bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Permeability Change Resulting from Active Mineral Precipitation in Pores of Rocks by 3D-DEM
Authors: Arkin Eldan , Mori Takumi , Himeno Ren , Sainoki Atsushi , Sato Akira
Published: January 2023

Carbon dioxide capture and storage (CCS) is a promising technique for reducing the concentration of CO2 in the atmosphere, and several million tons of CO2 are sequestered every year. The most important problem in CCS is ensuring aquifer safety. However, there is still room for improvement in the flow characteristics of aquifers to prevent CO2 leakage. To decrease the permeability of porous rocks, in this study, a method called ‘active mineral deposition’ was developed. In this method, some minerals are actively precipitated in aquifers, and the pores in the rock mass are closed by precipitated minerals. Because the pores are closed and stacked by minerals, the permeability of the rock mass is expected to decrease. For the precipitated minerals, CaCO3 is a promising mineral, and CaCO3 is precipitated in the pores of rocks. From microscopic observation, the approximate size of the precipitated mineral was estimated to be 10 μm in the rock pores. To verify the effect of the method, the permeability of the porous rocks was simulated using the three-dimensional discrete-element method (3D-DEM). Here, the rock minerals and pores were simulated using DEM elements, and the initial permeability of the models was estimated. Then, the small minerals, which represent precipitated minerals, were generated in the pore space, and changes in the intrinsic permeability, flow path, and pressure distributions in the rocks were estimated. The value of intrinsic permeability decreased to one tenth of the initial condition when 1% of the pore spaces were occupied by the precipitated minerals. A small amount of precipitation could change the permeability of the porous materials.
Validation of the Crack Mode-Changing Stress in Circular Tunnels Under Generalized Triaxial Tensile Stress States
Authors: Mutaz E , Serati M , Williams D J , Quintero O S
Published: January 2023

In the past century, mining depths have increased profoundly from a few hundred meters to several kilometres following improvements in drilling techniques and instrumentation methods. In highly-stressed tunnels, the predominant failure mechanism of underground rock is controlled by stress-induced fractures parallel to the excavation boundaries in terms of spalling failures or, in some severe cases, a violent slab ejection that forms a V-shaped notch around the excavation walls. Such failures can seriously affect production and shut down the operation temporarily or even permanently. To better characterize, predict, and prevent these catastrophic failures, many laboratory tests and scaled model tunnels have been conducted under uniaxial and biaxial loading conditions, with limited studies also available under true triaxial stress states. This paper extends the previous studies on the impact of true triaxial loading conditions on the spalling failure in high porosity sandstone and investigates further the validation of a new Crack Mode-Changing Stress (CMCS) parameter, defined as the minimum principal stress required to change rock fracturing from splitting to a sliding failure mode. The results revealed that the minor principal stress can significantly affect the propagation of the stress-induced fractures of spalling failure along the tunnel sidewall.
Instrumental response of borehole tensor strainmeters for oblique-incident seismic waves
Authors: Tian Jiayong , Zhang Kanghua , Lou Jiashu
Published: January 2023

It has been proven qualitatively that borehole tensor strainmeters (BTSM) could measure three surface-wave-induced strain components in the horizontal-normal plane. But strain waves are usually incident obliquely to borehole axis to induce not only horizontalnormal strain components but also the three other strain components in the plane of vertical normal, which are usually assumed to zero in conventional model of BTSM installed near the earth surface. Therefore quantitative kinematical-parameter measurement of strain waves of wave normal oblique to borehole axis by BTSM is still a challenging problem. In this paper, a scattering model of oblique-incidence seismic waves by an empty borehole is introduced to investigate instrumental responses of BTSM. Besides for the four gauges in conventional BTSM, three other gauges considering the influences of strain components in the plane of vertical normal are also introduced to build dynamic calibration matrix between instrumental and incident strains. It shows that within the effective bandwidth of BTSM, zero-frequency-gain for dynamic calibration matrix could be adopted approximately to build quantitative relation between instrumental strain waves of BTSM and oblique-incidence seismic strain waves. It is shown that the recommended gauge combinations could promise quantitative measurement of kinematic parameters of the incident strain P or S wave if high-resolution insitu calibration of BTSM has been conducted, which is important to the development of early warning system by borehole strainmeters.
Numerical and laboratory investigations of thermally induced fractures in rock salt
Authors: Körner Feline , Baumgärtel Lukas , Leuger Bastian
Published: January 2023

