bluuebunny/crossref_metadata_2025 huggingface dataset:
Coherent detection in medium grazing angle sea‐clutter
Authors: Rosenberg Luke , Watts Simon
Published: May 2017

The design of coherent detectors for targets in sea clutter presents particular challenges. The Doppler spectra of sea clutter are observed to be both time‐varying and range‐varying so that when data from a large number of surrounding cells are used to estimate the characteristics of the data in the cell under test, the results can be unreliable. Attempts to use smaller numbers of possibly more representative cells can result in numerical stability problems. In this study the authors extend earlier work on this subject and assess a number of traditional and model‐based techniques to see how well false alarms can be controlled while using data from only a small number of surrounding cells. The authors also compare the resulting detection performance when the detection thresholds are adjusted to give a constant false alarm rate at all Doppler frequencies.
Nickel-Promoted Reductive Cyclization Cascade: A Short Synthesis of a New Aromatic Strigolactone Analogue
Authors: Peng Yu , Xiao Jian , Wang Ya-Wen
Published: May 2017

A stereospecific synthesis of the tetrahydro-2H-indeno[1,2-b]furan skeleton, which is embedded in bioactive aromatic strigolactones such as GR24, is realized by a nickel-mediated tandem cross-coupling for the first time. The observed cis-stereoselectivity during the intramolecular formation of the Csp3–Csp2 bond is rationalized through conformation analysis and DFT calculations.
Efficient C(sp3)–H Bond Arylation of Tetrahydroisoquinolines with Knochel-Type Arylzinc Reagents under Oxidative Conditions
Authors: Peng Zhihua , Yu Zhi , Chen Dong-Huang , Liang Shuyuan , Zhang Liwei , Zhao Dezhi , Song Linhua , Jiang Cuiyu
Published: May 2017

A novel C(sp3)–H bond arylation of tetrahydroisoquinoline (THIQ) derivatives with Knochel-type arylzinc reagents has been developed. In the presence of MgCl2, arylzinc reagents readily reacted with THIQ derivatives under oxidative conditions, affording a wide range of potentially biologically active compounds in good yields. Moreover, the developed method can tolerate a variety of sensitive functional groups such as an ester group.
Donor-Site Morbidity of Free Muscle and Perforator Flaps: Comparison of the Gracilis Muscle Flap and the Anterolateral Thigh Flap
Authors: Rassner M. , Kiefer J. , Bannasch H. , Stark G. , Eisenhardt S. , Fricke Alba
Published: May 2017

Background Both the gracilis muscle flap and the anterolateral thigh (ALT) flap have been described as successful reconstructive options for defect coverage after trauma or tumor resection. In general, free perforator flaps are considered to generate less donor-site morbidity than muscle flaps. Here, we put this hypothesis to the test.

Methods In this study, 193 patients who had undergone free flap reconstruction with either free gracilis muscle flaps (n = 131) or ALT flaps (n = 62) were included. Subjective patient satisfaction with the aesthetic and functional outcome of the donor sites was assessed using a self-report questionnaire as well as the Lower Extremity Functional Scale (LEFS).

Results Comparing the donor-site morbidity of free ALT and gracilis flaps, the LEFS revealed no significant differences in functional impairment (p = 0.6447) of the lower extremity. The donor-site scar was significantly longer after ALT flap harvest (mean: 21.16 cm) than after gracilis muscle flap harvest (mean: 14.17 cm; p < 0.0001). Furthermore, donor-site numbness was significantly greater in the ALT group than in the gracilis group (p = 0.0068).

Conclusion No significant differences in functional impairment of the lower extremity were reported after gracilis muscle and ALT flap harvest. Regarding scar length and level of numbness of the donor site, the gracilis muscle flap was shown to be superior to the ALT flap.
Development and Evaluation of a Simulation Model for Microvascular Anastomosis Training
Authors: Wiersch John , Adams Andrew , Al Fayyadh Mohammed , Weber Robert , Wang Howard , Willis Ross
Published: May 2017

Background Many plastic surgery training programs have implemented microvascular preparatory courses. However, these courses vary in length across institutions, lack formal assessment, and trainees receive certificates of completion rather than competency. In addition, many institutions use animate tissues as practice models which may not be readily available, require special treatment or storage, and lack consistency across vessel segments. In this study, we developed a proficiency-based training microvascular anastomosis curriculum using a synthetic model. In addition, we developed and validated a scoring rubric and patency testing apparatus.

Methods Proficiency benchmarks were developed by evaluating four plastic surgeons performing interrupted end-to-end anastomoses on synthetic vessels mounted superficially and at depth. Using a pretest–posttest design, seven plastic surgery residents from two institutions were asked to train to proficiency on the superficial exercise. Skills transfer was evaluated using a vessel mounted at depth. Each anastomosis was scored on 11 metrics of mechanics, completion time, stenosis, and leakage.

Results Experts outperformed residents prior to engaging in the training curriculum, confirming construct validity. Residents' skills significantly improved on 10 of 14 metrics after training, confirming curriculum effectiveness. Only one resident was able to achieve all proficiency benchmarks on two consecutive training trials. Skills learned on the superficially mounted vessel moderately transferred to the vessel mounted at depth as evidenced by significant pre- to posttest learning gains for 4 of the 14 metrics.

