bluuebunny/crossref_metadata_2025 huggingface dataset:
New freshwater diatom genus, Edtheriotia gen. nov. of the Stephanodiscaceae (Bacillariophyta) from south‐central China
Authors: Kociolek John P. , You Qingmiin , Stepanek Joshua G. , Lowe Rex L. , Wang Quanxi
Published: September 2016

We describe a new genus and species of the diatom family Stephanodiscaceae with light and scanning electron microscopy from Libo Small Hole, Libo County, Guizhou Province, China. Edtheriotia guizhoiana gen. & sp. nov. has striae across the valve face of varying lengths, and are composed of fine striae towards the margin and onto the mantle. Many round to stellate siliceous nodules cover the exterior of the valve. External fultoportulae opening are short tubes; the opening of the rimportula lacks a tube. Internally a hyaline rim is positioned near the margin. Marginal fultoportulae possess two arcuate opercles. Areolae have domed cribra on the valve face. Those near the margin do not open to the interior. One to three sessile to slightly‐raised rimportulae are placed on the valve face towards the margin; they do not terminate shortened striae towards the center of the valve. This suite of features distinguishes this group from other known genera in the Stephanodicaeae. Cyclotella shanxiensis is transferred to Edtheriotia, making the new combination E. shanxiensis (Xie & Qi) Kociolek et al. comb. nov. It differs from E. guizhoiana by the presence of open pores near the margin of the valve. Features of the new genus are compared and contrasted with others in the Family Stephanodiscaceae. The two species of the genus, unlike most in the family, are known only from rivers and ponds from China and Japan.
Honesty, Diligence and Skill: Risk Sharing and Specialization in the Kiryu Silk Weaving Cluster, Japan
Authors: Nakabayashi Masaki
Published: September 2016

Many economies have seen growth in industrial clusters during their industrialization, and the relational contracts between manufacturers and subcontractors are often the organizational basis of clusters. We predict that, if manufacturers form relational contracts with subcontractors, if manufacturers closely collude with each other when trading with subcontractors, if information about subcontractors’ past actions is only imperfectly shared by manufacturers as hearsay, and if demand shock is considerable, then premium subcontractors suffer more from market volatility than ordinary subcontractors would and hence, it is optimal for manufacturers to shield premium subcontractors against the risk. We then study Kiryu, a kimono weaving cluster that expanded from the late nineteenth century with the development of new synthetic dyeing techniques. We show that premium subcontracting weavers were allowed long‐term relational contracts and specialization, which shielded already honest weavers against market volatility and induced them to be diligent and to acquire skills.
Media in the Policy Process: Using Framing and Narratives to Understand Policy Influences
Authors: Crow Deserai A. , Lawlor Andrea
Published: September 2016

Policy scholarship has long sought to understand the role of knowledge and information in the policy process. Of the actors, institutions, and resources involved in shaping policy processes and outcomes, media and narratives have been incorporated into empirical policy scholarship and theories with varying success. The Narrative Policy Framework (NPF) is a framework through which scholars can bring analysis of narratives into studies of policy making. The NPF moves the field forward in understanding the role of narratives, communication, and stakeholder beliefs in the policy process, while at the same time striving for theoretical rigor. We embed the discussion of frames and narratives in the NPF to provide an empirical and theoretical cohesion to our understanding of media and public policy and then provide a brief empirical example of how such an integration may prove fruitful for policy scholars.
BLM, the Administrative Presidency, and Policy Shifts: Policy Tools Affecting Oil and Gas Operations
Authors: Davis Charles
Published: September 2016

This paper addresses change in oil and gas policies pushed by the U.S. Bureau of Land Management (BLM) during the administrations of Presidents George W. Bush and Barack Obama. Administrative policy changes occurred not only because of election outcomes and the emergence of new governing coalitions but BLM's selective utilization of policy tools such as rulemaking, planning, environmental impact analyses, and the use of discretionary authority to increase or relax enforcement decisions. The data reveal that BLM put more emphasis on the use of discretionary authority to limit environmental inspections and to limit environmental reviews of proposed drilling projects under Bush while agency officials gave priority to adopting new planning procedures to allow greater stakeholder input under Obama as well as increasing the number of environmental inspections.
Transforming the Problem of the Other: Rethinking Merleau‐Ponty's Itinerary
Authors: Almog Meirav
Published: September 2016

