bluuebunny/crossref_metadata_2025 huggingface dataset:
Visible-Light-Mediated Synthesis of Pyrazines from Vinyl Azides Utilizing a Photocascade Process
Authors: Hossain Asik , Pagire Santosh , Reiser Oliver
Published: August 2017

A convenient method for the synthesis of substituted pyrazines from vinyl azides has been developed. This method is enabled by a dual-energy and electron-transfer strategy by visible-light photocatalysis. Initially, vinyl azides are activated by a triplet sensitization process from an excited ruthenium photocatalyst in the presence of water to form dihydropyrazines, followed by a single-electron-transfer (SET) process under oxygen (air) atmosphere that leads to the tetrasubstituted pyrazines in good to excellent yields.
Amputation und Prothesenversorgung – die untere Extremität
Authors: Ramczykowski Tim , Schildhauer Thomas
Published: August 2017

Auch durch die Fortschritte der heutigen Medizin ist es nicht immer möglich, eine Amputation zu verhindern. Die wesentliche und schwierigste Aufgabe in der Amputationschirurgie ist es, die richtige Indikation zu stellen und für jeden Patienten individuell zu entscheiden. Die anschließende Prothesenversorgung bleibt eine Herausforderung, um den steigenden Ansprüchen des Betroffenen standzuhalten.
An all-carbon vdW heterojunction composed of penta-graphene and graphene: Tuning the Schottky barrier by electrostatic gating or nitrogen doping
Authors: Guo Yaguang , Wang Fancy Qian , Wang Qian
Published: August 2017

The non-zero band gap together with other unique properties endows penta-graphene with potential for device applications. Here, we study the performance of penta-graphene as the channel material contacting with graphene to form a van der Waals heterostructure. Based on first-principles calculations, we show that the intrinsic properties of penta-graphene are preserved in the heterojunction, which is different from the conventional contact with metal surfaces. The stacked system forms an n-type Schottky barrier (Φe) at the vertical interface, while a negative band bending occurs at the lateral interface in a current-in-plane model. From the device point of view, we further demonstrate that a low-Φe or an Ohmic contact can be realized by applying an external electric field or doping graphene with nitrogen atoms. This allows the control of the Schottky barrier height, which is essential in fabricating penta-graphene-based nanotransistors.
Facile synthesis and electron transport properties of NiO nanostructures investigated by scanning tunneling microscopy
Authors: Mallick Govind , Labh Jyotsna , Giri Lily , Pandey Avinash C. , Karna Shashi P.
Published: August 2017

Due to their unique chemical, thermal, electronic and photonic properties, low -dimensional transition metal oxides, especially NiO, have attracted great deal of attention for potential applications in a wide range of technologies, such as, sensors, electrochromic coatings and self-healing materials. However, their synthesis involves multi-step complex procedures that in addition to being expensive, further introduce impurities. Here we present a low cost facile approach to synthesize uniform size NiO nanoparticles (NPs) from hydrothermally grown Ni(OH)2. Detailed transmission electron microscopic analysis reveal the average size of NiO NPs to be around 29 nm. The dimension of NiO NP is also corroborated by the small area scanning tunneling microscope (STM) measurements. Further, we investigate electron transport characteristics of newly synthesized Ni(OH)2 and NiO nanoparticles on p-type Si substrate using scanning tunneling microscopy. The conductivity of Ni(OH)2 and NiO are determined to be 1.46x10-3 S/cm and 2.37x10-5 S/cm, respectively. The NiO NPs exhibit a lower voltage window (∼0.7 V) electron tunneling than the parent Ni(OH)2.
Normal stress differences from Oldroyd 8-constant framework: Exact analytical solution for large-amplitude oscillatory shear flow
Authors: Saengow C. , Giacomin A. J.
Published: August 2017

The Oldroyd 8-constant framework for continuum constitutive theory contains a rich diversity of popular special cases for polymeric liquids. In this paper, we use part of our exact solution for shear stress to arrive at unique exact analytical solutions for the normal stress difference responses to large-amplitude oscillatory shear (LAOS) flow. The nonlinearity of the polymeric liquids, triggered by LAOS, causes these responses at even multiples of the test frequency. We call responses at a frequency higher than twice the test frequency higher harmonics. We find the new exact analytical solutions to be compact and intrinsically beautiful. These solutions reduce to those of our previous work on the special case of the corotational Maxwell fluid. Our solutions also agree with our new truncated Goddard integral expansion for the special case of the corotational Jeffreys fluid. The limiting behaviors of these exact solutions also yield new explicit expressions. Finally, we use our exact solutions to see how η∞ affects the normal stress differences in LAOS.
Instability in a channel with grooves parallel to the flow
Authors: Yadav Nikesh , Gepner S. W. , Szumbarski J.
Published: August 2017

