bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral/Directional RCS Attitude Control for Lift Reentry Vehicle in Large Dynamic Pressure Regime
Authors: Fan Pengfei , Fan Yonghua , Yan Jie
Published: April 2019

For the existence of aerodynamic coupling and big turbulence of reentry vehicle in large aerodynamic flight status, Conventional method for RCS controller designing is difficult to track the bank angle command quickly and accurately. To solve the problem, according to the feature that the lateral/directional coupling is significant and the yaw channel is more effective and stronger to turbulence when tracking the bank angle, a strategy is proposed by using the roll and yaw channel simultaneously to control the bank angle dynamic. Double loop dynamic inversion controller is designed in which the bank angle loop conduct as outer loop and the roll and yaw angle rate loop as inner loop. The convergence of sideslip angle is guaranteed by improving the design of roll angle rate controller and the influence of the controller parameters to converge mode is analyzed. PWPF modulator is applied to convert command moment into pulse signals. Numerical simulation is carried out to verify the benefits of the proposed control method, the results shows that the present method solved the problem that RCS controller designed in conventional manner, and improve control ability of RCS in large aerodynamic condition.
Small and Dim Ship Target Detection Based on Sea-Sky-Line
Authors: Hu Yaohui , Zhang Ke , Xing Chao
Published: April 2019

In order to solve the problem of small and dim ship target detection under complex sea-sky background, we propose a target detection algorithm based on sea-sky line detection. Firstly, the paper locates the sea-sky-line based on fully convolutional networks, through which target potential area can be determined and disturbance can be excluded. Then the method based on the mean of four detection gradient is adopted to detect the small and dim ship target. The simulation results show that the method of sea-sky-line detection based on fully convolutional networks can overcome the disadvantages of the traditional methods and is suitable for complex background. The detection method proposed can filter the white noise point on the sea surface and thus can reduce false alarm, through which the detection of small and dim ship can be completed well.
Numerical Simulation of Nonlinear Flow Based on Element-Free Galerkin Method
Authors: Meng Junnan , Pan Guang , Cao Yonghui , Li Linfeng , Li Zhencen , Zhou Bing
Published: April 2019

This paper focuses on the studying on some flow problems of nonlinear based on the Element Free Galerkin method. First the Navier-Stokes equation is discretized with the Galerkin method. The inertial term in the equation is discretized with the method of the speed term and direct deduction respectively. And the penalty function method is used to deal with the pressure and the essential boundary condition in the equation, and the discretization of two-dimensional N-S equation based on the EFG method is established. Then the flow problem of stationary nonlinear is studied. The flow problem of water in the rectangular domain squeezed by the two plates distributed above and below the calculated domain is studied with the method of EFG. The accuracy of the direct linear alternating interation method is shown by contrast with the analytical solution. Then the flow problem of unsteady nonlinear is studied. The θ-weighted method is used to discrete the time term of the N-S equation and the unsteady nonlinear solution matrix of EFG is established. The flow problem of flow around the square column is studied with the method of EFG and the flows under a series of low Reynolds are stimulated.
Exploring on Aerodynamic Characteristics of Low Reynolds Number Airfoil in Time-varying Wind Field
Authors: Zhao Wei , Zhu Xiaoping , Zhou Zhou , Xu Xiaoping
Published: April 2019

A solar-powered unmanned aerial vehicle generally encounters the problems that it has low Reynolds effects and is highly susceptible to gust response. Therefore, the grid velocity method was used to analyze the gust response characteristics of the airfoil FX63-137 under low Reynolds number. First, the reliability of the numerical simulation method at low Reynolds number and grid velocity method were verified with experimental data. Second, the gust response characteristics of FX63-137 airfoil under different Reynolds numbers and different angles of attack were numerically simulated. The results show that the magnitude of incremental lift coefficient in gust response decreases because laminar separation bubbles are complete as the Reynolds number decreases at a small angle of attack. They also show that laminar separation bubbles have an unloaded effect on gust response. At a high angle of attack, as the airfoil enters into stalling stage, the incremental lift coefficient begins to decline before reaching maximum gust disturbance. Because of the stalling of the airfoil, when the gust disappears, the incremental lift coefficient has a negative value. What's more, although the effective angle of attack is equal, the flow structure of the airfoil is somewhat different in upstream and downstream moments. Compared with the downstream moment, the incremental lift coefficient at the upstream moment is generally larger, and the incremental lift coefficient curve of the airfoil forms a non-closed hysteresis loop.
The Numerical Simulation of UAV's Landing in Ship Airwake
Authors: Li Xu , Zhu Xiaoping , Zhou Zhou , Xu Xiaoping
Published: April 2019

In order to investigate the influence of ship airwake on aerodynamic characteristics of the carrier-based aircraft, UAV's landings in different winds over deck were simulated by Overset Mesh method. Firstly, mesh factors, steady and unsteady methods were compared based on single aircraft carrier. The results showed that the boundary layer mesh around ship didn't show obvious influence for our simulation, and the calculation results between the steady and unsteady time average showed a similar trend. Then, aircraft carrier's flow fields in three wind directions were analyzed, and ship airwake variations with different direction winds over deck were concluded as well. Next, the reliability of Overset Mesh was verified though single UAV's landing simulation. Finally, the coupled flow fields of UAV/ship were studied. The calculation results indicated that aircraft was always in a low dynamic pressure condition, the lift and pitching moment of UAV had apparent changes in landing. Meanwhile, the aerodynamic fluctuations of UAV also revealed differences in different wind directions. The simulation results can be regarded as a reference for the safety assessment of carrier-based aircraft's landing and its control in the future.
Influence of Quiet Spike on Supersonic Transport for Low Boom Effect
Authors: Li Zhanke , Liu Yang , Ding Yulin , Lei Zhijin , Ma Boping
Published: April 2019