This essay offers a new understanding of Merleau‐Ponty's notion of the Other, the problem that revolves around it, and its far‐reaching repercussions by shedding light on aspects that usually go unnoticed in the interpretation of his late thought in these regards. I show how Merleau‐Ponty's emerging ontology in his late writings opens anew, in a complex manner, the problem of the Other, transforming it in a way that dismantles, to begin with, traditional epistemological questions regarding the Other, as well as principal difficulties regarding the Other's appearance within the realm of phenomena which have occupied phenomenology from its very beginning. I demonstrate how Merleau‐Ponty's late writings in fact bind the problem of the Other with the question regarding the very limits of phenomenology and the realm of meaning as a whole.
What (if Anything) Is Wrong with Capitalism? Dysfunctionality, Exploitation and Alienation: Three Approaches to the Critique of Capitalism
Authors: Jaeggi Rahel
Published: September 2016

What is the problem with capitalism? Is it wrong, unjust, irrational, or bad? Is it evil or dumb—or is it just not working? While critiques of capitalism have become commonplace—particularly since the most recent global economic crisis—it is often unclear what exactly is being condemned. Likewise, the normative presuppositions and criteria of such criticisms have been left unspecified. In this paper, I distinguish between three approaches to the critique of capitalism, distinguishing a functional, a moral, and an ethical argumentative strategy and paying special attention to the distinctive types of argumentation they mobilize. First, I consider the “functional” critique, typically directed against capitalism's straightforward dysfunctions or crises. We will find, however, that this sort of criticism presupposes a normative criterion that is frequently unarticulated, namely: the implied “purpose” of a well‐functioning economic system. Second, I examine a common “moral” critique, that is, that capitalism is premised on exploitation. Yet, the concept of exploitation, too, introduces certain difficulties, since the kind of moral wrong associated with it—unequal exchange—is hardly obvious to everyday observation and must be derived systematically. Third, I introduce and address the “ethical” critique, broadly, that capitalism constitutes a bad form‐of‐life. However, while I object to some of the forms this criticism has taken—in particular, I argue that much “alienation” diagnosis is tainted by nostalgia and naiveté—I nonetheless recommend developing a critique of capitalism as a form‐of‐life that would include ethical and functional criteria. I conclude with some remarks in this direction.
Preemptive reduction of immunosuppression upon high urinary polyomavirus loads improves patient survival without affecting kidney graft function
Authors: Broeders Emine Nilufer , Hamade Anwar , El Mountahi Fadoua , Racapé Judith , Hougardy Jean‐Michel , Le Moine Alain , Vereerstraeten Pierre
Published: September 2016

Background

Polyomavirus (PV) is a major cause of kidney graft disease. Monitoring by polymerase chain reaction (PCR) on blood is currently recommended. In order to avoid irreversible lesions, we investigated the clinical impact of preemptive reduction of immunosuppression (IS) in kidney transplant recipients (KTR) upon detection of high urinary PV (Upv) load, including BK virus and JC virus.

Material and methods

From 2000 to 2011, in our single center, 789 consecutive KTR were distributed into 4 groups, according to the maximal Upv levels (by PCR) during the first year and the therapeutic option: (A) Upv <104 copies (cp)/mL (n=573), (B) ≥104 Upv <107 cp/mL (n=100), and (C) Upv ≥107 cp/mL (n=116); in group C, the IS drug doses were reduced in subgroup Ca (n=102) only, as 14 patients (subgroup Cb) were at risk for graft rejection.

Results

The preemptive reduction of IS (group Ca) increased patient survival as compared with all other groups (P<.05), did not modify graft function, and increased graft survival vs group A (risk ratio: 5.7, confidence interval: 1.8–18.1, P=.003). Differences for risk factors are as follows (groups Ca vs A): incidence of human leukocyte antigen (HLA) immunization (>5% panel reactive antibodies): 3% vs 8% (P=.05), number of HLA mismatches: 2.7 vs 2.5 (P=.049), and incidence of acute rejection: 9.8% vs 24.2% (P=.005). PV‐associated nephropathy occurred only in group Ca (2% of total grafts) without effect on patient or graft outcome.

