour stimuli to an insect regardless of its location. Moths are subjected to pheromone pulses of different frequencies to test whether they show a behavioural pattern that is reset and restarted by a pheromone pulse. Moths on the ground are also subjected to crosswind shear to examine their detection of wind direction. Path analyses reveal that males surge upwind when they receive a pheromone pulse and exhibit casting by successive hops when they lose odour. This behavioural pattern appears to be similar to that of flying moths. When the direction of the airflow is switched orthogonally, males adjust their course angle accordingly when they are on the ground. It is suggested that, instead of optomotor anemotaxis, this ‘aim‐then‐shoot’ system aids the detection of wind direction, possibly by mechanosensory means.
Shifted generic cohomology
Authors: Parshall Brian J. , Scott Leonard L. , Stewart David I.
Published: August 2013

The idea that the cohomology of finite groups might be fruitfully approached via the cohomology of ambient semisimple algebraic groups was first shown to be viable in the papers [E. Cline, B. Parshall, and L. Scott, Cohomology of finite groups of Lie type, I, Publ. Math. Inst. Hautes Études Sci. 45 (1975), 169–191] and [E. Cline, B. Parshall, L. Scott and W. van der Kallen, Rational and generic cohomology, Invent. Math. 39 (1977), 143–163]. The second paper introduced, through a limiting process, the notion of generic cohomology, as an intermediary between finite Chevalley group and algebraic group cohomology. The present paper shows that, for irreducible modules as coefficients, the limits can be eliminated in all but finitely many cases. These exceptional cases depend only on the root system and cohomological degree. In fact, we show that, for sufficiently large $r$, depending only on the root system and $m$, and not on the prime $p$ or the irreducible module $L$, there are isomorphisms ${\mathrm{H} }^{m} (G({p}^{r} ), L)\cong {\mathrm{H} }^{m} (G({p}^{r} ), {L}^{\prime } )\cong { \mathrm{H} }_{\mathrm{gen} }^{m} (G, {L}^{\prime } )\cong {\mathrm{H} }^{m} (G, {L}^{\prime } )$, where the subscript ‘gen’ refers to generic cohomology and ${L}^{\prime } $ is a constructibly determined irreducible ‘shift’ of the (arbitrary) irreducible module $L$ for the finite Chevalley group $G({p}^{r} )$. By a famous theorem of Steinberg, both $L$ and ${L}^{\prime } $ extend to irreducible modules for the ambient algebraic group $G$ with ${p}^{r} $-restricted highest weights. This leads to the notion of a module or weight being ‘shifted $m$-generic’, and thus to the title of this paper. Our approach is based on questions raised by the third author in [D. I. Stewart, The second cohomology of simple ${\mathrm{SL} }_{3} $-modules, Comm. Algebra 40 (2012), 4702–4716], which we answer here in the cohomology cases. We obtain many additional results, often with formulations in the more general context of ${ \mathrm{Ext} }_{G({p}^{r} )}^{m} $ with irreducible coefficients.
Symmetrical Ball Check-Valve Based Rotation-Sensitive Pump
Authors: A. Rahal Fábio , Ketzer Saul Cyro
Published: August 2013

In this work an electromagnetically actuated membrane pump, which allows flow reversion with a simple rotation of its valve system, is presented as a proof of concept. The valve system combines two symmetrical ball check-valves (SBCV), fabricated using laser machining techniques on PMMA (poly-methyl methacrylate) and PDMS (polydimethylsiloxane). The best efficiencies were achieved using glass balls within the SBCVs. This configuration provides flow rates from 0.2 to 6.0 ml/min with pressures up to 7 kPa. We also present a model which allows simulating the pumping behavior qualitatively, including the reversion after the rotation. The main advantages of the presented pump are wide range flow rates, low driving voltage (below 30 V), same pressure and flow rate in both direct and reverse pumping modes, and easily scalable to both bigger and smaller dimensions.
Robust and Efficient Setup Procedure for Complex Triangulations in Immersed Boundary Simulations
Authors: Yang Jianming , Stern Frederick
Published: August 2013