One of the biggest technical challenges of supersonic flight is the mitigation of sonic boom. To deal with this problem, the Gulfstream Aerospace Corporation came up with the spike concept, and it showed to be efficient. However, there also remain several problems, the first one is that installing the spike makes it harder to balance for supersonic transport and the another one is that the movement equipment is complex. In this paper, a new concept by replacing the multi-stage of the normal spike with smooth transistion cones is proposed. The concept simultaneously uses the CFD solver HUNS3D based on the Reynolds average (RANS) equation and the far-field FL-BOOM sound explosion propagation program based on Thomas waveform parameter method. The effectiveness of the present scheme to suppress supersonic aircraft sound explosion is verified according to the concept. It is proved that the increased length is good for low blast and the main factor affecting the blast reduction effect of multistage mute cone is length rather than series by the analysis. The results have important reference value for the silent cone design of supersonic aircraft.
Yield of biliary stent cytology: Is it time to think lean?
Authors: Alagappan Muthuraman , Darras Natasha , Yang Lauren , Vanderlaan Paul , Mizrahi Meir , Sawhney Mandeep , Pleskow Douglas , Berzin Tyler
Published: April 2019

Background and study aims During evaluation of pancreaticobiliary strictures, it is common practice to send biliary stents for cytologic analysis. However, in recent years, complementary tissue acquisition techniques ranging from cholangioscopy to fine-needle biopsy have improved the ability to acquire tissue and diagnose malignancy. Data are limited on the current diagnostic yield and cost effectiveness of biliary stent analysis.

Patients and methods We performed a retrospective study of all pancreaticobiliary stents sent for analysis in a tertiary care academic medical center from June 2013 to September 2016. Patient demographics, stent information, and final diagnosis history were collected through chart review. Costs were determined using published reimbursement rates for Medicare.

Results Two hundred thirty-one stents from 175 patients were sent for cytologic analysis during the study period. Of the 62 stents obtained from patients ultimately diagnosed with malignancy, only one (1.6 %) had positive cytology for malignant cells, while the others were acellular/non-diagnostic (2/62, 3.2 %), negative (48/62, 77.4 %), or atypical (11/62, 17.7 %). The sensitivity of stent cytology for diagnosis of malignancy was 1.6 % (1/62). No cases were identified in which stent cytology changed clinical management. From a payer perspective, the mean estimated cost for each stent cytologic analysis is greater than $ 70.00.

Conclusions While stent cytologic analysis is a common clinical practice, the diagnostic yield and cost effectiveness of the practice must be reevaluated. With the rise of newer diagnostic technologies such as digital cholangioscopy and endoscopic ultrasound-guided fine-needle biopsy, it may be time to “think lean” and acknowledge a sunset for biliary stent cytology.
Warum gerade ich? – Subjektive Krankheitsursachen und Zusammenhänge zu sozialen Faktoren und wahrgenommener Stigmatisierung bei Brust-, Prostata-, Darm- und Lungenkrebspatienten
Authors: Roick Julia , Esser Peter , Hornemann Beate , Mehnert Anja , Ernst Jochen
Published: April 2019

Hintergrund Subjektive Krankheitsursachen gehen vielfach mit Selbstbeschuldigung und Schamgefühlen einher. Diese psychosozialen Belastungen können durch mögliche Stigmatisierungserfahrungen verstärkt werden. Die vorliegende Studie untersucht Annahmen zu subjektiven Krankheitsursachen von Krebspatienten und prüft Zusammenhänge mit sozialen Faktoren und dem Grad erlebter Stigmatisierung.

Methoden Im Rahmen einer bizentrischen Studie wurden 858 Patienten mit Brust-, Darm-, Lungen oder Prostatakrebs quantitativ befragt, von denen 815 in die Berechnungen eingingen. Subjektive Krankheitsursachen wurden durch ein Fragenset aus 17 Items mit den wichtigsten Ursachen von Krebserkrankungen erhoben und Stigmatisierung anhand der SIS-D (Social Impact Scale) erfasst. Die Daten werden uni- und multivariat ausgewertet.

Ergebnisse Das Durchschnittsalter liegt bei 60 Jahren, 54% sind männlich. Die Mehrheit der Patienten (95%) führt multiple Krankheitsursachen an. Umwelt wird von allen Entitäten als der wichtigste Einflussfaktor bewertet (M=3,0). Schuld/Strafe Gottes und Ansteckung wird am wenigsten Einfluss beigemessen (M=1,1). Ursachen, die auf den Lebensstil zurückzuführen sind, korrelieren nicht höher mit stigmatisierenden Aussagen als externe Ursachenannahmen (r=0,07–0,38). Patienten mit höherem Einkommen sehen weniger psychosoziale Faktoren (Beta=− 0,051 bis −0,086), Rauchen (Beta=− 0,087) und Schuld/Strafe Gottes (Beta=− 0,023) als Ursache ihrer Erkrankung. Je niedriger die Bildung, desto mehr Einfluss wird der Ansteckung (Beta=− 0,019) als Ursache beigemessen.

