bluuebunny/crossref_metadata_2025 huggingface dataset:
Singers and Steroids: A Multi-Disciplinary Discussion
Authors: Gaskill Christopher S. , Williams Melanie B. , McHugh Richard K.
Published: March 2015

Singers are often faced with acute onset of dysphonia, either due to recent phonotrauma or an illness, at a time when they are scheduled to sing in a performance. Many singers turn to steroid treatment prescribed by a health care professional who may or may not be equipped to provide a comprehensive exam or counsel the singer on the vocal risks involved. Steroids can be effective in reducing vocal inflammation, and therefore can provide singers with a quick solution to a very difficult situation. However, the risks of steroid treatment for a singer in crisis must be considered and weighed against any potential benefit. In college-age singers, pressure to perform can be great, and steroids can be easily obtained at campus health clinics. In this paper, we address the issues surrounding treatment decisions for acute dysphonia, especially regarding whether to recommend steroids for a young singer in training. We discuss the relevant factors from the viewpoint of a laryngologist, a speech-language pathologist, and a singing voice teacher. Finally, we make recommendations for equipping singers to make informed voice care decisions and for improving communication between our disciplines to ensure the best treatment outcomes for the young singer with acute dysphonia.
The Role of Cultural Competence in Serving Transgender Populations
Authors: Hancock Adrienne B.
Published: March 2015

Recent research indicates that our professions could improve in Lesbian, Gay, Bisexual, and Transgender (LGBT) cultural competency. As indicated by Turner, Wilson, and Shirah's (2006) model of cultural competency, one can begin by increasing knowledge of transgender (TG) culture and improving sensitivity and attitudes foundational to serving these populations appropriately. This article sheds light on the factors influencing quality of life for many TG people, including voice. Readers are encouraged to include appropriate measures of voice-related quality of life in treatment outcomes and are provided with suggestions for developing LGBT cultural competency.
Precoding designs for energy efficiency balancing for the cellular two way relay network
Authors: Dong Quan , Li Jiandong
Published: March 2015

This study investigates energy efficiency (EE) balancing precoding designs for the cellular two way relay network (CTWR). Owing to non‐convexity and NP hard property of the worst case EE problem, the authors use convex approximation and convex relaxation to modify the problem for better mathematical tractability. The Dinkelbach‐type method is adopted to solve the max‐min fractional problem. Then alternating optimisation method is used to solve the inner subproblem as its non‐convexity. After fixing the precoding of one station (base station or relay station), the subproblem is still non‐convex. Then successive convex approximation (SCA) and semi‐definite program relaxation methods are used to obtain the precoding matrices of BS and RS. The proposed algorithm, which can be extended to the two way relay system with direct link model or the one way relay system, has a wide range of application. Simulation results show that the proposed algorithm converges fast and achieves better EE balancing compared with existing method.
Novel One-Pot Multicomponent Strategy for the Synthesis of Pyrrolo[1,2-a]benzimidazole and Pyrrolo[1,2-a]quinoxaline Derivatives
Authors: Georgescu Emilian , Nicolescu Alina , Georgescu Florentina , Shova Sergiu , Teodorescu Florina , Macsim Ana-Maria , Deleanu Calin
Published: March 2015

A simple one-pot multicomponent procedure has been developed for the synthesis of pyrrolo[1,2-a]benzimidazole and pyrrolo[1,2-a]quinoxaline derivatives by heating a 1:2:1 molar mixture of a benzimidazole unsubstituted on the imidazole ring, a 2-bromoacetophenone derivative, and a nonsymmetrical activated alkyne in refluxing 2-ethyloxirane. The reaction can be performed under conventional reflux conditions or with microwave irradiation.
Highly Regioselective Arylation of 1,2,3-Triazole N-Oxides with Sodium Arenesulfinates via Palladium-Catalyzed Desulfitative Cross-Coupling Reaction
Authors: Huang Qing , Liu Liangxian , Zhu Jiayi , Chen Yu , Lin Feng , Wang Baoshuang
Published: March 2015

A convenient and highly regioselective palladium-catalyzed direct C5-arylation of 1,2,3-triazole N-oxides was developed in the presence of silver carbonate and tripotassium phosphate. This protocol allowed use of sodium arylsulfinates, diphenylphosphine oxide, and triphenylphosphine as arylating reagents to produce 2-aryl-5-aryl-1,2,3-triazole N-oxides in good to excellent yields, providing a complement to the existing methods for the direct arylation of 1,2,3-triazole N-oxides.
Prevalence of Klippel-Feil Syndrome in a Surgical Series of Patients with Cervical Spondylotic Myelopathy: Analysis of the Prospective, Multicenter AOSpine North America Study
Authors: Nouri Aria , Tetreault Lindsay , Zamorano Juan J. , Mohanty Chandan B. , Fehlings Michael G.
Published: March 2015

Study Design

Prospective study.

Objective

To evaluate the prevalence of Klippel-Feil syndrome (KFS) in a prospective data set of patients undergoing surgical treatment for cervical spondylotic myelopathy (CSM) and to evaluate if magnetic resonance imaging (MRI) features in patients with KFS are more pronounced than those of non-KFS patients with CSM.