In order to widen the basis for the dimensioning of storage caverns in rock salt, some special attention must be paid to the temperature developments within the cavity during its operation. Passed numerical investigations have shown that a temperature change in the storage medium, such as natural gas or hydrogen, can cause stress differences of several MPa in the rock mass surrounding the cavern. If, as a result, the difference between horizontal and vertical stresses is increased, the rock being additionally loaded by a fluid pressure can fracture orthogonally to the lowest principal stress. The knowledge of temperature conditions and heat flows in the cavern surrounding salt rock are therefore of great importance. A wide variety of factors must be considered when investigating such mechanisms. The novel test facility at the Institute of Geotechnical Engineering of the Leibniz University Hannover is used to simulate the situation that occurs at the caverns edge when storage medium is withdrawn. This means, the cooling and the gas pressure inside the cavity are reconstructed on hollow cylindrical test samples made of rock salt from various locations to draw conclusions about the propagation of fractures and thus the safety of salt caverns under gas-loading. Before inducing any mechanical loads by means of a triaxial cell, a comprehensive investigation of the temperature field, resulting from the locally limited, artificially induced cooling of a sample is carried out with the new testing facility. While local temperatures in the sample drop by about 20 Kelvin, it is free to contract inwards, causing thermal stresses to decrease significantly. Therefore, the facility needs to be optimized and the testing scheme is changed. Instead of reducing stresses thermally, one of the mechanical loadings is diminished while the gas pressure inside the borehole is kept constant. As a result, the material visibly fractures while mechanical loadings are at a fully-compressive state.
Effect of layer orientation on behaviour of 3D-printed rock specimens in indirect tensile testing
Authors: Yang Weiyi , Huang Zili , Verma Rupesh , Nguyen Giang D , Tung Tran T , Karakus Murat
Published: January 2023

The mineralogical composition, texture and fracture of natural rocks can be complicated due to the inherent heterogeneity of geomechanical properties, making it challenging to understand their behaviour. Due to the intrinsic layer by layer manufacturing process, 3D printing technology enables to create rock-like materials and specimens with known and controllable inhomogeneity. In this study, disc specimens of a rock-like material are fabricated using 3D printing of cement mortar for testing to understand fabric orientation effect on fracture behaviour better. For the first time, a novel technique, named AUSBIT (Adelaide University Snap-back Indirect Tensile test), for Brazilian disc tests is applied for obtaining both strength and snap-back post-peak behaviour of the 3D printed rock-like materials. Adopting Digital Image Correlation (DIC) technique, in conjunction with the use of AUSBIT, allows obtaining full-field strains and their evolutions, showing strong effects of fabric orientation on strain distributions and both pre-and post-peak responses.
Simulation of wire mesh bearing capacity using the distinct element method (DEM)
Authors: Winderholler Rodrigo , Valli Jouni , Hakala Matti
Published: January 2023

The response of wire mesh sheets anchored with rock bolts to excavation surfaces has been investigated using the distinct-element method (DEM). Wire mesh reinforcement is a common practice both in mining and civil underground structures, providing passive support in case of unstable blocks. When the mesh is not embedded in a sprayed concrete layer, its design is usually performed based on statistical analyses of laboratory test results according to Eurocode. A laboratory-based approach can result in technical and economical limitations, especially when studying non-conventional or accidental design scenarios such as asymmetric loading or failure of the anchoring rock bolts. The simulation of the loading of a sheet of wire mesh has been performed with 3D-DEM software (PFC3D, Itasca) by discretizing the wire elements as connected particles which can simulate the progressive failure mechanism of the wire mesh observed in laboratory tests. The strength and deformability of the wire elements were calibrated to replicate laboratory results. Based on a limited amount of laboratory test data required for calibration, the investigated approach can complement laboratory results by providing an estimation of the expected strength and strain of the wire mesh reinforcement system under various loading scenarios.
Stability analysis of tunnel composite liner using convergence-confinement method and support capacity diagram – A case study of the Notog railway tunnel in Indonesia
Authors: Prassetyo S H , Wattimena R K , Widodo N P , Simangunsong G M , Rai M A , Sulistianto B , Okatrisza Y , Septiyanto E
Published: January 2023