Schlussfolgerung Tatsächliche Krebsursachen und -risiken werden nur teilweise als solche eingeschätzt (z. B. Ernährung), während andere unterschätzt werden (z. B. Alkohol). Zukünftige Interventionen zur Aufklärung über Krebsursachen sollten v. a. Patienten mit niedriger Bildung fokussieren.
Brief Review: Effects of Isometric Strength Training on Strength and Dynamic Performance
Authors: Lum Danny , Barbosa Tiago M.
Published: April 2019

This review used a narrative summary of findings from studies that focused on isometric strength training (IST), covering the training considerations that affect strength adaptations and its effects on sports related dynamic performances. IST has been shown to induce less fatigue and resulted in superior joint angle specific strength than dynamic strength training, and benefited sports related dynamic performances such as running, jumping and cycling. IST may be included into athletes’ training regime to avoid getting overly fatigue while still acquiring positive neuromuscular adaptations; to improve the strength at a biomechanically disadvantaged joint position of a specific movement; to improve sports specific movements that require mainly isometric contraction; and when athletes have limited mobility due to injuries. To increase muscle hypertrophy, IST should be performed at 70–75% of maximum voluntary contraction (MVC) with sustained contraction of 3–30 s per repetition, and total contraction duration of>80–150 s per session for>36 sessions. To increase maximum strength, IST should be performed at 80–100% MVC with sustained contraction of 1–5 s, and total contraction time of 30–90 s per session, while adopting multiple joint angles or targeted joint angle. Performing IST in a ballistic manner can maximize the improvement of rate of force development.
Synthesis of peri-Diarylated Naphthalimides via Double Decarboxylative Cross-Coupling Reaction
Authors: Kantarod Kritchasorn , Naweephattana Phiphob , Reutrakul Vichai , Pohmakotr Manat , Soorukram Darunee , Kuhakarn Chutima , Surawatanawong Panida , Leowanawat Pawaret
Published: April 2019

A facile method for the synthesis of peri-diarylated naphthalimides was developed by using a palladium-catalyzed double decarboxylative cross-coupling reaction. The present work offers a convenient approach for tuning the optical properties of naphthalimide derivatives.
Chirality Transfer from a Chiral Primary Alcohol Equivalent Through Allyl Cyanate-to-Isocyanate Rearrangement: Synthesis of (+)-Geranyllinaloisocyanide
Authors: Ichikawa Yoshiyasu , Morimoto Hirofumi , Masuda Toshiya
Published: April 2019

A new approach was developed to construct quaternary stereogenic centers bearing nitrogen substituents in an enantioselective manner. The strategy takes advantage of [1,3]-chirality transfer from a chiral primary alcohol equivalent through an allyl cyanate-to-isocyanate rearrangement. This approach was employed in an efficient eight-step synthesis of the marine natural product, (+)-geranyllinaloisocyanide, in 43% overall yield.
Optimizing Results of Facial Surgery and Patient Satisfaction with Simultaneous Chemical Peels
Authors: Winslow Catherine
Published: April 2019

Facial antiaging surgery is widely regarded as safe and effective. Current techniques allow us to achieve a balance of restoring youth while minimizing stigmata of surgery to effect a refreshed, natural look. An important component of achieving this goal is to improve the appearance of fine lines and dyschromias which continue to add to the apparent age. Several options exist to improve the appearance of the skin, each with a separate set of indications, advantages, and disadvantages. A medium-depth 35% trichloroacetic acid peel can be safely combined with rejuvenating surgery to enhance patient satisfaction and results with the same downtime and low cost.
Comparing the Use of Injectable Fillers for the Youthful Lip and the More Mature Lip
Authors: Greene Ryan
Published: April 2019

Enhancement of the lips with facial fillers is currently one of the most popular nonsurgical cosmetic treatments worldwide. Patients from all age ranges have interest in these treatments, but there is wide variance of their esthetic goals. Practitioners must be aware of the challenges posed by both the youthful and mature lip, which usually requires different approaches and techniques. This article reviews the lip anatomy, aging changes in the lips and perioral region, techniques to produce consistent results, and ways to manage and avoid potential complications.
Comparison of Antibiotic Dosing Before and After Implementation of an Electronic Order Set
Authors: Nichols Kristen , Petschke Allison , Webber Emily , Knoderer Chad
Published: April 2019

Background To maximize resources, the antimicrobial stewardship program at a pediatric tertiary care hospital made pediatric dosing specific guidance within the electronic health record available to all hospitals within the health system.

Objective The objective of this study was to compare the appropriateness of antibiotic dosing before and after the implementation of an electronic intravenous (IV) antibiotic order set.

Methods This was a retrospective cohort study evaluating orders from patients younger than 18 years who received cefepime, piperacillin–tazobactam, tobramycin, or gentamicin at 12 health-system hospitals. Antibiotic dosing regimens and order set use were evaluated in patients who received the specified antibiotics during the 6-month time frame prior to and following electronic order set availability at each hospital.