Flow in a channel with corrugated walls has been studied, with the primary goal of establishing channel geometries that enhance achievable mixing at possibly low drag increase. The wall corrugation has the form of a sinusoidal wave oriented transversely, i.e., the lines of constant elevation (or phase) are parallel to the direction of the flow. The analysis is performed up to the Reynolds numbers resulting in the formation of secondary states. The first part of the analysis is focused on the properties of the two-dimensional, base flow. Mainly, the dependence of the drag on the channel’s geometry is characterized. The second part of the analysis discusses the onset of the three-dimensional traveling wave instability. Linear stability is investigated by the Direct Numerical Simulation of the Navier-Stokes equations. Critical conditions for the onset of instabilities at a range of geometric parameters are determined. Finally, nonlinear saturation of the unstable modes and the resulting secondary flows is examined. It is shown that the drag reduction property of the base flow can be maintained in the state resulting from non-linear saturation of the disturbance.
Instrumentation for ice crystal characterization in laboratory using interferometric out-of-focus imaging
Authors: Brunel M. , Demange G. , Fromager M. , Talbi M. , Zapolsky H. , Patte R. , Aït Ameur K. , Jacquot-Kielar J. , Coetmellec S. , Gréhan G. , Quevreux B.
Published: August 2017

Airborne characterization of ice crystals has important applications. The extreme difficulty of realizing in situ tests requires the development of a complete instrumentation in the laboratory. Such an installation should enable design, development, test, and calibration of instruments in conditions as close as possible to real ones. We present a set of numerical and experimental tools that have been developed to realize ice crystal sensors based on interferometric particle imaging. The set of tools covers the development of complementary simulators for crystal growth and interferometric particle imaging predictions, experimental generation of “programmable” ice crystals, and instrumentation of a freezing column where different techniques as in-focus imaging, out-of-focus imaging, and digital in-line holography can be combined simultaneously for test and calibration.
Global classical solution to the inelastic Boltzmann equation with potential force
Authors: Wang Xiaolong , Jiang Zhenglu
Published: August 2017

In this paper, motivated by Guo [Commun. Math. Phys. 218(2), 293–313 (2001)], we construct the global classical solution to the inelastic Boltzmann equation with potential force by using the standard contraction mapping theorem. Moreover, the dispersion estimates of the solution are obtained.
Electric-field effect on spin-wave resonance in a nanoscale CoFeB/MgO magnetic tunnel junction
Authors: Dohi T. , Kanai S. , Matsukura F. , Ohno H.
Published: August 2017

We investigate the electric-field effect on the exchange stiffness constant in a CoFeB/MgO junction through the observation of the spin-wave resonance in a nanoscale magnetic tunnel junction. We evaluate the electric-field dependence of the stiffness constant from the separation between resonance fields for the Kittel and spin-wave modes under electric fields. The obtained stiffness constant increases when the interfacial electron density is decreased. This dependence is consistent with that determined from the observation of electric-field dependent domain structures.
Amplification of local changes along the timescale processing hierarchy
Authors: Yeshurun Yaara , Nguyen Mai , Hasson Uri
Published: August 2017

Significance

Changing a few words in a story can drastically alter the interpretation of the narrative. How does the brain amplify sparse changes in word selection to create a unique neural representation for each narrative? In our study, participants listened to one of two stories while being scanned using fMRI. The stories had an identical grammatical structure but varied in a small number of words, resulting in two distinct narratives. We found that differences in neural responses between the stories were amplified as story information was transferred from low-level regions (that are sensitive to the words’ acoustic features) to high-level regions (that accumulate and integrate information across sentences). Our results demonstrate how subtle differences can be accumulated and amplified along the cortical hierarchy.
Temperature increase reduces global yields of major crops in four independent estimates
Authors: Zhao Chuang , Liu Bing , Piao Shilong , Wang Xuhui , Lobell David B. , Huang Yao , Huang Mengtian , Yao Yitong , Bassu Simona , Ciais Philippe , Durand Jean-Louis , Elliott Joshua , Ewert Frank , Janssens Ivan A. , Li Tao , Lin Erda , Liu Qiang , Martre Pierre , Müller Christoph , Peng Shushi , Peñuelas Josep , Ruane Alex C. , Wallach Daniel , Wang Tao , Wu Donghai , Liu Zhuo , Zhu Yan , Zhu Zaichun , Asseng Senthold
Published: August 2017

Significance

Agricultural production is vulnerable to climate change. Understanding climate change, especially the temperature impacts, is critical if policymakers, agriculturalists, and crop breeders are to ensure global food security. Our study, by compiling extensive published results from four analytical methods, shows that independent methods consistently estimated negative temperature impacts on yields of four major crops at the global scale, generally underpinned by similar impacts at country and site scales. Multimethod analyses improved the confidence in assessments of future climate impacts on global major crops, with important implications for developing crop- and region-specific adaptation strategies to ensure future food supply of an increasing world population.
Mechanosensing drives acuity of
αβ
T-cell recognition
Authors: Feng Yinnian , Brazin Kristine N. , Kobayashi Eiji , Mallis Robert J. , Reinherz Ellis L. , Lang Matthew J.
Published: August 2017

Significance

T-lymphocyte activation during immune surveillance begins with recognition by its

α
β

T-cell receptor (TCR) of a peptide ligand bound to an MHC molecule (pMHC) on infected or otherwise altered cells. Using optical traps, we show that activation is fostered at the single-molecule level through synergy between external load on the TCR–pMHC bond and internal, sustained stepping via motor-dependent transport. Chemical thresholds in the absence of load require much higher pMHC density than observed physiologically. With load, however, T lymphocytes can be reliably activated with

