bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor
Authors: Bosbach Benedikt , Rossi Ferdinand , Yozgat Yasemin , Loo Jennifer , Zhang Jennifer Q. , Berrozpe Georgina , Warpinski Katherine , Ehlers Imke , Veach Darren , Kwok Andrew , Manova Katia , Antonescu Cristina R. , DeMatteo Ronald P. , Besmer Peter
Published: September 2017

Significance

Oncogenic receptor tyrosine kinases (RTKs) are important drug targets in the clinical setting. While RTK inhibitors have become important tools in the clinic, as has been demonstrated with chronic myelogenous leukemia and gastrointestinal stromal tumors (GIST), drug resistance invariably develops. The tools and rationale for the treatment of RTK drug resistance are limited, and success is of short duration. The identification of secondary intracellular drug targets is thus of critical importance. By using new Kit-GIST mouse models in which specific Kit signaling cascades are inhibited, we show the importance of PI3 kinase signaling in tumor development, as well as the utility of PI3 kinase inhibition in the treatment of primary and imatinib-resistant GIST. These studies provide a rationale for targeting dominant molecular pathways in tumors driven by oncogenic kinases.
Copper nanoparticle ensembles for selective electroreduction of CO
2
to C
2
–C
3
products
Authors: Kim Dohyung , Kley Christopher S. , Li Yifan , Yang Peidong
Published: September 2017

Significance

Electrochemical conversion of CO
2
to carbon-based products, which can be used directly as fuels or indirectly as fuel precursors, is suggested as one of the promising solutions for sustainability. Not only does this process allow using renewables such as solar electricity as energy input, but CO
2
emitted from the consumption process can be recycled back into fuels. The success of this technology depends on the value added to the product that forms from CO
2
, and therefore it is important to facilitate multicarbon product generation. This work presents a copper-based catalyst, formed in situ from an ensemble of nanoparticles, that is able to selectively generate C
2
–C
3
products at low overpotentials with good stability, where their efficient formation has been difficult to achieve.
Manipulation of ionized impurity scattering for achieving high thermoelectric performance in n-type Mg
3
Sb
2
-based materials
Authors: Mao Jun , Shuai Jing , Song Shaowei , Wu Yixuan , Dally Rebecca , Zhou Jiawei , Liu Zihang , Sun Jifeng , Zhang Qinyong , dela Cruz Clarina , Wilson Stephen , Pei Yanzhong , Singh David J. , Chen Gang , Chu Ching-Wu , Ren Zhifeng
Published: September 2017

Significance

Higher carrier mobility can contribute to a larger power factor, so it is important to identify effective means for achieving higher carrier mobility. Since carrier mobility is governed by the band structure and the carrier scattering mechanism, its possible enhancement could be obtained by manipulating either or both of these. Here, we report a substantial enhancement in carrier mobility by tuning the carrier scattering mechanism in n-type Mg
3
Sb
2
-based materials. The ionized impurity scattering in these materials has been shifted into mixed scattering by acoustic phonons and ionized impurities. Our results clearly demonstrate that the strategy of tuning the carrier scattering mechanism is quite effective for improving the mobility and should also be applicable to other material systems.
Soft tubular microfluidics for 2D and 3D applications
Authors: Xi Wang , Kong Fang , Yeo Joo Chuan , Yu Longteng , Sonam Surabhi , Dao Ming , Gong Xiaobo , Lim Chwee Teck
Published: September 2017

Significance

The current cleanroom-based soft lithography microfabrication process is complicated and expensive. There is a need for low-cost, ready-to-use, modular components that can be easily assembled into microfluidic devices by users lacking proficiency or access to microfabrication facilities. We present a facile, low-cost, and efficient method of fabricating soft, elastic microtubes with different cross-sectional shapes and dimensions. These microtubes can be used as basic building blocks for the rapid construction of various 2D and 3D microfluidic devices with complex geometries, topologies, and functions. This approach avoids the conventional cumbersome photolithography process and thus, provides a feasible way for scaling up the production of microfluidic devices.
MIF and D-DT are potential disease severity modifiers in male MS subjects
Authors: Benedek Gil , Meza-Romero Roberto , Jordan Kelley , Zhang Ying , Nguyen Ha , Kent Gail , Li Jia , Siu Edwin , Frazer Jenny , Piecychna Marta , Du Xin , Sreih Antoine , Leng Lin , Wiedrick Jack , Caillier Stacy J. , Offner Halina , Oksenberg Jorge R. , Yadav Vijayshree , Bourdette Dennis , Bucala Richard , Vandenbark Arthur A.
Published: September 2017

Significance

The biological processes that are involved in the progression of multiple sclerosis (MS) are far from complete. Macrophage migration inhibitory factor (MIF) and its homolog, D-dopachrome tautomerase (D-DT), are immunoregulatory cytokines known to be involved in the worsening of various autoimmune disorders. We demonstrate that genetically controlled high MIF expression (and D-DT) promotes MS progression in males, suggesting that these two factors are sex-specific disease modifiers. In addition, we show that MIF or D-DT deficiency ameliorates the disease severity of the murine model of MS. Our data suggest that targeting CD74, the common receptor for MIF and D-DT, with therapies such as partial MHC class II constructs could be therapeutically beneficial for inhibiting MS clinical progression in selected patients.
Hydrologic regulation of plant rooting depth
Authors: Fan Ying , Miguez-Macho Gonzalo , Jobbágy Esteban G. , Jackson Robert B. , Otero-Casal Carlos
Published: September 2017