Results In the before and after implementation periods, 360 and 387 total antibiotic orders were included, respectively. Most orders were gentamicin (55.8% in the before implementation period and 54.5% in the after implementation period) followed by piperacillin-tazobactam (22.5% in the before period and 22.2% in the after period). Overall, 663 orders were classified as appropriate (88.8%). Appropriateness was similar in the before or after implementation periods (87.8 vs. 89.7%, p = 0.415). There was a significant difference in appropriateness if a blank order versus the electronic IV antibiotic order set was used (82.8 vs. 90.5%; p = 0.024).

Conclusion No difference in antibiotic appropriateness overall was found in the before and after implementation periods. However, when specifically compared with the appropriateness of dosing when blank order forms were used, dosing was more appropriate when electronic antibiotic order sets were used.
Morphometrics Analysis of Sagitta Otolith in Pool Barb, Puntius sophore (Hamilton, 1822)
Authors: Rani Anju , Rai Deepak , Tyor Anil K.
Published: April 2019

Introduction The use of otolith morphometrics could prove to be a powerful tool in fish identification. The aim of the present study was to analyze the shape of the otolith in pool barb, Puntius sophore.

Materials and Methods To accomplish the present study, samples of various sizes were collected from the Yamunanagar and from the Faridabad fish markets in Haryana, India. The sagitta otoliths were extracted by making a horizontal cut across the head of the fish.

Results The independent t-test revealed no statistically significant difference between the values of otolith length and width of both the right and left otoliths (p > 0.05). Furthermore, various shape indexes, such as form factor (FF); circularity (C); rectangularity (REC), and aspect ratio (AR) were calculated, and the general shape of the otoliths of P. sophore was described as rectangular and less elongated. The otolith length (OL) was found to be positively correlated with the AR, whereas the FF was found to be negatively correlated with REC and C. The present study expresses the relationship between the total length (TL) and the head length (HL) of the fish with the OL and the otolith width (OW) by a linear regression model. The results depicted that the OL and the OW were linearly correlated to the TL and to the HL of the fish.

Conclusion The present study also provides a better understanding in identification of fish stock.
The Seroprevalence of Hand-Foot-Mouth Disease in Preschool Children
Authors: Cinar Esma Merve , Kosecik Mustafa , Aslan Ferhat Gurkan , Buyukavcı Mustafa , Koroglu Mehmet , Elmas Bahri , Altındis Mustafa
Published: April 2019

Hand-foot-mouth disease (HFMD) is a systemic and mostly uncomplicated infectious disease caused by the virus of the enterovirus family and manifests as skin and mucosal lesions. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the most commonly detected infectious agents. It is generally observed in children under 5 years of age. In this study, our objective was to determine the seroprevalence of HFMD in preschool children in Sakarya region. A total of 380 children between 1 and 6 years of age were included in the study. Sociodemographic information, clinical findings, and possible risk factors were recorded on a data collection form. Later, serum anti-EV71 and anti-CA16 IgG (immunoglobulin G) antibodies were measured by ELISA. Amongst the 380 children, EV71 IgG positivity was 57.9% and CA16 IgG antibody positivity was 57.4%. There was no difference in seroprevalence between the genders (p > 0.05). Anti-EV71 and anti-CA16 IgG antibody positivity was significantly higher in children aged 1, 2, 3, and 4 years than in 5-year olds (p < 0.05). Seroprevalence was significantly lower in children of mothers who washed their hands before feeding (p < 0.01). High HFMD seroprevalence (> 50%) was observed in the preschool period in the Sakarya region, especially in children aged 1 to 4 years. To prevent infections for which there is no specific treatment, it is very important that the hygiene rules are complied with; in particular, children and their caregivers should pay attention to hand cleansing. We believe that more seroprevalence studies should be performed from different regions to show the status of the disease in our country.
Ultrafast growth rate and high mobility In2O3 films grown on c-sapphire via low pressure chemical vapor deposition
Authors: Zhang Yuxuan , Karim Md Rezaul , Feng Zixuan , Zhao Hongping
Published: April 2019

In this study, the growth of unintentionally doped semiconductor indium oxide with ultrafast growth rates on c-plane sapphire by low pressure chemical vapor deposition (LPCVD) was demonstrated. The effect of key growth parameters, such as oxygen flow rate and distance between the substrate to the indium source, on the growth rate, crystalline quality, surface morphology, as well as carrier transport properties were studied. The growth rate is highly dependent on the oxygen flow rate and the distance between the indium source and the substrate: (i) the growth rate reaches 113 μm/h with an oxygen flow rate of 75 sccm under the investigated growth condition; and (ii) it decreases exponentially with the increase of distance between the indium source and the substrate. X-ray diffraction characterization of the as-grown films indicates that the increase of oxygen flow rate leads to the suppression of (100) facet formation, significantly influencing the film morphology. The LPCVD growth conditions also determine the background doping and carrier mobility. With an oxygen flow rate of 75 sccm, a high electron mobility of 126 cm2 V−1 s−1 with a bulk concentration of 3.9 × 1017 cm−3 was obtained. Results from this work provide guidance on LPCVD growth of In2O3 with targeted growth rate, surface morphology, carrier concentration, and mobility.
Dynamics of a vertically vibrating mercury drop
Authors: Singla Tanu , Verma Dinesh Kumar , Tovar Josué Flores , Figueroa A. , Vázquez Federico , Yousif Farook Bashir , Rivera M.
Published: April 2019