Methods

A retrospective analysis of baseline MRI data from the AOSpine prospective and multicenter CSM-North American study was conducted. All the patients presented with at least one clinical sign of myelopathy and underwent decompression surgery. The MRIs and radiographs were reviewed by three investigators. The clinical and imaging findings were compared with patients without KFS but with CSM.

Results

Imaging analysis discovered 5 of 131 patients with CSM (∼3.82%) had single-level congenital fusion of the cervical spine. The site of fusion differed for all the patients. One patient underwent posterior surgery and four patients received anterior surgery. Postoperative follow-up was available for four of the five patients with KFS and indicated stable or improved functional status. All five patients demonstrated pathologic changes of adjacent segments and hyperintensity signal changes in the spinal cord on T2-weighted MRI. Multiple MRI features, most notably maximum canal compromise ( p = 0.05) and T2 signal hyperintensity area ( p = 0.05), were worse in patients with CSM and KFS.

Conclusions

The high prevalence of KFS in our surgical series of patients with CSM may serve as an indication that these patients are prone to increased biomechanical use of segments adjacent to fused vertebra. This supposition is supported by a tendency of patients with KFS to present with more extensive MRI evidence of degeneration than non-KFS patients with CSM.
Order within disorder: The atomic structure of ion-beam sputtered amorphous tantala (a-Ta2O5)
Authors: Bassiri Riccardo , Liou Franklin , Abernathy Matthew R. , Lin Angie C. , Kim Namjun , Mehta Apurva , Shyam Badri , Byer Robert L. , Gustafson Eric K. , Hart Martin , MacLaren Ian , Martin Iain W. , Route Roger K. , Rowan Sheila , Stebbins Jonathan F. , Fejer Martin M.
Published: March 2015

Amorphous tantala (a-Ta2O5) is a technologically important material often used in high-performance coatings. Understanding this material at the atomic level provides a way to further improve performance. This work details extended X-ray absorption fine structure measurements of a-Ta2O5 coatings, where high-quality experimental data and theoretical fits have allowed a detailed interpretation of the nearest-neighbor distributions. It was found that the tantalum atom is surrounded by four shells of atoms in sequence; oxygen, tantalum, oxygen, and tantalum. A discussion is also included on how these models can be interpreted within the context of published crystalline Ta2O5 and other a-T2O5 studies.
Time-domain self-consistent theory of frequency-locking regimes in gyrotrons with low-Q resonators
Authors: Ginzburg N. S. , Sergeev A. S. , Zotova I. V.
Published: March 2015

A time-domain theory of frequency-locking gyrotron oscillators with low-Q resonators has been developed. The presented theory is based on the description of wave propagation by a parabolic equation taking into account the external signal by modification of boundary conditions. We show that the developed model can be effectively used for simulations of both single- and multi-mode operation regimes in gyrotrons driven by an external signal. For the case of low-Q resonators typical for powerful gyrotrons, the external signal can influence the axial field profile inside the interaction space significantly and, correspondingly, the value of the electron orbital efficiency.
On resistive magnetohydrodynamic studies of sawtooth oscillations in tokamaks
Authors: Aydemir A. Y. , Kim J. Y. , Park B. H. , Seol J.
Published: March 2015

A fundamental requirement for the validity and accuracy of any large-scale computation is sufficiently well-resolved length and time scales relevant to the problem under study. Ironically, despite the enormous computational resources available today, poorly resolved length scales in sophisticated nonlinear calculations are not uncommon. Using the internal kink mode that is responsible for tokamak sawtooth oscillations as an example, consequences of not resolving in sufficient detail the linear and nonlinear layer widths of the resistive n = 1 mode and its nonlinear spectrum are examined. Poor radial and spectral resolution are shown to cause nonphysical, large-scale stochasticity that can be erroneously associated with a fast temperature collapse and sawtooth crash. With the assistance of a nonlinear mode coupling model, a sufficiently well-resolved toroidal spectrum is shown to require at least an order of magnitude more toroidal modes than is commonly used at dissipation levels relevant to today's tokamaks. A subgrid-scale model is introduced that helps with the spectral resolution problem by reducing the required number of degrees of freedom from that of a well-resolved direct numerical simulation.
LaTiO3/KTaO3 interfaces: A new two-dimensional electron gas system
Authors: Zou K. , Ismail-Beigi Sohrab , Kisslinger Kim , Shen Xuan , Su Dong , Walker F. J. , Ahn C. H.
Published: March 2015

We report a new 2D electron gas (2DEG) system at the interface between a Mott insulator, LaTiO3, and a band insulator, KTaO3. For LaTiO3/KTaO3 interfaces, we observe metallic conduction from 2 K to 300 K. One serious technological limitation of SrTiO3-based conducting oxide interfaces for electronics applications is the relatively low carrier mobility (0.5-10 cm2/V s) of SrTiO3 at room temperature. By using KTaO3, we achieve mobilities in LaTiO3/KTaO3 interfaces as high as 21 cm2/V s at room temperature, over a factor of 3 higher than observed in doped bulk SrTiO3. By density functional theory, we attribute the higher mobility in KTaO3 2DEGs to the smaller effective mass for electrons in KTaO3.
More than mere survival: violence, humanitarian governance, and practical material politics in a Kenyan refugee camp
Authors: Newhouse Léonie S
Published: March 2015