Significance

Knowledge of plant rooting depth is critical to understanding plant-mediated global change. Earth system models are highly sensitive to this particular parameter with large consequences for modeled plant productivity, water–energy–carbon exchange between the land and the atmosphere, and silicate weathering regulating multimillion-year-timescale carbon cycle. However, we know little about how deep roots go and why. Accidental discoveries of >70-m-deep roots in wells and >20-m-deep roots in caves offer glimpses of the enormous plasticity of root response to its environment, but the drivers and the global significance of such deep roots are not clear. Through observations and modeling, we demonstrate that soil hydrology is a globally prevalent force driving landscape to global patterns of plant rooting depth.
Identification of sialic acid-binding function for the Middle East respiratory syndrome coronavirus spike glycoprotein
Authors: Li Wentao , Hulswit Ruben J. G. , Widjaja Ivy , Raj V. Stalin , McBride Ryan , Peng Wenjie , Widagdo W. , Tortorici M. Alejandra , van Dieren Brenda , Lang Yifei , van Lent Jan W. M. , Paulson James C. , de Haan Cornelis A. M. , de Groot Raoul J. , van Kuppeveld Frank J. M. , Haagmans Bart L. , Bosch Berend-Jan
Published: September 2017

Significance

Middle East respiratory syndrome coronavirus (MERS-CoV) recurrently infects humans from its dromedary camel reservoir, causing severe respiratory disease with an ∼35% fatality rate. The virus binds to the dipeptidyl peptidase 4 (DPP4) entry receptor on respiratory epithelial cells via its spike protein. We here report that the MERS-CoV spike protein selectively binds to sialic acid (Sia) and demonstrate that cell-surface sialoglycoconjugates can serve as an attachment factor. Our observations warrant further research into the role of Sia binding in the virus’s host and tissue tropism and transmission, which may be influenced by the observed Sia-binding fine specificity and by differences in sialoglycomes among host species.
Imaginative resistance as imagistic resistance
Authors: Tooming Uku
Published: September 2017

When we are invited to imagine an unacceptable moral proposition to be true in fiction, we feel resistance when we try to imagine it. Despite this, it is nonetheless possible to suppose that the proposition is true. In this paper, I argue that existing accounts of imaginative resistance are unable to explain why only attempts to imagine (rather than to suppose) the truth of moral propositions cause resistance. My suggestion is that imagination, unlike supposition, involves mental imagery and imaginative resistance arises when imagery that one has formed does not match unacceptable propositions.
Controlled preparation of M(Ag, Au)/TiO2 through sulfydryl-assisted method for enhanced photocatalysis
Authors: Xia Hongbo , Wu Suli , Bi Jiajie , Zhang Shufen
Published: September 2017

Here a simple and effective method was explored to fabricate M/TiO2 (M = Ag, Au) composites, which required neither pre-treatment of TiO2 nor any additives as reducing agent. Using amorphous TiO2 spheres functionalized with SH groups as starting materials, the noble metallic ions (Ag, Au) can be adsorbed by TiO2 due to their special affinity with SH groups, which is beneficial to the uniform dispersion of metallic ions on the surface of TiO2. Then the adsorbed ions were reduced to form noble metal nanoparticles by heating process (95 °C) directly without additive as reduction agent. Meanwhile, the amorphous TiO2 was transformed into anatase phase during the heating process. Thus, the transformation of TiO2 along with the reduction of noble metallic ions (Ag, Au) was simultaneously carried out by heating. The XRD patterns proved the formation of anatase TiO2 after heating. The characterizations of XPS and TEM proved the formation of Ag and Au nanoparticles on the surface of TiO2. The element mapping indicated that Ag nanoparticles are dispersed uniformly on the surface of TiO2. The photocatalytic activity of the composites has been investigated by the degradation of methyl orange under visible light irradiation. The results showed that when Ag/TiO2 (2.8 wt%) was used as photocatalyst, about 98% of the MO molecules were degraded in 70 min.
Smoke pollution disrupted biodiversity during the 2015 El Niño fires in Southeast Asia
Authors: Lee Benjamin P Y-H , Davies Zoe G , Struebig Matthew J
Published: September 2017

Forest and peatland fires during the 2015 El Niño drought were amongst the worst on record in Southeast Asia. They were a major contributor of carbon emissions across the region, with the associated smoke-induced haze causing an air pollution crisis that affected millions of people. We present evidence of air pollution impacts on biodiversity. Using daily acoustic recordings in central Singapore, we monitored the dawn chorus before, during and after the haze event. We demonstrate that levels of ecological community acoustic activity dropped dramatically during the haze, and that this decline was significantly associated with levels of air pollution considered ‘unhealthy’ to the human population. Acoustic disruption was apparent across four common indices of soundscape activity, with only a partial recovery to pre-haze levels observed 16 weeks after the smoke had dissipated. These impacts on ecological communities were likely to be even more severe closer to the fires, where air pollution levels were reported to be 15-fold greater than those recorded in Singapore. Our results indicate that large-scale air pollution crises may have hitherto underestimated and potentially far-reaching impacts on biodiversity, especially in parts of the world prone to extensive forest fires.
MPAs in ABNJ: lessons from two high seas regimes
Authors: Smith Danielle , Jabour Julia
Published: September 2017