∼

10 pN per TCR molecule, mimicking native shear motions involving a mere two pMHCs at the interaction surface. Initial TCR triggering sensitivity results from synergistic mechanosensing rather than previously postulated serial engagement.
In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer
Authors: Kodama Michiko , Kodama Takahiro , Newberg Justin Y. , Katayama Hiroyuki , Kobayashi Makoto , Hanash Samir M. , Yoshihara Kosuke , Wei Zhubo , Tien Jean C. , Rangel Roberto , Hashimoto Kae , Mabuchi Seiji , Sawada Kenjiro , Kimura Tadashi , Copeland Neal G. , Jenkins Nancy A.
Published: August 2017

Significance

The poor prognosis of epithelial ovarian cancer (EOC) has not improved for several decades because of drug resistance to current anticancer drugs. Furthermore, few molecularly targeted agents are effective for EOC, likely because EOC has high tumor heterogeneity. Discovering new drug targets and mechanisms involved in the progression of EOC is therefore sorely needed. Our multiple CRISPR and RNAi-based in vivo loss-of-function screens have identified multiple new EOC candidate drug targets, including the druggable oncogene KPNB1, whose inhibition caused multiphased cell cycle arrest and induced apoptosis. Ivermectin, a Food and Drug Administration-approved antiparasitic drug, exerts KPNB1-dependent antitumor effects and synergistically inhibits tumor growth in combination with paclitaxel, and therefore represents a new potential combinatorial therapy for EOC through drug repositioning.
Obesity-associated gene
TMEM18
has a role in the central control of appetite and body weight regulation
Authors: Larder Rachel , Sim M. F. Michelle , Gulati Pawan , Antrobus Robin , Tung Y. C. Loraine , Rimmington Debra , Ayuso Eduard , Polex-Wolf Joseph , Lam Brian Y. H. , Dias Cristina , Logan Darren W. , Virtue Sam , Bosch Fatima , Yeo Giles S. H. , Saudek Vladimir , O’Rahilly Stephen , Coll Anthony P.
Published: August 2017

Significance

The growing size and sophistication of genome-wide association studies have led to the identification of variants which are clearly and reliably associated with obesity. A strong association between increased BMI and a region of human chromosome 2, near to the gene
TMEM18
, has been repeatedly demonstrated in children and adults. The function of TMEM18 in the control of appetitive behavior and body composition has been poorly characterized. In murine models, we show germline loss results in weight gain while adult onset hypothalamic overexpression results in weight loss, supporting the hypothesis that TMEM18 acting within the central nervous system can affect energy balance. We also report a structure and putative molecular function of TMEM18, challenging the current published model.
Bilingual formal meeting as a context of translatoriality
Authors: Koskela Merja , Koskinen Kaisa , Pilke Nina
Published: August 2017

Drawing on the concept of translatorial action by Justa Holz-Mänttäri, this article sets out to analyse the role of translation in a bilingual formal meeting without any professional translation or interpreting. The analysis reveals the central role of translatorial activities: 60% of the turns include some kind of translatoriality. The chair and expert speakers stand out as producers for most of the translations. Self-translation is the most prominent form of translation, but otherwise the translator role tends to vary dynamically with the role of the source text producer. Three types of translatorial action with varying degrees of replication of content were found: duplicating, summarizing, and expanding. In the meeting context, translatorial action is the primary means of enabling participation for all, regardless of language skills or language background, and this action was used by the participants in flexible and dynamic ways.
How metaphors are rendered in subtitles
Authors: Pedersen Jan
Published: August 2017

Metaphors have been thoroughly studied as translation problems in recent decades. However, they are still under-researched in the subfield of audiovisual translation. This is strange since this mode of translation, particularly subtitling, has very special conditions which complicate the translating of metaphors, such as the interplay between dialogue, image and subtitles, as well as severe time and space constraints. This paper investigates how metaphors in the British sitcom Yes, Prime Minister were subtitled into Swedish. The results show that subtitlers treat metaphors as an important language feature, less prone to omission than other features. Furthermore, monocultural metaphors, which are not shared between cultures, are subtitled using more strategies than transcultural ones. Metaphors are also subtitled differently depending on the degree of entrenchment. Typically for metaphor translation, there is a loss of metaphor force, but more research is needed to ascertain whether this is media-specific or a general translation effect of growing standardization.
Uniqueness theorems for topological higher-rank graph 𝐶*-algebras
Authors: Renault Jean , Sims Aidan , Williams Dana , Yeend Trent
Published: August 2017

We consider the boundary-path groupoids of topological higher-rank graphs. We show that all such groupoids are topologically amenable. We deduce that the

C
∗

C^*

-algebras of topological higher-rank graphs are nuclear and prove versions of the gauge-invariant uniqueness theorem and the Cuntz–Krieger uniqueness theorem. We then provide a necessary and sufficient condition for simplicity of a topological higher-rank graph

C
∗

C^*

-algebra, and a condition under which it is also purely infinite.
New maximal curves as ray class fields over Deligne-Lusztig curves
Authors: Skabelund Dane
Published: August 2017

We construct new covers of the Suzuki and Ree curves which are maximal with respect to the Hasse-Weil bound over suitable finite fields. These covers are analogues of the Giulietti-Korchmáros curve, which covers the Hermitian curve and is maximal over a base field extension. We show that the maximality of these curves implies that of certain ray class field extensions of each of the Deligne-Lusztig curves. Moreover, we show that the Giulietti-Korchmáros curve is equal to the above-mentioned ray class field extension of the Hermitian curve.
A hyperbolic universal operator commuting with a compact operator
Authors: Cowen Carl , Gallardo-Gutiérrez Eva
Published: August 2017