This paper frames the political import of refugees' material practices in Kakuma Refugee Camp through critical reflection on Eyal Weizman's notion of the humanitarian present. To begin, I explore how the production of the refugee camp as a space of containment takes place not through a unified humanitarian calculus, but through a set of articulated practices undertaken by various actors—governments, police, aid agencies, host populations, and refugees—all of which have profoundly material manifestations. Secondly, I argue that refugees' pursuits of material well-being through semilicit and illicit means should be read as a practical material critique of the declining standards of humanitarian support. These efforts to achieve sustenance, invest in the future, and exert autonomy serve as a public reminder that humanitarian assistance fails to meet the minimum standard to ensure human existence, and that refugees aim for something more than mere survival.
The sound environment and soundscape preservation in historic city centres—the case study of Lhasa
Authors: Huang Lingjiang , Kang Jian
Published: March 2015

The historic city centre of Lhasa has preserved special types of historic and cultural heritage for various reasons, including strong religious beliefs, preservation policy, and slow globalisation. In addition to visual cultural heritage, the sound environment represents a cultural heritage that requires preservation. This paper presents an analysis of the sound environment of Lhasa's historic city centre based on field investigations and soundwalk measurements during the tourism high season. First, Lhasa's historic urban form and cultural background are introduced. Second, the relationship between the historic urban space and the sounds is investigated according to the sound sources. The sound taxonomy and the cultural meanings of these sounds are examined and identified. Third, the sound environments are evaluated from the perspectives of sound sources and sound changes with time and frequency. The sound pressure level is found to be high in the historic centre, which might affect the sound sources associated with cultural identities. Additionally, significant variations within the centre—both spatial and temporal—that are indentified in the sound pressure levels and spectrums are reflected in the characteristics of local daily life and social activities. Finally, comparisons are made between Lhasa's historic centre and a number of other historic centres and squares. Possible implications of the results and principles of soundscape preservation are also discussed, based on the case study of Lhasa.
The Headscarf Effect Revisited: Further Evidence for a Culture-Based Internal Face Processing Advantage
Authors: Wang Yin , Thomas Justin , Weissgerber Sophia C , Kazemini Sahar , Ul-Haq Israr , Quadflieg Susanne
Published: March 2015

Encoding the internal features of unfamiliar faces poses a perceptual challenge that occasionally results in face recognition errors. Extensive experience with faces framed by a headscarf may, however, enhance perceivers' ability to process internal facial information. To examine this claim empirically, participants in the United Arab Emirates and the United States of America completed a standard part–whole face recognition task. Accuracy on the task was examined using a 2 (perceiver culture: Emirati vs American) x 2 (face race: Arab vs white) x 2 (probe type: part vs whole) x 3 (probe feature: eyes vs nose vs mouth) mixed-measures analysis of variance. As predicted, Emiratis outperformed Americans on the administered task. Although their recognition advantage occurred regardless of probe type, it was most pronounced for Arab faces and for trials that captured the processing of nose or mouth information. The findings demonstrate that culture-based experiences hone perceivers' face processing skills.
Management strategies for chicory (Cichorium intybus) and plantain (Plantago lanceolata): impact on dry matter yield, nutritive characteristics and plant density
Authors: Lee Julia M. , Hemmingson Nivonne R. , Minnee Elena M. K. , Clark Cameron E. F.
Published: March 2015

Chicory (Cichorium intybus L.) and narrow-leaved plantain (Plantago lanceolata L.) are able to grow a large amount of high-quality summer feed. Limited information is available on the effect of grazing management on plantain, and no comparison been undertaken of modern chicory and plantain cultivars used in dairy production systems. This study determined the effect of defoliation interval (as determined by the extended leaf height, ELH) and residual height on the yield, nutritive characteristics and plant density of chicory and plantain over 18 months. Chicory leaf yield was reduced in swards defoliated at 150 mm ELH compared with those defoliated at 250, 350 or 550 mm (14.3 v. 17.5 t DM ha–1), and chicory stem yield was least in swards defoliated at 150 or 250 mm. Plantain swards defoliated at 350 or 450 mm ELH yielded more leaf than those defoliated at 150 or 250 mm (20.4 v. 16.7 t DM ha–1); however, stem yield also increased with increasing defoliation interval. Over all seasons, as defoliation interval increased, generally, neutral detergent fibre content increased and crude protein, ash and digestibility declined. Residual height had less of an effect on yield and nutritive characteristics than did defoliation interval. To maximise chicory leaf growth while minimising growth of lower quality stem, the optimal ELH over 18 months was 250 mm, or if the chicory was used only as a 9-month ‘summer’ crop, 350 mm. Recommendations for plantain are not as simple because longer defoliation intervals increase both leaf and stem yield and reduce nutritive value. Defoliating plantain swards at 250 mm ELH appeared to provide a balance between yield and nutritive value; however, further work is required to determine the impact of applying these recommendations on a dairy farm system.
Antioxidant supplementation during in vitro culture improves mitochondrial function and development of embryos from aged female mice
Authors: Silva Elena , Greene Alison F. , Strauss Kevin , Herrick Jason R. , Schoolcraft William B. , Krisher Rebecca L.
Published: March 2015