Establishing a network of marine-protected areas (MPAs) in areas beyond national jurisdiction (ABNJ) is viewed as an important measure to protect marine biodiversity. To date 12 MPAs have been established: two in the Southern Ocean and 10 in the North-East Atlantic region, and more are proposed. The Southern Ocean MPAs were adopted by Members of the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) in a complex, slow and challenging process. The North-East Atlantic MPAs were established under the OSPAR Convention and although the MPA network was established swiftly, doubts remain about whether it was a successful institutional development for the protection of marine biodiversity or just a network of ‘paper parks’. This article analyses the planning and negotiation processes that took place in establishing the 12 current MPAs to identify lessons useful for establishing MPAs in ABNJ in the future.
Pulsar spin-down: the glitch-dominated rotation of PSR J0537−6910
Authors: Antonopoulou D. , Espinoza C. M. , Kuiper L. , Andersson N.
Published: September 2017

The young, fast-spinning X-ray pulsar J0537−6910 displays an extreme glitch activity, with large spin-ups interrupting its decelerating rotation every ∼100 d. We present nearly 13 yr of timing data from this pulsar, obtained with the Rossi X-ray Timing Explorer. We discovered 22 new glitches and performed a consistent analysis of all 45 glitches detected in the complete data span. Our results corroborate the previously reported strong correlation between glitch spin-up size and the time to the next glitch, a relation that has not been observed so far in any other pulsar. The spin evolution is dominated by the glitches, which occur at a rate of ∼3.5 per year, and the post-glitch recoveries, which prevail the entire interglitch intervals. This distinctive behaviour provides invaluable insights into the physics of glitches. The observations can be explained with a multicomponent model that accounts for the dynamics of the neutron superfluid present in the crust and core of neutron stars. We place limits on the moment of inertia of the component responsible for the spin-up and, ignoring differential rotation, the velocity difference it can sustain with the crust. Contrary to its rapid decrease between glitches, the spin-down rate increased over the 13 yr, and we find the long-term braking index nl = −1.22(4), the only negative braking index seen in a young pulsar. We briefly discuss the plausible interpretations of this result, which is in stark contrast to the predictions of standard models of pulsar spin-down.
When Listening Is Better Than Reading: Performance Gains on Cardiac Auscultation Test Questions
Authors: Short Kathleen , Bucak S. Deniz , Rosenthal Francine , Raymond Mark R.
Published: September 2017

Purpose

In 2007, the United States Medical Licensing Examination embedded multimedia simulations of heart sounds into multiple-choice questions. This study investigated changes in item difficulty as determined by examinee performance over time. The data reflect outcomes obtained following initial use of multimedia items from 2007 through 2012, after which an interface change occurred.

Method

A total of 233,157 examinees responded to 1,306 cardiology test items over the six-year period; 138 items included multimedia simulations of heart sounds, while 1,168 text-based items without multimedia served as controls. The authors compared changes in difficulty of multimedia items over time with changes in difficulty of text-based cardiology items over time. Further, they compared changes in item difficulty for both groups of items between graduates of Liaison Committee on Medical Education (LCME)-accredited and non-LCME-accredited (i.e., international) medical schools.

Results

Examinee performance on cardiology test items with multimedia heart sounds improved by 12.4% over the six-year period, while performance on text-based cardiology items improved by approximately 1.4%. These results were similar for graduates of LCME-accredited and non-LCME-accredited medical schools.

Conclusions

Examinees’ ability to interpret auscultation findings in test items that include multimedia presentations increased from 2007 to 2012.
Medical Education and Health Care Delivery: A Call to Better Align Goals and Purposes
Authors: Sklar David P. , Hemmer Paul A. , Durning Steven J.
Published: September 2017

The transformation of the U.S. health care system is under way, driven by the needs of an aging population, rising health care spending, and the availability of health information. However, the speed and effectiveness of the transformation of health care delivery will depend, in large part, upon engagement of the health professions community and changes in clinicians’ practice behaviors. Current efforts to influence practice behaviors emphasize changes in the health payment system with incentives to move from fee-for-service to alternative payment models.

The authors describe the potential of medical education to augment payment incentives to make changes in clinical practice and the importance of aligning the purpose and goals of medical education with those of the health care delivery system. The authors discuss how curricular and assessment changes and faculty development can align medical education with the transformative trends in the health care delivery system. They also explain how the theory of situated cognition offers a shared conceptual framework that could help address the misalignment of education and clinical care. They provide examples of how quality improvement, health care innovation, population care management, and payment alignment could create bridges for joining health care delivery and medical education to meet the health care reform goals of a high-performing health care delivery system while controlling health care spending. Finally, the authors illustrate how current payment incentives such as bundled payments, value-based purchasing, and population-based payments can work synergistically with medical education to provide high-value care.
Reproducibility of Bruch Membrane Opening-Minimum Rim Width Measurements With Spectral Domain Optical Coherence Tomography
Authors: Park Keunheung , Kim Jinmi , Lee Jiwoong
Published: September 2017

Purpose:

To evaluate the reproducibility of Bruch membrane opening-minimum rim width (BMO-MRW) measurements obtained with Spectralis optical coherence tomography (OCT) in normal and glaucoma subjects.