Conclusion The proficiency goals may have been overly stringent; however, residents improved microvascular anastomosis skills on the majority of metrics by engaging in simulation-based training using a readily available synthetic model.
Evaluating Surgical Delay Using Infrared Thermography in an Island Pedicled Perforator Flap Rat Model
Authors: Li Xiucun , Chen Miao , Maharjan Suraj , Cui Jianli , Lu Laijin , Gong Xu
Published: May 2017

Background The aim of this study was to examine the usefulness of infrared (IR) thermography in visualizing the dilation of the choke vessels in a delayed pedicled perforator flap rat model.

Methods A three-territory island flap was designed and harvested on one side of the rat dorsum. The flap was divided into five regions. In the normal group (n = 8), IR thermal imaging was correlated with the postmortem arteriography for the location of angiosomes, linking patterns, perforator diameter, and temperature on each region. The delay group (n = 35) was divided into seven groups according to various delay periods. At different time intervals, the delay group was compared with the normal group according to link pattern and temperature on each region.

Results IR thermal imaging showed that a white hotspot existed on the surface of each angiosome; the true anastomotic vessels manifested a continuous white band linking the white hotspots on angiosomes, whereas the choke vessels presented a red zone in between adjacent hotspots. After delay, the dilation of the choke vessels manifested itself as the replacement of the red zone between adjacent hotspots by the white band on IR thermography. In addition, the delayed flap presented a phenomenon of rise and fall in temperature over time.

Conclusion IR thermography can accurately visualize the process of the dilation of choke vessels after a surgical delay. The chronological change in the IR thermal imaging combined with the temperature change in the delayed flap might be useful to determine the optimal delay period.
Accuracy of diagnosing invasive colorectal cancer using computer-aided endocytoscopy
Authors: Takeda Kenichi , Kudo Shin-ei , Mori Yuichi , Misawa Masashi , Kudo Toyoki , Wakamura Kunihiko , Katagiri Atsushi , Baba Toshiyuki , Hidaka Eiji , Ishida Fumio , Inoue Haruhiro , Oda Masahiro , Mori Kensaku
Published: May 2017

Background and study aims Invasive cancer carries the risk of metastasis, and therefore, the ability to distinguish between invasive cancerous lesions and less-aggressive lesions is important. We evaluated a computer-aided diagnosis system that uses ultra-high (approximately × 400) magnification endocytoscopy (EC-CAD).

Patients and methods We generated an image database from a consecutive series of 5843 endocytoscopy images of 375 lesions. For construction of a diagnostic algorithm, 5543 endocytoscopy images from 238 lesions were randomly extracted from the database for machine learning. We applied the obtained algorithm to 200 endocytoscopy images and calculated test characteristics for the diagnosis of invasive cancer. We defined a high-confidence diagnosis as having a ≥ 90 % probability of being correct.

Results Of the 200 test images, 188 (94.0 %) were assessable with the EC-CAD system. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were 89.4 %, 98.9 %, 94.1 %, 98.8 %, and 90.1 %, respectively. High-confidence diagnosis had a sensitivity, specificity, accuracy, PPV, and NPV of 98.1 %, 100 %, 99.3 %, 100 %, and 98.8 %, respectively.

Conclusion: EC-CAD may be a useful tool in diagnosing invasive colorectal cancer.
Endocytoscopy can be used to assess histological healing in ulcerative colitis
Authors: Nakazato Yoshihiro , Naganuma Makoto , Sugimoto Shinya , Bessho Rieko , Arai Mari , Kiyohara Hiroki , Ono Keiko , Nanki Kosaku , Mutaguchi Makoto , Mizuno Shinta , Kobayashi Taku , Hosoe Naoki , Shimoda Masayuki , Abe Takayuki , Inoue Nagamu , Ogata Haruhiko , Iwao Yasushi , Kanai Takanori
Published: May 2017

Background and study aim Endocytoscopy (ECS) is used in the in vivo microscopic inspection of microstructural mucosal features and enables endoscopists to assess the histological severity of ulcerative colitis (UC). The aim of this study was to assess histological healing in UC patients by using ECS.

Patients and methods A total of 64 patients in clinical and endoscopic remission who underwent ECS were selected. The correlation between the ECS score and Geboes score at the rectum was evaluated in patients with a Mayo endoscopic score (MES) of 0. The diagnostic accuracy of the ECS score for histological remission (Geboes score ≤ 2) was also assessed.

Results The ECS score ranged from 0 to 5 in patients with endoscopic remission on conventional white-light images (MES of 0). The agreement between histological remission regarding the ECS score and the Geboes score had a κ value of 0.72, and the ECS score showed high accuracy for histological remission, with a sensitivity of 0.77, a specificity of 0.97, and a diagnostic accuracy of 0.86.

Conclusion ECS can be used to assess histological healing in patients with UC without the need for biopsy specimens.
Diterpene Lipo-Alkaloids with Selective Activities on Cardiac K+ Channels
Authors: Kiss Tivadar , Borcsa Botond , Orvos Péter , Tálosi László , Hohmann Judit , Csupor Dezső
Published: May 2017

Aconitum diterpene alkaloids are known for their remarkable toxicity, which is due to their effect on ion channels. Activation of voltage-gated Na+ channels is the major cause of their cardiotoxicity, however, influence on K+ channels may also play a role in the overall effect.

