bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic and pharmacodynamic modeling of the metastin/kisspeptin analog, TAK‐448, for its anti‐tumor efficacy in a rat xenograft model
Authors: Kogame Akifumi , Ishikawa Kaori , DeJongh Joost , Tagawa Yoshihiko , Matsui Hisanori , Moriya Yuu , Kondo Takahiro , Asahi Satoru
Published: June 2020

TAK‐448 is the investigational metastin/kisspeptin analog, which is known to have an anti‐tumor effect through suppression of androgen hormones (luteinizing hormone and testosterone) levels. This study developed pharmacokinetic‐pharmacodynamic (PK/PD) models of TAK‐448 and leuprorelin acetate (TAP‐144) in a rat vertebral‐cancer of the prostate (VCaP) androgen‐sensitive prostate cancer xenograft model to quantitatively assess and compare the anti‐tumor effects of both drugs. A potential contribution of the hormone‐independent direct effects of TAK‐448 to the tumor growth inhibition was also investigated in the in vivo rat xenograft model, because our in vitro experiments revealed that TAK‐448 may also directly suppress VCaP cellular proliferation. The PK/PD model successfully described the time course of tumor growth inhibition after drug treatment as well as the development of resistance to the inhibition of androgen hormones, following drug treatment or castration. The EC50 of the hormone‐dependent inhibitory effect of TAK‐448 was much lower than that of TAP‐144, and TAK‐448 also has a faster onset of anti‐tumor effect than TAP‐144, demonstrating that TAK‐448 has a stronger overall anti‐tumor effect than TAP‐144. In addition, model inference, by incorporating a hormone‐independent inhibition pathway of TAK‐448 into the PK‐PD model, suggested that such a direct inhibition pathway for TAK‐448 cannot be excluded, as also indicated by in vitro studies, but its EC50 would be approximately three orders of magnitude higher than that of the hormone‐dependent pathway. This study helps to understand the potential and mechanism of TAK‐448 as a prostate cancer treatment.
The functional networks of a novel environment: Neural activity mapping in awake unrestrained rats using positron emission tomography
Authors: McGregor Matthew , Richer Kaleigh , Ananth Mala , Thanos Panayotis K.
Published: June 2020

Introduction

Novel environment stimulation is thought to have an important role in cognitive development and has been shown to encourage exploratory behavior in rats. However, psychopathology or perceived danger or stress can impede this exploratory drive. The balance between brain circuits controlling the exploratory drive elicited by a novel environment, and the avoidance response to stressors, is not well understood.

Methods

Using positron emission tomography (PET) and the glucose analog [18F]fluorodeoxyglucose (18F‐FDG), we assessed awake brain glucose metabolism (BGluM) in rats while in a novel environment (cage of an unfamiliar male rat) and non‐novel environment (the animal's home cage).

Results

Exposure to the novel environment increased BGluM in regions associated with vision (visual cortex), motor function and motivated behavior (striatum and motor cortex), and anxiety (stria terminalis), and decreased BGluM in regions associated with auditory processing (auditory cortex, insular cortex, inferior colliculus), locomotor activity (globus pallidus, striatum, motor cortex, ventral thalamic nucleus), spatial navigation (retrosplenial cortex), and working memory (hippocampus, cingulate cortex, prelimbic cortex, orbitofrontal cortex).

Conclusion

These results suggest that the novel cage is a stressful environment that inhibits activity in brain regions associated with exploratory behavior. Patterns of inhibition in the novel cage also support the proposed rat default mode network, indicating that animals are more cognitively engaged in this environment. Additionally, these data support the unique capability of combining FDG‐PET with psychopharmacology experiments to examine novelty seeking and brain activation in the context of decision making, risk taking, and cognitive function more generally, along with response to environmental or stress challenges.
Effects of intraaortic balloon counterpulsation on translesional coronary hemodynamics
Authors: Seto Arnold H. , Yu Jeannie , Iwaz James , Kern Morton J.
Published: June 2020

The intraaortic balloon pump (IABP) provides counterpulsation by displacing a 40–50 cc blood volume during diastole augmenting diastolic pressure. The rapid deflation of the balloon timed to the initiation of systole reduces the afterload of ventricular ejection and thus peak systolic pressure. As a direct result, IABP increases mean arterial pressure (MAP) and peak diastolic pressure while reducing systolic pressure and myocardial work. IABP increases coronary flow velocity in non‐obstructed vessels, but does not increase flow across a severe obstruction as shown by intracoronary Doppler flow studies (Kern et al., Circulation, 1993;87:500–511 and Kern et al., Circulation 1991;84:II‐485). There are few studies using pressure sensor guidewires to confirm these responses. We present a case illustrating the translesional hemodynamics using an angioplasty sensor pressure wire across a severe stenosis and the unique influence of the IABP.
Analysis of structural effects on coloring mechanism of Ru celadon porcelain
Authors: Chen Yen‐Yu , Bai Yi‐Wun , Wei Wen‐Cheng J.
Published: June 2020