Materials and Methods:

In total, 123 eyes from 123 subjects (65 healthy, 58 glaucoma subjects) were included. BMO-MRW measurements were repeated 3 times during the same visit using Spectralis OCT. The BMO points and internal limiting membrane were identified with automated software and corrected manually when necessary. The intravisit repeatability, coefficient of variation (CV), and intraclass correlation coefficient were analyzed for each sector and global BMO-MRW. The Spearman rank correlation coefficient was used to estimate correlations between CV and multiple variables. Multiple linear regression analysis was used to identify significant associations.

Results:

The intravisit repeatability ranged from 2.97 μm (global) to 10.25 μm (inferotemporal sector) in healthy subjects and from 3.31 μm (global) to 12.09 μm (inferonasal sector) in glaucoma subjects. The CVs ranged from 1.17% (global) to 3.56% (inferotemporal sector) in healthy subjects and from 2.57% (global) to 6.46% (superotemporal and inferotemporal sector) in glaucoma subjects. Intraclass correlation coefficients ranged from 0.974 (superotemporal sector) to 0.997 (nasal sector) in normal subjects and from 0.988 (temporal sector) to 0.997 (global and nasal sector) in glaucoma subjects. Multiple regression analysis showed that the CV in global BMO-MRW measurements was inversely associated with global BMO-MRW and visual field mean deviation (P=0.001 and 0.002, respectively).

Conclusions:

The Spectralis SD-OCT showed excellent reproducibility in BMO-MRW measurements in both normal and glaucoma subjects. The measurements variability was worse in more advanced glaucoma.
Reproducibility and Agreement of Anterior Segment Parameter Measurements Obtained Using the CASIA2 and Spectralis OCT2 Optical Coherence Tomography Devices
Authors: Xu Benjamin Y. , Mai Derek D. , Penteado Rafaella C. , Saunders Luke , Weinreb Robert N.
Published: September 2017

Purpose:

To assess the reproducibility and agreement of measurement values obtained from the Tomey CASIA2 and Heidelberg Spectralis OCT2 anterior segment optical coherence tomographic devices.

Methods:

Twenty eyes from 10 subjects ranging from age 28 to 45 years with no history of eye conditions or intraocular surgery were included. Two scans were obtained with each device in a standardized dark room environment after a period of dark adaptation. One anterior segment optical coherence tomography image along the horizontal (temporal nasal) meridian was analyzed per eye and per scan. Lens vault, pupil diameter, anterior chamber width, angle opening distance, trabecular iris space area, and scleral spur angle were measured using manufacturer-provided image analysis programs. Intraclass correlation coefficient (ICC) values, coefficients of variation, and Bland-Altman plots were computed to assess the intradevice correlation and interdevice agreement of measurement values.

Results:

There was excellent intradevice reproducibility of measurement values for both the CASIA (ICC range, 0.86 to 0.99) and Spectralis (ICC range, 0.79 to 1.00). There was also excellent interdevice correlation of measurement values (ICC range, 0.78 to 0.93) for all parameters except anterior chamber width (ICC 0.20). Linear regression models and Bland-Altman plots showed that this relationship was strongest when measurement values were small.

Conclusions:

There is excellent intradevice reproducibility and good interdevice agreement of anterior segment parameter measurement values for the CASIA2 and Spectralis OCT2. However, the measurements obtained with each device should not be considered interchangeable.
Acquired Intermittent Pediatric Horner Syndrome due to Neuroblastoma
Authors: Cohen Liza M. , Elliott Alexandra , Freitag Suzanne K.
Published: September 2017

A 3-month-old male developed intermittent left upper eyelid ptosis at the age of 1 month that was gradually increasing in frequency and duration. Examination revealed anisocoria and left upper and lower eyelid ptosis, consistent with a left Horner syndrome. Imaging showed a mass in the left superior posterior mediastinum, which was resected, and pathology was consistent with neuroblastoma. Eight months thereafter, the patient underwent left upper eyelid ptosis repair. Cases of infantile acquired Horner syndrome due to neuroblastoma are rare. To the authors’ knowledge, there has only been one case described that presented with intermittent symptoms. The authors report the second case of intermittent acquired Horner syndrome due to neuroblastoma. This case demonstrates the importance of recognizing that Horner syndrome may present with subtle and intermittent symptoms. In a pediatric patient, one should maintain suspicion for neuroblastoma.
What Matters Most to Whom:
Authors: Collins Rebecca L. , Haas Ann , Haviland Amelia M. , Elliott Marc N.
Published: September 2017

Background:

Some aspects of patient experience are more strongly related to overall ratings of care than others, reflecting their importance to patients. However, little is known about whether the importance of different aspects of this experience differs across subgroups.

Objectives:

To determine whether the aspects of health care most important to patients differ according to patient race, ethnicity, and language preference.