Here we report the synthesis of a series of lipo-alkaloids, including four new compounds, based on the 14-benzoylaconine structure, which is the core of a vast number of diterpene alkaloids naturally occurring in Aconitum species. The activities of these compounds were measured in vitro on K+ ion channels using the whole-cell patch-clamp technique. Structure-activity analysis was carried out based on the data of 51 compounds (32 genuine diterpene alkaloids, 5 fatty acids, and 14 lipo-alkaloids). Depending on their substitution, these compounds exert different activities on GIRK (G protein-coupled inwardly-rectifying potassium channel) and hERG (human ether-à-go-go-related gene) channels. Fatty acids and diterpene alkaloids show lower activity on the GIRK channel than lipo-alkaloids. Lipo-alkaloids also have less pronounced hERG inhibitory activity compared to the cardiotoxic aconitine. Considering the GIRK/hERG selectivity as an indicator of perspective therapeutic applicability, lipo-alkaloids are significantly more selective than the genuine diterpene alkaloids. 14-Benzoyl-8-O-eicosa-8Z,11Z,14Z-trienoate and 14-benzoyl-8-O-eicosa-11Z,14Z,17Z-trienoate are strong and selective inhibitors of GIRK channels, thus, they are promising subjects for further studies to develop diterpene alkaloid-based antiarrhythmic pharmacons.
Darcy-Weisbach friction factor at the nanoscale: From atomistic calculations to continuum models
Authors: Liakopoulos A. , Sofos F. , Karakasidis T. E.
Published: May 2017

A modification of the Darcy-Weisbach friction factor applicable to nanoscale liquid transport processes is proposed. Non-equilibrium molecular dynamics simulations allow us to access the atomic behaviour of liquids moving in nanochannels, and by comparing atomistic simulation results with continuum Navier-Stokes solutions, we extend the applicability of continuum theory to nanoscale liquid flows. We find that classical continuum theory predictions of power dissipation do not apply in the case of nanochannels and have to be modified accordingly with input from atomistic simulations such as slip velocity and profiles of variable viscosity. The mathematical form of the friction factor expression persists for quite small nanochannel widths, i.e., the form of the relation for the friction factor f Re = const. is practically maintained even at the nanoscale, but the value of the constant significantly increases with increasing hydrophilicity.
Photodissociation dynamics of OCS at ∼210 nm: The role of c(23A″) state
Authors: Bai Xilin , Liang Hao , Zhou Zhengfang , Hua Zefeng , Jiang Bin , Zhao Dongfeng , Chen Yang
Published: May 2017

Photodissociation dynamics of carbonyl sulfide (OCS) in the deep ultraviolet region is investigated using a time-sliced ion velocity map imaging technique. The measured total kinetic energy release spectra from the photodissociation of OCS at ∼210 nm shows three dissociation channels to the fragment S(1D2), corresponding to low, medium, and high kinetic energy release (ET), respectively. The high ET channel is found to be a new dissociation channel opening with photolysis wavelength at ∼210 nm. Based on the aq(k)(p) polarization parameters as well as the anisotropy parameters β determined from the images of S(1D2), the dissociation of OCS to S(1D2) + CO at 210 nm is concluded to involve a direct vertical excitation of the triplet c(23A″) state from the ground state, followed by processes as: the low ET component arises from a non-adiabatic transition from the repulsive A(21A′) state to the electronic ground state X(11A′); the medium ET component arises from a simultaneous excitation to two repulsive excited states; and the high ET component arises from the intersystem crossing from the triplet c(23A″) state to the repulsive A(21A′) state. The present study shows that, due to the strong spin-orbit coupling between the triplet c(23A″) state and the repulsive A(21A′) state, a direct excitation to c(23A″) significantly contributes to the photodissociation dynamics of OCS in the deep-UV region.
Magnetic properties, exchange bias, and memory effects in core-shell superparamagnetic nanoparticles of La0.67Sr0.33MnO3
Authors: Rostamnejadi A. , Venkatesan M. , Salamati H. , Ackland K. , Gholizadeh H. , Kameli P. , Coey J. M. D.
Published: May 2017

The static magnetic properties and memory and exchange bias effects have been studied in sol-gel prepared La0.67Sr0.33MnO3 (LSMO) nanoparticles. Transmission electron microscopy (TEM) micrographs and static magnetization show log-normal particle and magnetic size distributions with a core-shell structure. Analysis of the magnetization measurements indicates the presence of a magnetic structure with a 7.8 nm core radius and a magnetic dead layer of thickness 1.6 nm in the LSMO nanoparticles, which comprises about 40% of the volume. The disordered spins in the shell freeze at lower temperatures than the core and produce a surface spin glass state exhibiting a weak exchange bias effect. Field cooled and zero-field cooled magnetization measurements have been carried out to study the slow dynamics of the sample and associated magnetic memory effects; the results reveal the superparamagnetic behavior of LSMO nanoparticles described in terms of the magnetic size distribution rather than a superspin glass state.
Continuous tuning of two-section, single-mode terahertz quantum-cascade lasers by fiber-coupled, near-infrared illumination
Authors: Hempel Martin , Röben Benjamin , Niehle Michael , Schrottke Lutz , Trampert Achim , Grahn Holger T.
Published: May 2017

The dynamical tuning due to rear facet illumination of single-mode, terahertz (THz) quantum-cascade lasers (QCLs) which employ distributed feedback gratings are compared to the tuning of single-mode QCLs based on two-section cavities. The THz QCLs under investigation emit in the range of 3 to 4.7 THz. The tuning is achieved by illuminating the rear facet of the QCL with a fiber-coupled light source emitting at 777 nm. Tuning ranges of 5.0 and 11.9 GHz under continuous-wave and pulsed operation, respectively, are demonstrated for a single-mode, two-section cavity QCL emitting at about 3.1 THz, which exhibits a side-mode suppression ratio better than −25 dB.
A concept of wireless and passive very-high temperature sensor
Authors: Nicolay P. , Matloub R. , Bardong J. , Mazzalai A. , Muralt P.
Published: May 2017