This paper presents the findings of a case study of the stability of a tunnel composite liner using the convergence-confinement method (CCM) and a support capacity diagram by means of 2-D numerical analysis. The height of the loose zone and the induced loads exerted on the composite liner from the numerical analysis are compared to the empirical calculation proposed by Terzaghi’s rock load theory. The case study is taken from a recently completed double-track railway tunnel located in Notog district, Central Java, Indonesia. The numerical result shows the loose zone height is 15 m or roughly 1.5B, where B = tunnel width, giving rock load of 32 ton/m2 and composite liner FoS of 2.4. This is within the estimates obtained from Terzaghi’s rock load theory, which amounts to 12-21 m, giving the rock load of 25-46 ton/m2 and corresponding composite liner FoS of 3.1 to 1.7. It is also observed that each supporting element in the composite liner can sustain the induced loads due to excavation, with FoS well beyond 2.0. Compared to the supporting capacity of each supporting element, the loads carried by the steel-sets are significantly lower than those carried by the shotcrete.
Numerical modelling of rock fragmentation for TBM based on peridynamics
Authors: Li Yuanbai , Liu Jie , Xue Yadong
Published: January 2023

With the rapid development of tunnelling engineering construction, especially the deep buried long tunnels, the full-face hard rock tunnel boring machines (TBMs) have been widely used in excavation process because of its significant advantages including fast advance rate, excellent safety, low disturbance to surrounding rock, and so on. Figuring out clearly the rock fragmentation mechanism is very important for a tunnel project, which attracts extensive attention worldwide all the time. In this study, a 3D model of rock fragmentation induced by a disc cutter was established based on peridynamic theory (PD) to explore and comprehend it. Based on the reasonable values of the model parameters, a series of numerical simulation tests were implemented to investigate the evolution cracks with increase of the penetration. The simulation results shown that the entire process of rock breaking had a good agreement by comparing with results in existing literature. In this paper, the proposed model based on PD provided a novel approach to study further the rock fragmentation mechanism taking more complex conditions into consideration in the future.
A numerical study on THM coupled behavior in the high-level radioactive waste disposal system
Authors: Kim Taehyun , Park Chan-Hee , Lee Changsoo , Kim Jin-Seop
Published: January 2023

It is essential to securely isolate high-level radioactive waste from the biosphere, and geologic disposal of it at a deep underground repository is considered the most effective method. Therefore, it is crucial to research the complex thermo-hydro-mechanical-chemical (THMC) coupled behavior in geological disposal systems parallel with numerical simulation. DECOVALEX is an international cooperating project to efficiently develop numerical methods and models and validate through test results for predicting the THMC interactions in the disposal systems. In Task C of DECOVALEX-2023, the modeling teams focus on understanding pore pressure development and THM interactions in the host rock and buffer material during the FE experiment, a 1:1 scale in-situ heater test based on Nagra’s Reference repository design. We used OGS-FLAC3D for the numerical simulation, combining OpenGeoSys for TH simulation and FLAC3D for M simulation. At the first phase of the task, a simple two-dimensional benchmark problem was defined to set up the numerical model. THM coupled processes in the bentonite were simulated with a two-phase flow system, and we investigated the temperature and pressure variations on the given monitoring position. Vaporization induced by a temperature increase in the bentonite was observed at the heater’s vicinity, and flow occurred by capillarity, and pressure difference was well simulated. Additionally, the flow process was dominant in the near field of engineering barrier, while we observed thermal pressurization in the far-field area. We plan to apply the developed model to a full-scale three-dimensional numerical simulation for the next phase.
Interpretation of changing pore pressure on heated unsaturated/saturated bentonite-sand mixture
Authors: Nishimura T
Published: January 2023