Research Design:

In response to the 2013 Medicare Consumer Assessment of Health Plans Study (CAHPS) survey, patients rated their overall health care and completed items measuring five patient experience domains. We estimated a linear regression model to assess associations between overall rating of care and the 5 domains, testing for differences in these relationships for race/ethnicity/language groups, controlling for covariates.

Subjects:

In total 242,782 Medicare beneficiaries, age 65 years or older.

Measures:

Overall rating of health care, composite patient experience scores for: doctor communication, getting needed care, getting care quickly, customer service, and care coordination.

Results:

A joint test of the interactions between the composite scores and the 5 largest racial/ethnic/language subgroups was statistically significant (P <0.0001), suggesting the importance of domains varied across subgroups. Doctor communication had the strongest relationship with care ratings for non-Hispanic whites and English-preferring Hispanics. Getting needed care had the strongest relationship for Spanish-preferring Hispanics and Asian/Pacific Islanders. Doctor communication and getting care quickly were strongest for African Americans.

Conclusions:

Tailoring quality improvement programs to the factors most important to the racial, ethnic, and language mix of the patient population of the practice, hospital, or plan may more efficiently reduce disparities and improve quality.
Trends in Opioid-related Inpatient Stays Shifted After the US Transitioned to ICD-10-CM Diagnosis Coding in 2015
Authors: Heslin Kevin C. , Owens Pamela L. , Karaca Zeynal , Barrett Marguerite L. , Moore Brian J. , Elixhauser Anne
Published: September 2017

Background:

Trend analyses of opioid-related inpatient stays depend on the availability of comparable data over time. In October 2015, the US transitioned diagnosis coding from International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to ICD-10-CM, increasing from ∼14,000 to 68,000 codes. This study examines how trend analyses of inpatient stays involving opioid diagnoses were affected by the transition to ICD-10-CM.

Subjects:

Data are from Healthcare Cost and Utilization Project State Inpatient Databases for 14 states in 2015−2016, representing 26% of acute care inpatient discharges in the US.

Study Design:

We examined changes in the number of opioid-related stays before, during, and after the transition to ICD-10-CM using quarterly ICD-9-CM data from 2015 and quarterly ICD-10-CM data from the fourth quarter of 2015 and the first 3 quarters of 2016.

Results:

Overall, stays involving any opioid-related diagnosis increased by 14.1% during the ICD transition—which was preceded by a much lower 5.0% average quarterly increase before the transition and followed by a 3.5% average increase after the transition. In stratified analysis, stays involving adverse effects of opioids in therapeutic use showed the largest increase (63.2%) during the transition, whereas stays involving abuse and poisoning diagnoses decreased by 21.1% and 12.4%, respectively.

Conclusions:

The sharp increase in opioid-related stays overall during the transition to ICD-10-CM may indicate that the new classification system is capturing stays that were missed by ICD-9-CM data. Estimates of stays involving other diagnoses may also be affected, and analysts should assess potential discontinuities in trends across the ICD transition.
A Survey of Glucocorticoid Adverse Effects and Benefits in Rheumatic Diseases
Authors: Black Rachel J. , Goodman Susan M. , Ruediger Carlee , Lester Susan , Mackie Sarah L. , Hill Catherine L.
Published: September 2017

Objective

The aim of this study was to explore, from the patient's perspective, the beneficial and adverse effects (AEs) of glucocorticoids (GCs) in patients with rheumatic diseases, to be used in the development of a patient-reported outcome measure.

Methods

A cross-sectional survey, capturing benefits and AEs of GC use, was administered to 2 groups of patients: (1) those attending a tertiary rheumatology clinic with various rheumatic diseases who had used GCs within the past year and (2) patients from the Hospital for Special Surgery rheumatoid arthritis database.

Results

Cohort 1 had 55 GC users, and cohort 2 had 95 GC users and 29 nonusers. The majority of GC users in both cohorts reported at least 1 AE (100%, 86%). The AE prevalence per person was 50% higher in cohort 1 compared with GC users in cohort 2 (7.7 vs. 5.3; AE ratio, 1.5; 95% confidence interval, 1.3–1.7) and 2-fold greater in cohort 2 GC users compared with GC nonusers (5.3 vs. 2.6; AE ratio, 2.0; 95% confidence interval, 1.6–2.6). In both cohorts, AEs identified as “worst” by GC users included skin thinning/easy bruising, sleep disturbance, mood disturbance, and change in facial shape. Most felt GCs helped their disease “a lot” (78%/62%) and that the benefits were greater than the AEs (55%/64%). Many AEs were more frequent in GC users than in nonusers.

Conclusions

Patients receiving GC therapy for rheumatic conditions report a large number of AEs and those that have the greatest life impact are often difficult for physicians to measure. These results will inform the development of a patient-reported outcome measure to capture the effects of GCs from the patient's perspective.
Acceptability and Practicality of the Turkish Translation of Pediatric Gait Arm Legs and Spine in Turkish Children
Authors: Batu Ezgi Deniz , Keniş Coşkun Özge , Sönmez Hafize Emine , Karali Duygu , Arslanoğlu Aydin Elif , Bilginer Yelda , Karadağ Saygi Evrim , Özen Seza
Published: September 2017

Background

The pediatric Gait, Arms, Leg, and Spine (pGALS) is a practical questionnaire for musculoskeletal (MSK) system evaluation in school-age children.