The glazes in celadon are Ca‐Al‐Si‐O based glasses with a trace of Fe species doped as a coloring agent. The color of celadon is generated by a dual‐coloring mechanism of chemico‐compositional coloring by Fe species, and structural coloring by inhomogeneities. In order to identify the effects on the structural coloring mechanism, Fe doped Ca‐Al‐Si‐O glasses based on the composition of celadon were systematically synthesized by a thermal melting method to compare with that of the shard of ancient Ru‐ware. The results show that the as‐prepared glazes consisted of bubbles, crystalline precipitates, and dual‐phasic glass areas. The crystalline precipitates are mainly facet anorthite grains surrounded by Ca‐Al‐Si‐O glasses. Spinodal decomposition of the Ca‐Al‐Si‐O glasses was observed, whose morphologies are either a spherical or a worm‐like patterns. From the analysis of optical spectra, the intensities of wavelengths in the green (495‐570 nm), yellow (570‐590 nm), and orange (590‐620 nm) are in mixture hybrid. The dominant factor of the structural coloring might due to Rayleigh scattering by the nano‐textures of duel‐phasic glasses (50‐100 nm), which increases the blue opalescence. The spinodal decomposition of celadon porcelain after the anorthite grains precipitated was also identified in this study.
High Temperature Co‐Electrolysis as a Key Technology for CO2 Emission Mitigation – A Model‐Based Assessment of CDA and CCU
Authors: Herz Gregor , Müller Nils , Adam Paul , Megel Stefan , Reichelt Erik , Jahn Matthias
Published: June 2020

The mitigation of CO2 emissions is a major challenge for modern society. While the mitigation of energy‐related emissions can be achieved comparatively easy by switching to renewable energy sources, reduction of process‐related industrial emissions is considerably more challenging. To reduce industrial CO2 emissions, two basic routes are available: carbon direct avoidance (CDA) and carbon capture and utilization (CCU). It is shown that in terms of efficiency, CDA is to be favored when applicable. However, for applications where emissions cannot be avoided, CCU can be a viable approach allowing for emission mitigation.
One pot synthesis of nano Ag in calcium alginate beads and its catalytic application in p‐Nitrophenol reduction with kinetic parameter estimation and model fitting
Authors: Supriya  , Pal Chandan K. , Sengupta Sonali , Basu Jayanta K.
Published: June 2020

In this work, one step process of synthesis of silver nanoparticles (Agnp) embedded in insitu formed calcium alginate (CA) beads is stated. CA, formed from the reaction between sodium alginate and calcium hydroxide, acts as reducing and stabilizing agent as well as support for nanoparticles. The reaction mechanism for the formation and stabilization of Agnp is proposed where the vicinal dihydroxy groups of alginate are assumed to act as the reducing agent for Ag+ to Ag°. Transmission electron microscopy (TEM), x‐ray diffraction (XRD), UV‐vis spectroscopy, field emission scanning electron microscopy (FESEM), and atomic absorption spectroscopy (AAS) were used to characterize the Agnp. The formation of spherical nanoparticles with average size range of 4‐5 nm was confirmed by TEM. Catalytic activity of this nano silver‐calcium alginate (Agnp‐CA) composite was evaluated in the reduction of p‐nitrophenol. Concentrations of sodium alginate, calcium hydroxide, and AgNO3 are found to be the parameters that critically affect the synthesis of Agnp. The efficacy of the catalyst is expressed on the basis of suitable reaction parameters. Both pseudo‐homogeneous and heterogeneous kinetic models are proposed for the reaction to find the best model and the Eley‐Riedel model is found to fit well with the experimental data. The novelty of this work is that the tandem process of CA bead formation, Agnp formation, and Agnp entrapment in CA have been transformed into a single‐step process. Moreover, elaborations of each step of the ionic mechanisms of Agnp formation and p‐NP reduction with Agnp and the establishment of a heterogeneous kinetic model for the reaction are reported for the first time here.
Diffuse domain method for needle insertion simulations
Authors: Jerg Katharina I. , Austermühl René Phillip , Roth Karsten , Große Sundrup Jonas , Kanschat Guido , Hesser Jürgen W. , Wittmayer Lisa
Published: June 2020

We present a new strategy for needle insertion simulations without the necessity of meshing. A diffuse domain approach on a regular grid is applied to overcome the need for an explicit representation of organ boundaries. A phase field function captures the transition of tissue parameters and boundary conditions are imposed implicitly. Uncertainties of a volume segmentation are translated in the width of the phase field, an approach that is novel and overcomes the problem of defining an accurate segmentation boundary. We perform a convergence analysis of the diffuse elastic equation for decreasing phase field width, compare our results to deformation fields received from conforming mesh simulations and analyze the diffuse linear elastic equation for different widths of material interfaces. Then, the approach is applied to computed tomography data of a patient with liver tumors. A three‐class U‐Net is used to automatically generate tissue probability maps serving as phase field functions for the transition of elastic parameters between different tissues. The needle tissue interaction forces are approximated by the absolute gradient of a phase field function, which eliminates the need for explicit boundary parameterization and collision detection at the needle‐tissue interface. The results show that the deformation field of the diffuse domain approach is comparable to the deformation of a conforming mesh simulation. Uncertainties of tissue boundaries are included in the model and the simulation can be directly performed on the automatically generated voxel‐based probability maps. Thus, it is possible to perform easily implementable patient‐specific elastomechanical simulations directly on voxel data.
Predictive value of MCM5 (ADXBLADDER) analysis in urine of men evaluated for the initial diagnosis of bladder cancer: A comparative prospective study
Authors: Anastasi Emanuela , Maggi Martina , Tartaglione Sara , Angeloni Antonio , Gennarini Giuseppina , Leoncini Pier Paolo , Sperduti Isabella , Di Lascio Giovanni , De Stefano Virgilio , Di Pierro Giovanni Battista , Del Giudice Francesco , Busetto Gian Maria , De Berardinis Ettore , Sciarra Alessandro
Published: June 2020

Background

To compare predictive value of MCM5 to urinary cytology (UC) for the primary diagnosis of bladder cancer (BCa).

