bluuebunny/crossref_metadata_2025 huggingface dataset:
Behaviour of transmission and distribution networks with big consumption, the stress test
Authors: Eparu C N , Neacsu S , Prundurel A P , Radulescu R , Neacșa A
Published: September 2019

Customers of gas transmission and distribution networks consume gas as they needed. Such consumptions vary continuously. It was found that within one day, in most of the cases, there are two major peaks. Because the gas is compressible, the load peaks can be covered from the network’s linepack, with the condition that their dynamics are known and the network is prepared in advance, that is, “today” for “tomorrow”. The paper presents the tools and the analysis of the natural gas networks and the limits of their safe operation. The paper also proposes a network stress test to verify the future behaviour of the network at high loads as well as to determine the necessary parameters for the next period of maintenance.
Analysis of a high-pressure screw compressor performances
Authors: Eparu C N , Neacșa A , Prundurel A P , Rădulescu R , Slujitoru C , Toma N , Nițulescu M
Published: September 2019

Oil flooded screw compressors with discharge pressures of up to 26 bar have been available, commercially for some years. However, demands for higher pressure operation led to the design, construction and testing of a compressor operating with discharge pressures of up to 45 bar. To maximize the compressor efficiency, extensive performance simulations were carried out. Since 1980 oil flooded screw compressors have been used in many process gas compression applications and in the last year the higher pressure and larger capacity was realized. From 2010 to 2015 INCDT COMOTI manufactured screw compressors under GHH-Rand license (CU type, with max. delivery pressure 26 bar). Experience gain in this process gives us the power to develop the new type of screw compressors - based on license - with high delivery pressure - max. 45 bar. This paper will present details about the tests with a new high pressure screw compressor test in a closed loop test configuration. The machine was then tested in a closed loop test rig and, as is shown, the measured performance agrees well with that predicted by the numerical model. The parameters will be analysed starting from CFD modelling of the process and finally comparative analysis with actual parameters. The demonstrated advantages of this type of compressor, like high reliability, simple foundations, low operational cost, low initial cost, suitability for process fluctuation - gas pressure, gas composition - led to a significant demand for such compressors.
Analysis of a proportional pressure regulator
Authors: Avram M , Ștefănescu M-F , Șerban A , Dobrovicescu A , Grămescu B
Published: September 2019

The paper deals with the theoretical and experimental analysis of a proportional pneumatic device. Such a piece of equipment can be integrated in the structure of an intelligent system that works with compressed gases. Different constructive variants of this type of equipment are analyzed. Authors focus their attention on a device that makes use of an electro-mechanic actuator operating with a proportional electromagnet. For the mathematical model some simplifying assumptions are identified. The mathematical model is numerically integrated. The behavior of the proportional pneumatic device at the variation of the inlet pressure and outlet mass flow rate consumption is pointed out.
Effect of yaw angle on the global performances of Horizontal Axis Wind Turbine - QBlade simulation
Authors: Husaru D E , Bârsănescu P D , Zahariea D
Published: September 2019

The yaw angle has a great importance in the wind turbine working. Even though most of the large turbines have yaw mechanisms, they do not have an instant response. The aerodynamic forces and torque on the blades fluctuate, depending on the yaw angle. The design and the numerical simulation of the wind turbine were performed with the Blade Element Momentum method in open source QBlade software. The power coefficient, torque, thrust and power output generated by wind turbine in non-yawed flow were analysed. The simulations have been performed for non-yawed flow, in rotational speed range between 2100 and 3300 rpm and wind velocity of 15 m/s. Simulations for yaw angle range have been performed between ± 60°, with 5° step at rated rotational speed of 2700 rpm. The results are presented through charts for global parameters in both non-yawed flow, and yawed flow. The effect of yaw angle on global performances of the wind turbines is more important after the value of 25° when the power output decrease with about 15% from power output in non-yawed flow. The average value of the exponent from conventional relation of power coefficient in yawed flow is 1.77 in good concordance with experimental tests.
Modelling and simulation of a hydraulic system used for wind turbines
Authors: Pelin R-I , Tița I
Published: September 2019

For wind turbines, pitch control is essential. In some cases, especially in the case of large scale wind turbines, hydraulic control is used. In this paper a hydraulic system used in wind turbine pitch control is analysed. Modelling and simulation of hydraulic systems is necessary in order to acknowledge the drawbacks and advantages before starting the design of the system. By acknowledging, the differences between the model of a physical system and a system in a virtual environment, one can handle the improvement, in terms of price or time-consumption. Considering the proposed diagram of the pitch control hydraulic system, it is presented the block diagram created in MATLAB Simscape Fluids. Some results of the simulation are presented. There are included conclusions and plans for future work.
SCUBA-2 observations of candidate starbursting protoclusters selected by Planck and Herschel-SPIRE
Authors: Cheng T , Clements D L , Greenslade J , Cairns J , Andreani P , Bremer M , Conversi L , Cooray A , Dannerbauer H , De Zotti G , Eales S , González-Nuevo J , Ibar E , Leeuw L , Ma J , Michałowski M J , Nayyeri H , Riechers D A , Scott D , Temi P , Vaccari M , Valtchanov I , van Kampen E , Wang L
Published: September 2019