A Hilbert space operator is called universal (in the sense of Rota) if every operator on the Hilbert space is similar to a multiple of the restriction of the universal operator to one of its invariant subspaces. We exhibit an analytic Toeplitz operator whose adjoint is universal in the sense of Rota and which commutes with a quasinilpotent, injective, compact operator with dense range, but unlike other examples, it acts on the Bergman space instead of the Hardy space and this operator is associated with a “hyperbolic” composition operator.
Positive and relaxed selection associated with flight evolution and loss in insect transcriptomes
Authors: Mitterboeck T. Fatima , Liu Shanlin , Adamowicz Sarah J. , Fu Jinzhong , Zhang Rui , Song Wenhui , Meusemann Karen , Zhou Xin
Published: August 2017

The evolution of powered flight is a major innovation that has facilitated the success of insects. Previously, studies of birds, bats, and insects have detected molecular signatures of differing selection regimes in energy-related genes associated with flight evolution and/or loss. Here, using DNA sequences from more than 1000 nuclear and mitochondrial protein-coding genes obtained from insect transcriptomes, we conduct a broader exploration of which gene categories display positive and relaxed selection at the origin of flight as well as with multiple independent losses of flight. We detected a number of categories of nuclear genes more often under positive selection in the lineage leading to the winged insects (Pterygota), related to catabolic processes such as proteases, as well as splicing-related genes. Flight loss was associated with relaxed selection signatures in splicing genes, mirroring the results for flight evolution. Similar to previous studies of flight loss in various animal taxa, we observed consistently higher nonsynonymous-to-synonymous substitution ratios in mitochondrial genes of flightless lineages, indicative of relaxed selection in energy-related genes. While oxidative phosphorylation genes were not detected as being under selection with the origin of flight specifically, they were most often detected as being under positive selection in holometabolous (complete metamorphosis) insects as compared with other insect lineages. This study supports some convergence in gene-specific selection pressures associated with flight ability, and the exploratory analysis provided some new insights into gene categories potentially associated with the gain and loss of flight in insects.
Changing Paradigms in the Endovascular Management of Ruptured Anterior Communicating Artery Aneurysms
Authors: Moon Karam , Park Min S. , Albuquerque Felipe C. , Levitt Michael R. , Mulholland Celene B. , McDougall Cameron G.
Published: August 2017

BACKGROUND

Approximately 17% of ruptured anterior communicating artery (ACoA) aneurysms were deemed unsuitable for coil embolization during the Barrow Ruptured Aneurysm Trial (BRAT), most commonly due to unfavorable dome-to-neck ratio or small size.

OBJECTIVE

To compare patients treated by coil embolization for ruptured ACoA aneurysms during the trial to those treated after the trial to determine whether advances in endovascular techniques have allowed for effective treatment of these lesions.

METHODS

All cases of ruptured ACoA aneurysms treated by endovascular modalities during BRAT (2003-2007) and post-BRAT (2007-2012) were reviewed for patient and aneurysm characteristics, treatment types, and clinical and angiographic outcomes at 3-yr or last follow-up.

RESULTS

The BRAT ACoA cohort included 39 patients treated with coiling (excluding those crossed over to clipping). The post-BRAT cohort included 93 patients who were significantly older (mean age, 59.5 vs 52.8 yr, P = .005) than the BRAT cohort; there were no significant cohort differences in sex, Hunt and Hess grade, or mean aneurysm size. The use of balloon remodeling was significantly higher in the post-BRAT cohort (31.2% [29/93] vs 5.1% [2/39], P = .001), as was the proportion of wide-necked aneurysms treated (66.7% [62/93] vs 30.8% [12/39], P < .001). There was no significant difference in clinical outcome or retreatment rate between the 2 cohorts (P = .90 and P = .48, respectively).

CONCLUSION

ACoA lesions thought unamenable to endovascular therapy in an earlier randomized trial are now successfully coiled with increased use of adjunctive techniques, without sacrificing patient outcome or treatment durability.
Antifungal Susceptibility Testing Practices at Acute Care Hospitals Enrolled in the National Healthcare Safety Network, United States, 2011–2015
Authors: Vallabhaneni Snigdha , Sapiano Mathew , Weiner Lindsey M , Lockhart Shawn R , Magill Shelley
Published: August 2017

We assessed availability of antifungal susceptibility testing (AFST) at nearly 4000 acute care hospitals enrolled in the National Healthcare Safety Network. In 2015, 95% offered any AFST, 28% offered AFST at their own laboratory or at an affiliated medical center, and 33% offered reflexive AFST. Availability of AFST improved from 2011 to 2015, but substantial gaps exist in the availability of AFST.
Identity of Distance: How Economically Marginalized Black and Latina Women Navigate Risk Discourse and Employ Feminist Ideals
Authors: Ray Ranita
Published: August 2017