Methods

We prospectively enrolled 91 patients who presented macroscopic hematuria or persistent lower urinary tract symptoms at our institution. Single voided mid‐stream urine specimens were collected for UC and MCM5 (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, United Kingdom) assessment. Cystoscopy was used as confirmatory test, and positive cases underwent transurethral resection of bladder tumor with histopathological evaluation.

Results

Forty cases (43.9%) showed a positive cystoscopy for BCa. Histology was obtained in 37 cases: 16 (43.2%) high‐grade (HG) and 21 (56.8%) low‐grade (LG) transitional cell carcinoma (TCC). UC had a sensitivity of 62.5%, specificity of 86.3%, PPV of 78.1% and NPV of 74.6%. Sensitivity, specificity, PPV and NPV of MCM5 were 60.0%, 88.2%, 80.0% and 73.8%, respectively. According to tumor grade, MCM5 and UC showed a sensitivity of 47.6% and 52.4% in LG, and 87.5% and 75.0%, respectively, in HG TCC. False‐positive rates were 11.8% and 13.7% of negative cases for BCa with MCM5 and UC test, whereas false‐negative results were found in 40.0% and 37.5% of BCa cases, respectively. The combination of the two tests showed a sensitivity of 71.4% in LG, and 93.8% in HG TCC.

Conclusion

In the present analysis, MCM5 showed lower sensitivity than UC in predicting BCa primary diagnosis. According to tumor grade, MCM5 showed a higher sensitivity in the detection of HG BCa compared to UC, although values were not significantly different.
Closing the gap from transcription to the structural connectome enhances the study of connections in the human brain
Authors: Charvet Christine J.
Published: June 2020

The brain is composed of a complex web of networks but we have yet to map the structural connections of the human brain in detail. Diffusion MR imaging is a high‐throughput method that relies on the principle of diffusion to reconstruct tracts (ie, pathways) across the brain. Although diffusion MR tractography is an exciting method to explore the structural connectivity of the brain in development and across species, the tractography has at times led to questionable interpretations. There are at present few if any alternative methods to trace structural pathways in the human brain. Given these limitations and the potential of diffusion MR imaging to map the human connectome, it is imperative that we develop new approaches to validate neuroimaging techniques. I discuss our recent studies integrating neuroimaging with transcriptional and anatomical variation across humans and other species over the course of development and in adulthood. Developing a novel framework to harness the potential of diffusion MR tractography provides new and exciting opportunities to study the evolution of developmental mechanisms generating variation in connections and bridge the gap between model systems to humans.
Pregnant Women in Trials of Covid‐19: A Critical Time to Consider Ethical Frameworks of Inclusion in Clinical Trials
Authors: Farrell Ruth , Michie Marsha , Pope Rachel
Published: June 2020

Ethical issues abound during this unprecedented international public health crisis of Covid‐19. While the trade‐off between societal and individual interests that occurs at the intersection of public health ethics and clinical ethics affects all populations, this calculus has particular relevance for pregnant women and the question of when they will have access to new Covid‐19 therapies and vaccines. Pregnant women are a “scientifically complex” population whose inclusion in clinical research must be done with consideration of the unique state of pregnancy. Yet research on the impact of Covid‐19 on pregnant women is lagging. In a rush to prevent and treat SARS‐CoV‐2 infection, it is crucial that the interests of pregnant women be prioritized to enable them to make autonomous, informed decisions about participating in clinical trials. The global pandemic calls for a revisiting of frameworks for the inclusion of pregnant women in research, as these women have an important stake in the prevention and treatment of Covid‐19.
Nonuniform but highly preferential stemflow routing along bark surfaces and actual smaller infiltration areas than previously assumed: A case study on European beech (Fagus sylvatica L.) and sycamore maple (Acer pseudoplatanus L.).
Authors: Tischer Alexander , Michalzik Beate , Lotze Robert
Published: June 2020

Canopy and tree morphology are assumed to play a significant role in modulating the amount of rainfall water during its routing throughout the vegetation and the near‐surface Critical Zone. One crucial point of research addresses the spatial extent of stemflow (SF) infiltration, because its concentration over small areas at the trunk base appears to affect the magnitude and timing of water and solutes input to the soil and hence amplify biogeochemical cycling. By a Brilliant Blue tracer experiment, we examined the flow patterns of SF water along the trunk surface of two broadleaved tree species (Fagus sylvatica and Acer pseudoplatanus) and the infiltration area at the trunk base and down to 0.12‐m soil depth following natural rainfall events.

Our results point to highly preferential SF with smaller washed‐off stem areas for sycamore maple (≤15%) compared with European beech (≤39%). The infiltration area is remarkably smaller than the basal area (BA), accounting for only 17% of the BA for beech and for 30% for maple. Differences in decolourized stem areas between the trees do not relate to the magnitude of infiltration areas at the soil surface, suggesting a strong effect of coarse root abundance and run‐off properties on the funnelling of SF water.