Conclusion

The reduction of IS in patients with high Upv loads is beneficial for patient survival and does not affect graft survival or graft function.
Viscoelastic Properties of Human Tracheal Tissues
Authors: Safshekan Farzaneh , Tafazzoli-Shadpour Mohammad , Abdouss Majid , Shadmehr Mohammad B.
Published: September 2016

The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.
Effects of Prosthetic Mismatch and Subscapularis Tear on Glenohumeral Contact Patterns in Total Shoulder Arthroplasty: A Numerical Musculoskeletal Analysis
Authors: Sins Lauranne , Tétreault Patrice , Nuño Natalia , Hagemeister Nicola
Published: September 2016

Prosthetic components' mismatch and subscapularis (SC) tear are determining factors for glenoid failure complication in nonconforming total shoulder arthroplasty (NC-TSA). Risk factors are linked to glenoid prosthetic loading. However, the mechanisms underlying the clinical observations remain unclear. This study assessed the combined impact of mismatch and subscapularis tear on glenoid loading. It was assumed that adequate glenoid loading was associated with minimal, but non-null, humeral head translations and contact pressure, as well as with maximal glenoid contact area, and that the center of pressure (COP) on the glenoid would have a centered displacement pattern. A numerical model was used to achieve two objectives. The first was to verify whether an optimum mismatch existed, for which failure risk would be minimal. The second was to explore the effect of subscapularis tear on the position of applied forces on the glenoid. A shoulder AnyBody musculoskeletal model was adapted to the arthroplasty context by introducing humeral head translations and contact between implants. Ten simulations were computed to compare combinations of varying mismatches (1.4 mm, 3.4 mm, 6.4 mm, 8.6 mm, and 9 mm) with two shoulder conditions (intact-muscle or subscapularis tear). Humeral head translations, center-of-pressure, contact area, contact pressure, and glenohumeral joint contact forces were numerically estimated. Mismatches between 3.4 mm and 6.4 mm were associated with the most minimal humeral translations and contact pressure, as well as with maximal contact area. Center of pressure displacement pattern differed according to shoulder condition, with an outward anterior tendency in presence of tear.
Acute Optogenetic Modulation of Cardiac Twitch Dynamics Explored Through Modeling
Authors: Aboelkassem Yasser , Campbell Stuart G.
Published: September 2016

Optogenetic approaches allow cellular membrane potentials to be perturbed by light. When applied to muscle cells, mechanical events can be controlled through a process that could be termed “optomechanics.” Besides functioning as an optical on/off switch, we hypothesized that optomechanical control could include the ability to manipulate the strength and duration of contraction events. To explore this possibility, we constructed an electromechanical model of the human ventricular cardiomyocyte while adding a representation of channelrhodopsin-2 (ChR2), a light-activated channel commonly used in optogenetics. Two hybrid stimulus protocols were developed that combined light-based stimuli with traditional electrical current (all-or-none) excitation. The first protocol involved delivery of a subthreshold optical stimulus followed 50–90 ms later by an electrical stimulus. The result was a graded inhibition of peak cellular twitch force in concert with a prolongation of the intracellular Ca2+ transient. The second protocol was comprised of an electrical stimulus followed by a long light pulse (250–350 ms) that acted to prolong the cardiac action potential (AP). This created a pulse duration-dependent prolongation of the intracellular Ca2+ transient that in turn altered the rate of muscle relaxation without changing peak twitch force. These results illustrate the feasibility of acute, optomechanical manipulation of cardiomyocyte contraction and suggest that this approach could be used to probe the dynamic behavior of the cardiac sarcomere without altering its intrinsic properties. Other experimentally meaningful stimulus protocols could be designed by making use of the optomechanical cardiomyocyte model presented here.
Multiscale Characterization of Engineered Cardiac Tissue Architecture
Authors: Drew Nancy K. , Johnsen Nicholas E. , Core Jason Q. , Grosberg Anna
Published: September 2016

In a properly contracting cardiac muscle, many different subcellular structures are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single structures over multiple scales, from subcellular to tissue scale as well as correlation of organization of multiple structures. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters (COOPs). Similarly, neonatal rat ventricular myocytes were selected for their consistent architectural behavior. The engineered cells and tissues were stained for four architectural structures: actin, tubulin, sarcomeric z-lines, and nuclei. We applied the orientational metrics to cardiac cells of various shapes, isotropic cardiac tissues, and anisotropic globally aligned tissues. With these novel tools, we discovered: (1) the relationship between cellular shape and consistency of self-assembly; (2) the length-scales at which unguided tissues self-organize; and (3) the correlation or lack thereof between organization of actin fibrils, sarcomeric z-lines, tubulin fibrils, and nuclei. All of these together elucidate some of the current mysteries in the relationship between force production and architecture, while raising more questions about the effect of guidance cues on self-assembly function. These types of metrics are the future of quantitative tissue engineering in cardiovascular biomechanics.
Elastic Microplane Formulation for Transversely Isotropic Materials
Authors: Jin Congrui , Salviato Marco , Li Weixin , Cusatis Gianluca
Published: September 2016