The dynamics of vertically vibrating liquid drops has been studied by several researchers and different phenomena have been reported. In the present work, we report experimental results for some interesting phenomena that can be observed in a liquid drop subjected to vertical vibrations. For this purpose, a drop of Mercury was kept on a spherical watch glass and it was perturbed with different amplitudes and frequencies. The oscillations of the drop were recorded using a video camera and image analysis was used to further understand its behavior. The method of correlation was then employed to analyze the videos recorded with different perturbations. We report phenomena like subharmonic oscillations and rotation of the drop; and also the resonance and superpropulsion in the droplet ejection.
Improving the efficiency of a water-treatment system based on water cavitation and plasma using a nozzle-less reactor
Authors: Ihara Satoshi , Nishiyama Hiroki , Matsunaga Takashi , Yoshida Yuuki , Tokuyama Yuka , Terato Hiroaki
Published: April 2019

This study has been carried out to achieve high energy efficiency for a water purification method using a plasma generation with cavitation bubbles. In the method proposed herein, the pressure loss in the water flow path of the treatment reactor is reduced by removing the nozzle for the generation of cavitation. Cavitation bubbles can be generated between the electrodes installed in the flow path by adjusting the water flow rate. With and without nozzle, a similar degree of Escherichia coli sterilization was achieved. In the proposed system, the power consumption of the pump was reduced by removing the nozzle, and as a result, the total power consumption of the apparatus could be reduced.
The effect of graphene oxide reduction temperature on the kinetics of low-temperature sorption of hydrogen
Authors: Dolbin A. V. , Vinnikov N. A. , Esel’son V. B. , Gavrilko V. G. , Basnukaeva R. M. , Khlistuck M. V. , Maser W. K. , Benito A. M.
Published: April 2019

The effect of thermal reduction of graphene oxide on the hydrogen sorption and desorption kinetics was studied by temperature-programmed desorption in the 7–120 K temperature range. The heat treatment of graphene oxide samples resulted in a decrease in the activation energy for hydrogen diffusion by more than an order of magnitude (by a factor of 12–13) compared with the initial graphite oxide. This change in the activation energy is, most likely, caused by exfoliation (loosening) of the graphite oxide carbon sheets upon the thermal removal of intercalated water, which changes the sorption character by decreasing the influence of the opposite walls in the interlayer spaces.
Invasive pneumococcal disease and serotype emergence in the Auckland region during the vaccine era 2009–16
Authors: Eichler Nick , Reynolds Edwin , Jackson Catherine , Thornley Simon , Peters Julia
Published: April 2019

ABSTRACT
INTRODUCTIONThere is a deficit of knowledge in New Zealand as the epidemiology of invasive pneumococcal disease varies significantly between countries.
AIMTime trends and sociodemographic characteristics of cases of invasive pneumococcal disease (IPD) in the Auckland region are reviewed after the introduction of a conjugate vaccination, to provide evidence for future vaccine policy and to ensure Auckland region analysis is representative of national trends for subsequent IPD analysis.
METHODSData on all cases of IPD occurring in Waitemata, Auckland and Counties Manukau District Health Boards between 2009 and 2016 were extracted from EpiSurv. Denominator data were drawn from mid-year estimates supplied by Statistics New Zealand. Descriptive epidemiology and time-series regression was performed to analyse trends.
RESULTSRates of IPD have fallen in the Auckland region over the past 8 years by 32%. While absolute rates in the elderly have reduced by 12%, they have the highest disease burden at 32/100,000. The ethnic disparity continues with Pacific people (33/100,000) and Māori (14/100,000) over represented compared to European (10/100,000). In the elderly, the 19A serotype has increased from an incidence of 0 in 2008 to 8.2/100,000.
DISCUSSIONLarge ethnic and age-related disparities are observed in the Auckland region, consistent with the rest of the country, since the start of the pneumococcal vaccination era. Extending immunisation to the elderly may help close these gaps. As with other countries, there is 19A serotype replacement occurring following conjugate vaccine introduction.
Using the Multiple Mini Interview for selection into vocational general practice training
Authors: Lillis Steven , Lack Liza , Mbita Allan , Ashford Melissa
Published: April 2019

ABSTRACT
INTRODUCTIONInterviews for selection into post graduate training courses are an accepted method of selection. There is the presumption that such interview processes are fair to both candidates and the training scheme.
AIMDue to concerns over unconscious bias and a desire to move to best practice, the Royal New Zealand College of General Practitioners introduced the Mini Multiple Interview (MMI) process as the selection process for doctors wishing to enter vocational training in general practice.
METHODSAspects assessed during the interviews were developed through wide consultation and included: reason for wanting to undertake training, managing poor compliance, addressing issues of equity, managing complaints, insight and understanding the role of general practitioners in chronic care. There were 218 applicants who took the MMI. Demographic data as well as scores were collected.
RESULTSThe MMI process has good reliability and performs well in several aspects of validity. All three interview venues had similar results. There was no gender difference in overall result or scores. New Zealand graduates scored higher than overseas graduates. Of the 218 candidates, 12 were considered not yet ready to enter training.
DISCUSSIONThe MMI process appears to have acceptable reliability and good validity. The structure of the MMI is likely to have reduced unconscious bias. Further research will study the predictive validity of the MMI for this cohort of candidates.
Uniquely human CHRFAM7A gene increases the hematopoietic stem cell reservoir in mice and amplifies their inflammatory response
Authors: Costantini Todd W. , Chan Theresa W. , Cohen Olga , Langness Simone , Treadwell Sabrina , Williams Elliot , Eliceiri Brian P. , Baird Andrew
Published: April 2019