In essence, our investigation exhibited that SF routing along bark surfaces and infiltration at the trunk base were spatially more concentrated than commonly assumed. The outcome of this study might contribute to our understanding on hydrological and biogeochemical interlinkages between the plant cover and the near‐surface Critical Zone.
Detection of fuel‐oxidizer explosives utilizing portable capillary electrophoresis with wipe‐based sampling
Authors: Krauss Shannon T. , Forbes Thomas P. , Lawrence Jeffrey A. , Gillen Greg , Verkouteren Jennifer R.
Published: June 2020

Portable analytical instrumentation that can provide an alarm indication for the presence of explosives and related components is critical for the identification of explosives‐based hazards and threats. Many explosives incident reports involve an inorganic oxidizer‐fuel mixture which can include pyrotechnics, fireworks, flash powders, black powders, black powder substitutes, and improvised or homemade explosives. A portable CE instrument with targeted analysis of common inorganic oxidizer ions, for example, chlorate, perchlorate, and nitrate, was used here as a rapid detection platform. Unlike frequently used gas‐phase separation and detection instrumentation such as ion mobility spectrometry (IMS), an automated liquid extraction mechanism is required for CE separation using acetate paper sample collection wipes. Target inorganic oxidizers were inkjet‐printed onto sample wipes to investigate instrument response relative to the collected analyte spatial distribution. Overall, analyte signal intensities increased with off‐center sample deposition due to improved sample extraction from wipes and no change in response was observed for varied array distributions across wipes. The system demonstrated sub 200 ng detection limits for all target analytes, with further improvement when normalizing to an internal standard.
Hubs of long‐distance co‐alteration characterize brain pathology
Authors: Cauda Franco , Mancuso Lorenzo , Nani Andrea , Ficco Linda , Premi Enrico , Manuello Jordi , Liloia Donato , Gelmini Gabriele , Duca Sergio , Costa Tommaso
Published: June 2020

It is becoming clearer that the impact of brain diseases is more convincingly represented in terms of co‐alterations rather than in terms of localization of alterations. In this context, areas characterized by a long mean distance of co‐alteration may be considered as hubs with a crucial role in the pathology. We calculated meta‐analytic transdiagnostic networks of co‐alteration for the gray matter decreases and increases, and we evaluated the mean Euclidean, fiber‐length, and topological distance of its nodes. We also examined the proportion of co‐alterations between canonical networks, and the transdiagnostic variance of the Euclidean distance. Furthermore, disease‐specific analyses were conducted on schizophrenia and Alzheimer's disease. The anterodorsal prefrontal cortices appeared to be a transdiagnostic hub of long‐distance co‐alterations. Also, the disease‐specific analyses showed that long‐distance co‐alterations are more able than classic meta‐analyses to identify areas involved in pathology and symptomatology. Moreover, the distance maps were correlated with the normative connectivity. Our findings substantiate the network degeneration hypothesis in brain pathology. At the same time, they suggest that the concept of co‐alteration might be a useful tool for clinical neuroscience.
Prevalence of PD‐L1 expression in head and neck squamous precancerous lesions: a systematic review and meta‐analysis
Authors: Girolami Ilaria , Pantanowitz Liron , Munari Enrico , Martini Maurizio , Nocini Riccardo , Bisi Nicola , Molteni Gabriele , Marchioni Daniele , Ghimenton Claudio , Brunelli Matteo , Eccher Albino
Published: June 2020

Background

Studies concerning programmed death‐ligand 1 (PD‐L1) expression in precancerous lesions of head and neck (HN) region have shown variable results.

Methods

We systematically reviewed the published evidence on PD‐L1 expression in HN precancerous lesions.

Results

Of 1058 original articles, 14 were included in systematic review and 9 in meta‐analysis. The pooled estimate of PD‐L1 expression was 48.25% (confidence interval [CI] 21.07‐75.98, I2 98%, tau2 0.18). PD‐L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65‐4.03, I2 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43‐1.08, I2 91%, tau2 0.22).

Conclusions

PD‐L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD‐L1 expression in HN precancerous lesions.
Impact of 3D printed medical equipment on the management of the Covid19 pandemic
Authors: Belhouideg Soufiane
Published: June 2020

Very high mortality rates of coronavirus pandemic (COVID‐19) are observed around the world due to lack of medical equipment. The increased need for medical devices and personal protective equipment (PPE) has kept several healthcare professionals at risk. Fortunately, 3D printing technology allows to overcome the lack of medical supplies. This study highlights the impact of 3D printing on the combat against COVID19, and its importance in the medical product supply chain. Indeed, the existing medical equipment fabricated by 3D printing technology and its role in the management of Covid19 pandemic is presented. Moreover, the last works are examined to know whether the models of the medical equipment are free of use and whether useful informations are presented (eg, available design data and setup guidelines).
A review of heat and fluid flow characteristics in microchannel heat sinks
Authors: Coskun Turgay , Cetkin Erdal
Published: June 2020