Objective

The aim of this study was to evaluate the acceptability/practicality of pGALS Turkish translation in Turkey (cross-sectional study).

Methods

The Turkish translation of pGALS was administered to children (4–18 years) who attended to the Pediatric Emergency Department of Hacettepe University, Ankara, Turkey, and the outpatient clinic of the Physical Therapy and Rehabilitation Department of Marmara University, Istanbul, Turkey, during 1 month in 2016. The demographics, complaints, final diagnoses, and pGALS parameters were noted. The acceptability of pGALS was evaluated using visual analog scale.

Results

Ninety-five patients (median age, 108 months; male/female, 1.1) were enrolled. Sixteen patients (16.8%) had MSK diagnosis, whereas 79 (83.2%) had non-MSK diagnoses. Musculoskeletal diagnoses were as follows: scoliosis (n = 4), metatarsus adductus (n = 4), soft tissue injury (n = 3), lumber disk herniation (n = 2), muscle spasm (n = 1), Achilles tendinitis (n = 1), and tibia torsion (n = 1). The sensitivity was 64.7%, and specificity was 89.7% for positive response to 1 or more pGALS screening questions to detect abnormal pGALS. The most sensitive question was pain question. The most common abnormal pGALS components were spine and posture. The sensitivity and specificity of pGALS for detecting MSK diagnosis were 93.7% and 97.4%, respectively. The median duration of pGALS examination was 4 minutes. Most patients/parents found the duration acceptable (94.7%/97.9%, respectively) and reported that pGALS caused little/no discomfort (97.9%/96.8%, respectively).

Conclusion

This is the first study showing the Turkish version of pGALS as a valid, acceptable, and practical screening test in Turkey.
Peripheral Bacterial Septic Arthritis
Authors: Hassan Ahmed S. , Rao Allison , Manadan Augustine M. , Block Joel A.
Published: September 2017

Septic arthritis refers to an infection in a joint due to a bacterial, mycobacterial, or fungal cause. Joint infections are a serious cause of morbidity and mortality and constitute a true musculoskeletal emergency. The estimated incidence of septic arthritis in the general population is between 2 and 6 cases per 100,000 people per year. The most common presentation is an acute monoarthritis. Identification of organisms in the synovial fluid is the criterion standard for diagnosis. Synovial fluid aspiration should be performed prior to initiating antibiotics. While no diagnostic cutoff exists for synovial fluid white blood cell count, increasing leukocytosis is associated with a higher likelihood of an infectious cause of arthritis, and patients commonly present with values greater than 50,000/μL. The cornerstones of treating septic bacterial arthritis are adequate drainage and antimicrobials. Joint drainage is always recommended in septic arthritis; however, no clear guidelines or strong evidence exist to guide the preferred method of drainage. Options for joint drainage include daily needle aspiration, arthroscopy, or open surgical drainage via arthrotomy.
Peripheral Muscle Near-Infrared Spectroscopy Variables are Altered Early in Septic Shock
Authors: Orbegozo Diego , Su Fuhong , Xie Keliang , Rahmania Lokmane , Taccone Fabio Silvio , De Backer Daniel , Vincent Jean-Louis , Creteur Jacques
Published: September 2017

Background:

Noninvasive evaluation of muscle perfusion using near-infrared spectroscopy (NIRS) coupled with a vascular occlusion test (VOT) may provide an early and simple marker of altered perfusion and microcirculatory function in sepsis.

Objective:

The aim of the study was to compare the time-course of NIRS-derived variables with systemic measures of perfusion in an experimental model of peritonitis.

Methods:

Peritonitis was induced in eight anesthetized, mechanically ventilated, adult sheep (24–34 kg), by injecting autologous feces into the peritoneal cavity. Animals were followed until death or for a maximum of 30 h. Muscle tissue oxygen saturation (StO2) was determined using NIRS on the right posterior leg and arterial VOTs were performed by intermittent intra-aortic balloon inflation. Microdialysis was used to measure muscle lactate and pyruvate levels.

Results:

Muscle StO2 was significantly lower than baseline values from 8 h after sepsis induction, but with considerable intersubject variability. The NIRS VOT ascending (Asc) slope decreased to values <120%/min in most animals from 12 h after sepsis induction. Muscle lactate/pyruvate ratios were higher than baseline from 16 h after sepsis induction. Mixed venous oxygen saturation (SvO2) decreased to <70% and blood lactate levels increased to >2 mmol/L in most of the animals only 24 and 28 h after sepsis induction, respectively. Muscle NIRS StO2 correlated strongly with femoral venous oxygen saturation (r = 0.820) and moderately with SvO2 (r = 0.436).