There is a need for sensors capable operating at temperatures above 1000 °C. We describe an innovative sensor that might achieve this goal. The sensor comprises two main elements: a thermocouple and a surface acoustic wave (SAW) strain sensor. The cold junction of the thermocouple is electrically connected to a highly piezoelectric thin layer, deposited on top of a SAW substrate. In operation, the voltage generated by the temperature gradient between the hot (>1000 °C) and cold junction (<350 °C) generates a strain field in the layer, which is mechanically transmitted to the substrate. This modifies the SAW propagation conditions and therefore the sensors' radiofrequency response. The change depends on the applied voltage and thus on the hot junction temperature. As SAW devices are passive elements that can be remotely interrogated, it becomes possible to infer the hot junction temperature from the radiofrequency response, i.e., to remotely read temperatures above 1000 °C, without embedded electronics. In this paper, we demonstrate the feasibility of this concept, using AlN layers deposited on Y-Z Lithium Niobate (LN). The achieved sensitivity of 80 Hz/V at 400 MHz is constant over a wide voltage range. Numerical simulations were performed to compute the main properties of the demonstrators and suggest optimization strategies. Improvements are expected from the use of stronger piezoelectric layers, such as AlScN or Pb(Ti,Zr)O3 (PZT), which could increase the sensitivity by factors of 3 and 20, as estimated from their transverse piezoelectric coefficients. As a first step in this direction, thin PZT layers have been deposited on Y-Z LN.
Effect of crystallinity on UV degradability of poly[methyl(phenyl)silane] by energy-resolved electrochemical impedance spectroscopy
Authors: Schauer F. , Tkáč L. , Ožvoldová M. , Nádaždy V. , Gmucová K. , Jergel M. , Šiffalovič P.
Published: May 2017

Low stability and degradability of polymers by ambient air, UV irradiation or charge transport are major problems of molecular electronics devices. Recent research tentatively suggests that the presence of a crystalline phase may increase polymer stability due to an intensive energy trapping in the ordered phase. Using the UV degradability, we demonstrate this effect on an archetypal model σ bonded polymer - poly[methyl(phenyl)silane] (PMPSi) - with partially crystalline and amorphous-like layers. UV degradation with 345 nm, derived from the branching state generation rate, was inversely proportional to the crystalline phase content, changing from 4.8x1011 s-1 (partially crystalline phase) to 1.8x1013 s-1 (amorphous-like phase). A model is proposed where crystallites formed by molecular packing act as effective excitation energy traps with a suppressed nonradiative recombination improving thus PMPSi film stability. The molecular packing and higher crystalline phase proportion may be a general approach for stability and degradability improvement of polymers in molecular electronics.
Structure and composition of oxides in FeCrAl ODS alloy with Zr addition
Authors: Xu Haijian , Lu Zheng , Wang Dongmei , Zhang Zhiwei , Han Yanfa , Liu Chunming
Published: May 2017

FeCrAl ODS (oxide dispersion strengthened) alloy with Zr addition was investigated with the main focus on the structure and composition of oxide particles. The results reveal that almost all the small particles (diameter <2 nm) were found to be consistent with trigonal δ-phase Y4Zr3O12, with cubic Y3Al5O12 (YAG) oxides occasionally detected. The large particles (>2 nm) were mainly identified as monoclinic Al2O3 oxides. A core/shell structure is found in slightly large oxide particles. Oxide cores are Al and O while shell regions are enriched in Y. This leads us a promising way to control the structure and size of the oxides and develop the high-performance FeCrAl ODS alloys.
Electric Fish Handling Gloves Provide Effective Immobilization and Do Not Impede Reflex Recovery of Adult Largemouth Bass
Authors: Ward Taylor D. , Brownscombe Jacob W. , Gutowsky Lee F. G. , Ballagh Robert , Sakich Nicholas , McLean Derek , Quesnel Geneviѐve , Gambhir Sahil , O'Connor Constance M. , Cooke Steven J.
Published: May 2017

Electric fish handling gloves (FHGs) have been developed to immobilize fish during handling, with the potential benefit of reducing the time needed for sedation and recovery of fish relative to chemical anaesthetics. We examined the secondary stress responses (i.e., hematocrit, blood glucose, lactate, and pH) and reflex responses of Largemouth Bass Micropterus salmoides that were immobilized in water using electric FHGs for multiple durations (0, 30, and 120 s) relative to fish that were handled using only bare hands in water. We also evaluated the efficacy of the immobilization by quantifying the number of volitional movements that were observed during handling. Our findings suggested that when FHGs were used, fish tended to remain still (i.e., to show full reflex impairment) during handling relative to controls. Fish that were held with FHGs showed negligible reflex impairment immediately after the electricity was terminated. After a 30-min posttreatment retention period, blood chemistry and ventilation rates were similar between fish held with FHGs and those held with bare hands. This study supports the notion that electric FHGs are a safe and effective tool for practitioners who need to temporarily immobilize fish for handling, enumeration, or performing various scientific procedures.