This contribution investigates the extension of the microplane formulation to the description of transversely isotropic materials such as shale rock, foams, unidirectional composites, and ceramics. Two possible approaches are considered: (1) the spectral decomposition of the stiffness tensor to define the microplane constitutive laws in terms of energetically orthogonal eigenstrains and eigenstresses and (2) the definition of orientation-dependent microplane elastic moduli. The first approach, as demonstrated previously, provides a rigorous way to tackle anisotropy within the microplane framework, which is reviewed and presented herein in a clearer manner; whereas the second approach represents an approximation which, however, makes the formulation of nonlinear constitutive equations much simpler. The efficacy of the second approach in modeling the macroscopic elastic behavior is compared to the thermodynamic restrictions of the anisotropic parameters showing that a significant range of elastic properties can be modeled with excellent accuracy. Further, it is shown that it provides a very good approximation of the microplane stresses provided by the first approach, with the advantage of a simpler formulation. It is concluded that the spectral stiffness decomposition represents the best approach in such cases as for modeling composites, in which accurately capturing the elastic behavior is important. The introduction of orientation-dependent microplane elastic moduli provides a simpler framework for the modeling of transversely isotropic materials with remarked inelastic behavior, as in the case, for example, of shale rock.
Thermal Hydraulic and Safety Assessment of First Wall Helium Cooling System of a Generalized Test Blanket System in ITER Using RELAP/SCDAPSIM/MOD4.0 Code
Authors: Saraswat S. P. , Munshi P. , Khanna A. , Allison C.
Published: September 2016

The key objective of the test blanket module (TBM) program is to develop the design technology for DEMO and future power-producing fusion reactors. The proposed first wall of the test blanket system (TBS) is a generalized concept for testing in ITER, an experimental fusion reactor under construction in France presently. The first wall of TBM (TBM FW) directly faces the plasma and is cooled by the first wall helium cooling system (FWHCS), which is considered as a critical component from an ITER safety point of view. The scope of this work comprises thermal hydraulic analysis of the FWHCS of a generalized TBS and the assessment of postulated initiating events (PIEs) on the ITER safety with the help of thermal-hydraulic code RELAP/SCDAPSIM/MOD4.0. The three reference accidents: in-vacuum vessel (VV) loss of coolant accident (in-vessel LOCA), ex-vessel LOCA, and loss of flow accident (LOFA) in FWHCS are selected for the safety assessment. This safety assessment addresses safety concerns resulting from FWHCS component failure, such as VV pressurization, TBM FW temperature profile, pressurization of port cell (PC) and Tokomak cooling water system vault annex (TCWS-VA), and passive decay heat removal capability. The analysis shows that the critical parameters are under the design limit and have large safety margins, in the investigated accident scenarios. A comparative analysis is also carried out with the previous results to validate the results.
Treatment of gastric cancer cells with nonthermal atmospheric plasma generated in water
Authors: Chen Zhitong , Lin Li , Cheng Xiaoqian , Gjika Eda , Keidar Michael
Published: September 2016

Nonthermal atmospheric plasma (NTAP) can be applied to living tissues and cells as a novel technology for cancer therapy. The authors report on a NTAP argon solution generated in deionized (DI) water for treating human gastric cancer cells (NCI-N87). Our findings show that the plasma generated in DI water with 30-min duration has the strongest effect on apoptosis in precultured human gastric cancer cells. This result can be attributed to the presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced in water during treatment. Furthermore, the data show that the elevated levels of RNS may play a more significant role than ROS in the rate of cell death.
Critical nitric oxide concentration for Pseudomonas aeruginosa biofilm reduction on polyurethane substrates
Authors: Neufeld Bella H. , Reynolds Melissa M.
Published: September 2016