Conclusions:

The muscle NIRS Asc slope after a VOT is altered earlier than global markers of tissue hypoperfusion during sepsis. This simple noninvasive test can detect early changes in peripheral perfusion in sepsis.
An ‘invisible’ ubiquitin conformation is required for efficient phosphorylation by PINK1
Authors: Gladkova Christina , Schubert Alexander F. , Wagstaff Jane L. , Pruneda Jonathan N. , Freund Stefan M.V. , Komander David
Published: September 2017

The Ser/Thr protein kinase PINK1 phosphorylates the well-folded, globular protein ubiquitin (Ub) at a relatively protected site, Ser65. We had previously shown that Ser65-phosphorylation results in a conformational change, in which Ub adopts a dynamic equilibrium between the known, common Ub conformation and a distinct, second conformation in which the last β-strand is retracted to extend the Ser65 loop and shorten the C-terminal tail. We here show using Chemical Exchange Saturation Transfer (CEST) NMR experiments, that a similar, C-terminally retracted (Ub-CR) conformation exists in wild-type Ub. Ub point mutations in the moving β5-strand and in neighbouring strands shift the Ub/Ub-CR equilibrium. This enabled functional studies of the two states, and we show that the Ub-CR conformation binds to the PINK1 kinase domain through its extended Ser65 loop and is a superior PINK1 substrate. Together our data suggest that PINK1 utilises a lowly populated yet more suitable Ub-CR conformation of Ub for efficient phosphorylation. Our findings could be relevant for many kinases that phosphorylate residues in folded proteins or domains.
The ERA-related GTPase AtERG2 associated with mitochondria 18S RNA is essential for early embryo development inArabidopsis
Authors: Cheng Pengyu , Li Hongjuan , Yuan Linlin , Li Huiyong , Xi Lele , Zhang Junjie , Liu Jin , Wang Yingdian , Zhao Heping , Zhao Huixin , Han Shengcheng
Published: September 2017

The ERA (E. coliRAS-like protein)-related GTPase (ERG) is a nuclear-encoded GTPase with two conserved domains: a GTPase domain and a K Homology domain. ERG plays a vital role in early seed development inAntirrhinum majus. However, the mechanism that regulates seed development remains unclear. Blasting the genome sequence revealed two homologies of ERG, AtERG1, and AtERG2 inArabidopsis. In this study, we found that AtERG2 is localised in the mitochondria and binds mitochondrial 18S RNA. Promoter and transcript analyses indicated thatAtERG2was mainly expressed in the leaf vein, trichome, mature pollen, and ovule. The mutants ofAtERG2showed recessive lethal, gametophytic maternal effects, silique shortage, and early seed abortion, in which some seeds arrested in the zygotic stage at 1.5 days after pollination (DAP) and aborted at 2.0 DAP inaterg2-1+/-. Reactive oxygen species (ROS) accumulated at 1.5 DAP in the arrested seeds, and the transcription of several ROS-responsible genes,WRKY40,ANAC017, andAOXla, was up-regulated in theaterg2-1+/- seeds which were arrested 1.5 and 2.0 DAP but not in wild-type (WT) andaterg2-1+/- seeds. The cell death-related gene BAG6 was also transcriptionally activated inaterg2-1+/- seeds arrested at 2.0 DAP. Chloramphenicol treatment during pollination induced a similar phenotype and gene expression pattern but showed no transcriptional changes of ANAC017 in WT. These results suggested thatAtERG2promotes early seed development by affecting the maturation of the mitochondria ribosome small subunit and mitochondrial protein translation inArabidopsis.
Communication between DNA and nucleotide binding sites facilitates stepping by the RecBCD helicase
Authors: Gaydar Vera , Zananiri Rani , Dvir Or , Kaplan Ariel , Henn Arnon
Published: September 2017

Double-strand DNA breaks are the severest type of genomic damage, requiring rapid response to ensure survival. RecBCD helicase in prokaryotes initiates processive and rapid DNA unzipping essential for break repair. Yet, the energetics of RecBCD during translocation along the DNA track needs to be quantitatively clarified. Specifically, it’s essential to understand how RecBCD switches between its binding states to enable its translocation. Here we determine, by systematic affinity measurements, the degree of coupling between DNA and nucleotide binding to RecBCD. We show that, in the presence of ADP, RecBCD binds weakly to DNA that harbors a double overhang mimicking an unwinding intermediate. Consistently, RecBCD binds weakly to ADP in the presence of the same DNA. We did not observe coupling between DNA and nucleotide binding for DNA molecules having only a single overhang, suggesting that RecBCD subunits must both bind DNA to “sense” the nucleotide state. Excitingly, we observed weak coupling for AMPpNp as RecBCD remains strongly bound to DNA in its presence. Detailed thermodynamic analysis of RecBCD reaction mechanism suggests an ‘energetic compensation’ between RecB and RecD, which may be essential for rapid unwinding. Our findings provide the basis for a ‘stepping mechanism’ during the processive translocation of RecBCD.
Coalescent theory of migration network motifs
Authors: Alcala Nicolas , Goldberg Amy , Ramakrishnan Uma , Rosenberg Noah A.
Published: September 2017