Maternal aging results in reduced oocyte and blastocyst quality, thought to be due, in part, to mitochondrial dysfunction and accumulation of reactive oxygen species. To reduce oxidative stress, the antioxidants α-lipoic acid (ALA; 10 µM), α-tocopherol (250 µM), hypotaurine (1 mM) and N-acetylcysteine (NAC; 1 mM), and sirtuin (100 ng mL–1) were added to embryo culture medium (AntiOX) and compared with a control (CON) without antioxidants to assess blastocyst development after in vitro maturation and fertilisation of oocytes from aged B6D2F1 female mice (13.5 months). Development to the blastocyst stage increased in the AntiOX compared with CON group (87.6% vs 72.7%, respectively; P < 0.01), in addition to higher mitochondrial membrane potential and ATP levels in the AntiOX group. Expression of genes associated with oxidative stress (PI3K, FOXO3A and GLRX2) was upregulated in the CON compared with AntiOX group. In addition to AntiOX, a medium containing only NAC and ALA (rAntiOX) was used to culture embryos from young CF1 females (6–8 weeks). More blastocysts developed in the rAntiOX compared with CON group (64.1% vs 43.3%, respectively; P < 0.01), although AntiOX (48.0% blastocysts) did not result in improved development in young mice. Antioxidants improved mitochondrial activity, gene expression and development in embryos of older female mice, whereas a reduced level of antioxidants during culture was beneficial to embryos from young mice.
Relating fuel loads to overstorey structure and composition in a fire-excluded Sierra Nevada mixed conifer forest
Authors: Lydersen Jamie M. , Collins Brandon M. , Knapp Eric E. , Roller Gary B. , Stephens Scott
Published: March 2015

Although knowledge of surface fuel loads is critical for evaluating potential fire behaviour and effects, their inherent variability makes these difficult to quantify. Several studies relate fuel loads to vegetation type, topography and spectral imaging, but little work has been done examining relationships between forest overstorey variables and surface fuel characteristics on a small scale (<0.05 ha). Within-stand differences in structure and composition would be expected to influence fuel bed characteristics, and thus affect fire behaviour and effects. We used intensive tree and fuel measurements in a fire-excluded Sierra Nevada mixed conifer forest to assess relationships and build predictive models for loads of duff, litter and four size classes of downed woody fuels to overstorey structure and composition. Overstorey variables explained a significant but somewhat small percentage of variation in fuel load, with marginal R2 values for predictive models ranging from 0.16 to 0.29. Canopy cover was a relatively important predictor for all fuel components, although relationships varied with tree species. White fir abundance had a positive relationship with total fine woody fuel load. Greater pine abundance was associated with lower load of fine woody fuels and greater load of litter. Duff load was positively associated with total basal area and negatively associated with oak abundance. Knowledge of relationships contributing to within-stand variation in fuel loads can increase our understanding of fuel accumulation and improve our ability to anticipate fine-scale variability in fire behaviour and effects in heterogeneous mixed species stands.
p63 sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling
Authors: Memmi Elisa Maria , Sanarico Anna Giulia , Giacobbe Arianna , Peschiaroli Angelo , Frezza Valentina , Cicalese Angelo , Pisati Federica , Tosoni Daniela , Zhou Huiqing , Tonon Giovanni , Antonov Alexey , Melino Gerry , Pelicci Pier Giuseppe , Bernassola Francesca
Published: March 2015

Significance

p63, the sister homolog of p53, is a master regulator of epithelial stem cell (SC) biology. p63 is indeed intimately implicated in the maintenance of the self-renewal capacity of stratified epithelia and their derivatives, including the mammary gland. Although the physiological role of p63 in normal mammary SCs is now acknowledged, proof of its implications in breast cancer SCs remains elusive. Here, we find that mammary cancer stem cells (CSCs) possess increased levels of p63 expression compared with normal progenitors. p63 promotes self-renewal and expansion of mammary CSCs and breast tumor growth in vivo. Additionally, this study provides a link between p63 and the Sonic Hedgehog signaling pathway in the regulation of breast cancer stemness.
Basolateral sorting of chloride channel 2 is mediated by interactions between a dileucine motif and the clathrin adaptor AP-1
Authors: de la Fuente-Ortega Erwin , Gravotta Diego , Bay Andres Perez , Benedicto Ignacio , Carvajal-Gonzalez Jose Maria , Lehmann Guillermo L. , Lagos Carlos F. , Rodríguez-Boulan Enrique
Published: March 2015

In spite of the many key cellular functions of chloride channels, the mechanisms that mediate their subcellular localization are largely unknown. ClC-2 is a ubiquitous chloride channel usually localized to the basolateral domain of epithelia that regulates cell volume, ion transport, and acid–base balance; mice knocked out for ClC-2 are blind and sterile. Previous work suggested that CLC-2 is sorted basolaterally by TIFS812LL, a dileucine motif in CLC-2's C-terminal domain. However, our in silico modeling of ClC-2 suggested that this motif was buried within the channel's dimerization interface and identified two cytoplasmically exposed dileucine motifs, ESMI623LL and QVVA635LL, as candidate sorting signals. Alanine mutagenesis and trafficking assays support a scenario in which ESMI623LL acts as the authentic basolateral signal of ClC-2. Silencing experiments and yeast three-hybrid assays demonstrated that both ubiquitous (AP-1A) and epithelium-specific (AP-1B) forms of the tetrameric clathrin adaptor AP-1 are capable of carrying out basolateral sorting of ClC-2 through interactions of ESMI623LL with a highly conserved pocket in their γ1-σ1A hemicomplex.
Colistin and doripenem combinations against Pseudomonas aeruginosa: profiling the time course of synergistic killing and prevention of resistance
Authors: Ly Neang S. , Bulitta Jürgen B. , Rao Gauri G. , Landersdorfer Cornelia B. , Holden Patricia N. , Forrest Alan , Bergen Phillip J. , Nation Roger L. , Li Jian , Tsuji Brian T.
Published: March 2015