Heat transfer and flow characteristic in microchannel heat sinks (MCHS) are extensively studied in the literature due to high heat transfer rate capability by increased heat transfer surface area relative to the macroscale heat sinks. However, heat transfer and fluid flow characteristics in MCHS differ from conventional ones because of the scaling effects. This review summarizes the studies that are mainly based on heat transfer and fluid flow characteristic in MCHS. There is no consistency among the published results; however, everyone agrees on that there is no new physical phenomenon in microscale that does not exist at macroscale. Only difference between them is that the effect of some physical phenomena such as viscous dissipation, axial heat conduction, entrance effect, rarefaction, and so forth, is negligibly small at macroscale, whereas it is not at microscale. The effect of these physical phenomena on the heat transfer and flow characteristics becomes significant with respect to specified conditions such as Reynolds number, Peclet number, hydraulic diameter, and heat transfer boundary conditions. Here, the literature was reviewed to document when these physical phenomena become significant and insignificant.
Fracture toughness of zirconia with a nanometer size notch fabricated using focused ion beam milling
Authors: Liao Yifeng , Gruber Max , Lukic Henry , Chen Si , Megremis Spiro
Published: June 2020

Objectives

Zirconia with 3 mol% yttria (3Y‐TZP) has been used for dental crowns and bridges due to its excellent mechanical behavior. Performing fracture toughness testing on this nanograin material, however, can be a challenge. For reliable results, fracture toughness testing requires an extremely sharp notch in the test specimen that closely approximates a very sharp crack. This study was to investigate an alternative method to produce nanometer‐sized notches, which are less than the average grain size of 3Y‐TZP, during the preparation of single‐edge V‐notched beam specimens and report the resulting fracture toughness value.

Methods

We present a method using focused ion beam (FIB) milling to fabricate nanometer‐sized notches in 3Y‐TZP. The notch tip is <100 nm wide, which is smaller than the grain size, and is consistent throughout the thickness of the specimen.

Results

The FIB‐notched specimens show a much reduced average fracture toughness of 5.64 ± 1.14 MPa√m compared to 8.90 ± 0.23 MPa√m for the specimens without FIB‐notches. The FIB‐milling did not appear to create any monoclinic phase prior to fracture toughness testing. Fractures originated at the FIB‐notches, and the notch size can be readily identified post‐mortem using a microscope. A considerable amount of tetragonal‐to‐monoclinic phase transformation was observed throughout the fracture surfaces.

Significance

FIB milling provides an alternative method to fabricate nanometer‐sized notches that are smaller than the grain size of tetragonal zirconia polycrystal. The fracture toughness determined using FIB‐notches was ~5.64 MPa√m, smaller than the specimens with V‐notches fabricated using saw blades.
Ultrasound‐assisted fermentation for production of β‐1,3‐glucanase and chitinase by Beauveria bassiana
Authors: Schmaltz Silvana , Aita Bruno C , Alves Eliana A , Fochi Alex , Bolson Vinícius F , Navarro‐Díaz Helmut J , Kuhn Raquel C , Mazutti Marcio A
Published: June 2020

BACKGROUND

Ultrasound (US) treatment was applied to increase the production of β‐1,3‐glucanase and chitinase by Beauveria bassiana (IBCB 66) cultivated in submerged fermentation. Application of US at different growth stages, US power outputs, time of ultrasonication, and duty cycles were the parameters evaluated.

RESULTS

The best strategy comprised ultrasonication during 5 min at 24 h of fermentation with a power output of 195 W (fixed frequency of 24 kHz) and a duty cycle of 0.5 s.s−1 (0.5 s ON, 0.5 s OFF). The US treatment resulted in a production increase of 46% for β‐1,3‐glucanase and 42% for chitinase compared to the non‐sonicated control. Fragmentations of the mycelia in the sonicated samples were observed in Scanning Electron Microscopy (SEM) micrographs after the US application, supporting the idea of a better release of enzymes to outside the cell.

CONCLUSION

Ultrasound‐assisted fermentation was a promising tool to increase the production of β‐1,3‐glucanase and chitinase by Beauveria bassiana (IBCB 66). The combination of US parameters showed to be decisive in obtaining higher enzyme production when compared to the control non‐sonicated experiment. Therefore, this work brings a significant contribution to the field of stimulation of bioprocesses with ultrasound since it shows a strategy to obtain higher enzyme production when compared to traditional fermentation. © 2020 Society of Chemical Industry
Static mixer proposal for tubular photobioreactors to reduce mixing energy consumption and enhance light–dark cycles
Authors: Salguero‐Rodríguez Yulánderson , Gómez‐Pérez C A , Arango‐Restrepo Juan P , Espinosa Jairo
Published: June 2020

BACKGROUND

Tubular Photobioreactors (PBR) present better productivity using static mixers but they consume large amounts of energy. In this study, a tubular PBR is presented with a new static mixer that produces swirl mixing, inducing light–dark (LD) cycles, and adequate uptake of nutrients in the culture. This study was focused on diminishing the pumping energy required for culture transport while improving productivity by the development of LD cycles in microalgae culture.