Bacterial colonies that reside on a surface, known as biofilms, are intrinsically impenetrable to traditional antibiotics, ultimately driving research toward an alternative therapeutic approach. Nitric oxide (NO) has gained attention for its biologically beneficial properties, particularly centered around its antibacterial capabilities. NO donors that can release the molecule under physiological conditions (such as S-nitrosothiols) can be utilized in clinical settings to combat bacterial biofilm infections. Herein the authors describe determining a critical concentration of NO necessary to cause >90% reduction of a Pseudomonas aeruginosa biofilm grown on medical grade polyurethane films. The biofilm was grown under optimal culture conditions [in nutrient broth media (NBM) at 37 °C] for 24 h before the addition of the NO donor S-nitrosoglutathione (GSNO) in NBM for an additional 24 h. The cellular viability of the biofilm after the challenge period was tested using varying concentrations of NO to determine the critical amount necessary to cause at least a 90% reduction in bacterial biofilm viability. The critical GSNO concentration was found to be 10 mM, which corresponds to 2.73 mM NO. Time kill experiments were performed on the 24 h biofilm using the critical amount of NO at 4, 8, 12, and 16 h and it was determined that the 90% biofilm viability reduction occurred at 12 h and was sustained for the entire 24 h challenge period. This critical concentration was subsequently tested for total NO release via a nitric oxide analyzer. The total amount of NO released over the 12 h challenge period was found to be 5.97 ± 0.66 × 10−6 mol NO, which corresponds to 1.49 ± 0.17 μmol NO/ml NBM. This is the first identification of the critical NO concentration needed to elicit this biological response on a medically relevant polymer.
Gobbling up inflammation to ameliorate autoimmunity
Authors: Whitehead Kathryn A.
Published: September 2016

Nucleic acid scavenging polymers combat autoimmune disease without compromising the ability to fight infection.
In Vitro
Synergistic Activity of Antimicrobial Agents in Combination against Clinical Isolates of Colistin-Resistant Acinetobacter baumannii
Authors: Bae Seongman , Kim Min-Chul , Park Su-Jin , Kim Hee Sueng , Sung Heungsup , Kim Mi-Na , Kim Sung-Han , Lee Sang-Oh , Choi Sang-Ho , Woo Jun Hee , Kim Yang Soo , Chong Yong Pil
Published: September 2016

Emerging resistance to colistin in clinical
Acinetobacter baumannii
isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the
in vitro
activities of various antimicrobial combinations against colistin-resistant
A. baumannii
. Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant
A. baumannii
were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant
A. baumannii
. Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant
A. baumannii
.
Endoperoxide Drug Cross-Resistance Patterns for Plasmodium falciparum Exhibiting an Artemisinin Delayed-Clearance Phenotype
Authors: Siriwardana A. , Iyengar K. , Roepe P. D.
Published: September 2016

The ring-stage susceptibility assay was modified to quantify the susceptibilities of multiple strains of control and delayed-clearance phenotype (DCP)
Plasmodium falciparum
strains to seven endoperoxide antimalarial drugs. The susceptibility of all of the DCP lines to six of the drugs was lower than that of the controls. In contrast, DCP parasites did not show reduced susceptibility to the synthetic endoperoxide drug OZ439. These data show that it is possible to circumvent emerging artemisinin resistance with a modified endoperoxide drug.
Evaluation of a Multiplex PCR Assay To Rapidly Detect Enterobacteriaceae with a Broad Range of β-Lactamases Directly from Perianal Swabs
Authors: Chavda Kalyan D. , Satlin Michael J. , Chen Liang , Manca Claudia , Jenkins Stephen G. , Walsh Thomas J. , Kreiswirth Barry N.
Published: September 2016

We developed and evaluated multiplexed molecular beacon probes in a real-time PCR assay to identify prominent extended-spectrum-β-lactamase, plasmid-mediated AmpC β-lactamase (pAmpC) and carbapenemase genes directly from perianal swab specimens within 6 h. We evaluated this assay on 158 perianal swabs collected from hematopoietic stem cell transplant recipients and found that this assay was highly sensitive and specific for detection of CTX-M-, pAmpC-, and KPC-producing
Enterobacteriaceae
compared to culture on chromogenic agar.
Extracellular Superoxide Dismutase Enhances Recruitment of Immature Neutrophils to the Liver
Authors: Break Timothy J. , Witter Alexandra R. , Indramohan Mohanalaxmi , Mummert Mark E. , Dory Ladislav , Berg Rance E.
Published: September 2016