Objectives

Colistin is an ‘old’ drug, which is being increasingly utilized due to limited therapeutic options. However, resistance emergence during monotherapy is concerning. Here, our objective was to optimize colistin combinations against Pseudomonas aeruginosa by profiling the time course of synergistic killing and prevention of resistance.

Methods

Hollow-fibre infection models over 10 days simulated clinically relevant dosage regimens of colistin and doripenem against two heteroresistant P. aeruginosa strains (MIC 1 mg/L) and one resistant (MIC 128 mg/L) strain (inoculum 109.3 cfu/mL). New mathematical mechanism-based models (MBMs) were developed using S-ADAPT.

Results

Against heteroresistant P. aeruginosa strains, colistin monotherapy resulted in initial killing (up to 2.64 log10 cfu/mL) within 24 h followed by regrowth. High-intensity combinations involving free steady-state colistin concentrations of 5 mg/L achieved complete eradication (>9.3 log10 killing) within 48 h. These combinations achieved synergy with up to 9.38 log10 greater killing compared with the most active monotherapy. Against the colistin-resistant strain, the combination yielded marked initial synergy with up to 6.11 log10 cfu/mL bacterial reductions within 72 h followed by regrowth. The MBMs quantified total and resistant subpopulations and the proposed synergy between colistin and doripenem.

Conclusions

Our findings provide insight into optimal antibiotic treatment and may serve as a framework for new drug combinations and combination modelling.
Wide dissemination of linezolid-resistant Staphylococcus epidermidis in Greece is associated with a linezolid-dependent ST22 clone
Authors: Karavasilis Vasilios , Zarkotou Olympia , Panopoulou Maria , Kachrimanidou Melina , Themeli-Digalaki Katerina , Stylianakis Antonios , Gennimata Vassiliki , Ntokou Eleni , Stathopoulos Constantinos , Tsakris Athanasios , Pournaras Spyros ,   on behalf of the Greek Study Group on Staphylococcal Linezolid Resistance, Kouskouni E. , Vrioni G. , Mamali V. , Kousouli E. , Papagiannakopoulou P. , Kristo I. , Dafopoulou K. , Hadjichristodoulou C. , Carle P. , Kimouli M. , Perivolioti E. , Nepka M. , Foudoulis K. , Stathoulopoulou F. , Papanikolaou P. , Poulou A. , Tsorlini Eleni
Published: March 2015

Objectives

Dependence on linezolid was recently described as significant growth acceleration of linezolid-resistant Staphylococcus epidermidis (LRSE) isolates upon linezolid exposure. We investigated the possible contribution of linezolid dependence to LRSE dissemination in Greece.

Methods

Linezolid resistance rates were estimated in six tertiary hospitals located throughout Greece between 2011 and 2013. Sixty-three randomly selected LRSE recovered in these hospitals during this period were studied. Growth curve analysis was conducted with and without linezolid. Clonality of the isolates was investigated by PFGE and MLST.

Results

During the study period, the LRSE rate in the participating hospitals rose significantly from 6.9% to 9% (P = 0.006); the increase was more prominent in ICUs (from 15.1% to 20.9%; P = 0.005). Forty-seven (74.6%) of the 63 LRSE, derived from all study hospitals, clearly exhibited linezolid dependence, growing significantly faster in the presence of 16 and 32 mg/L linezolid. Of note, 61 (96.8%) LRSE exhibited a single macrorestriction pattern and belonged to ST22, which included all linezolid-dependent LRSE. The remaining two LRSE belonged to unique STs. Five of six linezolid-dependent isolates tested also exhibited linezolid dependence upon exposure to 8 mg/L linezolid. Interestingly, five of six ST22 linezolid-non-dependent isolates tested developed linezolid dependence when linezolid exposure preceded growth analysis.

Conclusions

The rapid LRSE dissemination in Greek hospitals threatens linezolid activity. The observation that most LRSE belonged to ST22 and expressed dependence on linezolid clearly implies that the spread of linezolid resistance should have been driven by this trait, which provided the LRSE with a selective advantage under linezolid pressure.
HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia
Authors: Armenia D. , Fabeni L. , Alteri C. , Di Pinto D. , Di Carlo D. , Bertoli A. , Gori C. , Carta S. , Fedele V. , Forbici F. , D'Arrigo R. , Svicher V. , Berno G. , Pizzi D. , Nicastri E. , Sarmati L. , Pinnetti C. , Ammassari A. , D'Offizi G. , Latini A. , Andreoni M. , Antinori A. , Ceccherini-Silberstein F. , Perno C. F. , Santoro M. M.
Published: March 2015

Objectives

Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51–1000 copies/mL) and resistance in raltegravir-failing patients.