We present SCUBA-2 850 $\mathrm{ \mu}$m observations of 13 candidate starbursting protoclusters selected using Planck and Herschel data. The cumulative number counts of the 850 $\mathrm{ \mu}$m sources in 9 of 13 of these candidate protoclusters show significant overdensities compared to the field, with the probability <10−2 assuming the sources are randomly distributed in the sky. Using the 250, 350, 500, and 850 $\mathrm{ \mu}$m flux densities, we estimate the photometric redshifts of individual SCUBA-2 sources by fitting spectral energy distribution templates with an MCMC method. The photometric redshift distribution, peaking at 2 < z < 3, is consistent with that of known z > 2 protoclusters and the peak of the cosmic star formation rate density (SFRD). We find that the 850 $\mathrm{ \mu}$m sources in our candidate protoclusters have infrared luminosities of $L_{\mathrm{IR}}\gtrsim 10^{12}\, \mathrm{L}_{\odot }$ and star formation rates of SFR  = (500–1500) M⊙ yr−1. By comparing with results in the literature considering only Herschel photometry, we conclude that our 13 candidate protoclusters can be categorized into four groups: six of them being high-redshift starbursting protoclusters, one being a lower redshift cluster or protocluster, three being protoclusters that contain lensed dusty star-forming galaxies or are rich in 850 $\mathrm{ \mu}$m sources, and three regions without significant Herschel or SCUBA-2 source overdensities. The total SFRs of the candidate protoclusters are found to be comparable or higher than those of known protoclusters, suggesting our sample contains some of the most extreme protocluster population. We infer that cross-matching Planck and Herschel data is a robust method for selecting candidate protoclusters with overdensities of 850 $\mathrm{ \mu}$m sources.
On the mass segregation of cores and stars
Authors: Alcock Hayley L , Parker Richard J
Published: September 2019

Observations of pre- and proto-stellar cores in young star-forming regions show them to be mass segregated, i.e. the most massive cores are centrally concentrated, whereas pre-main-sequence stars in the same star-forming regions (and older regions) are not. We test whether this apparent contradiction can be explained by the massive cores fragmenting into stars of much lower mass, thereby washing out any signature of mass segregation in pre-main-sequence stars. Whilst our fragmentation model can reproduce the stellar initial mass function, we find that the resultant distribution of pre-main sequence stars is mass segregated to an even higher degree than that of the cores, because massive cores still produce massive stars if the number of fragments is reasonably low (between one and five). We therefore suggest that the reason cores are observed to be mass segregated and stars are not is likely due to dynamical evolution of the stars, which can move significant distances in star-forming regions after their formation.
Can redshift errors bias measurements of the Hubble Constant?
Authors: Davis Tamara M , Hinton Samuel R , Howlett Cullan , Calcino Josh
Published: September 2019

Redshifts have been so easy to measure for so long that we tend to neglect the fact that they too have uncertainties and are susceptible to systematic error. As we strive to measure cosmological parameters to better than 1 per cent it is worth reviewing the accuracy of our redshift measurements. Surprisingly small systematic redshift errors, as low as 10−4, can have a significant impact on the cosmological parameters we infer, such as H0. Here, we investigate an extensive (but not exhaustive) list of ways in which redshift estimation can go systematically astray. We review common theoretical errors, such as adding redshifts instead of multiplying by (1 + z); using v = cz; and using only cosmological redshift in the estimates of luminosity and angular diameter distances. We consider potential observational errors, such as rest wavelength precision, air to vacuum conversion, and spectrograph wavelength calibration. Finally, we explore physical effects, such as peculiar velocity corrections, galaxy internal velocities, gravitational redshifts, and overcorrecting within a bulk flow. We conclude that it would be quite easy for small systematic redshift errors to have infiltrated our data and be impacting our cosmological results. While it is unlikely that these errors are large enough to resolve the current H0 tension, it remains possible, and redshift accuracy may become a limiting factor in near future experiments. With the enormous efforts going into calibrating the vertical axis of our plots (standard candles, rulers, clocks, and sirens) we argue that it is now worth paying a little more attention to the horizontal axis (redshifts).
Heavy negative ion growth in Titan’s polar winter
Authors: Wellbrock A , Coates A J , Jones G H , Vuitton V , Lavvas P , Desai R T , Waite J H
Published: September 2019

A significant but unexpected result of the Cassini mission was the discovery of heavy organic negative ions in Titan’s ionosphere at altitudes between about 950 and 1400 km by the CAPS Electron Spectrometer (ELS). The heaviest ions were observed during the T16 fly-by with masses over 13 000 u/q. This is significantly higher than the maximum masses observed during other fly-bys. We study T16 CAPS-ELS observations and examine the evolution of mass spectra at different altitudes. We also study maximum mass trends using a large data set from all available CAPS-ELS observations of the Cassini mission in order to investigate the conditions necessary to allow negative ions to grow to the highest masses. For the first time, we are able to investigate the relationship between the highest mass particles and seasonal effects. We find that the combination of high latitude and winter conditions, resulting in long-term restricted solar flux, create an environment in which ion growth can reach the highest masses, as observed during T16. Restricting solar flux long term, and hence photodestruction reactions such as photodetachment, appears to be essential for negative ions to grow beyond 10 000 u/q.
A solution of Jupiter’s gravitational field from Juno data with the orbit14 software
Authors: Serra Daniele , Lari Giacomo , Tommei Giacomo , Durante Daniele , Gomez Casajus Luis , Notaro Virginia , Zannoni Marco , Iess Luciano , Tortora Paolo , Bolton Scott J
Published: September 2019