Racialized and classed “risk” narratives of sexuality in the United States construct economically marginalized young women of color as sexually precocious, potential teen mothers who are likely to end up as burdens on the state. Some scholars underline the utility of recognizing reproductive inequalities involved in constructing teen motherhood as an unequivocal social problem, and they stress the importance of exploring teen mothers’ agency in navigating dominant risk narratives. Fewer studies analyze how young women who are not pregnant or parenting produce, reproduce, and challenge dominant risk narratives about their sexuality. Drawing on three years of intensive fieldwork among 13 young economically marginalized black and Latina women, I demonstrate how feminist ideologies of empowerment interact with pervasive risk narratives in the everyday lives of marginalized women coming of age in the “shadow of the women’s movement.” My observations show that the young women strategically navigate circulating risk narratives about their sexuality by constructing an identity of distance characterized by feminist ideals of independence, self-respect, and self-development to distance themselves from these narratives. However, as they construct this identity of distance, they also stigmatize young mothers and police their own bodies and the bodies of their friends and sisters. I draw on women-of-color feminism to reflect on the uncomfortable relationship—evident in the process of a group of young women’s identity construction—between feminist ideologies of empowerment and bourgeois heteronormativity that marginalizes young women’s sexualities by constructing teen motherhood as inherently problematic.
The Rising Challenge of Training Physician–Scientists: Recommendations From a Canadian National Consensus Conference
Authors: Strong Michael J. , Busing Nick , Goosney Danika L. , Harris Ken A. , Horsley Tanya , Kuzyk Alexandra , Lingard Lorelei , Norman Wendy V. , Rosenblum Norman D. , Saryeddine Tina , Wang Xin
Published: August 2017

Physician–scientists are individuals who actively participate in patient care, have undergone additional research training, and devote the majority of their time to research. Physician–scientists are traditionally the primary catalysts in bridging the translational gap—that is, the failure to link fundamental new knowledge in the pathobiology of disease with advances in health care and health policy in a timely manner. However, there has been a shift away from training physician–scientists, and financial support for the physician–scientist is diminishing globally, causing the translational gap to grow. Given its socialized health care system and cultural and geographic diversity, Canada can serve as a unique case study in understanding how to address this phenomenon as a national priority. To this end, a Canadian national consensus conference was convened to develop recommendations for training programs and early-career supports for physician–scientists. Five recommendations were generated: (1) Establish an independent, national council whose mandate is to provide pan-Canadian oversight of physician–scientist training programs; (2) develop capacity for funding and mentorship support for physician-scientists; (3) develop coherent networks across a broad range of clinician–scientists, including physician–scientists, to reflect the unique cultural and geographic diversity of Canada and to reflect the interdisciplinarity of health research; (4) ensure that medical school curricula integrate, as a core curriculum feature, an understanding of the scientific basis of health care, including research methodologies; and (5) ensure that the funding of the physician–scientist trainee is viewed as portable and distinct from the operational funding provided to the training program itself.
Interprofessional QI Training Enhances Competency and QI Productivity Among Graduates: Findings From Nationwide Children’s Hospital
Authors: Bartman Thomas , Heiser Karen , Bethune Andrew , Crandall Wallace , McClead Richard , Davis J. Terrance , Brilli Richard J.
Published: August 2017

Purpose

Significant resources are expended on quality improvement (QI) training courses. The authors sought to determine whether education provided in QI course training improves self-assessed QI content competence and QI-related productivity among course graduates.

Method

“Quality Improvement Essentials” is a four-month didactic and experiential course designed to prepare multidisciplinary professionals to participate in and lead QI efforts at Nationwide Children’s Hospital (NCH). This study used a milestone-based self-assessment survey of graduates from 2012 to 2014 to gauge change in participants’ self-assessed QI competency after course completion. Four competency domains were evaluated: QI knowledge; testing and implementing change using teams; data management and analysis; and spreading and sustaining science. Metrics for assessing individual QI productivity were presentation or publication of QI work outside NCH; local, regional, or national QI teaching; serving on a local, regional, or national QI committee; appointment as a QI leader; involvement in an internal or external QI collaborative; and leading a maintenance of certification Part IV project approved by NCH.

Results

Course participation more than doubled participants’ self-assessed QI competence across all four domains. Gains continued after the course, increasing with time rather than degrading. Self-assessed competency increase was significantly associated with increased QI productivity.

Conclusions

Self-assessed QI competence dramatically improved after participation in an educational course and continued to increase over time. Increased self-assessed QI competency correlated with increased individual QI productivity. Further studies are necessary to fully evaluate “return on investment” for this type of course.
The Problems With Burnout Research
Authors: Eckleberry-Hunt Jodie , Kirkpatrick Heather , Barbera Thomas
Published: August 2017

Burnout among physicians and physicians-in-training is well established as a potential threat to the health and well-being of health care providers and patients. However, there are myriad problems with current burnout research and its ongoing measurement that threaten the validity of the conclusions. For example, researchers have used differing ways of defining and measuring burnout. Those who have used the Maslach Burnout Inventory vary in recommended use of the instrument and cutoff scores. As a result, the authors suggest that the term “burnout” may be misused and recommend some reconsideration of the meaning of burnout. The measurement and discussion of burnout have strong implications for interventions and policy alike. In this article, the authors review the problems with burnout research and ask important questions about the future directions of research efforts. The authors recommend a consistent measurement approach and perhaps moving toward a focus on physician wellness from a positive psychology perspective.
New insights into the recognition, classification and management of systemic sclerosis-associated pulmonary hypertension
Authors: Mullin Christopher J. , Mathai Stephen C.
Published: August 2017

Purpose of review

Pulmonary hypertension is a common complication of systemic sclerosis (SSc), and remains a leading cause of morbidity and mortality. We will review recent developments in the recognition, classification and treatment of pulmonary hypertension in SSc.