RESULTS

Three types of tubular PBRs with mixers that induce swirl flow were simulated using computational fluid dynamics (CFD). Pumping energy and mixing degree were estimated. Mixing conditions and swirl flow were calculated through the swirl number. Evaluation of the illumination periodic behavior induced by the proposed new configuration in the frequency domain, using the Discrete Fourier Transform (DFT), revealed a distinctive correlation between main frequencies and average flow velocity. Energy consumption results showed that the proposed mixer consumes the least energy in comparison with others proposed previously in the literature; moreover, the proposed mixer also is simpler than traditional types. Thus, there are cost benefits in using this static mixer in tubular PBR mixing. © 2020 Society of Chemical Industry
Sample preparation and microscopical investigation techniques for metal and ceramics containing graphite and graphene‐like layered particles
Authors: Baskut Sinem , Turan Servet
Published: June 2020

Scanning electron microscopy (SEM) techniques are widely used in microstructural investigations of materials since it can provide surface morphology, topography, and chemical information. However, it is important to use correct imaging and sample preparation techniques to reveal the microstructures of materials composed of components with different polishing characteristics such as grey cast iron, graphene platelets (GPLs)‐added SiAlON composite, SiC and B4C ceramics containing graphite or graphene‐like layered particles. In this study, all microstructural details of gray cast iron were successfully revealed by using argon ion beam milling as an alternative to the standard sample preparation method for cast irons, that is, mechanical polishing followed by chemical etching. The in‐lens secondary electron (I‐L‐SE) image was clearly displayed on the surface details of the graphites that could not be revealed by backscattered electron (BSE) and Everhart–Thornley secondary electron (E‐T SE) images. Mechanical polishing leads to pull‐out of GPLs from SiAlON surface, whereas argon ion beam milling preserved the GPLs and resulted in smooth surface. Grain and grain boundaries of polycrystalline SiC and B4C were easily revealed by using I‐L SE image in the SEM after only mechanical polishing without any etching process. While the BSE and E‐T SE images did not clearly show the residual graphites in the microstructure, their distribution in the B4C matrix was fully revealed in the I‐L SE image.
Cost‐effectiveness analysis of integrating screening and treatment of selected non‐communicable diseases into HIV/AIDS treatment in Uganda
Authors: Sando David , Kintu Alexander , Okello Samson , Kawungezi Peter Chris , Guwatudde David , Mutungi Gerald , Muyindike Winnie , Menzies Nicolas A , Danaei Goodarz , Verguet Stéphane
Published: June 2020

Introduction

Despite growing enthusiasm for integrating treatment of non‐communicable diseases (NCDs) into human immunodeficiency virus (HIV) care and treatment services in sub‐Saharan Africa, there is little evidence on the potential health and financial consequences of such integration. We aim to study the cost‐effectiveness of basic NCD‐HIV integration in a Ugandan setting.

Methods

We developed an epidemiologic‐cost model to analyze, from the provider perspective, the cost‐effectiveness of integrating hypertension, diabetes mellitus (DM) and high cholesterol screening and treatment for people living with HIV (PLWH) receiving antiretroviral therapy (ART) in Uganda. We utilized cardiovascular disease (CVD) risk estimations drawing from the previously established Globorisk model and systematic reviews; HIV and NCD risk factor prevalence from the World Health Organization’s STEPwise approach to Surveillance survey and global databases; and cost data from national drug price lists, expert consultation and the literature. Averted CVD cases and corresponding disability‐adjusted life years were estimated over 10 subsequent years along with incremental cost‐effectiveness of the integration.

Results

Integrating services for hypertension, DM, and high cholesterol among ART patients in Uganda was associated with a mean decrease of the 10‐year risk of a CVD event: from 8.2 to 6.6% in older PLWH women (absolute risk reduction of 1.6%), and from 10.7 to 9.5% in older PLWH men (absolute risk reduction of 1.2%), respectively. Integration would yield estimated net costs between $1,400 and $3,250 per disability‐adjusted life year averted among older ART patients.

Conclusions

Providing services for hypertension, DM and high cholesterol for Ugandan ART patients would reduce the overall CVD risk among these patients; it would amount to about 2.4% of national HIV/AIDS expenditure, and would present a cost‐effectiveness comparable to other standalone interventions to address NCDs in low‐ and middle‐income country settings.
Diffusion Imaging in the Post HCP Era
Authors: Moeller Steen , Pisharady Kumar Pramod , Andersson Jesper , Akcakaya Mehmet , Harel Noam , Ma Ruoyun(Emily) , Wu Xiaoping , Yacoub Essa , Lenglet Christophe , Ugurbil Kamil
Published: June 2020

Diffusion imaging is a critical component in the pursuit of developing a better understanding of the human brain. Recent technical advances promise enabling the advancement in the quality of data that can be obtained. In this review the context for different approaches relative to the Human Connectome Project are compared. Significant new gains are anticipated from the use of high‐performance head gradients. These gains can be particularly large when the high‐performance gradients are employed together with ultrahigh magnetic fields. Transmit array designs are critical in realizing high accelerations in diffusion‐weighted (d)MRI acquisitions, while maintaining large field of view (FOV) coverage, and several techniques for optimal signal‐encoding are now available. Reconstruction and processing pipelines that precisely disentangle the acquired neuroanatomical information are established and provide the foundation for the application of deep learning in the advancement of dMRI for complex tissues.