Methods

An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006–13. Genotyping success rate was determined according to the following viraemia levels: 51–500, 501–1000, 1001–10 000, 10 001–100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients.

Results

Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51–500 and 501–1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51–500 copies/mL = 18.2%; 501–1000 = 37.5%; 1001–10 000 = 53.7%; 10 001–100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL.

Conclusions

Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.
Efficacy of tenofovir and efavirenz in combination with lamivudine or emtricitabine in antiretroviral-naive patients in Europe
Authors: Swartz J. E. , Vandekerckhove L. , Ammerlaan H. , de Vries A. C. , Begovac J. , Bierman W. F. W. , Boucher C. A. B. , van der Ende M. E. , Grossman Z. , Kaiser R. , Levy I. , Mudrikova T. , Paredes R. , Perez-Bercoff D. , Pronk M. , Richter C. , Schmit J. C. , Vercauteren J. , Zazzi M. , Židovec Lepej S. , De Luca A. , Wensing A. M. J.
Published: March 2015

Background

The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice.

Methods

A multicentre cohort study was performed in therapy-naive patients initiating ART with TELE before July 2009. Efficacy was studied using ITT (missing or switch = failure) and on-treatment (OT) analyses. Genotypic susceptibility scores (GSSs) were determined using the Stanford HIVdb algorithm.

Results

Efficacy analysis of 1608 patients showed virological suppression to <50 copies/mL at 48 weeks in 91.5% (OT) and 70.6% (ITT). Almost a quarter of all patients (22.9%) had discontinued TELE at week 48, mainly due to CNS toxicity. Virological failure within 48 weeks was rarely observed (3.3%, n = 53). In multilevel, multivariate analysis, infection with subtype B (P = 0.011), baseline CD4 count <200 cells/mm³ (P < 0.001), GSS <3 (P = 0.002) and use of lamivudine (P < 0.001) were associated with a higher risk of virological failure. After exclusion of patients using co-formulated compounds, virological failure was still more often observed with lamivudine. Following virological failure, three-quarters of patients switched to a PI-based regimen with GSS <3. After 1 year of second-line therapy, viral load was suppressed to <50 copies/mL in 73.5% (OT).

Conclusions

In clinical practice, treatment failure on TELE regimens is relatively frequent due to toxicity. Virological failure is rare and more often observed with lamivudine than with emtricitabine. Following virological failure on TELE, PI-based second-line therapy was often successful despite GSS <3.
Small molecule inhibitors of the annexin A2 heterotetramer prevent human papillomavirus type 16 infection
Authors: Woodham Andrew W. , Taylor Julia R. , Jimenez Andrew I. , Skeate Joseph G. , Schmidt Thomas , Brand Heike E. , Da Silva Diane M. , Kast W. Martin
Published: March 2015

Objectives

High-risk human papillomavirus (HPV) infection leads to the development of several human cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is the most common of the cancer-causing genotypes and gains entry to the basal cells of the epithelium through a non-canonical endocytic pathway that involves the annexin A2/S100A10 heterotetramer (A2t). A2t is composed of two annexin A2 monomers bound to an S100A10 dimer and this interaction is a potential target to block HPV16 infection. Here, recently identified small molecule inhibitors of A2t (A2ti) were investigated for their ability to prevent HPV16 infection in vitro.

Methods

A2ti were added to HeLa cells in increasing concentrations prior to the addition of HPV16. Cytotoxicity was evaluated via trypan blue exclusion. HPV16 pseudovirion infection and fluorescently labelled HPV16 capsid internalization was measured with flow cytometry.

Results

A2ti blocked HPV16 infection by 100% without substantial cellular toxicity or reduction in cell growth. Furthermore, A2ti blocked HPV16 entry into epithelial cells by 65%, indicating that the observed inhibition of HPV16 infection is in part due to a block in entry and that non-infectious entry may occur in the absence of A2t binding.

Conclusions

These results demonstrate that targeting A2t may be an effective strategy to prevent HPV16 infection.
A blind CO detection of a distant red galaxy in the HS1700+64
protocluster
Authors: Chapman S. C. , Bertoldi F. , Smail Ian , Blain A. W. , Geach J. E. , Gurwell M. , Ivison R. J. , Petitpas G. R. , Reddy N. , Steidel C. C.
Published: March 2015