Immersed boundary methods have been widely used for simulating flows with complex geometries, as quality boundary-conforming grids are usually difficult to generate for complex geometries, especially when motion and/or deformation is involved. A major task in immersed boundary simulations is to inject the immersed boundary information into the background Cartesian grid, such as the inside/outside status of a grid point with regard to the immersed boundary and the accurate subcell position of the immersed boundary for a grid point next to it. Complex geometries in immersed boundary methods can be conveniently represented with triangulated surfaces placed upon underlying Cartesian grids in a Lagrangian manner. Regular, intuitive implementations using triangulations can be error-prone and/or cumbersome in dealing with robustness issues. In addition, they can be prohibitively expensive for high resolution simulations with complex moving/deforming boundaries. In this paper, a simple, robust, and fast procedure is developed for setting up complex triangulations in immersed boundary simulations. Central to this setup procedure are a ray casting and closest surface point computation algorithms. Several illustrative examples, including high resolution cases with Cartesian grids of up to 2.1 × 109 points and triangulations of up to 1.3 × 106 surface elements, are performed to demonstrate the robustness and efficiency of our procedure.
Effect of Axis Ratio on Fluid Flow Around an Elliptic Cylinder—A Numerical Study
Authors: Raman S. Kalyana , Arul Prakash K. , Vengadesan S.
Published: August 2013

The bluff body simulations over canonical forms like circular and square cylinders are very well studied and the correlations for bulk parameters like mean drag coefficient and Strouhal numbers for the same are reported widely. In the case of elliptic cylinder, the literature is very sparse, especially for moderate Reynolds number (Re). Hence, in this work, a detailed study about fluid flow characteristics over an elliptic cylinder placed in a free stream is performed. Simulations are carried out for different Re ranging from 50 to 500 with axis ratio (AR) varied between 0.1 to 1.0 in steps of 0.1. Immersed boundary method is used for the solid boundary condition implementation which avoids the grid generation for each AR and a single Cartesian grid is used for all the simulations. The effect of AR for various Reynolds numbers is also focused on using the in-house code. The influence of AR is phenomenal for all the Re and the values of wake length, drag coefficient, and Strouhal number decrease with decreasing AR for a particular Re. The critical ARs, for vortex shedding and wake formation, are identified for various Re. Detailed correlations for wake length, critical ARs for vortex shedding and wake formation, mean drag coefficient and Strouhal number, in terms of AR, are reported in this work.
Vibration and Acoustic Emission Measurements Evaluating the Separation of the Balls and Raceways With Lubricating Film in a Linear Bearing Under Grease Lubrication
Authors: Ohta Hiroyuki , Nakajima Yuko , Kato Soichiro , Tajimi Hideyuki
Published: August 2013

This paper deals with vibration and acoustic emission (AE) measurements evaluating the separation of the balls and raceways with lubricating film in a linear-guideway–type recirculating ball bearing (linear bearing) under grease lubrication. In the experiments, three types of commercial grease, AS2, LG2, and PS2, were used. The vibratory acceleration, AE, temperature, and electric conductivity (contact voltage) in the test bearing were measured, while a carriage of the test bearing was driven at a certain linear velocity. Experimental results showed that the measured vibratory acceleration, AE, and contact voltage of the test bearing were affected by the linear velocity and the base oil viscosity of the grease. Next, the rail side film parameter ΛR and the carriage side film parameter ΛC were examined for the test bearing in operation, and it was shown that the ΛR value was lower than the ΛC value. In addition, a condition for the separation of all the balls and raceways with lubricating film was presented. Finally, it was shown that the measured root-mean-square (RMS) values of vibratory acceleration or AE can be used for evaluating the separation of all the balls and raceways with lubricating film in the test bearing.
Identification of a Titin-Derived HLA-A1–Presented Peptide as a Cross-Reactive Target for Engineered MAGE A3–Directed T Cells
Authors: Cameron Brian J. , Gerry Andrew B. , Dukes Joseph , Harper Jane V. , Kannan Vivekanandan , Bianchi Frayne C. , Grand Francis , Brewer Joanna E. , Gupta Minnal , Plesa Gabriela , Bossi Giovanna , Vuidepot Annelise , Powlesland Alex S. , Legg Alison , Adams Katherine J. , Bennett Alan D. , Pumphrey Nicholas J. , Williams Daniel D. , Binder-Scholl Gwendolyn , Kulikovskaya Irina , Levine Bruce L. , Riley James L. , Varela-Rohena Angel , Stadtmauer Edward A. , Rapoport Aaron P. , Linette Gerald P. , June Carl H. , Hassan Namir J. , Kalos Michael , Jakobsen Bent K.
Published: August 2013