Level of Evidence: 3

Technical Efficacy Stage: Stage 3
Planning for a pandemic: Mitigating risk to radiation therapy service delivery in the COVID‐19 era
Authors: Anderson Nigel , Thompson Kenton , Andrews Judy , Chesson Brent , Cray Alison , Phillips Damien , Ryan Michelle , Soteriou Sally , Trainor Glenn , Touma Nilgun
Published: June 2020

The novel coronavirus (COVID‐19) has rapidly impacted all of our lives following its escalation to pandemic status on 11 March 2020. Government guidelines and restrictions implemented to mitigate the risk of COVID‐19 community transmission have forced radiation therapy departments to promptly adjust to the significant impact on our ability to deliver best clinical care. The inherent nature of our tri‐partied professions relies heavily on multidisciplinary teamwork and patient–clinician interactions. Teamwork and patient interaction are critical to the role of a radiation therapist. The aim of this paper is to describe the experience of the Peter MacCallum Cancer Centre’s (Peter Mac) radiation therapy services during the preliminary stages of the COVID‐19 pandemic in minimising risk to patients, staff and our clinical service. Four critical areas were identified in developing risk mitigation strategies across our service: (a) Workforce planning, (b) Workforce communication, (c) Patient safety and wellbeing, and (d) Staff safety and wellbeing. Each of these initiatives had a focus on continuum of clinical care, whilst minimising risk of cross infection for our radiation therapy workforce and patients alike. Initiatives included, but were not limited to, establishing COVID‐Eclipse clinical protocols, remote access to local applications, implementation of Microsoft Teams, personal protective equipment (PPE) guidelines and virtual ‘Division of Radiation Oncology’ briefing/updates. The COVID‐19 pandemic has dictated change in conventional radiation therapy practice. It is hoped that by sharing our experiences, the radiation therapy profession will continue to learn, adapt and navigate this period together, to ensure optimal outcomes for ourselves and our patients.
Validation of the Ottawa knee rule in adults: A single centre study
Authors: Sims Jordan I. , Chau Minh , Davies Josephine
Published: June 2020

Introduction

This clinical audit aimed to evaluate performance of the Ottawa Knee Rule (OKR) and degree of compliance by emergency referrers for acute knee injuries in adults.

Methods

Knee radiography requests were analysed retrospectively for eligibility. Data were extracted from eligible requests under headings describing the OKR criteria, patient history, diagnosis and referrer profession. Sensitivity, specificity, negative likelihood ratio and positive likelihood ratio were calculated with 95% CI for the entire sample and each profession (consultant doctors, resident medical officers [RMO], physiotherapists and triage nurses) individually. The frequency of each OKR criterion and correlation with fracture, referrer compliance to the rule and the relative reduction in radiography were also calculated.

Results

Of 713 patients identified, 149 were enrolled by the eligibility criteria. The overall sensitivity, specificity, negative likelihood ratio and positive likelihood ratio of the OKR for knee fracture were 71% (95%CI, 49‐87%), 46% (95%CI, 37‐55%), 0.64 (95%CI, 0.33‐1.22) and 1.3 (95%CI, 0.96‐1.76), respectively. Physiotherapists and triage nurses demonstrated better rule performance than consultant doctors and RMOs, with a sensitivity of 100% and negative likelihood ratio of 0.0. Physiotherapists were most compliant at 73% (19/26). Only 85 requests were OKR positive and, when abiding by the rule, this would have reduced radiography by 43% (64/149).

Conclusions

In this first Australian study, moderate OKR performance and variable compliance by emergency referrers were observed. This led to unnecessary irradiation of patients without a fracture. The findings suggest emergency referrers could benefit from education on applying and documenting the OKR on radiography requests.
Apolipoprotein C‐III O‐glycoform profiling of 500 serum samples by matrix‐assisted laser desorption/ionization mass spectrometry for diagnosis of congenital disorders of glycosylation
Authors: Wada Yoshinao , Okamoto Nobuhiko
Published: June 2020

Congenital disorders of glycosylation (CDG) are caused by defects in various genes governing glycoconjugate biosynthesis. Several responsible genes have been identified in the protein N‐glycosylation process. Analyses of mucin‐type core‐1 O‐glycoform of apolipoprotein C‐III (apoCIII) have recently revealed combined N‐ and O‐glycosylation defects. We applied matrix‐assisted laser desorption/ionization mass spectrometry profiling of apoCIII glycoforms to 500 serum samples for CDG screening, and reference values were determined. The content of unglycosylated apoCIII was low in early infancy, indicating that the O‐glycan occupancy should be assessed based on age‐matched reference values. The samples from patients with mutations in the ALG1, ATP6V0A2, B4GALT1, COG2, GCS1, PGM1, SLC35A2, and TRAPPC11 genes were analyzed. B4GALT1‐ and TRAPPC11‐CDG were accompanied by under‐sialylation of O‐glycans and are now recognized as combined N‐ and O‐glycosylation disorders.
HSPGs glypican‐1 and glypican‐4 are human neuronal proteins characteristic of different neural phenotypes
Authors: Oikari Lotta E. , Yu Chieh , Okolicsanyi Rachel K. , Avgan Nesli , Peall Ian W. , Griffiths Lyn R. , Haupt Larisa M.
Published: June 2020