Received November 15, 2016; accepted February 26, 2017 Published online May 4, 2017
Spatial and Temporal Segregation of Wild and Hatchery Winter Steelhead Populations in Eagle Creek, Oregon
Authors: Brignon William R.
Published: May 2017

A segregated hatchery program promotes conservation by limiting the amount of overlap in return timing and spawning locations of hatchery- and natural-origin fish. The objective of the present study was to use radiotelemetry data collected from 2005 to 2007 to better understand the level of spatial and temporal segregation between hatchery and natural-origin steelhead Oncorhynchus mykiss in the Eagle Creek basin, Oregon. The analysis resulted in three key findings. First, hatchery-origin winter steelhead were unlikely to migrate into the North Fork Eagle Creek, a tributary that has historically lacked any hatchery releases or influence, suggesting a high level of segregation from the natural-origin population returning to that stream. Second, hatchery fish arrived at the lower fish ladder on Eagle Creek and at Eagle Creek National Fish Hatchery (NFH) earlier than natural-origin fish, suggesting that broodstock management practices to maintain an early returning hatchery stock (i.e., temporal segregation) have been somewhat successful. Finally, regardless of the differential arrival timing to Eagle Creek NFH, there is evidence of an increased probability of spatial and temporal overlap of the populations as the return progresses, and this may be explained by successful reproduction of hatchery-origin fish in main-stem Eagle Creek. Integrated and segregated hatchery programs should be monitored periodically to ensure that they are meeting their stated goals.

Received October 12, 2016; accepted March 14, 2017 Published online May 4, 2017
Liberia’s run-up to 2017: continuity and change in a long history of electoral politics
Authors: Pailey Robtel Neajai , Harris David
Published: May 2017

If successfully orchestrated, the October 2017 elections in Liberia will mark the first time in recent memory when a democratically elected Liberian president – Ellen Johnson Sirleaf – will hand over power to a similarly elected head of state. This is very likely to be a close election and our Briefing investigates changes and continuities in the candidates, political parties, electoral processes and the workings of the Liberian state at a watershed moment in a long and shifting democratic history.
Optimized ultra-high-pressure-assisted extraction of procyanidins from lychee pericarp improves the antioxidant activity of extracts
Authors: Zhang Ruifen , Su Dongxiao , Hou Fangli , Liu Lei , Huang Fei , Dong Lihong , Deng Yuanyuan , Zhang Yan , Wei Zhencheng , Zhang Mingwei
Published: May 2017

To establish optimal ultra-high-pressure (UHP)-assisted extraction conditions for procyanidins from lychee pericarp, a response surface analysis method with four factors and three levels was adopted. The optimum conditions were as follows: 295 MPa pressure, 13 min pressure holding time, 16.0 mL/g liquid-to-solid ratio, and 70% ethanol concentration. Compared with conventional ethanol extraction and ultrasonic-assisted extraction methods, the yields of the total procyanidins, flavonoids, and phenolics extracted using the UHP process were significantly increased; consequently, the oxygen radical absorbance capacity and cellular antioxidant activity of UHP-assisted lychee pericarp extracts were substantially enhanced. LC-MS/MS and high-performance liquid chromatography quantification results for individual phenolic compounds revealed that the yield of procyanidin compounds, including epicatechin, procyanidin A2, and procyanidin B2, from lychee pericarp could be significantly improved by the UHP-assisted extraction process. This UHP-assisted extraction process is thus a practical method for the extraction of procyanidins from lychee pericarp.
Integrin-targeted cancer immunotherapy elicits protective adaptive immune responses
Authors: Kwan Byron H. , Zhu Eric F. , Tzeng Alice , Sugito Harun R. , Eltahir Ahmed A. , Ma Botong , Delaney Mary K. , Murphy Patrick A. , Kauke Monique J. , Angelini Alessandro , Momin Noor , Mehta Naveen K. , Maragh Alecia M. , Hynes Richard O. , Dranoff Glenn , Cochran Jennifer R. , Wittrup K. Dane
Published: May 2017

Certain RGD-binding integrins are required for cell adhesion, migration, and proliferation and are overexpressed in most tumors, making them attractive therapeutic targets. However, multiple integrin antagonist drug candidates have failed to show efficacy in cancer clinical trials. In this work, we instead exploit these integrins as a target for antibody Fc effector functions in the context of cancer immunotherapy. By combining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2.5F-Fc), significant survival improvements are achieved in three syngeneic mouse tumor models, including complete responses with protective immunity. Functional integrin antagonism does not contribute significantly to efficacy; rather, this therapy recruits both an innate and adaptive immune response, as deficiencies in either arm result in reduced tumor control. Administration of this integrin-targeted immunotherapy together with an anti–PD-1 antibody further improves responses and predominantly results in cures. Overall, this well-tolerated therapy achieves tumor specificity by redirecting inflammation to a functional target fundamental to tumorigenic processes but expressed at significantly lower levels in healthy tissues, and it shows promise for translation.
International comparison CCQM-K113—noble gas mixture
Authors: Lim Jeong Sik , Lee Jinbok , Moon Dongmin , Tshilongo James , Qiao Han , Shuguo Hu , Tiqiang Zhang , Kelley Michael E , Rhoderick George C , Konopelko L A , Kolobova A V , Vasserman I I , Zavyalov S V , Gromova E V , Efremova O V
Published: May 2017

Noble gases are one of the key elements used in the various processes of the bulbs industry, automotive industry, space industry, lasers industry, display industry as well as the semiconductor industry. Considering continuous growth, the provision of a reliable standard is required for those industries to improve their productivity.