Recent findings

Advances in screening for pulmonary arterial hypertension (PAH) and use of exercise haemodynamics may help to identify pulmonary vascular disease earlier in SSc. Recent studies have led to changes in recommendations for adjunct therapy and selection of pulmonary vasodilators for the treatment of SSc-associated PAH.

Recent advances in the diagnosis, classification and management of pulmonary hypertension in SSc have continued to improve our understanding of this challenging disease. Ongoing investigation in the pathogenesis of this disease will afford the opportunity to develop targeted therapies to improve outcomes for SSc patients with pulmonary hypertension.
Postoperative Changes in Presepsin Level and Values Predictive of Surgical Site Infection After Spinal Surgery
Authors: Koakutsu Tomoaki , Sato Tetsuya , Aizawa Toshimi , Itoi Eiji , Kushimoto Shigeki
Published: August 2017

Study Design.

Single-institutional, prospective observational study.

Objective.

To elucidate the perioperative kinetics of presepsin (PSEP) in patients undergoing spinal surgery, and to evaluate the possibility of PSEP in the early diagnosis of surgical site infection (SSI).

Summary of Background Data.

Early diagnosis of SSI after spinal surgery is important. Although several biomarkers have been used as early indicators of SSI, the specificity of these markers in SSI diagnosis was not high. PSEP was found as a novel diagnostic marker for bacterial sepsis in 2004. However, its kinetics after spinal surgery and its usefulness in early diagnosis of SSI have never been evaluated.

Methods.

A total of 118 patients who underwent elective spinal surgery were enrolled. PSEP was measured before, immediately after, 1 day after, and 1 week after surgery. In patients without postoperative infection, perioperative kinetics of PSEP were analyzed. PSEP levels in patients with postoperative infection were also recorded separately, and their utility in SSI diagnosis was evaluated.

Results.

In the 115 patients without postoperative infection, the median PSEP value was 126, 171, 194, and 147 pg/mL before, immediately after, 1 day after, and 1 week after surgery, respectively. Compared with the preoperative value, PSEP was significantly higher immediately after surgery and the next day, and return to the preoperative level 1 week after surgery. The estimated reference value for 95 percentile in patients without postoperative infection was 297 pg/mL 1 week after surgery. In three patients with postoperative infection, higher levels (>300 pg/mL) were observed 1 week after surgery.

Conclusion.

In patients after spinal surgery without infectious complications, blood levels of PSEP may immediately increase and return to preoperative levels 1 week after surgery. The PSEP value of 300 pg/mL 1 week after surgery might be used as a novel indicator for suspected SSI.

Level of Evidence: 4
Analysis of the Relationship Between the Epidural Spinal Cord Compression (ESCC) Scale and Paralysis Caused by Metastatic Spine Tumors
Authors: Uei Hiroshi , Tokuhashi Yasuaki , Maseda Masafumi
Published: August 2017

Study Design.

A retrospective, single-institute, and radiographic study.

Objective.

To evaluate the relationship between the epidural spinal cord compression (ESCC) scale and the severity of metastatic spine tumor–induced paralysis.

Summary of Background Data.

The ESCC scale is used to evaluate the grade of spinal cord compression on T2-weighted magnetic resonance imaging (MRI). However, few studies have investigated the relationship between such MRI findings and paralysis.

Methods.

The subjects were 467 patients with metastatic spine tumors and grade 1b or worse spinal cord compression according to the ESCC scale. Evaluations using this scale were performed by three spine surgeons, and results that were obtained by two or more surgeons were adopted. We also examined patients whose spinal cord compression deteriorated by one grade or more to American Spinal Injury Association (ASIA) grade C or worse within the first 3 weeks after MRI.

Results.

The kappa coefficients for inter- and intraexaminer variability were 0.90 and 0.95, respectively. ASIA grade D or worse paralysis developed in at least 50% of the patients with ESCC grade 1b or worse spinal cord compression at the C1-T2 and at least 50% of those with ESCC grade 1c or worse spinal cord compression at the T3-L5. The frequency of ASIA grade C or worse paralysis was high among the patients with ESCC grade 2 or worse spinal cord compression at the C7-L1. Nineteen patients experienced rapid deterioration of one grade or more to ASIA grade C or worse paralysis within the first 3 weeks after MRI. Of these, paralysis occurred in at least 30% of the patients with anterolateral or circumferential cord compression combined with ESCC grade 2 or 3 compression at the C7-L1.

Conclusion.

The severity of paralysis was not correlated with the ESCC scale. Patients with anterolateral or circumferential ESCC grade 2 or 3 cord compression at the C7-L1 are at high risk of rapidly progressive paralysis.

Level of Evidence: 4
Is Two-level Cervical Disc Replacement More Cost-effective Than Anterior Cervical Discectomy and Fusion at 7 Years?
Authors: Merrill Robert K. , McAnany Steven J. , Albert Todd J. , Qureshi Sheeraz A.
Published: August 2017

Study Design.

Cost-effectiveness analysis.

Objective.

To investigate 7-years cost-effectiveness of two-level cervical disc replacement (CDR) and anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.

CDR and ACDF are both effective treatment strategies for managing degenerative conditions of the cervical spine. CDR has been shown to be a more-cost effective intervention in the short term, but the long-term cost-effectiveness has not been established.