Significance

The emergence of uniquely human genes during hominid speciation enabled numerous human-specific adaptations that presumably included changes in resilience to disease but potentially increased susceptibility as well. Here we show that the transgenic expression of one such gene, called CHRFAM7A, changes the mouse reservoir of hematopoietic stem cells in bone marrow and amplifies the mouse inflammatory response in a model of human systemic inflammatory response syndrome (SIRS). Because the CHRFAM7A gene is a dominant-negative inhibitor of ligand binding to α7 nicotinic acetylcholine receptor (α7nAChR), a neurotransmitter receptor implicated in immunity, inflammation, neurodegeneration, and cognitive function, the results underscore the importance of understanding the contribution of species-specific genes to human disease and the impact they may have on the fidelity of animal models for translational medicine.
Adiponectin accounts for gender differences in hepatocellular carcinoma incidence
Authors: Manieri Elisa , Herrera-Melle Leticia , Mora Alfonso , Tomás-Loba Antonia , Leiva-Vega Luis , Fernández Delia I. , Rodríguez Elena , Morán Laura , Hernández-Cosido Lourdes , Torres Jorge L. , Seoane Luisa M. , Cubero Francisco Javier , Marcos Miguel , Sabio Guadalupe
Published: April 2019

Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α. This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics.
The desmosome is a mesoscale lipid raft–like membrane domain
Authors: Lewis Joshua D. , Caldara Amber L. , Zimmer Stephanie E. , Stahley Sara N. , Seybold Anna , Strong Nicole L. , Frangakis Achilleas S. , Levental Ilya , Wahl James K. , Mattheyses Alexa L. , Sasaki Takashi , Nakabayashi Kazuhiko , Hata Kenichiro , Matsubara Yoichi , Ishida-Yamamoto Akemi , Amagai Masayuki , Kubo Akiharu , Kowalczyk Andrew P.
Published: April 2019

Desmogleins (Dsgs) are cadherin family adhesion molecules essential for epidermal integrity. Previous studies have shown that desmogleins associate with lipid rafts, but the significance of this association was not clear. Here, we report that the desmoglein transmembrane domain (TMD) is the primary determinant of raft association. Further, we identify a novel mutation in the DSG1 TMD (G562R) that causes severe dermatitis, multiple allergies, and metabolic wasting syndrome. Molecular modeling predicts that this G-to-R mutation shortens the DSG1 TMD, and experiments directly demonstrate that this mutation compromises both lipid raft association and desmosome incorporation. Finally, cryo-electron tomography indicates that the lipid bilayer within the desmosome is ∼10% thicker than adjacent regions of the plasma membrane. These findings suggest that differences in bilayer thickness influence the organization of adhesion molecules within the epithelial plasma membrane, with cadherin TMDs recruited to the desmosome via the establishment of a specialized mesoscale lipid raft–like membrane domain.
Newly synthesized claudins but not occludin are added to the basal side of the tight junction
Authors: Van Itallie Christina M. , Lidman Karin Fredriksson , Tietgens Amber Jean , Anderson James Melvin
Published: April 2019

A network of claudin strands creates continuous cell–cell contacts to form the intercellular tight junction barrier; a second protein, occludin, is associated along these strands. The physiological barrier remains stable despite protein turnover, which involves removal and replacement of claudins both in the steady state and during junction remodeling. Here we use a pulse–block–pulse labeling protocol with fluorescent ligands to label SNAP/CLIP-tags fused to claudins and occludin to identify their spatial trafficking pathways and kinetics in Madin–Darby canine kidney monolayers. We find that claudins are first delivered to the lateral membrane and, over time, enter the junction strand network from the basal side; this is followed by slow replacement of older claudins in the strands. In contrast, even at early times, newly synthesized occludin is found throughout the network. Taking the results together with our previous documentation of the mechanism for claudin strand assembly in a fibroblast model, we speculate that newly synthesized claudins are added at strand breaks and free ends; these are most common in the basalmost edge of the junction. In contrast, occludin can be added directly within the strand network. We further demonstrate that claudin trafficking and half-life depend on carboxy-terminal sequences and that different claudins compete for tight junction localization.
ARHGAP4 regulates the cell migration and invasion of pancreatic cancer by the HDAC2/β-catenin signaling pathway
Authors: Shen Yehua , Xu Litao , Ning Zhouyu , Liu Luming , Lin Junhua , Chen Hao , Meng Zhiqiang
Published: April 2019