T cells engineered to express affinity-enhanced TCRs directed to a MAGE A3 peptide cross-react with a similar, but unrelated, self-peptide.
Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing
Authors: Hoang Margaret L. , Chen Chung-Hsin , Sidorenko Viktoriya S. , He Jian , Dickman Kathleen G. , Yun Byeong Hwa , Moriya Masaaki , Niknafs Noushin , Douville Christopher , Karchin Rachel , Turesky Robert J. , Pu Yeong-Shiau , Vogelstein Bert , Papadopoulos Nickolas , Grollman Arthur P. , Kinzler Kenneth W. , Rosenquist Thomas A.
Published: August 2013

The mutational signature of aristolochic acid exemplifies how genome-wide sequencing can be used to identify environmental exposures leading to cancer.
Adenosine Receptor Antagonists Including Caffeine Alter Fetal Brain Development in Mice
Authors: Silva Carla G. , Métin Christine , Fazeli Walid , Machado Nuno J. , Darmopil Sanja , Launay Pierre-Serge , Ghestem Antoine , Nesa Marie-Pascale , Bassot Emilie , Szabó Eszter , Baqi Younis , Müller Christa E. , Tomé Angelo R. , Ivanov Anton , Isbrandt Dirk , Zilberter Yuri , Cunha Rodrigo A. , Esclapez Monique , Bernard Christophe
Published: August 2013

Exposure to adenosine receptor antagonists in utero affects fetal brain development in mice.
Genomics Traces Carcinogen Fingerprints
Authors: Lee William , Ladanyi Marc
Published: August 2013

Genome-wide sequencing highlights the distinctive pattern of mutations caused by a plant that contains a potent carcinogen.
REG1B: A Marker of Childhood Stunting
Authors: MAHFUZ MUSTAFA
Published: August 2013

Stool regenerating gene 1b (REG1B) may serve as a noninvasive biomarker of future childhood stunting.
Science Translational Medicine
Podcast: 7 August 2013
Authors: Teh Bin Tean , Nusinovich Yevgeniya
Published: August 2013

In this podcast, Bin Tean Teh explains the carcinogenic effects of aristolochic acid, an herbal compound used in traditional Chinese medicine.
Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury
Authors: Gralinski Lisa E. , Bankhead Armand , Jeng Sophia , Menachery Vineet D. , Proll Sean , Belisle Sarah E. , Matzke Melissa , Webb-Robertson Bobbie-Jo M. , Luna Maria L. , Shukla Anil K. , Ferris Martin T. , Bolles Meagan , Chang Jean , Aicher Lauri , Waters Katrina M. , Smith Richard D. , Metz Thomas O. , Law G. Lynn , Katze Michael G. , McWeeney Shannon , Baric Ralph S.
Published: August 2013

Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV.

IMPORTANCESevere acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and 2003, and infected patients developed an atypical pneumonia, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) leading to pulmonary fibrosis and death. We identified sets of differentially expressed genes that contribute to ALI and ARDS using lethal and sublethal SARS-CoV infection models. Mathematical prioritization of our gene sets identified the urokinase and extracellular matrix remodeling pathways as the most enriched pathways. By infecting Serpine1-knockout mice, we showed that the urokinase pathway had a significant effect on both lung pathology and overall SARS-CoV pathogenesis. These results demonstrate the effective use of unbiased modeling techniques for identification of high-priority host targets that regulate disease outcomes. Similar transcriptional signatures were noted in 1918 and 2009 H1N1 influenza virus-infected mice, suggesting a common, potentially treatable mechanism in development of virus-induced ALI.
Differential Brain Effects of Laser and Needle Acupuncture at Lr8 Using Functional Mri
Authors: Quah-Smith Im , Williams Mark A , Lundeberg Thomas , Suo Chao , Sachdev Perminder
Published: August 2013

Objective

While needle acupuncture is a well-accepted technique, laser acupuncture is being increasingly used in clinical practice. The differential effects of the two techniques are of interest. We examine this in relation to brain effects of activation of LR8, a putative acupuncture point for depression, using functional MRI (fMRI).