Listeria monocytogenesis a Gram-positive intracellular pathogen that causes spontaneous abortion in pregnant women, as well as septicemia, meningitis, and gastroenteritis, primarily in immunocompromised individuals. AlthoughL. monocytogenescan usually be effectively treated with antibiotics, there is still around a 25% mortality rate with individuals who develop clinical listeriosis. Neutrophils are innate immune cells required for the clearance of pathogenic organisms, includingL. monocytogenes. The diverse roles of neutrophils during both infectious and noninfectious inflammation have recently gained much attention. However, the impact of reactive oxygen species, and the enzymes that control their production, on neutrophil recruitment and function is not well understood. Using congenic mice with varying levels of extracellular superoxide dismutase (ecSOD) activity, we have recently shown that the presence of ecSOD decreases clearance ofL. monocytogeneswhile increasing the recruitment of neutrophils that are not protective in the liver. The data presented here show that ecSOD activity does not lead to a cell-intrinsic increase in neutrophil-homing potential or a decrease in protection againstL. monocytogenes. Instead, ecSOD activity enhances the production of neutrophil-attracting factors and protects hyaluronic acid (HA) from damage. Furthermore, neutrophils from the livers of ecSOD-expressing mice have decreased intracellular and surface-bound myeloperoxidase, are less capable of killing phagocytosedL. monocytogenes, and have decreased oxidative burst. Collectively, our data reveal that ecSOD activity modulates neutrophil recruitment and function in a cell-extrinsic fashion, highlighting the importance of the enzyme in protecting tissues from oxidative damage.
Genomic Landscape of Intrahost Variation in Group A Streptococcus: Repeated and Abundant Mutational Inactivation of the
fabT
Gene Encoding a Regulator of Fatty Acid Synthesis
Authors: Eraso Jesus M. , Olsen Randall J. , Beres Stephen B. , Kachroo Priyanka , Porter Adeline R. , Nasser Waleed , Bernard Paul E. , DeLeo Frank R. , Musser James M.
Published: September 2016

To obtain new information about
Streptococcus pyogenes
intrahost genetic variation during invasive infection, we sequenced the genomes of 2,954 serotype M1 strains recovered from a nonhuman primate experimental model of necrotizing fasciitis. A total of 644 strains (21.8%) acquired polymorphisms relative to the input parental strain. The
fabT
gene, encoding a transcriptional regulator of fatty acid biosynthesis genes, contained 54.5% of these changes. The great majority of polymorphisms were predicted to deleteriously alter FabT function. Transcriptome-sequencing (RNA-seq) analysis of a wild-type strain and an isogenic
fabT
deletion mutant strain found that between 3.7 and 28.5% of the
S. pyogenes
transcripts were differentially expressed, depending on the growth temperature (35°C or 40°C) and growth phase (mid-exponential or stationary phase). Genes implicated in fatty acid synthesis and lipid metabolism were significantly upregulated in the
fabT
deletion mutant strain. FabT also directly or indirectly regulated central carbon metabolism genes, including pyruvate hub enzymes and fermentation pathways and virulence genes. Deletion of
fabT
decreased virulence in a nonhuman primate model of necrotizing fasciitis. In addition, the
fabT
deletion strain had significantly decreased survival in human whole blood and during phagocytic interaction with polymorphonuclear leukocytes
ex vivo
. We conclude that FabT mutant progeny arise during infection, constitute a metabolically distinct subpopulation, and are less virulent in the experimental models used here.
Zika Virus Is Not Uniquely Stable at Physiological Temperatures Compared to Other Flaviviruses
Authors: Goo Leslie , Dowd Kimberly A. , Smith Alexander R. Y. , Pelc Rebecca S. , DeMaso Christina R. , Pierson Theodore C.
Published: September 2016