The latest estimation of Jupiter’s gravitational field was obtained by processing the Doppler data from two gravity orbits of NASA’s Juno mission, using the Jet Propulsion Laboratory software monte. In this work, we present the results of the analysis of the same measurements employing the orbit determination software orbit14, developed at the University of Pisa, used here for the first time with real data. We found that the estimated values of Jupiter’s spherical harmonic coefficients from the two solutions are consistent within the formal uncertainty. The analysis is complemented with a discussion on the results obtained with alternative set-ups.
ALMACAL – VI. Molecular gas mass density across cosmic time via a blind search for intervening molecular absorbers
Authors: Klitsch Anne , Péroux Céline , Zwaan Martin A , Smail Ian , Nelson Dylan , Popping Gergö , Chen Chian-Chou , Diemer Benedikt , Ivison R J , Allison James R , Muller Sébastien , Swinbank A Mark , Hamanowicz Aleksandra , Biggs Andrew D , Dutta Rajeshwari
Published: September 2019

We are just starting to understand the physical processes driving the dramatic change in cosmic star formation rate between z ∼ 2 and the present day. A quantity directly linked to star formation is the molecular gas density, which should be measured through independent methods to explore variations due to cosmic variance and systematic uncertainties. We use intervening CO absorption lines in the spectra of mm-bright background sources to provide a census of the molecular gas mass density of the Universe. The data used in this work are taken from ALMACAL, a wide and deep survey utilizing the ALMA calibrator archive. While we report multiple Galactic absorption lines and one intrinsic absorber, no extragalactic intervening molecular absorbers are detected. However, due to the large redshift path surveyed (Δz = 182), we provide constraints on the molecular column density distribution function beyond z ∼ 0. In addition, we probe column densities of N(H2) > 1016 atoms cm−2, 5 orders of magnitude lower than in previous studies. We use the cosmological hydrodynamical simulation IllustrisTNG to show that our upper limits of $\rho ({\rm H}_2)\lesssim 10^{8.3}\, \text{M}_{\odot }\, \text{Mpc}^{-3}$ at 0 < z ≤ 1.7 already provide new constraints on current theoretical predictions of the cold molecular phase of the gas. These results are in agreement with recent CO emission-line surveys and are complementary to those studies. The combined constraints indicate that the present decrease of the cosmic star formation rate history is consistent with an increasing depletion of molecular gas in galaxies compared to z ∼ 2.
A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System
Authors: Tran Diem Kieu , Paff Michelle , Mnatsakanyan Lilit , Sen-Gupta Indranil , Lin Jack J , Hsu Frank P K , Vadera Sumeet
Published: September 2019

BACKGROUND

The responsive neurostimulation system (RNS) (NeuroPace Inc, Mountain View, California) was approved as an adjunctive therapy for medically refractory focal epilepsy. RNS detects epileptiform patterns and delivers electrical stimulation to abort seizures.

OBJECTIVE

To describe a novel technique of RNS lead implantation using robotic-assisted targeting of ictal-onset zones based on stereoelectroencephalography (sEEG) localization. Secondary objectives are to report the accuracy of robotic-assisted lead implantation using the ROSA robot as well as to report the clinical outcome achieved after RNS implantation by this method.

METHODS

A total of 16 patients with medically refractory focal epilepsy underwent sEEG implantation for ictal-onset localization followed by robotic RNS implantation. The electrode most correlative with ictal onset on sEEG was chosen as the target for the RNS electrode. Seizure control was measured at 6-mo and 1-yr follow-up. Ictal-onset electrocorticography (ECoG) data from RNS were compared with ictal onset from sEEG leads based on calculations of lead target to actual lead location from the ROSA robot.

RESULTS

At 6-mo follow-up, the average percent seizure reduction was 82% based upon self-reported seizure diaries. At 1-yr follow-up, 8 patients had an average of 90% seizure reduction. The location of seizure onset from ECoG data show similar onset from sEEG leads within 0.165-mm discrepancy.

CONCLUSION

The ROSA robot provides an ideal method for targeting subcortical ictal-onset zones. This method of RNS lead implantation achieves high accuracy and is associated with favorable clinical outcomes.
Microsurgical Anatomy of the Meningeal Branch of the Dorsolateral Medullary Plexus
Authors: Tayebi Meybodi Ali , Zhao Xiaochun , Borba Moreira Leandro , Preul Mark C , Alhilali Lea M , Lawton Michael T
Published: September 2019

BACKGROUND

Meningeal branches originating from intradural arteries may be involved in several diseases such as meningeal tumors and arteriovenous lesions. These “pial-dural” arterial connections have been described for anterior cerebral, posterior cerebral, and cerebellar arteries. However, to the best of our knowledge, meningeal supply originating from the arterial plexus over the dorsolateral aspect of the medulla oblongata (dorsolateral medullary plexus [DLMP]) has not been described.