In this report, a result of the key comparison, CCQM-K113: noble gas mixture, is presented. Nominal amount-of-substance fractions of argon, neon, krypton, and xenon in helium are 20, 10, 2, and 1 cmol/mol, respectively.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Regulation of circular dorsal ruffles, macropinocytosis, and cell migration by RhoG and its exchange factor, Trio
Authors: Valdivia Alejandra , Goicoechea Silvia M. , Awadia Sahezeel , Zinn Ashtyn , Garcia-Mata Rafael
Published: May 2017

Circular dorsal ruffles (CDRs) are actin-rich structures that form on the dorsal surface of many mammalian cells in response to growth factor stimulation. CDRs represent a unique type of structure that forms transiently and only once upon stimulation. The formation of CDRs involves a drastic rearrangement of the cytoskeleton, which is regulated by the Rho family of GTPases. So far, only Rac1 has been consistently associated with CDR formation, whereas the role of other GTPases in this process is either lacking or inconclusive. Here we show that RhoG and its exchange factor, Trio, play a role in the regulation of CDR dynamics, particularly by modulating their size. RhoG is activated by Trio downstream of PDGF in a PI3K- and Src-dependent manner. Silencing RhoG expression decreases the number of cells that form CDRs, as well as the area of the CDRs. The regulation of CDR area by RhoG is independent of Rac1 function. In addition, our results show the RhoG plays a role in the cellular functions associated with CDR formation, including macropinocytosis, receptor internalization, and cell migration. Taken together, our results reveal a novel role for RhoG in the regulation of CDRs and the cellular processes associated with their formation.
twoddpcr: an R/Bioconductor package and Shiny app for Droplet Digital PCR analysis
Authors: Chiu Anthony , Ayub Mahmood , Dive Caroline , Brady Ged , Miller Crispin J
Published: May 2017

Droplet Digital PCR (ddPCR) is a sensitive platform used to quantify specific nucleic acid molecules amplified by polymerase chain reactions. Its sensitivity makes it particularly useful for the detection of rare mutant molecules, such as those present in a sample of circulating free tumour DNA obtained from cancer patients. ddPCR works by partitioning a sample into individual droplets for which the majority contain only zero or one target molecule. Each droplet then becomes a reaction chamber for PCR, which through the use of fluorochrome labelled probes allows the target molecules to be detected by measuring the fluorescence intensity of each droplet. The technology supports two channels, allowing, for example, mutant and wild type molecules to be detected simultaneously in the same sample. As yet, no open source software is available for the automatic gating of two channel ddPCR experiments in the case where the droplets can be grouped into four clusters. Here, we present an open source R package ‘twoddpcr’, which uses Poisson statistics to estimate the number of molecules in such two channel ddPCR data. Using the Shiny framework, an accompanying graphical user interface (GUI) is also included for the package, allowing users to adjust parameters and see the results in real-time.

Availability and implementation

twoddpcr is available from Bioconductor (3.5) at https://bioconductor.org/packages/twoddpcr/. A Shiny-based GUI suitable for non-R users is available as a standalone application from within the package and also as a web application at http://shiny.cruk.manchester.ac.uk/twoddpcr/.

Package maintainer

anthony.chiu@cruk.manchester.ac.uk
Modelling community formation driven by the status of individual in a society
Authors: Snellman Jan E , Iñiguez Gerardo , Govezensky Tzipe , Barrio R A , Kaski Kimmo K
Published: May 2017

In human societies, people’s willingness to compete and strive for better social status, as well as being envious of those perceived in some way superior, lead to social structures that are intrinsically hierarchical. Here, we propose an agent-based, network model to mimic the ranking behaviour of individuals and its possible repercussions in human society. The main ingredient of the model is the assumption that the relevant feature of social interactions is each individual’s keenness to maximize his or her status relative to others. The social networks produced by the model are homophilous and assortative, as frequently observed in human communities, and most of the network properties seem quite independent of its size. However, we see that for a small number of agents the resulting network consists of disjoint weakly connected communities, while being highly assortative and homophilic. On the other hand, larger networks turn out to be more cohesive with larger communities but less homophilic. We find that the reason for these changes is that larger network size allows agents to use new strategies for maximizing their social status, allowing for more diverse links between them.
Development and Validation of a Novel Adult Spinal Deformity Surgical Invasiveness Score: Analysis of 464 Patients
Authors: Neuman Brian J , Ailon Tamir , Scheer Justin K , Klineberg Eric , Sciubba Daniel M , Jain Amit , Zebala Lukas P , Passias Peter G , Daniels Alan H , Burton Douglas C , Protopsaltis Themi S , Hamilton D Kojo , Ames Christopher P ,   International Spine Study Group
Published: May 2017

BACKGROUND

A surgical invasiveness index (SII) has been validated in general spine procedures but not adult spinal deformity (ASD).

OBJECTIVE

To assess the ability of the SII to determine the invasiveness of ASD surgery and to create and validate a novel ASD index incorporating deformity-specific factors, which could serve as a standardized metric to compare outcomes and risk stratification of different ASD procedures for a given deformity.

METHODS

Four hundred sixty-four patients who underwent ASD surgery between 2009 and 2012 were identified in 2 multicenter prospective registries. Multivariable models of estimated blood loss (EBL) and operative time were created using deformity-specific factors. Beta coefficients derived from these models were used to attribute points to each component. Scoring was iteratively refined to determine the R2 value of multivariate models of EBL and operative time using adult spinal deformity-surgical (ASD-S) as an independent variable. Similarly, we determined weighting of postoperative changes in radiographical parameters, which were incorporated into another index (adult spinal deformity-surgical and radiographical [ASD-SR]). The ability of these models to predict surgical invasiveness was assessed in a validation cohort.