Methods

Sixteen healthy participants were randomised to receive low intensity laser acupuncture to LR8 on one side and needle acupuncture to the contralateral LR8. Stimulation was in an on-off block design and brain patterns were recorded under fMRI.

Results

Significant activation occurred in the left precuneus during laser acupuncture compared with needle acupuncture and significant activation occurred in the left precentral gyrus during needle acupuncture compared with laser acupuncture.

Conclusions

Laser and needle acupuncture at LR8 in healthy participants produced different brain patterns. Laser acupuncture activated the precuneus relevant to mood in the posterior default mode network while needle acupuncture activated the parietal cortical region associated with the primary motor cortex. Further investigations are warranted to evaluate the clinical relevance of these effects.
Naltrexone may block euphoria-like placebo effect
Authors: Samokhvalov Andriy V , Gamaleddin Islam , Sproule Beth , Rehm Jürgen
Published: August 2013

Naltrexone is a first-line treatment for alcohol use disorders in North America and Europe. It was prescribed to a 63-year-old patient in order to help control amounts of alcohol consumed per drinking occasion. The patient experienced a paradoxical, but consistent side effect of feeling inebriated each time he took naltrexone. In order to investigate this phenomenon we administered naltrexone and a placebo in a randomised double-blind fashion. The patient exhibited a ‘high-like’ response to all placebo capsules and a decrease in the subjectively perceived euphoria shortly after ingestion of naltrexone. Given that this placebo effect could be mediated via opioid receptors we suggest that this case illustrates the ability of naltrexone to eliminate the placebo effect. This feature of naltrexone, upon further investigation, might be used in randomised clinical trials in addition to or as an alternative to a placebo.
Agranulocytosis with deferiprone treatment of superficial siderosis
Authors: Huprikar Nikhil , Gossweiler Marisa , Callaghan Maureen , Bunge Paul
Published: August 2013

Superficial siderosis of the central nervous system is a rare neurological disorder caused by deposits of haemosiderin on subplial brain matter. Characterised by a thin dark layer surrounding the brain stem, cerebellum and cortical fissures on the T2-weighted MRI, symptoms include sensorineural hearing loss and progressive gait ataxia. A specific aetiology for the blood in the subarachnoid space is identified in less than 50% of cases. While identification of a specific vascular defect allows for vascular repair, treatment options are limited for idiopathic superficial siderosis. Recently, a pilot safety study demonstrated promising results using an iron chelator, deferiprone. While this approach is promising, we present a potential serious complication of this therapy—the first report of agranulocytosis in the treatment of superficial siderosis following deferiprone therapy.
Full-term broad ligament pregnancy
Authors: Rudra Samar , Gupta Suhasini , Taneja Bal Krishan , Garg Manish
Published: August 2013

A broad ligament pregnancy is an extremely rare condition. The eventuality of such pregnancies reaching full term is even rarer. A full-term broad ligament pregnancy occurring through a rent in a previous lower segment caesarean scar has only been mentioned in literature but not reported. Our patient is an unbooked case, reported to us at 39 weeks of pregnancy. On clinical examination, an ultrasound and an MRI, a diagnosis of abdominal pregnancy was made. Ultimately the final diagnosis was made only on laparotomy. A broad ligament pregnancy was found with a rent in the previous caesarean scar communicating the fetal sac.
Macrocytosis in Crohn's disease: a devastating blast
Authors: Lee Lennard Y W , Santharam Vidya , Macfaul George
Published: August 2013