We report the blind detection of 12CO emission from a distant red galaxy, HS1700.DRG55. We have used the IRAM Plateau de Bure Interferometer WideX, with its 3.6 GHz of instantaneous dual-polarization bandwidth, to target 12CO(3–2) from galaxies lying in the protocluster at z = 2.300 in the field HS1700+64. If indeed this line in DRG55 is 12CO(3–2), its detection at 104.9 GHz indicates zCO = 2.296. None of the other eight known z ∼ 2.30 protocluster galaxies lying within the primary beam (PB) are detected in 12CO, although the limits are ∼2 × worse towards the edge of the PB where several lie. The optical/near-IR magnitudes of DRG55 (RAB > 27, KAB = 22.3) mean that optical spectroscopic redshifts are difficult with 10-m-class telescopes, but near-IR redshifts would be feasible. The 24-μm-implied star formation rate (210 M⊙ yr−1), stellar mass (∼1011 M⊙) and 12CO line luminosity (3.6 × 1010 K km s−1 pc2) are comparable to other normal12CO-detected star-forming galaxies in the literature, although the galaxy is some ∼2 mag (∼6 ×) fainter in the rest-frame UV than 12CO-detected galaxies at z > 2. The detection of DRG55 in 12CO complements three other 12CO detected UV-bright galaxies in this protocluster from previous studies, and suggests that many optically faint galaxies in the protocluster may host substantial molecular gas reservoirs, and a full blind census of 12CO in this overdense environment is warranted.
Predictors of subjective versus objective cognitive functioning in patients with stable grades II and III glioma
Authors: Gehring Karin , Taphoorn Martin J.B. , Sitskoorn Margriet M. , Aaronson Neil K.
Published: March 2015

Background

Studies in cancer and noncancer populations demonstrate lower than expected correlations between subjective cognitive symptoms and cognitive functioning as determined by standardized neuropsychological tests. This paper systematically examines the association between subjective and objective cognitive functioning in patients with low-grade glioma and the associations of these indicators of cognitive function with clusters of sociodemographic, clinical, and self-reported physical and mental health factors.

Methods

Multiple regression analyses with the subjective and 2 objective indicators of cognitive functioning as dependent variables and 4 clusters of predictor variables were conducted in 169 patients with predominantly low-grade glioma.

Results

Correlations between the subjective and the 2 objective cognitive indicators were negligible (0.04) to low (0.24). Objective cognitive deficits were predominantly associated with sociodemographic (older age, lower education, male sex) and clinical (left hemisphere tumor) variables, while lower ratings of subjective cognitive function were more closely related to self-reported mental health symptoms (fatigue, lower mental well-being), physical (motor) dysfunction and female sex. Self-reported communication deficits were associated significantly with both subjective and objective dysfunction.

Conclusions

We recommend that both subjective and objective measures of cognitive functioning, together with a measure of psychological distress, be used for comprehensive neuropsychological assessments of patients with glioma to determine which areas are most affected and which specific intervention strategies are most appropriate.
Acute Pancreatitis in the Pediatric Intensive Care Unit
Authors: Goday Praveen S. , Wakeham Martin , Kuhn Evelyn M. , Collins Maureen M. , Werlin Steven L.
Published: March 2015

Aim:

The aim of this study is to describe the demographics and outcomes of children with a discharge diagnosis of acute pancreatitis (AP) from the pediatric intensive care unit (PICU).

Methods:

Data for this retrospective cohort study were obtained from a multisite, clinical PICU database. PICU discharges with a primary or secondary diagnosis of AP (SAP) between 2009 and 2013 from 113 centers were reviewed. We also obtained the Pediatric Index of Mortality 2 Risk of Mortality (PIM2ROM), an indicator of the severity of illness.

Results:

Of 360,162 PICU discharges, 2026 with a diagnosis of AP were analyzed further (0.56%)—331 had a primary diagnosis of AP, whereas 1695 had a SAP. Among children with primary AP, median PIM2ROM was 1.0% (interquartile range [IQR] 0.8%–1.4%). Fifty‐five children with primary AP (16.6%) required mechanical ventilation (MV) for a median of 3.8 days (IQR 1.0–9.3). The length of stay (LOS) in PICU was a median of 2.95 days (IQR 1.53–5.90). Only 1 patient died (mortality 0.3%). Among children with secondary AP, median PIM2ROM was 1.1% (IQR 0.8%–4.0%). A total of 711 children (42.0%) with secondary AP required MV for a median of 5.8 days (IQR 1.8–14.0). PICU LOS was a median of 4.43 days (IQR 1.84–11.22). There were 115 deaths in this group (mortality 6.8%). Median PIM2ROM, PICU LOS, mortality (all P < 0.001), and length of MV (P = 0.035) were significantly greater in children with secondary AP than with primary AP.

Conclusions:

Unlike in adult series, children with AP rarely die. Patients with secondary AP experience more morbidity and mortality than patients with primary AP.
When Doing Wrong Feels So Right: Normalization of Deviance
Authors: Price Mary R. , Williams Teresa C.
Published: March 2015

Normalization of deviance is a term first coined by sociologist Diane Vaughan when reviewing the Challenger disaster. Vaughan noted that the root cause of the Challenger disaster was related to the repeated choice of NASA officials to fly the space shuttle despite a dangerous design flaw with the O-rings. Vaughan describes this phenomenon as occurring when people within an organization become so insensitive to deviant practice that it no longer feels wrong. Insensitivity occurs insidiously and sometimes over years because disaster does not happen until other critical factors line up. In clinical practice, failing to do time outs before procedures, shutting off alarms, and breaches of infection control are deviances from evidence-based practice. As in other industries, health care workers do not make these choices intending to set into motion a cascade toward disaster and harm. Deviation occurs because of barriers to using the correct process or drivers such as time, cost, and peer pressure. As in other industries, operators will often adamantly defend their actions as necessary and justified. Although many other high-risk industries have embraced the normalization of deviance concept, it is relatively new to health care. It is urgent that we explore the impact of this concept on patient harm. We can borrow this concept from other industries and also the steps these other high-risk organizations have found to prevent it.
Medication Review and Patient Outcomes in an Orthopedic Department: A Randomized Controlled Study
Authors: Lisby Marianne , Bonnerup Dorthe Krogsgaard , Brock Birgitte , Gregersen Pernille Axelsen , Jensen Joern , Larsen Maren-Lis , Rungby Joergen , Sonne Jesper , Mainz Jan , Nielsen Lars Peter
Published: March 2015

Objective

We investigated the health-related effect of systematic medication review performed by a clinical pharmacist and a clinical pharmacologist on nonelective elderly orthopedic patients.