Methods.

We analyzed 7-years follow-up data from the two-level Medtronic Prestige LP investigational device exemption study. Short-form 36 (SF-36) data were converted into health utility scores using the SF-6D algorithm. Costs were based on direct costs from the payer perspective, and effectiveness was measured as quality-adjusted life years (QALYs). The willingness-to-pay (WTP) threshold was set to $50,000/QALY. A probabilistic sensitivity analysis was conducted via Monte Carlo simulation.

Results.

Two-level CDR had a 7-year cost of $176,654.19, generated 4.65 QALYs, and had a cost-effectiveness ratio of $37,993.53/QALY. Two-level ACDF had a 7-year cost of $158,373.48, generated 4.44 QALYs, and had a cost-effectiveness ratio of $35,635.72. CDR was associated with an incremental cost of $18,280.71 and an incremental effectiveness of 0.21 QALYs, resulting in an incremental cost-effectiveness ratio (ICER) of $89,021.04, above the WTP threshold. Our Monte Carlo simulation demonstrated CDR would be chosen 46% of the time based on 10,000 simulations.

Conclusion.

Two-level CDR and ACDF are both cost-effective procedures at 7-year follow up for treating degenerative conditions of the cervical spine. Based on an ICER of $89,021.04/QALY, we cannot conclude which treatment is the more cost-effective option at 7-years. CDR would be chosen 46% of the time based on 10,000 iterations of our Monte Carlo probabilistic sensitivity analysis.

Level of Evidence: 3
The Relationship Between Fear-Avoidance and Objective Biomechanical Measures of Function in Patients With Adult Degenerative Scoliosis
Authors: Haddas Ram , Lieberman Isador H. , Block Andrew
Published: August 2017

Study Design.

A prospective cohort study.

Objective.

The current study utilized quantitative gait analysis to examine the relationship of fear-avoidance beliefs to gait patterns in patients with adult degenerative scoliosis (ADS).

Summary of Background Data.

Among patients with chronic spine pain, fear-avoidance beliefs are predictive of behavioral deficiencies, poor work, and surgery outcomes. The impact of such beliefs on patients with major spinal deformity has yet to be investigated. Patients with ADS have previously been shown to have an altered gait pattern. Utilizing quantified gait analysis, this study aims to examine correlations between fear-avoidance and various aspects of gait in patients with ADS.

Methods.

Twenty-five ADS patients completed the Tampa Scale for Kinesiophobia (TSK) questionnaire and the Fear Avoidance Beliefs Questionnaire (FABQ). Each patient performed a series of overground gait trials at a self-selected comfortable speed. Pearson product correlation analysis was used to determine the relationship between the self-reported fear of movement measures and the objective gait analysis biomechanical data.

Results.

TSK score correlated strongly with gait speed, stride, step, double support times, and step length, and correlated moderately with cadence, and stride length. The FABQ physical portion strongly correlated with stride length and step length. The FABQ physical portion was moderately correlated with gait speed and single support time. The FABQ work portion was correlated with stride length and step length.

Conclusion.

This study demonstrates a strong correlation between biomechanical gait parameters, as measured with gait analysis, and fear-avoidance of movement, as measured with the TSK and FABQ. Further, it demonstrates that quantified gait analysis can be a useful tool to evaluate patients with spine deformity and to assess the outcomes of treatments in this group of patients. This study extends previous research on the role of fear-avoidance to include patients with spinal deformity.

Level of Evidence: 3
ECHO Pain Curriculum: Balancing Mandated Continuing Education With the Needs of Rural Health Care Practitioners
Authors: Shelley Brian M. , Katzman Joanna G. , Comerci George D. , Duhigg Daniel J. , Olivas Cynthia , Kalishman Summers , Monette Rebecca , Britt Melissa , Flatow-Trujillo Lainey , Arora Sanjeev
Published: August 2017

Chronic pain is a common problem in the United States. Health care professions training at the undergraduate and graduate levels in managing chronic pain is insufficient. The Chronic Pain and Headache Management TeleECHO Clinic (ECHO Pain) is a telehealth approach at Project ECHO (Extension for Community Healthcare Outcomes), which supports clinicians interested in improving their knowledge and confidence in treating patients with chronic pain and safe opioid management. It is a vehicle for educating practicing clinicians (at the “spoke”) based on work-place learning with cases selected by participants from their patient panels combined with short lectures by experts (at the “hub”). ECHO Pain has designed an innovative, interprofessional longitudinal curriculum appropriate for individual and team-based clinicians which includes relevant basic and advanced pain topics. The specific design and delivery of the curriculum enhances its relevance and accessibility to busy clinicians in practice, yet also satisfies statutory requirements for CME in New Mexico. Specific features which balance hub-and-spoke needs are presented in this descriptive article, which is intended to serve as a guide to other clinician educators interested in developing or implementing similar telehealth curricula.
The safety of pembrolizumab in metastatic melanoma and rheumatoid arthritis
Authors: Puri Akshjot , Homsi Jade
Published: August 2017