A 47-year-old woman with a 36-month history of Crohn's disease with one previous bowel resection treated with azathioprine was found to have a persistently raised mean corpuscular volume (MCV) on routine complete blood count testing. Despite vitamin B12replacement, her MCV remained elevated. A bone marrow biopsy was performed, which demonstrated myelodysplastic syndrome. Macrocytosis is a common abnormality in patients with Crohn's disease, most commonly due to vitamin B12deficiency and secondarily due to bacterial overgrowth. However, it is important to recognise that myelodysplastic syndrome is a common under-reported complication of azathioprine therapy. One-third of cases progress to acute myeloid leukaemia with poor prognosis. In patients with suspected myelodysplastic syndrome, azathioprine therapy should be immediately discontinued.
Inspiratory muscle training protocol for patients with chronic obstructive pulmonary disease (IMTCO study): a multicentre randomised controlled trial
Authors: Charususin Noppawan , Gosselink Rik , Decramer Marc , McConnell Alison , Saey Didier , Maltais Francois , Derom Eric , Vermeersch Stefanie , van Helvoort Hanneke , Heijdra Yvonne , Klaassen Mariska , Glöckl Rainer , Kenn Klaus , Langer Daniel
Published: August 2013

Introduction

Inspiratory muscle training (IMT) has been applied during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD). However, it remains unclear if the addition of IMT to a general exercise training programme leads to additional clinically relevant improvements in patients with COPD. In this study, we will investigate whether the addition of IMT to a general exercise training programme improves 6 min walking distance, health-related quality of life, daily physical activity and inspiratory muscle function in patients with COPD with inspiratory muscle weakness.

Methods and analysis

Patients with COPD (n=170) with inspiratory muscle weakness (Pi,max<60 cm H2O or <50%pred) will be recruited to a multicentre randomised placebo controlled trial of IMT and allocated into one of the two groups. Patients in both groups will follow a 3 month general exercise training programme, in combination with home-based IMT. IMT will be performed with a recently developed device (POWERbreathe KH1). This device applies an inspiratory load that is provided by an electronically controlled valve (variable flow resistive load). The intervention group (n=85) will undertake an IMT programme at a high intensity (≥50% of their Pi,max), whereas the placebo group (n=85) will undertake IMT at a low training intensity (≤10% of Pi,max). Total daily IMT time for both groups will be 21 min (6 cycles of 30 breaths). Improvement in the 6 min walking distance will be the primary outcome. Inspiratory muscle function, health-related quality of life and daily physical activity will be assessed as secondary outcomes.

Ethics and dissemination

Ethics approval has been obtained from relevant centre committees and the study has been registered in a publicly accessible clinical trial database. The results will be easily interpretable and should immediately be communicated to healthcare providers, patients and the general public.

Results

This can be incorporated into evidence-based treatment recommendations for clinical practice.

ClinicalTrials.gov

NCT01397396.
Hospital performance based on treatment delays: comparison of ranking methods
Authors: Leleu Henri , Capuano Frédéric , Nitenberg Gérard , Travental Lydie , Minvielle Etienne
Published: August 2013

Background

Reducing time-to-care is crucial in many acute and chronic diseases. Quality indicators based on target delays derived from guidelines are used to compare hospital performance but there is no accepted methodology for comparing performance when no target delay has been established.

Aim

To explore by different statistical methods the uncertainty in hospital comparisons that are based on delay indicators, when no target delay is available.

Methods

Data for hospital door-to-needle time were extracted from a 2010 study of 1699 patients in 57 hospitals with ST-elevated myocardial infarction. We determined whether the times in each hospital were statistically different from the overall mean time or the median time for all hospitals by (i) one-way analysis of variance (ANOVA), (ii) non-parametric ANOVA with Nelson–Hsu adjustment (ANOVA R) and (iii) the proportional hazard model (PHM). We also tested for the assumptions underlying the methods: normal distribution for ANOVA, homogeneity of variances (homoscedasticity) for ANOVA and ANOVA R, and proportionality for PHM.