OBJECTIVE

To define the microsurgical anatomy of the meningeal branch of DLMP.

METHODS

A total of 20 cadaver heads (40 sides) underwent far-lateral craniotomy and the cerebellomedullary cisterns were explored to find the DLMP and any meningeal branches. Additionally, de-identified intraoperative images of 85 patients with vertebral artery (VA)/posterior inferior cerebellar artery aneurysms who had undergone far-lateral craniotomy were studied to find any meningeal branches of DLMP.

RESULTS

The meningeal branches of DLMP were identified in 4 cadavers/sides. These branches reached the region of jugular tubercle (JT) after crossing the accessory nerve. In 3 specimens, these branches were joined by a small twig from V4-VA before penetrating the dura. DLMP meningeal branches were found in 12 patients of the studied cohort (14%) with similar anatomical features as those found in the cadaveric study.

CONCLUSION

DLMP may give rise to meningeal branches to the adjacent dura of JT. The actual prevalence of this anatomic variation is difficult to estimate using our data. However, when present, these branches may have important clinical implications, ie, diseases such as dural arteriovenous fistulas, pial arteriovenous malformations (AVMs), and meningeal-based tumors.
Vascular Endothelial Growth Factor A Signaling Promotes Spinal Central Sensitization and Pain-related Behaviors in Female Rats with Bone Cancer
Authors: Hu Xue-Ming , Yang Wei , Du Li-Xia , Cui Wen-Qiang , Mi Wen-Li , Mao-Ying Qi-Liang , Chu Yu-Xia , Wang Yan-Qing
Published: September 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization.

Methods

This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell patch-clamp recordings. The primary outcome was the effect of pharmacologic intervention of spinal vascular endothelial growth factor A/vascular endothelial growth factor receptor 2–signaling on bone cancer pain behaviors.

Results

The mRNA and protein expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 were upregulated in tumor-bearing rats. Spinal blocking vascular endothelial growth factor A or vascular endothelial growth factor receptor 2 significantly attenuated tumor-induced mechanical allodynia (mean ± SD: vascular endothelial growth factor A, 7.6 ± 2.6 g vs. 5.3 ± 3.3 g; vascular endothelial growth factor receptor 2, 7.8 ± 3.0 g vs. 5.2 ± 3.4 g; n = 6; P < 0.0001) and thermal hyperalgesia (mean ± SD: vascular endothelial growth factor A, 9.0 ± 2.4 s vs. 7.4 ± 2.7 s; vascular endothelial growth factor receptor 2, 9.3 ± 2.5 s vs. 7.5 ± 3.1 s; n = 6; P < 0.0001), as well as spontaneous pain and abnormal gaits. Exogenous vascular endothelial growth factor A enhanced excitatory synaptic transmission in a vascular endothelial growth factor receptor 2–dependent manner, and spinal injection of exogenous vascular endothelial growth factor A was sufficient to cause pain hypersensitivity via vascular endothelial growth factor receptor 2–mediated activation of protein kinase C and Src family kinase in naïve rats. Moreover, spinal blocking vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 pathways suppressed protein kinase C-mediated N-methyl-d-aspartate receptor activation and Src family kinase-mediated proinflammatory cytokine production.

Conclusions

Vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 contributes to central sensitization and bone cancer pain via activation of neuronal protein kinase C and microglial Src family kinase pathways in the spinal cord.
Prediction of Unilateral Meniere’s Disease Attack Using Inner Ear Test Battery
Authors: Wu Po-Hsuan , Chang Chih-Ming , Lo Wu-Chia , Wang Chi-Te , Wen Ming-Hsun , Huang Tsung-Wei , Young Yi-Ho , Cheng Po-Wen
Published: September 2019

Objectives:

In the clinical setting, a variety of inner ear test results are obtained from patients with unilateral Meniere’s disease (MD). In this study, the authors use inner ear test results as parameters to illustrate the relationship between inner ear function and vertigo attack frequency.

Design:

We retrospectively enrolled 50 unilateral MD patients. In addition to clinical symptoms, the results of pure-tone audiometry and caloric, acoustic cervical vestibular-evoked myogenic potential (cVEMP), galvanic cVEMP, vibratory ocular VEMP (oVEMP), and galvanic oVEMP tests were collected via chart review. The multiple linear regression method was used to examine which independent variables have a statistically significant influence on vertigo attacks.

Results:

In affected ears, the abnormal rate of the caloric, acoustic cVEMP, galvanic cVEMP, vibratory oVEMP, and galvanic oVEMP tests was 74%, 76%, 48%, 34%, and 30%, respectively. According to the regression model, the abnormal galvanic cVEMP response and abnormal galvanic oVEMP response had significantly negative correlations with the frequency of vertigo attacks after logarithmic transformation. A predictive model for disease attack frequency using significant parameters and their regression coefficients was proposed:

JOURNAL/earher/04.03/00003446-202005000-00014/inline-graphic1/v/2023-07-26T063803Z/r/image-tiff

Conclusions:

Using the proposed model with galvanic VEMP, clinicians could develop better strategies to manage vertigo attacks in patients with MD.
Assessing Femoral Rotation: A Survey Comparison of Techniques
Authors: Marchand Lucas S. , Jacobson Lance G. , Stuart Ami R. , Haller Justin M. , Higgins Thomas F. , Rothberg David L.
Published: September 2019

Objectives:

To compare 3 common techniques for assessing femoral malrotation through a response analysis.