Zika virus (ZIKV) is a flavivirus that has emerged as a global health threat due in part to its association with congenital abnormalities. Other globally relevant flaviviruses include dengue virus (DENV) and West Nile virus (WNV). High-resolution structures of ZIKV reveal many similarities to DENV and suggest some differences, including an extended glycan loop (D. Sirohi, Z. Chen, L. Sun, T. Klose, T. C. Pierson, et al., 352:467–470, 2016, http://dx.doi.org/10.1126/science.aaf5316) and unique interactions among envelope (E) protein residues that were proposed to confer increased virion stability and contribute mechanistically to the distinctive pathobiology of ZIKV (V. A. Kostyuchenko, E. X. Lim, S. Zhang, G. Fibriansah, T. S. Ng, et al., Nature 533:425–428, 2016, http://dx.doi.org/10.1038/nature17994). However, in the latter study, virus stability was inferred by measuring the loss of infectivity following a short incubation period. Here, we rigorously assessed the relative stability of ZIKV, DENV, and WNV by measuring changes in infectivity following prolonged incubation at physiological temperatures. At 37°C, the half-life of ZIKV was approximately twice as long as the half-life of DENV (11.8 and 5.2 h, respectively) but shorter than that of WNV (17.7 h). Incubation at 40°C accelerated the loss of ZIKV infectivity. Increasing virion maturation efficiency modestly increased ZIKV stability, as observed previously with WNV and DENV. Finally, mutations at E residues predicted to confer increased stability to ZIKV did not affect virion half-life. Our results demonstrate that ZIKV is not uniquely stable relative to other flaviviruses, suggesting that its unique pathobiology is explained by an alternative mechanism.

IMPORTANCE
Zika virus (ZIKV) belongs to the
Flavivirus
genus, which includes other clinically relevant mosquito-borne pathogens such as dengue virus (DENV) and West Nile virus (WNV). Historically, ZIKV infection was characterized by a self-limiting, mild disease, but recent outbreaks have been associated with severe clinical complications, including Guillain-Barré syndrome and microcephaly, which are atypical of other flavivirus infections. Moreover, ZIKV has been detected in saliva, urine, and semen, and it may be sexually transmitted. Analysis of a high-resolution cryo-electron microscopic reconstruction of ZIKV hypothesized that the unusual stability of this virus contributes to its distinctive pathobiology. Here, we directly compared the stability of ZIKV to that of other flaviviruses following prolonged incubation in solution at physiological temperatures. We found that the stability of multiple ZIKV strains, including those from recent outbreaks, is intermediate between that of DENV and WNV, suggesting an alternative explanation for the unique clinical manifestations of ZIKV infection.
Delayed diagnosis of Pendred syndrome
Authors: Smith Natalie , U-King-Im Jean-Marie , Karalliedde Janaka
Published: September 2016

We describe a case of a delayed diagnosis of Pendred syndrome. The patient had a history of hearing loss from childhood and presented to the endocrine clinic when aged 32 with an enlarging goitre. The characteristic Mondini deformity was noted on auditory canal MRI scan. Genetic tests confirmed the diagnosis. Pendred syndrome is an autosomal recessive disorder, characterised by congenital sensorineural hearing loss, goitre and impaired iodide organification and can present at any age. We highlight to the general physician the classical features of this syndrome that would aid early diagnosis.
Methodology of AA CRASH: a prospective observational study evaluating the incidence and pathogenesis of adverse post-traumatic sequelae in African-Americans experiencing motor vehicle collision
Authors: Linnstaedt Sarah D , Hu JunMei , Liu Andrea Y , Soward April C , Bollen Kenneth A , Wang Henry E , Hendry Phyllis L , Zimny Erin , Lewandowski Christopher , Velilla Marc-Anthony , Damiron Kathia , Pearson Claire , Domeier Robert , Kaushik Sangeeta , Feldman James , Rosenberg Mark , Jones Jeffrey , Swor Robert , Rathlev Niels , McLean Samuel A
Published: September 2016

Introduction

A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed.

Methods and analysis

The African-American CRASH (AA CRASH) study is an NIH-funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC.

Ethics and dissemination

AA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal.
Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial
Authors: Goldberg Andrew J , Zaidi Razi , Thomson Claire , Doré Caroline J , Skene Simon S , Cro Suzie , Round Jeff , Molloy Andrew , Davies Mark , Karski Michael , Kim Louise , Cooke Paul
Published: September 2016

Introduction

Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years.

Methods and analysis

TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis.