RESULTS

Each index was a significant, independent predictor of EBL and operative time (P < .001). On multivariate analysis, ASD-S and ASD-SR explained more variability in EBL and operative time than did the SII (P < .001). The ASD-SR explained 21% of the variation in EBL and 10% of the variation in operative time, whereas the SII explained 17% and 3.2%, respectively.

CONCLUSION

The ASD-SR, which incorporates deformity-specific components, more accurately predicts the magnitude of ASD surgery than does the SII.
Cytomegalovirus Infection With Retinitis After Brentuximab Vedotin Treatment for CD30+ Lymphoma
Authors: Tudesq Jean-Jacques , Vincent Laure , Lebrun Julie , Hicheri Yosr , Gabellier Ludovic , Busetto Timothé , Merle Corinne , Fegueux Nathalie , Ceballos Patrice , Quittet Philippe , Navarro Robert , Hillaire-Buys Dominique , Cartron Guillaume
Published: May 2017

Brentuximab vedotin is an antibody-conjugated chemotherapy targeting CD30 indicated in treatment of several lymphomas. We report the first 3 cases of cytomegalovirus severe infections with retinitis following this treatment. Evolution was favorable, but relapse occurred after treatment rechallenge. We suggest vigilance about cytomegalovirus in patients treated with brentuximab vedotin.
Expression of Elafin in Dermatitis Herpetiformis
Authors: Ollague Jose E. , Nousari Carlos H.
Published: May 2017

Background:

Elafin is a serine protease inhibitor that has various epithelial cell regulatory and immunomodulatory effects including inactivation of neutrophil elastases. This later role originated the interest of elafin in certain neutrophil-rich dermatoses. Interestingly, it has been speculated that elafin has a protective role by slowing the deamidation process of gliadin in celiac disease (CD), despite the typical absence of neutrophils in intestinal histologic samplings. Dermatitis herpetiformis (DH) is a chronic recurrent vesicular dermatitis associated with gluten hypersensitivity and also characterized by a neutrophilic infiltrate and granular immunoglobulin A deposits in papillary dermis.

Materials and Methods:

We selected 31 formalin-fixed paraffin-embedded skin specimens of DH that demonstrated typical immunopathologic findings and probed them with rabbit polyclonal immunoglobulinG antielafin antibodies through standard immunohistochemistry analysis. Negative controls consisted of normal skin from elbow and knee surgical re-excisions specimen lacking residual tumor. Positive controls included skin biopsies of active plaque psoriasis, Sweet syndrome, and pyoderma gangrenosum.

Results:

Similar to what has been previously reported in intestinal sampling of patients with active CD, abnormal expression of elafin was noted in virtually all probed skin biopsies of DH patients with active cutaneous disease.

Conclusion:

Under normal circumstances, keratinocytes overexpress elafin to downregulate a neutrophil mediated inflammatory response. The deficient expression of elafin in the aforementioned probed DH specimens correlates with previous similar elafin underexpression in intestinal samples of active CD. These histological findings suggest that these 2 gluten mediated disorders carry an abnormal elafin underexpression during disease activity.
Progressive Surgical Autonomy in a Plastic Surgery Resident Clinic
Authors: Day Kristopher M. , Scott Jillian K. , Gao Lani , Lee Tara M. , Waldrop Jimmy L. , Sargent Larry A. , Kennedy J. Woody , Rehm Jason P. , Brzezienski Mark A.
Published: May 2017

Background:

Resident clinics are thought to catalyze educational milestone achievement through opportunities for progressively autonomous surgical care, but studies are lacking for general plastic surgery resident clinics (PSRCs). We demonstrate the achievement of increased surgical autonomy and continuity of care in a PSRC.

Methods:

A retrospective review of all patients seen in a PSRC from October 1, 2010, to October 1, 2015, was conducted. Our PSRC is supervised by faculty plastic surgery attendings, though primarily run by chief residents in an accredited independent plastic surgery training program. Surgical autonomy was scored on a 5-point scale based on dictated operative reports. Graduated chief residents were additionally surveyed by anonymous online survey.

Results:

Thousand one hundred forty-four patients were seen in 3,390 clinic visits. Six hundred fifty-three operations were performed by 23 total residents, including 10 graduating chiefs. Senior resident autonomy averaged 3.5/5 (SD = 1.5), 3.6/5 (SD = 1.5), to 3.8/5 (SD = 1.3) in postgraduate years 6, 7, and 8, respectively. A linear mixed model analysis demonstrated that training level had a significant impact on operative autonomy when comparing postgraduate years 6 and 8 (P = 0.026). Graduated residents’ survey responses (N = 10; 100% response rate) regarded PSRC as valuable for surgical experience (4.1/5), operative autonomy (4.4/5), medical knowledge development (4.7/5), and the practice of Accreditation Council of Graduate Medical Education core competencies (4.3/5). Preoperative or postoperative continuity of care was maintained in 93.5% of cases.