Methods:

Ten intact human cadaveric pelvis-to-knee specimens were used to create a fracture model. A mobile C-arm x-ray system was used to capture images of an intact control femur and a contralateral test femur on each specimen. A midshaft femoral osteotomy was created on the test femur and it was then internally and externally rotated in 5-degree intervals up to 20 degrees. Images were obtained and stored at each increment of malrotation. Eight surveys of 20-paired images each were generated and presented for surgeon review. Accuracy of predicting femoral malrotation using the true lateral technique (TLT), neck horizontal angle (NHA) method, and lesser trochanter profile (LTP) was measured.

Results:

Eighty-five surgeons completed a survey with 80 surgeons (94%) acknowledging the use of a described fluoroscopic method for assisting with rotational alignment. Surgeons correctly accepted a fracture rotated less than 20 degrees and rejected a fracture rotated 20 degrees or more 63% of the time. The ability to correctly identify 20 degrees of malrotation varied per technique used to assess rotation. With the LTP and NHA method, 67% of surgeons responded correctly. Surgeons performed significantly worse when using the TLT with only 53% providing correct responses (P < 0.0001).

Conclusions:

Surgeons using described fluoroscopic methods to identify acceptable rotation in femoral shaft fractures are correct 63% of the time. The LTP and NHA techniques are equally reliable and more effective than the TLT at detecting clinically significant femoral malrotation.
Aluminum Chloride–Induced Apoptosis Leads to Keratinization Arrest and Granular Parakeratosis
Authors: Fujii Mizue , Kishibe Mari , Honma Masaru , Anan Takashi , Ishida-Yamamoto Akemi
Published: September 2019

Aluminum chloride (AlCl3) is the main active ingredient in commonly used antiperspirant. Antiperspirant use may cause a rare keratinization disease, granular parakeratosis (GP), then AlCl3 may be associated with the etiology of GP. The objective of this study is to elucidate the skin effect of topical aluminum application using a mouse model. We sprayed 20% aluminum chloride every day on the depilated mice skin and analyzed the skin clinically, histopathologically, and immunohistologically. We have succeeded in the histological replication of GP on mouse skin. The basophilic granules in the stratum corneum contained filaggrin, and processing of profilaggrin to filaggrin was disrupted in aluminum-treated mouse skin (Al-mouse). In Al-mouse, cytochrome c and cleaved-caspase 3 were upregulated mainly in the granular layer, and caspase 3 p20 subunit was upregulated. TUNEL-positive cells increased significantly in the Al-mouse from the granular to the horny layer. Caspase 3 inhibitor inhibited granular parakeratotic change of Al-mouse. Our results indicated that aluminum-induced apoptosis leads to keratinization arrest and acceleration of nuclear degradation before completion of profilaggrin processing. This could lead to retention of the basophilic granules composed of underprocessed profilaggrin in the horny layer of Al-mouse skin, the hallmark of GP.
Clinical outcome of open surgery versus laparoscopic surgery for cirrhotic hepatocellular carcinoma patients: a meta-analysis
Authors: Xing Li , Guo Huai-Bin , Kan Jin-Long , Liu San-Guang , Lv Hai-Tao , Liu Jian-Hua , Bian Wei
Published: September 2019

Background and aim

Open surgery remains the major approach to treat hepatocellular carcinoma, and laparoscopy-assisted liver resection has been recommended as a superior treatment. However, the efficacy of laparoscopic surgery versus open surgery for cirrhotic patients is under debate. Therefore, the aim of this meta-analysis was to compare the clinical outcomes of laparoscopic and open resection of hepatocellular carcinoma in patients with cirrhosis.

Methods

Electronic databases were searched for eligible literature updated on November 2018. After rigorous review of quality, the data were extracted from eligible trials. All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated.

Results

Fourteen trials met the inclusion criteria. According to the pooled result of surgery duration, laparoscopic surgery was associated with significantly shorter hospital stay [STD mean difference (SMD) = −0.61, 95% confidence interval −0.89 to −0.32; P < 0.0001], lower intraoperative blood loss (SMD = −0.56, 95% confidence interval −0.99 to −0.12; P = 0.01), fewer complications (odds ratio = 0.38, 95% confidence interval 0.28 to 0.52; P < 0.00001) and lower transfusion rate (odds ratio = 0.58, 95% confidence interval 0.36–0.93; P = 0.02). Nevertheless, there was no remarkable difference in operative time (SMD = 0.17, 95% confidence interval −0.25 to −0.59; P = 0.42) between the two groups. The pooled analysis of overall survival showed that laparoscopic surgery did not achieve benefit compared with open surgery (P = 0.02). Moreover, the pooled results of three subgroups indicated that laparoscopic surgery was associated with significantly better disease-free survival (P < 0.05).