Results

Door-to-needle times were available for 889 patients in 44 hospitals. Data distribution was not Gaussian. Test assumptions were verified for ANOVA R (homoscedasticity) for one data subset (>48-h times (48H) excluded) and for PHM (proportionality) for two data subsets (48H or >95th percentile (P95) times excluded). The same five significantly better performers were identified in each case (although ANOVA R missed one). ANOVA R (48H) identified two significantly poorer performers, PHM (48H) identified three and PHM (P95) just one. Poorer performers differed according to method.

Conclusions

The tested statistical methods yielded broadly similar results but no method was truly satisfactory. A transparency statement should therefore always specify the ranking method used to compare hospital performance.
Tropical skin diseases in British military personnel
Authors: Bailey Mark S
Published: August 2013

Skin complaints are common in travellers to foreign countries and are responsible for up to 25% of medical consultations by military personnel during deployments in the tropics. They also have relatively high rates of field hospital admission, medical evacuation and referral to UK Role 4 healthcare facilities. Non-infectious tropical skin diseases include sunburn, heat rash, arthropod bites, venomous bites, contact dermatitis and phytophotodermatitis. During tropical deployments skin infections that commonly occur in military personnel may become more frequent, severe and difficult to treat. Several systemic tropical infections have cutaneous features that can be useful in making early diagnoses. Tropical skin infections such as cutaneous larva migrans, cutaneous myiasis, cutaneous leishmaniasis and leprosy do occur in British troops and require specialist clinical management. This illustrated review focuses on the most significant tropical skin diseases that have occurred in British military personnel in recent years. Clinical management of these conditions on deployments would be improved and medical evacuations could be reduced if a military dermatology ‘reach-back’ service (including a telemedicine facility) was available.
Skin and soft tissue infections in the military
Authors: Lamb Lucy , Morgan M
Published: August 2013

Skin and soft tissue infections (SSTI) are common in military populations regularly living and training in close contact with each other. The majority of such infections are simple and can be easily treated with antibiotics and appropriate infection control practices. Some, however, can progress to become complex and even life threatening, such as Panton-Valentine Leukocidin (PVL)-associatedstaphylococcus aureuspneumonia, orStreptococcus pyogenesnecrotising fasciitis, which carry a mortality rate of up to 65% and 30%, respectively. This review focuses on the most important SSTIs and those more commonly affecting military personnel with advice on how they are best managed.
Treatment of rectal war wounds
Authors: van Waes Oscar J F , Halm J A , Vermeulen J , McAlister V C
Published: August 2013

Treatment strategies for penetrating rectal injuries (PRI) in civilian settings are still not uniformly agreed, in part since high-energy transfer PRI, such as is frequently seen in military settings, are not taken into account. Here, we describe three cases of PRI, treated in a deployed combat environment, and outline the management strategies successfully employed. We also discuss the literature regarding PRI management. Where there is a major soft tissue component, repetitive debridement and vacuum therapy is useful. A loop or end colostomy should be used, depending on the degree of damage to the anal sphincter complex.
Changing patterns of disseminated gonococcal infection in France: cross-sectional data 2009–2011
Authors: Belkacem Anna , Caumes Eric , Ouanich Jocelyne , Jarlier Vincent , Dellion Sophie , Cazenave Benoit , Goursaud Régis , Lacassin Flore , Breuil Jacques , Patey Olivier ,   for the working group FRA-DGI
Published: August 2013

Objectives

Disseminated gonococcal infections (DGIs) are rare. We describe the characteristics of DGIs in France.

Methods

This is a 3-year retrospective analysis of DGI cases collected through two networks of microbiologists and infectious disease specialists in France between 2009 and 2011. DGI was defined either by the isolation ofNeisseria gonorrhoeaefrom blood and synovial fluid or by the existence of a clinical syndrome consistent with DGI and the isolation ofN gonorrhoeaefrom any site. We describe the epidemiological, clinical and microbiological characteristics and outcomes of DGIs.