Conclusion:

The achievement of progressive surgical autonomy may be demonstrated within a PSRC model.
The Use of Virtual Reality Technology in the Treatment of Anxiety and Other Psychiatric Disorders
Authors: Maples-Keller Jessica L. , Bunnell Brian E. , Kim Sae-Jin , Rothbaum Barbara O.
Published: May 2017

Learning objectives

After participating in this activity, learners should be better able to:

• Evaluate the literature regarding the effectiveness of incorporating virtual reality (VR) in the treatment of psychiatric disorders

• Assess the use of exposure-based intervention for anxiety disorders

Virtual reality (VR) allows users to experience a sense of presence in a computer-generated, three-dimensional environment. Sensory information is delivered through a head-mounted display and specialized interface devices. These devices track head movements so that the movements and images change in a natural way with head motion, allowing for a sense of immersion. VR, which allows for controlled delivery of sensory stimulation via the therapist, is a convenient and cost-effective treatment. This review focuses on the available literature regarding the effectiveness of incorporating VR within the treatment of various psychiatric disorders, with particular attention to exposure-based intervention for anxiety disorders. A systematic literature search was conducted in order to identify studies implementing VR-based treatment for anxiety or other psychiatric disorders. This article reviews the history of the development of VR-based technology and its use within psychiatric treatment, the empirical evidence for VR-based treatment, and the benefits for using VR for psychiatric research and treatment. It also presents recommendations for how to incorporate VR into psychiatric care and discusses future directions for VR-based treatment and clinical research.
Internet-Based Cognitive-Behavioral Therapy for Depression: Current Progress and Future Directions
Authors: Webb Christian A. , Rosso Isabelle M. , Rauch Scott L.
Published: May 2017

The World Health Organization estimates that during a given 12-month period, approximately 34 million people suffering from major depressive disorder go untreated in Europe and the Americas alone. Barriers to treatment include geographic distance, lack of mental health insurance, prohibitive cost of treatment, long wait-lists, and perceived stigma. Over the past two decades, Internet-based cognitive-behavioral therapy (iCBT) programs have proliferated. A growing body of research supports the efficacy of iCBT for depression and other psychiatric conditions, and these programs may help address barriers that hinder access to effective treatment. The present review describes common iCBT programs along with the evidence base supporting their efficacy in reducing symptoms of depression, reviews research on moderators of treatment response, and provides suggestions for future directions in research and care.
Practical Issues in Delivery of Clinician-to-Patient Telemental Health in an Academic Medical Center
Authors: Abrams Jessica , Sossong Sarah , Schwamm Lee H. , Barsanti Lauren , Carter Michael , Kling Naomi , Kotarski Meghan , Leddy Jaclyn , Meller Benjamin , Simoni Marcy , Sullivan Michael , Wozniak Janet
Published: May 2017

Background

In the age of online communication, psychiatric care can now be provided via videoconferencing technologies. While virtual visits as a part of telepsychiatry and telemental health provide a highly efficient and beneficial modality of care, the implementation of virtual visits requires attention to quality and safety issues. As practitioners continue to utilize this technology, issues of clinician licensing, treatment outcomes of virtual visits versus in-person visits, and cost offset require ongoing study.

Methods

This review provides an overview of the topics of technology, legal and regulatory issues, clinical issues, and cost savings as they relate to practicing psychiatry and psychology via virtual visits in an academic medical center. We review the telepsychiatry/telemental health effectiveness literature from 2013 to the present. Our literature searches used the following terms: telemental health effective, telepsychiatry effective, telepsychiatry efficacy, and telemental health efficacy. These searches produced 58 articles, reduced to 16 when including only articles that address effectiveness of clinician-to-patient services.

Results

The technological, legal, and regulatory issues vary from state to state and over time. The emerging research addressing diverse populations and disorders provides strong evidence for the effectiveness of telepsychiatry. Cost savings are difficult to precisely determine and depend on the scope of the cost and benefit measured.

Conclusion

Establishing a telepsychiatry program requires a comprehensive approach with up-to-date legal and technological considerations.
PROGRESSIVE RETINAL DETACHMENT IN INFANTS WITH RETINOPATHY OF PREMATURITY TREATED WITH INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB
Authors: Yonekawa Yoshihiro , Wu Wei-Chi , Nitulescu Cristina E. , Chan R.V. Paul , Thanos Aristomenis , Thomas Benjamin J. , Todorich Bozho , Drenser Kimberly A. , Trese Michael T. , Capone Antonio
Published: May 2017

Purpose:

Fibrovascular contraction and tractional retinal detachment (TRD) are recognized complications associated with the use of anti–vascular endothelial growth factor agents in vasoproliferative vitreoretinopathies. The authors characterize TRDs that developed after intravitreal bevacizumab or ranibizumab therapy for vascularly active retinopathy of prematurity.

Methods:

This is an international, multicenter, interventional, retrospective, case series. Thirty-five eyes from 23 infants were included. Inclusion required anti–vascular endothelial growth factor treatment of Type 1 retinopathy of prematurity with progression to TRD.

Results:

Mean gestational age was 26 ± 2 weeks, and mean birth weight was 873 ± 341 g. Mean postmenstrual age on the day of injection was 35 ± 2 weeks. Retinal detachment was noted a mean of 70 days (median, 34; range, 4–335) after injection. Eleven percent detached within 1 week, 23% within 2 weeks, and 49% within 4 weeks. The highest stage of retinopathy of prematurity noted was 4A in 29%, 4B in 37%, and 5 in 34% of eyes. Time to RD negatively correlated with postmenstrual age at the time of injection (Rho = −0.54; P < 0.01). Three TRD configurations were observed: 1) conventional peripheral elevated ridge or volcano-shaped Stage 5 detachment, 2) midperipheral detachment with tight circumferential vectors, and 3) very posterior detachment with prepapillary contraction. Full or partial reattachment was achieved with surgical intervention in 86% of eyes.

Conclusion:

Progressive atypical TRD may occur after anti–vascular endothelial growth factor injections for retinopathy of prematurity. The configuration of the detachment varies with the extent of primary retinal vascularization present at the time of treatment.