Conclusion

The current analysis indicates that laparoscopic liver resection for hepatocellular carcinoma improved intraoperative and disease-free survival, with similar overall survival compared to the open procedure. Laparoscopic surgery may serve as a safe and feasible alternative for selected hepatocellular carcinoma patients with cirrhosis.
Population-Based Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Children*
Authors: Alobaidi Rashid , Morgan Catherine , Goldstein Stuart L. , Bagshaw Sean M.
Published: September 2019

Objectives:

We describe the epidemiology, characteristics, risk factors, and incremental risks associated with acute kidney injury in critically ill children at a population-level.

Design:

Population-based retrospective cohort study.

Setting:

PICUs in Alberta, Canada.

Patients:

All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015.

Interventions:

None.

Measurements and Main Results:

A total of 1,017 patients were included. Acute kidney injury developed in 308 patients (30.3%; 95% CI, 28.1–33.8%) and severe acute kidney injury (Kidney Disease: Improving Global Outcomes stage 2 and 3) developed in 124 patients (12.2%; 95% CI, 10.3–14.4%). Incidence rates for critical illness-associated acute kidney injury and severe acute kidney injury were 34 (95% CI, 30.3–38.0) and 14 (95% CI, 11.38–16.38) per 100,000 children-year, respectively. Severe acute kidney injury incidence rates were greater in males (incidence rate ratio, 1.55; 95% CI, 1.08–2.33) and infants younger than 1 year old (incidence rate ratio, 14.77; 95% CI, 10.36–21.07). Thirty-two patients (3.1%) did not survive to PICU discharge. The acute kidney injury-associated PICU mortality rate was 2.3 (95% CI, 1.4–3.5) per 100,000 children-year. In multivariate analysis, severe acute kidney injury was associated with greater PICU mortality (odds ratio, 11.93; 95% CI, 4.68–30.42) and 1-year mortality (odds ratio, 5.50; 95% CI, 2.76–10.96). Severe acute kidney injury was further associated with greater duration of mechanical ventilation, duration of vasoactive support, and lengths of PICU and hospital stay.

Conclusions:

The population-level burden of acute kidney injury and its attributable risks are considerable among critically ill children. These findings emphasize the need for enhanced surveillance for acute kidney injury, identification of modifiable risks, and evaluation of interventional strategies.
Offspring Versus Nonoffspring to Parent Living Donor Liver Transplantation: Does Donor Relationship Matter?
Authors: Dagan Amir , Choudhury Rashikh A. , Yaffe Hillary , Yoeli Dor , Moore Hunter B. , Conzen Kendra D. , Adams Megan , Wachs Michael , Pomposelli James J. , Pomfret Elizabeth A. , Nydam Trevor L.
Published: September 2019

Background.

Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation.

Methods.

A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly 3 HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling.

Results.

A total of 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% versus 72%; P < 0.001) and patient survival (52% versus 81%; P < 0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered among male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR = 2.87; P = 0.04) and mortality (hazard ratio = 3.89; P = 0.03). Again, this association was not seen with male recipients.

Conclusions.

Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection.
Predicting Cost-Effectiveness of Generic Versus Brand Dabigatran Using Pharmacometric Estimates among Patients with Atrial Fibrillation in the United States
Authors: Wang Ching-Yu , Pham Phuong N. , Kim Sarah , Lingineni Karthik , Schmidt Stephan , Diaby Vakaramoko , Brown Joshua
Published: September 2019

Generic entry of newer anticoagulants is expected to decrease the costs of atrial fibrillation management. However, when making switches between brand and generic medications, bioequivalence failures are possible. The objectives of this study were to predict and compare the lifetime cost-effectiveness of brand dabigatran with hypothetical future generics. Markov micro-simulations were modified to predict the lifetime costs and quality-adjusted life years of patients on either brand or generic dabigatran from a U.S. private payer perspective. Event rates for generics were predicted using previously developed pharmacokinetic-pharmacodynamic models. The analyses showed that generic dabigatran with lower-than-brand systemic exposure was dominant. Meanwhile, generic dabigatran with extremely high systemic exposure was not cost-effective compared to the brand reference. Cost-effectiveness of generic medications cannot always be assumed as shown in this example. Combined use of pharmacometric and pharmacoeconomic models can assist in decision making between brand and generic pharmacotherapies.
A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping
Authors: Fabbri Chiara , Kasper Siegfried , Kautzky Alexander , Zohar Joseph , Souery Daniel , Montgomery Stuart , Albani Diego , Forloni Gianluigi , Ferentinos Panagiotis , Rujescu Dan , Mendlewicz Julien , Uher Rudolf , Lewis Cathryn M. , Serretti Alessandro
Published: September 2019

Treatment-resistant depression (TRD) occurs in ∼30% of patients with major depressive disorder (MDD) but the genetics of TRD was previously poorly investigated.

Whole exome sequencing and genome-wide genotyping were performed in 1320 MDD patients. Response to the first pharmacological treatment was compared to non-response to one treatment and non-response to two or more treatments (TRD). Differences in the risk of carrying damaging variants were tested. A score expressing the burden of variants in genes and pathways was calculated weighting each variant for its functional (Eigen) score and frequency, considering rare variants only and rare + common variants. Gene- and pathway-based scores were used to develop predictive models of TRD and non-response using gradient boosting in 70% of the sample (training) which were tested in the remaining 30% (testing), evaluating also the addition of clinical predictors. Independent replication was tested in STAR*D and GENDEP using exome array-based data.