Methods

This is a nonblinded randomized controlled study of 108 patients 65 years or older treated with at least 4 drugs. For the intervention, the clinical pharmacist reviewed the participants' medication after completion of the usual medication routine. Information was collected from medical charts, interviews with participants, and database registrations of drug purchase. Results were conferred with the clinical pharmacologist, and recommendations were delivered directly to the ward physicians. The control was usual medication routine, that is, physicians prescribing admitting orders. The primary outcome was time to the first unplanned contact to a physician after discharge (i.e., general practitioner, emergency department visit, or readmission) during 3-month follow-up. Secondary outcomes included other health-related outcomes, for example, length of in-hospital stay, mortality, and quality of life.

Results

Time to the first unplanned contact to a physician was 14.9 days (95% confidence interval, 8.9–21.0) in the intervention group compared with 27.3 days (95% confidence interval, 18.9–35.7) in the controls (P= 0.05). Overall, no statistically significant differences were seen in the secondary outcomes apart from “number of” and “time to first” emergency department visits, which were in favor of the intervention group. A marked hesitation of the ward physicians to comply with recommendations was noted (18%).

Conclusions

The study showed that the patients receiving usual care had a significantly longer time to the first unplanned contact to a physician after discharge; however, the fact that less than 1 of 5 recommendations was adopted by the physicians raises concerns as to whether this finding could be attributable to the intervention.
Reducing Isozyme Competition Increases Target Fatty Acid Accumulation in Seed Triacylglycerols of Transgenic Arabidopsis
Authors: van Erp Harrie , Shockey Jay , Zhang Meng , Adhikari Neil D. , Browse John
Published: March 2015

One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on hydroxy fatty acids (HFAs) and conjugated polyenoic FAs (α-eleostearic acids [ESAs]) using Arabidopsis (Arabidopsis thaliana) as a model. These FAs are found naturally in seed oils of castor (Ricinus communis) and tung tree (Vernicia fordii), respectively, and used for the production of lubricants, nylon, and paints. Transgenic oils typically contain less target FA than that produced in the source species. We hypothesized that competition between endogenous and transgenic isozymes for substrates limits accumulation of unique FAs in Arabidopsis seeds. This hypothesis was tested by introducing a mutation in Arabidopsis diacylglycerol acyltransferase1 (AtDGAT1) in a line expressing castor FA hydroxylase and acyl-Coenzyme A:RcDGAT2 in its seeds. This led to a 17% increase in the proportion of HFA in seed oil. Expression of castor phospholipid:diacylglycerol acyltransferase 1A in this line increased the proportion of HFA by an additional 12%. To determine if our observations are more widely applicable, we investigated if isozyme competition influenced production of ESA. Expression of tung tree FA conjugase/desaturase in Arabidopsis produced approximately 7.5% ESA in seed lipids. Coexpression of VfDGAT2 increased ESA levels to approximately 11%. Overexpression of VfDGAT2 combined with suppression of AtDGAT1 increased ESA accumulation to 14% to 15%. Our results indicate that isozyme competition is a limiting factor in the engineering of unusual FAs in heterologous plant systems and that reduction of competition through mutation and RNA suppression may be a useful component of seed metabolic engineering strategies.
Understanding the traveling behavior of Muslims in the United States
Authors: Shakona Maloud , Backman Kenneth , Backman Sheila , Norman William , Luo Ye , Duffy Lauren
Published: March 2015

Purpose

– The purpose of this paper is to explore the influence of Islamic beliefs and practices on leisure and travel behavior of Muslims in Clemson, South Carolina. With the increase of Muslims in the USA, from both conversion and immigration, it is important to examine the effects of their religion on leisure and travel behavior.

Design/methodology/approach

– Using the grounded theory approach, semi-structured interviews with six Muslim men and six Muslim women of different nationalities were conducted in English in the local Mosque of Clemson, South Carolina, in the fall of 2011.

Findings

– The results provide some evidence that Islamic beliefs and behavioral practices influence leisure and travel behavior of Muslims in the USA. The study identifies seven major themes that play an important role in determining leisure and travel behavior of Muslims in Clemson. These are the importance of mosques, traveling with a Mohram, Hijab and a dress code for men and women, drinking alcohol and being in places where alcohol is served, eating pork, Holy Month of Ramadan and Dabiha.

Practical implications

– The study highlights the need for tourism marketers to pay more attention to the influence of religion on leisure and travel behavior of Muslim travelers.

Originality/value

– The study provides the tourism industry with a better understanding of the importance of religion influences on the special needs of Muslim travelers and shows how the industry can better accommodate these needs.