Results

21 patients (9 women, 12 men; 18–62 years old) were diagnosed with DGI. The number of DGI cases increased between 2009 and 2011. Two men who had sex with men were coinfected with HIV. We found 28 extragenital locations, including arthritis (14 cases), tenosynovitis (7), skin lesions (4), endocarditis (1), prostatitis (1) and pelvic inflammatory disease (1). Genital signs were present in five patients. The diagnosis was confirmed by cultures in 20 patients—blood (4), synovial fluid (11), genital (3), throat (1), urine (1)—and by molecular biology on a pharyngeal swab in 1 patient. Seven cases were resistant to fluoroquinolones. The patients were treated with ceftriaxone, associated with corticosteroids (two cases) and surgery (six cases). Four patients had joint sequelae.

Conclusions

DGIs are increasing. Men seem to be at higher risk than women. Joint involvement was common. Microbiological diagnosis was based on culture, however molecular biology using pharyngeal swabs was helpful when cultures were negative.
Experimental investigation of reverse end bearing of offshore shallow foundations
Authors: Mana Divya S.K. , Gourvenec Susan , Randolph Mark F.
Published: August 2013

Shallow skirted foundations can mobilize uplift resistance from end bearing in the short to medium term. However, uncertainty exists over the magnitude of reverse end bearing resistance compared with resistance in compression, and how this might be affected by a gap between the external face of the foundation skirt and the adjacent soil. The study presented in this paper explores this problem through centrifuge model tests, investigating the effect of skirt embedment ratio on (i) the magnitude of reverse end bearing capacity compared with compression capacity, (ii) the uplift displacement associated with spontaneous loss of suction during uplift, and (iii) the existence of a vertical gap along the external skirt–soil interface. The results show that (i) peak uplift capacity equivalent to compression capacity can be mobilized for a fully sealed foundation with an intact skirt–soil interface, (ii) suction required for reverse end bearing can be maintained through considerable foundation displacement, even for a low skirt embedment ratio, and (iii) the presence of a vertical gap along the external skirt–soil interface causes abrupt loss of suction beneath the top plate after minimal foundation displacement, with subsequent uplift capacity being markedly reduced.
Multifunctional gold-loaded TiO2 thin film: photocatalyst and recyclable SERS substrate
Authors: Fu Xiaoqi , Zhang Guolin , Wu Tingshuang , Wang Shuang
Published: August 2013

A simple strategy for synthesizing gold-loaded TiO2 thin film (Au/TiO2) for use as multifunctional photocatalyst and recyclable surface-enhanced Raman scattering (SERS) substrate is introduced. Macroporous TiO2 thin film is prepared through the dip-coating method and made the SERS activity by deposition of gold nanoparticles on its surface. Owing to the high photocatalytic activity of TiO2, the substrate can degrade adsorbates into small inorganic molecules under UV irradiation. In this manner, the substrate is able to self-clean and be reused for a new SERS detection cycle. The photodegradation and SERS experimental results show that Au/TiO2 is a good candidate for both photocatalyst and SERS substrate and exhibits high recyclability in the detection of organic pollutants.
REVIEW OF R MEASUREMENTS
Authors: DENIG ACHIM
Published: August 2013

We review the status of R measurements in the energy range below 12 GeV, where recently a major progress has been achieved recently. These measurements are phenomenologically motivated by their impact on precision QCD and on electroweak parameters. We also report on improved results which can be expected in near future from presently running or upcoming facilities.
GENERALIZED MOVING AVERAGES, DISTANCE MEASURES AND OWA OPERATORS
Authors: MERIGÓ JOSÉ M. , YAGER RONALD R.
Published: August 2013

The concept of moving average is studied. We analyze several extensions by using generalized aggregation operators, obtaining the generalized moving average. The main advantage is that it provides a general framework that includes a wide range of specific cases including the geometric and the quadratic moving average. This analysis is extended by using the generalized ordered weighted averaging (GOWA) and the induced GOWA (IGOWA) operator. Thus, we get the generalized ordered weighted moving average (GOWMA) and the induced GOWMA (IGOWMA) operator. Some of their main properties are studied. We further extend this approach by using distance measures suggesting the concept of distance moving average and generalized distance moving average. We also consider the case with the OWA and the IOWA operator, obtaining the generalized ordered weighted moving averaging distance (GOWMAD) and the induced GOWMAD (IGOWMAD) operator. The paper ends with an application in multi-period decision making.