After quality control 1209 subjects were included. TRD and non-responders did not show higher risk to carry damaging variants compared to responders. Genes/pathways associated with TRD included those modulating cell survival and proliferation, neurodegeneration and immune response. Significant prediction of TRD vs. response was observed in the testing sample which was improved by the addition of clinical factors. Some models were replicated, with a weaker prediction, in STAR*D and GENDEP when considering also clinical factors and in the extremes of the genetic score distribution.

These results suggested relevant biological mechanisms implicated in TRD and a new methodological approach to the prediction of TRD.
Mutations in the SPTLC1 gene are a cause of juvenile amyotrophic lateral sclerosis that may be amenable to serine supplementation
Authors: Johnson J. O. , Chia R. , Miller D. E. , Li R. , Abramzon Y. , Kumaran R. , Alahmady N. , Faghri F. , Renton A. E. , Topp S. D. , Pliner H. A. , Gibbs J. R. , Ding J. , Smith N. , Landeck N. , Nalls M. A. , Cookson M. R. , Pletnikova O. , Troncoso J. , Scholz S. W. , Sabir M. S. , Ahmed S. , Dalgard C. L. , Troakes C. , Jones A. R. , Shatunov A. , Iacoangeli A. , Al Khleifat A. , Ticozzi N. , Silani V. , Gellera C. , Blair I. P. , Dobson-Stone C. , Kwok J. B. , England B. K. , Bonkowski E. S. ,   The International ALS Genomics Consortium,   The ITALSGEN Consortium,   The FALS Sequencing Consortium,   The American Genome Center, Tienari P. J. , Stone D. J. , Morrison K. E. , Shaw P. J. , Al-Chalabi A. , Brown R. H. , Brunetti M. , Calvo A. , Mora G. , Al-Saif H. , Gotkine M. , Leigh F. , Chang I. J. , Perlman S. J. , Glass I. , Shaw C. E. , Landers J. E. , Chiò A. , Crawford T. O. , Smith B. N. , Traynor B. J.
Published: September 2019

Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of childhood motor disorder with a heterogeneous clinical presentation. The underlying causes of this condition are poorly understood, hindering the development of effective therapies. In a whole-exome sequencing trio-family study of three unrelated juvenile patients diagnosed with ALS and failure to thrive, we identified de-novo mutations in SPTLC1 (p.Ala20Ser in two patients and p.Ser331Tyr) not present in their healthy parents or siblings. SPTLC1 encodes a subunit of the serine palmitoyltransferase complex, a key enzyme in sphingolipid biosynthesis. Mutations in this gene are known to cause hereditary sensory autonomic neuropathy, type 1A, with a characteristic increase in plasma levels of neurotoxic deoxymethyl-sphinganine. We found an increase of this metabolite in one of our patients carrying the p.Ala20Ser mutation. Treatment of one of the patients with high dose, oral L-serine led to an increase in body weight, suggesting that serine supplementation may be beneficial among patients carrying mutations in this gene.
Network effects of the neuropsychiatric 15q13.3 microdeletion on the transcriptome and epigenome in human induced neurons
Authors: Zhang Siming , Zhang Xianglong , Ma Shining , Purmann Carolin , Davis Kasey , Wong Wing Hung , Bernstein Jonathan , Hallmayer Joachim , Urban Alexander E
Published: September 2019

Heterozygous deletions in the 15q13.3 region are associated with several neuropsychiatric disorders including autism, schizophrenia, and attention deficit hyperactivity disorder. Several genes within the 15q13.3 deletion region may play a role in neuronal dysfunction, based on association studies in humans and functional studies in mice, but the intermediate molecular mechanisms remain unknown. We analyzed the genome-wide effects of the 15q13.3 microdeletion on the transcriptome and epigenome. Induced pluripotent stem cell (iPSC) lines from three patients with the typical heterozygous 15q13.3 microdeletion and three sex-matched controls were generated and converted into induced neurons (iNs) using the neurogenin-2 induction method. We analyzed genome-wide gene expression using RNA-Seq, genome-wide DNA methylation using SeqCap-Epi, and genome-wide chromatin accessibility using ATAC-Seq, in both iPSCs and iNs. In both cell types, gene copy number change within the 15q13.3 microdeletion was accompanied by significantly decreased gene expression and no compensatory changes in DNA methylation or chromatin accessibility, supporting the model that haploinsufficiency of genes within the deleted region drives the disorder. Further, we observed global effects of the deletion on the transcriptome and epigenome, with the effects being cell type specific and occurring at discrete loci. Several genes and pathways associated with neuropsychiatric disorders and neuronal development were significantly altered, including Wnt signaling, ribosome biogenesis, DNA binding, and clustered protocadherins. This molecular systems analysis of a large neuropsychiatric microdeletion can also be applied to other brain relevant chromosomal aberrations to further our etiological understanding of neuropsychiatric disorders.
Feedback adaptation to unpredictable force fields in 250ms
Authors: Crevecoeur Frédéric , Mathew James , Bastin Marie , Lefevre Philippe
Published: September 2019