Ethics and dissemination

The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NCT02128555.
Step 4: stick or twist? A review of asthma therapy
Authors: Slater Mariel G , Pavord Ian D , Shaw Dominick E
Published: September 2016

Many people with asthma do not achieve disease control, despite bronchodilators and inhaled corticosteroid therapy. People with uncontrolled asthma are at higher risk of an asthma attack and death, with mortality rates estimated at 1000 deaths/year in England and Wales. The recent National Review of Asthma Deaths (NRAD) report, ‘Why asthma still kills’, recommended that patients at step 4 or 5 of the British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidance must be referred to a specialist asthma service. This article reviews the 2014 evidence base for therapy of asthma patients at BTS/SIGN step 4 of the treatment cascade, in response to key findings of the NRAD report and lack of preferred treatment option at this step.
Pulmonary artery perfusion versus no pulmonary perfusion during cardiopulmonary bypass in patients with COPD: a randomised clinical trial
Authors: Buggeskov Katrine B , Sundskard Martin M , Jonassen Thomas , Andersen Lars W , Secher Niels H , Ravn Hanne B , Steinbrüchel Daniel A , Jakobsen Janus C , Wetterslev Jørn
Published: September 2016

Introduction

Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery.

Methods

90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital.

Results

21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes.

Discussion

Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing cardiac surgery. Pulmonary artery perfusion with hypothermic HTK solution does not seem to improve postoperative oxygenation.

Trial registration number

NCT01614951; Pre-results.
Low eosinophil and low lymphocyte counts and the incidence of 12 cardiovascular diseases: a CALIBER cohort study
Authors: Shah Anoop Dinesh , Denaxas Spiros , Nicholas Owen , Hingorani Aroon D , Hemingway Harry
Published: September 2016

Background

Eosinophil and lymphocyte counts are commonly performed in clinical practice. Previous studies provide conflicting evidence of association with cardiovascular diseases.

Methods

We used linked primary care, hospitalisation, disease registry and mortality data in England (the CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records) programme). We included people aged 30 or older without cardiovascular disease at baseline, and used Cox models to estimate cause-specific HRs for the association of eosinophil or lymphocyte counts with the first occurrence of cardiovascular disease.

Results

The cohort comprised 775 231 individuals, of whom 55 004 presented with cardiovascular disease over median follow-up 3.8 years. Over the first 6 months, there was a strong association of low eosinophil counts (<0.05 compared with 0.15–0.25×109/L) with heart failure (adjusted HR 2.05; 95% CI 1.72 to 2.43), unheralded coronary death (HR 1.94, 95% CI 1.40 to 2.69), ventricular arrhythmia/sudden cardiac death and subarachnoid haemorrhage, but not angina, non-fatal myocardial infarction, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, subarachnoid haemorrhage or abdominal aortic aneurysm. Low eosinophil count was inversely associated with peripheral arterial disease (HR 0.63, 95% CI 0.44 to 0.89). There were similar associations with low lymphocyte counts (<1.45 vs 1.85–2.15×109/L); adjusted HR over the first 6 months for heart failure was 2.25 (95% CI 1.90 to 2.67). Associations beyond the first 6 months were weaker.

Conclusions

Low eosinophil counts and low lymphocyte counts in the general population are associated with increased short-term incidence of heart failure and coronary death.

Trial registration number

NCT02014610; results.
Suspected anaphylaxis after intravenous injection of rocuronium in a dog
Authors: Küls Nina , Rocchi Attilio , Larenza Paula Maria
Published: September 2016

A nine‐year‐old female Yorkshire Terrier weighing 5.8 kg required anaesthesia for a bilateral phacoemulsification to treat diabetic cataracts. Perioperatively, rocuronium bromide was administered intravenously to achieve centralisation of the eye. Immediately after injection of the rocuronium, the dog developed tachycardia, hypertension and bronchospasm. At this time, no association between the rocuronium and the adverse reaction was made due to the lack of reports of such an event in dogs. A second dose was therefore administered once the animal's spontaneous efforts to breathe indicated partial loss of neuromuscular blockade, this time without adverse effects. However, a third dose of rocuronium resulted in similar signs as the first injection, suggesting an association between the rocuronium and the observed reaction. The signs resolved spontaneously and the dog recovered uneventfully in the intensive care unit from where it was discharged 48 hours after the surgery.
Bengt Saltin and exercise physiology: a perspective
Authors: Joyner Michael J.
Published: September 2016

This perspective highlights some of the key contributions of Professor Bengt Saltin (1935–2014) to exercise physiology. The emergence of exercise physiology from work physiology as his career began is discussed as are his contributions in a number of areas. Saltin’s open and question-based style of leadership is a model for the future of our field.