β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway that mediates multiple cellular processes, such as cell migration and invasion. HDAC2 (histone deacetylase 2), a deacetylase that maintains histone H3 in a deacetylated state in the promoter region of Wnt-targeted genes where β-catenin is bound, negatively regulating β-catenin activation. However, the regulation of HDAC2/β-catenin pathway remains unclear. Here, we report ARHGAP4 as a new regulator of the β-catenin pathway that regulates cell invasion and migration of pancreatic cancer as well as the downstream effector MMP2 and MMP9 expression in vitro. Mechanistically, ARHGAP4 interacts with and ubiquitinates HDAC2, which in turn inhibits β-catenin activation. Furthermore, treatment of CAY10683, an HDAC2 inhibitor, and XAV939, a Wnt/β-catenin pathway inhibitor, attenuated the effects of ARHGAP4 silencing on pancreatic cancer cells. Overall, our findings establish ARHGAP4 as a novel regulator of HDAC2/β-catenin pathway with a critical role in tumorigenesis.
Hollywood in the Hinterland: Newspapers, Itinerant Films and Community Identity in the 1920s
Authors: Cieslik-Miskimen Caitlin
Published: April 2019

Itinerant films represented a substantial media and cultural phenomenon during the first half of the 20th century, and provided a localized form of a mass culture product. Through an analysis of archival materials and newspaper accounts related to the production of 11 itinerant movies filmed in the Midwestern United States in the 1920s, this article examines the relationship between the itinerant films and community newspapers. By supporting these productions, these newspapers used a relatively new communication technology as a way to solidify their civic position. They helped create an intensely local product featuring recognizable landmarks, businesses and people that offered readers a way to combat the loss of community and place in an increasingly networked society.
Serotypes of Streptococcus pneumoniae in Children Aged <5 Years Hospitalized With or Without Pneumonia in Developing and Emerging Countries: A Descriptive, Multicenter Study
Authors: Dananché Cédric , Paranhos-Baccalà Gláucia , Messaoudi Mélina , Sylla Mariam , Awasthi Shally , Bavdekar Ashish , Sanghavi Sonali , Diallo Souleymane , Pape Jean-William , Rouzier Vanessa , Chou Monidarin , Eap Tekchheng , Rakoto-Andrianarivelo Mala , Maeder Muriel , Wang Jianwei , Ren Lili , Dash-Yandag Budragchaagiin , Nymadawa Pagbajabyn , Guillen Rosa , Russomando Graciela , Endtz Hubert , Komurian-Pradel Florence , Vanhems Philippe , Sánchez Picot Valentina
Published: April 2019

Background

Improving knowledge regarding Streptococcus pneumoniae distribution in pneumonia cases is important to better target preventive and curative measures. The objective was to describe S. pneumoniae serotypes in children with or without pneumonia

Methods

It was a case-control study carried out in 8 developing and emerging countries between 2010 and 2014. Cases were children aged <5 years admitted to the hospital for pneumonia. Controls were children admitted for surgery or routine outpatient care.

Results

In nasopharyngeal samples, S. pneumoniae were detected in 68.2% of the cases and 47.5% of the controls (P < .001). Nasopharyngeal carriage was associated with a higher risk of being a case in 6/8 study sites (adjusted odds ratio ranged from 0.71 [95% confidence interval [CI], .39–1.29; P = .26] in India [Pune/Vadu] to 11.86 [95% CI, 5.77–24.41; P < .001] in Mongolia). The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were more frequently detected in cases with nasopharyngeal carriage (67.1%) than in controls with nasopharyngeal carriage (54.6%), P < .001. Streptococcus pneumoniae was detected in blood by polymerase chain reaction in 8.3% of the cases. Of 34 cases with an S. pneumoniae serotype detected in blood, 27 (79%) had the same serotype in the nasopharyngeal sample.

Conclusions

The results confirm the assumption that the isolate carrying or causing disease in an individual is of the same serotype. Most serotypes independently associated with nasopharyngeal carriage or pneumonia are covered by PCV13, suggesting that increased PCV coverage would reduce the burden of S. pneumoniae–related pneumonia.
Isavuconazole Prophylaxis in Patients With Hematologic Malignancies and Hematopoietic Cell Transplant Recipients
Authors: Fontana Lauren , Perlin David S , Zhao Yanan , Noble Brie N , Lewis James S , Strasfeld Lynne , Hakki Morgan
Published: April 2019

Background

Isavuconazole (ISA) is an attractive candidate for primary mold-active prophylaxis in high-risk patients with hematologic malignancies or hematopoietic cell transplant (HCT) recipients. However, data supporting the use of ISA for primary prophylaxis in these patients are lacking.

Methods

We conducted a retrospective review of breakthrough invasive fungal infections (bIFIs) among adult hematologic malignancy patients and HCT recipients who received ≥7 days of ISA primary prophylaxis between 1 September 2016 and 30 September 2018. The incidence of bIFIs in patients receiving ISA was compared to those receiving posaconazole (POS) and voriconazole (VOR) during the same time period.

Results

One hundred forty-five patients received 197 courses of ISA prophylaxis. Twelve bIFIs (Aspergillus fumigatus [5], Aspergillus species [2], Mucorales [2], Fusarium species [2], and Candida glabrata [1]) occurred, representing 8.3% of patients and 6.1% of courses, after a median duration of 14 days of ISA prophylaxis. All bIFIs occurred during periods of neutropenia. Seven patients (58.3%) died within 42 days of onset of bIFI. In addition, bIFIs complicated 10.2% of ISA, 4.1% of POS, and 1.1% of VOR courses among patients with de novo or relapsed/refractory acute myeloid leukemia during the study period, with invasive pulmonary aspergillosis (IPA) complicating 6.8% of ISA, 1.3% of POS, and zero VOR courses.