Motor learning and adaptation are important functions of the nervous system. Classical studies have characterized how humans adapt to changes in the environment during tasks such as reaching, and have documented improvements in behavior across movements. Yet little is known about how quickly the nervous system adapts to such disturbances. In particular, recent work has suggested that adaptation could be sufficiently fast to alter the control strategies of an ongoing movement. To further address the possibility that learning occurred within a single movement, we designed a series of human reaching experiments to extract in muscles recordings the latency of feedback adaptation. Our results confirmed that participants adapted their feedback responses to unanticipated force fields applied randomly. In addition, our analyses revealed that the feedback response was specifically and finely tuned to the ongoing perturbation not only across trials with the same force field, but also across different kinds of force fields. Finally, changes in muscle activity consistent with feedback adaptation occurred in about 250ms following reach onset. We submit this estimate as the latency of motor adaptation in the nervous system.
Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish
Authors: Foulkes Matthew J. , Henry Katherine M. , Renshaw Stephen A. , Jones Simon
Published: September 2019

During inflammation, dysregulated neutrophil behaviour can play a major role in chronic inflammatory diseases such as chronic obstructive pulmonary disease, for which current treatments are generally ineffective. Recently, tanshinones have shown promising antiinflammatory effects by targeting neutrophilsin vivo, yet are still an underexplored general group of compounds. Here, an existing six step synthetic route was optimised and used to prepare a small family of substituted tanshinone and isomeric isotanshinone analogues, together with the synthesis of other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of inflammation revealed that many of these compounds exhibit promising anti-inflammatory effectsin vivo. Several compounds affect neutrophil recruitment and/or resolution of neutrophilic inflammation, and broad structure-activity relationships were constructed. In particular, the methoxy-substituted tanshinone39specifically accelerates resolution of inflammation without affecting organism host defence, making this a particularly attractive candidate for potential pro-resolution therapeutics. On the other hand, β-lapachones exhibit effects on neutrophil recruitment yet not on resolution. Notable differences in toxicity profiles between compound classes were also observed.
Genome-wide association analyses identify variants inIRF4associated with acute myeloid leukemia and myelodysplastic syndrome susceptibility
Authors: Wang Junke , Clay-Gilmour Alyssa I. , Karaesmen Ezgi , Rizvi Abbas , Zhu Qianqian , Yan Li , Preus Leah , Liu Song , Wang Yiwen , Griffiths Elizabeth , Stram Daniel O. , Pooler Loreall , Sheng Xin , Haiman Christopher , Van Den Berg David , Webb Amy , Brock Guy , Spellman Stephen , Pasquini Marcelo , McCarthy Philip , Allan James , Stölzel Friedrich , Onel Kenan , Hahn Theresa , Sucheston-Campbell Lara E.
Published: September 2019

The role of common genetic variation in susceptibility to acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS), a group of rare clonal hematologic disorders characterized by dysplastic hematopoiesis and high mortality, remains unclear. We performed AML and MDS genome-wide association studies (GWAS) in the DISCOVeRY-BMT cohorts (2309 cases and 2814 controls). Association analysis based on subsets (ASSET) was used to conduct a summary statistics SNP-based analysis of MDS and AML subtypes. For each AML and MDS case and control we used PrediXcan to estimate the component of gene expression determined by their genetic profile and correlate this imputed gene expression level with risk of developing disease in a transcriptome-wide association study (TWAS). ASSET identified an increased risk forde novoAML and MDS (OR=1.38, 95% CI, 1.26-1.51, Pmeta=2.8×10-12) in patients carrying the T allele at rs12203592 inInterferon Regulatory Factor 4(IRF4), a transcription factor which regulates myeloid and lymphoid hematopoietic differentiation. Our TWAS analyses showed increasedIRF4gene expression is associated with increased risk ofde novoAML and MDS (OR=3.90, 95% CI, 2.36-6.44, Pmeta=1.0×10-7). The identification ofIRF4by both GWAS and TWAS contributes valuable insight on the role of genetic variation in AML and MDS susceptibility.
FBL17 targets CDT1a for degradation in early S-phase to prevent Arabidopsis genome instability
Authors: Desvoyes Bénédicte , Noir Sandra , Masoud Kinda , López María Isabel , Genschik Pascal , Gutierrez Crisanto
Published: September 2019

Maintenance of genome integrity depends on controlling the availability of DNA replication initiation proteins, e.g., CDT1, a component of the pre-replication complexes that regulates chromatin licensing for replication. To understand the evolutionary history of CDT1 regulation, we have identified the mechanisms involved in CDT1 dynamics. During cell cycle, CDT1a starts to be loaded early after mitotic exit and maintains high levels until the G1/S transition. Soon after the S-phase onset, CDT1a is rapidly degraded in a proteasome-dependent manner. Plant cells use a specific SCF-mediated pathway that relies on the FBL17 F-box protein for CDT1a degradation, which is independent of CUL4a-containing complexes. A similar oscillatory pattern occurs in endoreplicating cells, where CDT1a is loaded just after finishing the S-phase. CDT1a is necessary to maintain genome stability, an ancient strategy although unique proteins and mechanisms have evolved in different eukaryotic lineages to ensure its degradation during S-phase.

Impact statement

The DNA replication protein CDT1a is crucial for genome integrity and is targeted for proteasome degradation just after S-phase initiation by FBL17 in proliferating and endoreplicating cells of Arabidopsis