Immunotherapy has been in use for the treatment of melanoma since a very long time, but only recently have the cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab and programmed cell death-1 inhibitors such as nivolimumab and pembrolizumab been shown to induce marked improvements in survival in patients with metastatic melanoma. An important concern arises in terms of the safety of the use of these agents in patients with autoimmune diseases, solid organ transplant recipients on immunosuppression, patients with a history of previous hepatitis B or C, and patients with HIV infections as these patients were excluded from pivotal immunotherapy studies. Here, we report on the safety and efficacy of pembrolizumab in a melanoma patient with multiple medical problems including poorly controlled rheumatoid arthritis and we review the available literature on the use of immunotherapy and autoimmune diseases. The weight of evidence suggests that these patients should be offered the opportunity to benefit from immune check point inhibitors, with drugs targeting programmed cell death-1 being preferred. More research is required to study the long-term effects of immunotherapy on patients with autoimmune diseases.
Hypoalbuminemia is a Predictive Factor for Fistula Formation in Recurrent Cervical Cancer
Authors: Palavalli Parsons Lavanya H. , Roane Brandon , Manders Dustin B. , Richardson Debra L. , Kehoe Siobhan M. , Carlson Matthew , Miller David S. , Lea Jayanthi S.
Published: August 2017

Objective:

Antivascular endothelial growth factor monoclonal antibodies inhibit tumor angiogenesis, consequently impeding the recruitment of new vasculature to existing and new tumor lesions. We sought to evaluate toxicities in women with recurrent cervical cancer after receiving bevacizumab combination chemotherapy.

Methods:

A review was conducted of women with recurrent and metastatic cervical cancer who were treated with salvage chemotherapy with or without bevacizumab between 2005 and 2015. Clinicopathologic data and reasons for treatment discontinuation were recorded. Patients that were excluded had other histology than squamous or adenocarcinoma, received 1 cycle of salvage chemotherapy, single agent bevacizumab, currently on treatment, or noncompliant. Statistical analysis was performed using the Fishers Exact Test, logistic regression, and Kaplan-Meier Survival Analysis.

Results:

A total of 74 patients were included in analysis. Twenty-six patients were treated with bevacizumab (BEV) and chemotherapy and 48 patients with chemotherapy alone (chemotherapy). The progression free survival was significant with median 12 months versus 7 months for the BEV cohort (P<0.01) and the overall survival was a median 74 months versus 23 months for the BEV cohort (P=0.06). Cessation of treatment secondary to severe toxicities was seen in 46% (n=12) of BEV cohort versus 15% (n=7) of chemotherapy cohort (P<0.01). Twenty-seven percent (n=7) of patients in the BEV cohort stopped secondary because of fistula formations. Lower albumin levels and use of bevacizumab were identified as an independent predictor factors for fistula formation (P=0.004 and 0.024, respectively).

Conclusions:

Hypoalbuminemia and bevacizumab treatments are significant predictive factors of fistula formation in patients treated for recurrent cervical cancer.
Reflectance Confocal Microscopy Criteria of Pigmented Squamous Cell Carcinoma In Situ
Authors: Shahriari Neda , Grant-Kels Jane M. , Rabinovitz Harold S. , Oliviero Margaret , Scope Alon
Published: August 2017

Pigmented squamous cell carcinoma in situ (pSCCis) is difficult to diagnose based on clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) allows noninvasive differentiation between malignant and benign pigmented skin lesions. We determined the frequency of key RCM features of pSCCis and correlated the RCM criteria with the corresponding dermoscopic and histopathologic criteria. The study included 28 lesions with biopsy-proven diagnosis of pSCCis derived from 28 patients. Clinical, dermoscopic, and RCM images of these lesions were retrospectively analyzed by 3 independent observers. Assessment for the presence of RCM criteria revealed scale or parakeratosis (20/28; 71%); irregular honeycomb pattern in the spinous-granular layer (28/28; 100%); spindle-shaped cells with dendritic branches infiltrating the epidermis (12/28; 43%); edged papillae (24/28; 86%), and dilated looped blood vessels within the papillae (18/28; 64%). Fifty-three percent of the cases displayed at least 4 RCM criteria and 96% of cases displayed at least 3 RCM criteria. We propose that the diagnosis of pSCCis could be established based on 1 major criterion—irregular honeycomb pattern—and 2 of the following minor criteria—scale or parakeratosis, spindle-shaped cells with dendritic branches infiltrating the epidermis, edged papillae, and dilated looped blood vessels within the papillae.
Nicolau Syndrome (Embolia Cutis Medicamentosa): A Rare and Poorly Recognized Iatrogenic Cause of Cutaneous Thrombotic Vasculopathy
Authors: Tabor Dominic , Bertram Chandra G. , Williams Andrew J. K. , Mathers Marie E. , Biswas Asok
Published: August 2017

Nicolau syndrome is a rare form of iatrogenic cutaneous necrosis which affects injection sites. Although classically associated with intramuscular injections, it may develop after subcutaneous or other routes of parenteral drug administration. Clinically, it manifests as necrotic ulcers that often develop in a background of erythematous and livedoid reticular patches. The histopathologic characteristics of Nicolau syndrome are poorly documented in the dermatopathology literature and features only rarely as one of the obscure causes of cutaneous thrombotic vasculopathy. We report a case of Nicolau syndrome developing secondary to subcutaneous injection of cyclizine to familiarize the clinicians and pathologists to this unusual condition. Given that it is potentially avoidable, pathologists should alert the clinicians to the possibility of Nicolau syndrome when a skin biopsy from an injection site shows signs of extensive thrombotic vasculopathy.