Natural populations display a variety of spatial arrangements, each potentially with a distinctive impact on genetic diversity and genetic differentiation among subpopulations. Although the spatial arrangement of populations can lead to intricate migration networks, theoretical developments have focused mainly on a small subset of such networks, emphasizing the island-migration and stepping-stone models. In this study, we investigate all small network motifs: the set of all possible migration networks among populations subdivided into at most four subpopulations. For each motif, we use coalescent theory to derive expectations for three quantities that describe genetic variation: nucleotide diversity,FST, and half-time to equilibrium diversity. We describe the impact of network properties on these quantities, finding that motifs with a large mean node degree have the largest nucleotide diversity and the longest time to equilibrium, whereas motifs with small density have the largestFST. In addition, we show that the motifs whose pattern of variation is most strongly influenced by loss of a connection or a subpopulation are those that can be split easily into several disconnected components. We illustrate our results using two example datasets—sky island birds of genusBrachypteryxand Indian tigers—identifying disturbance scenarios that produce the greatest reduction in genetic diversity; for tigers, we also compare the benefits of two assisted gene flow scenarios. Our results have consequences for understanding the effect of geography on genetic diversity and for designing strategies to alter population migration networks to maximize genetic variation in the context of conservation of endangered species.
4-Aminobenzoic acid 4-methylpyridine/4-methylpyridinium 4-aminobenzoate 0.58/0.42: a redetermination from the original data
Authors: Fábry Jan
Published: September 2017

The title structure, 4-aminobenzoic acid 4-methylpyridine/4-methylpyridinium 4-aminobenzoate 0.58/0.42, 0.58(C6H7N·C7H7NO2)·0.42(C6H8N+·C7H6NO2−), has been redetermined from the data published by Kumaret al.(2015).Acta Cryst.E71, o125-o126. The improvement of the present redetermination consists in the introduction of disorder of the methyl group over two positions as well as in the correction of the positional parameters of the hydrogen atoms that are involved in the O—H...N or N—H...O hydrogen bonds. After the correction, the hydroxyl hydrogen atom turned out to be disordered over two positions about the centre of the O...N bond, which is relatively long [2.642 (2) Å], while the H atoms of the primary amine group account more realistically for the hydrogen-bond pattern after the removal of the positional constraints. All the O—H...N or N—H...O hydrogen bonds which are present in the title structure are of moderate strength.
Agroecology accounting: biodiversity and sustainable livelihoods from the margins
Authors: Lanka Sanjay V. , Khadaroo Iqbal , Böhm Steffen
Published: September 2017

Purpose

The purpose of this paper is to provide a socio-ecological counter account of the role that agroecology plays in supporting the sustainable livelihoods of a co-operative of smallholder coffee farmers, where very little value is created at their end of the coffee commodity chain. Agroecology may be defined as the science that provides the ecological principles and concepts for the design and management of productive agricultural ecosystems that conserve natural resources.

Design/methodology/approach

This study uses a case study design of a coffee-producing co-operative in India using data collected from participant observation, focus groups and unstructured interviews with indigenous smallholder farmers. It combines the science of agroecology with the labour theory of value as a theoretical framework.

Findings

An agroecological approach supports agricultural biodiversity, while promoting sustainable livelihoods since members of the co-operative are able to reduce their use of external inputs. However, an agroecological transformation is curtailed by the continued dependence on corporate value chains. A framework using the labour theory of value is used to explain the extraction of surplus value from the labour of both the smallholder farmers as well as nature. This study provides evidence of the role of government policy and practice in perpetuating the status quo by not promoting either research on agroecology or direct consumer to producer value chains while providing subsidies for the inputs of industrial agriculture.

Originality/value

There have been very few studies that have provided an account of the limited value generated in agricultural commodity chains for smallholder farmers due to the need to purchase the inputs of industrial agriculture supported by government subsidies. This study extends the field of accounting for biodiversity into agriculture using the science of agroecology to explain the role played by biodiversity in increasing the amount of value generated by smallholder farmers. By utilising the labour theory of value, the authors have introduced the notion of the labour power of nature as represented by the environmental services that nature provides.
What can auditors tell us about accounting manipulations?
Authors: Aljinovic Barac Zeljana , Vuko Tina , Šodan Slavko
Published: September 2017

Purpose

This paper aims to examine the frequency and the nature of International Financial Reporting Standards/International Accounting Standards (IFRS/IAS) violations that resulted in modified audit opinions (MAOs); determinants of MAO decision; and underlying motives, targets and techniques of accounting manipulations.

Design/methodology/approach

Descriptive statistics and in-depth investigation on archival data collected from the published audit reports are used to analyse the frequency and the nature of IFRS violations that resulted in MAOs, while the logistic regression is applied to identify the possible determinants of MAO decisions. A survey instrument is used to identify the relative importance of different manipulation motives, targets and techniques from the perspective of an external auditor.

Findings

Results from the archival research show that MAOs are expressed in 29% of audit reports of listed companies in Croatia. A majority of the qualifications refer to noncompliance with provisions of IAS 39, IAS 16, IAS 1, IAS 2 and IAS 36. The survey results show that manipulations are principally oriented towards creditors, tax authorities and suppliers with the intention to hide bad performance, get better terms of crediting and minimize fiscal and political costs. Results from the field study complement and confirm the archival research results in respect to the accounting areas and techniques used for manipulation purposes.

Originality/value

The analysis provides a rather robust estimation of the extent of accounting manipulations, compared to commonly used earnings management metrics. Application of multi-method research that integrates archival research and field study offers significant contribution to the existing earnings management literature in methodological approach. The results directly address particular provisions of the IFRS that are frequently violated and provide better understanding of the features of accounting manipulations in a specific institutional setting.