Generating neurons from human stem cells has potential for brain damage therapy and neurogenesis modeling, but current efficacy is limited by culture heterogeneity and the lack of markers. We have previously reported the heparan sulfate proteoglycans (HSPGs) glypican‐1 (GPC1) and ‐4 (GPC4) as the markers of lineage‐specific human neural stem cells (hNSCs) and mediators of hNSC lineage potential. Here, we further examined phenotypical characteristics and GPC1 and GPC4 during neural differentiation of hNSCs in the presence of two neurogenic growth factors reported to bind to heparan sulfate: brain‐derived neurotrophic factor (BDNF) and platelet‐derived growth factor‐B (PDGF‐B). In hNSC neural cultures, GPC1 and GPC4 were expressed along neurites and cell bodies in long‐term (40–60 days) neural differentiation cultures demonstrating the areas of differential localization—suggesting potentially different functions. Neural differentiation cultures in the presence of BDNF or PDGF‐B generated phenotypically different neural cells with BDNF treatment associated with higher GPC4 versus GPC1 expression, increased heterogeneity, and differential neuron subtype marker expression to PDGF‐B cultures. PDGF‐B cultures exhibited higher levels of spontaneous activity and reduced heterogeneity over long‐term culture associated with decreased GPC4. Untreated neural cultures were highly variable, supporting the use of neuroregulatory growth factors for guided differentiation. Targeted siRNA downregulation of GPC1/4 reduced neural differentiation markers and altered response to exogenous BDNF and PDGF‐B. This work confirms GPC1 and GPC4 as regulators of human neural differentiation and supports their use as novel markers of neural cell characterization.
Representation of the Indian Ocean Walker circulation in climate models and links to Kenyan rainfall
Authors: King James A. , Washington Richard , Engelstaedter Sebastian
Published: June 2020

Reliable climate change projections over East Africa are vital because of regional vulnerability to precipitation changes. However, global climate models from Coupled Model Intercomparison Project Phase 5 (CMIP5) display significant biases in their representation of key East African rainfall seasons, which call into question the reliability of projected climate change. We investigate the links between models' representation of rainfall over Kenya during the long and short rains and the proximate Walker circulation. There is a strong correlation in the short rains between model biases in Kenyan rainfall and in the mid‐to‐upper tropospheric vertical velocity associated with this circulation. The overturning Indian Ocean Walker cell at the equator is absent in 5/25 models during the short rains – these models exhibit wet biases. In the long rains, dry biased models overestimate the strength of the descending limb of the circulation over East Africa. Omega biases over the Congo Basin are linked to broader Walker circulation biases. During the long rains, models overestimate equatorial descent more generally across the Western Hemisphere Tropics (0°E–200°E). A significant correlation is obtained across the model ensemble between model rainfall over Kenya and Western Hemisphere equatorial ascent during November. Atmosphere‐only models display some improvements over coupled models, but biases of a similar magnitude remain. We therefore propose Indian Ocean Walker circulation errors as a key source of bias in CMIP5 East African rainfall. The results add to recent work on CMIP5 biases in this region, demonstrating that the Indian Ocean Walker circulation should be a focus for future model improvement and a consideration when assessing the reliability of climate projections over East Africa. Further work is needed on the causes of Walker circulation biases (in particular the role of SST), and on understanding the impact of Walker circulation biases on modelled tropical rainfall elsewhere in the world.
Early hypermetabolism is uncommon in trauma intensive care unit patients
Authors: Byerly Saskya , Vasileiou Georgia , Qian Sinong , Mantero Alejandro , Lee Eugenia E. , Parks Jonathan , Mulder Michelle , Pust Daniel G. , Rattan Rishi , Lineen Edward , Byers Patricia , Namias Nicholas , Yeh D. Dante
Published: June 2020

Background

Classic experiments demonstrating hypermetabolism after major trauma were performed in a different era of critical care. We aim to describe the modern posttraumatic metabolic response in the trauma intensive care unit (TICU).

Methods

This prospective observational study enrolled TICU mechanically ventilated adults (aged ≥18) from 3/2018‐2/2019. Multiple, daily resting energy expenditure (REE) measurements were recorded. Basal energy expenditure (BEE) was calculated by the Harris‐Benedict equation. Hypometabolism was defined as average daily REE < 0.85*BEE and hypermetabolism defined as average daily REE > 1.15*BEE. Demographics, interventions, and clinical outcomes were abstracted. Descriptive statistics and multivariable logistical regression models evaluating demographics with the outcome variable of hypermetabolism for the first 3 days (“sustained hypermetabolism”) were performed, along with group‐based trajectory modeling (GBTM).

Results

Fifty‐five patients were analyzed: median age was 38 (28–56) years; 38 (69%) were male; body mass index (kg/m2) was 28 (26–32); and Injury Severity Score was 27 (19–34), with (38 [71%] blunt, 8 [15%] penetrating, 7 [13%] burn) injury mechanism. Overall, 19 (35%) had hypermetabolism on day 1 (“immediate hypermetabolism”), and 11 (21%) had sustained hypermetabolism for the first 3 days. Logistic regression analysis identified penetrating mechanism (adjusted odds ratio [AOR], 16.4; 95% CI, 1.9–199.6; p = .015), burn mechanism (AOR, 11.1; 95% CI, 1.3–116.8; p =.029), and maximum temperature (AOR, 4.2; 95% CI, 1.3–20.3; p= .041) as independent predictors of sustained hypermetabolism. GBTM identified 4 nutrition phenotypes, with 2 hyperconsumptive phenotypes associated with increased risk of malnutrition at discharge.

Conclusion

Only a minority of injured patients is hypermetabolic in the first week after injury. Elevated temperature, penetrating mechanism, and burn mechanism are independently associated with sustained hypermetabolism. Hyperconsumptive phenotype patients are more likely to develop malnutrition during hospitalization.