Conclusions

Although ISA has been approved for treatment of invasive Aspergillus and mucormycosis, we observed an increased rate of bIFI, notably IPA, using ISA for primary prophylaxis. These results support the need for further study to determine the role of ISA as primary prophylaxis.
Coupling of the Na+/K+-ATPase to Ankyrin B controls Na+/Ca2+ exchanger activity in cardiomyocytes
Authors: Skogestad Jonas , Aronsen Jan Magnus , Tovsrud Nils , Wanichawan Pimthanya , Hougen Karina , Stokke Mathis Korseberg , Carlson Cathrine Rein , Sjaastad Ivar , Sejersted Ole Mathias , Swift Fredrik
Published: April 2019

Aims

Ankyrin B (AnkB) is an adaptor protein that assembles Na+/K+-ATPase (NKA) and Na+/Ca2+ exchanger (NCX) in the AnkB macromolecular complex. Loss-of-function mutations in AnkB cause the AnkB syndrome in humans, characterized by ventricular arrhythmias and sudden cardiac death. It is unclear to what extent NKA binding to AnkB allows regulation of local Na+ and Ca2+ domains and hence NCX activity.

Methods and results

To investigate the role of NKA binding to AnkB in cardiomyocytes, we synthesized a disruptor peptide (MAB peptide) and its AnkB binding ability was verified by pulldown experiments. As opposed to control, the correlation between NKA and NCX currents was abolished in adult rat ventricular myocytes dialyzed with MAB peptide, as well as in cardiomyocytes from AnkB+/− mice. Disruption of NKA from AnkB (with MAB peptide) increased NCX-sensed cytosolic Na+ concentration, reduced Ca2+ extrusion through NCX, and increased frequency of Ca2+ sparks and Ca2+ waves without concomitant increase in Ca2+ transient amplitude or SR Ca2+ load, suggesting an effect in local Ca2+ domains. Selective inhibition of the NKAα2 isoform abolished both the correlation between NKA and NCX currents and the increased rate of Ca2+ sparks and waves following NKA/AnkB disruption, suggesting that an AnkB/NKAα2/NCX domain controls Ca2+ fluxes in cardiomyocytes.

Conclusion

NKA binding to AnkB allows ion regulation in a local domain, and acute disruption of the NKA/AnkB interaction using disruptor peptides lead to increased rate of Ca2+ sparks and waves. The functional effects were mediated through the NKAα2 isoform. Disruption of the AnkB/NKA/NCX domain could be an important pathophysiological mechanism in the AnkB syndrome.
The effect of diet on hypertensive pathology: is there a link via gut microbiota-driven immunometabolism?
Authors: Jama Hamdi A , Beale Anna , Shihata Waled A , Marques Francine Z
Published: April 2019

Over the past decade, the immune system has emerged as an important component in the aetiology of hypertension. There has been a blooming interest in the contribution of the gut microbiota, the microbes that inhabit our small and large intestine, to blood pressure (BP) regulation. The gastrointestinal tract houses the largest number of immune cells in our body, thus, it is no surprise that its microbiota plays an important functional role in the appropriate development of the immune system through a co-ordinated sequence of events leading to immune tolerance of commensal bacteria. Importantly, recent evidence supports that the gut microbiota can protect or promote the development of experimental hypertension and is likely to have a role in human hypertension. One of the major modulators of the gut microbiota is diet: diets that emphasize high intake of fermentable fibre, such as the Mediterranean diet and the Dietary Approaches to Stop Hypertension, promote expansion of protective microbes that release gut metabolites such as short-chain fatty acids, which are immune-, BP-, and cardio-protective, likely acting through G-coupled protein receptors. In contrast, diets lacking fibre or high in salt and fat, such as the Western diet, reduce prevalence of commensal microbial species and support a pathogenic and pro-inflammatory environment, including the release of the pro-atherosclerotic trimethylamine N-oxide. Here, we review the current understanding of the gut microbiota-driven immune dysfunction in both experimental and clinical hypertension, and how these changes may be addressed through dietary interventions.
Digital expression explorer 2: a repository of uniformly processed RNA sequencing data
Authors: Ziemann Mark , Kaspi Antony , El-Osta Assam
Published: April 2019

Background

RNA sequencing (RNA-seq) is an indispensable tool in the study of gene regulation. While the technology has brought with it better transcript coverage and quantification, there remain considerable barriers to entry for the computational biologist to analyse large data sets. There is a real need for a repository of uniformly processed RNA-seq data that is easy to use.

Findings

To address these obstacles, we developed Digital Expression Explorer 2 (DEE2), a web-based repository of RNA-seq data in the form of gene-level and transcript-level expression counts. DEE2 contains >5.3 trillion assigned reads from 580,000 RNA-seq data sets including species Escherichia coli, yeast, Arabidopsis, worm, fruit fly, zebrafish, rat, mouse, and human. Base-space sequence data downloaded from the National Center for Biotechnology Information Sequence Read Archive underwent quality control prior to transcriptome and genome mapping using open-source tools. Uniform data processing methods ensure consistency across experiments, facilitating fast and reproducible meta-analyses.

Conclusions

The web interface allows users to quickly identify data sets of interest using accession number and keyword searches. The data can also be accessed programmatically using a specifically designed R package. We demonstrate that DEE2 data are compatible with statistical packages such as edgeR or DESeq. Bulk data are also available for download. DEE2 can be found at http://dee2.io.