Generation of electricity in nuclear power plants have supply further energy to society in the world, and remain arising of radioactive waste as results of performance industry with activity. Radioactive waste has to be isolated from the human habitat for absolutely so long time period until its radioactivity has decayed to an innocuous situation. To end disposal completely, every country operated Nuclear Energy plant foresees further deep geological repository. This study focused on couple phenomena associate to THMC properties for bentonite-sand mixture that particularly, soil moisture movement and occurrence of fluid pressure under maximum temperature 80 degrees Celsius. Modified stainless mould contributed on a series of testing, which had specialized pressure sensor having high temperature resistance. Used materials are sodium bentonite and silica sand. Also, salinity water comparison to distilled water on soil moisture movement under heating for saturated bentonite-sand mixture. Other hand, it is obviously that fluid pressure in bentonite-san mixture induced by heating increased due to increment temperature, and obtained pressures were difference with location point for measurement in specimen. Heating action applied to specimens under isotopically conductivity.
Visco-elastic constitutive law to simulate large creep deformations using particle based simulation approach
Authors: Zhang Miao , Konietzky Heinz , Herbst Martin
Published: January 2023

So far there are only very few publications which consider large creep deformations of solids using particle based approaches, however large creep deformations will occur in underground salt or soft rock pillars after decades even hundred years. This paper is dedicated towards a specific constitutive model called BurgerFG which is based on SSPM (Stiff Spherical Particle Method). The implementation is performed in the particle based software PFC3D. A solution for time-step optimization to simulate long-term creep processes is proposed. The model allows to simulate creep including damage and healing processes like typically observed for salt material under loading.
Impact identification on flexible rockfall barriers: on site test of a wireless monitoring system
Authors: Segalini A , Valletta A , Carri A , Savi R
Published: January 2023

Flexible rockfall barriers represent an effective measure to mitigate hazard related to falling boulders. The monitoring activity of these protection structures is essential to guarantee their functionality, and usually aims to verify the barrier conditions and to identify any impact on the net. The system here presented, called D-Fence, was specifically developed for the realtime monitoring of flexible rockfall barriers. It consists of a series of separate battery-powered devices installed on the uprights of the monitored structure and transmit data to the elaboration center through a wireless local network. Each module includes a 3D tilt sensor, allowing the near real-time monitoring of the rotation of the uprights, while the integration of a shock sensor makes it possible to measure in real-time the accelerations experienced by the barrier. The onsite test of the D-Fence system involved the installation of four modules on a prototype barrier located in a pilot site in Northern Italy. Each device was placed on a different upright and was connected to a local Wi-Fi network. In this configuration, two different concrete boulders were dropped on the barrier in order to test the D-Fence ability to measure the tilt variation of the uprights and identify the overcoming of a predefined acceleration threshold.
Stress wave analysis of high-voltage pulse discharge rock fragmentation based on plasma channel impedance model
Authors: HUANG Shijie , LIU Yi , ZHAO Yong , XU Youlai , LIN Fuchang , LI Hua , ZHANG Qin , LI Liuxia
Published: January 2023

High-voltage pulse discharge (HVPD) rock fragmentation controls a plasma channel forming inside the rock by adjusting the electrical parameters, electrode type, etc. In this work, an HVPD rock fragmentation test platform was built and the test waveforms were measured. Considering the effects of temperature, channel expansion and electromagnetic radiation, the impedance model of the plasma channel in the rock was established. The parameters and initial values of the model were determined by an iterative computational process. The model calculation results can reasonably characterize the development of the plasma channel in the rock and estimate the shock wave characteristics. Based on the plasma channel impedance model, the temporal and spatial distribution characteristics of the radial stress and tangential stress in the rock were calculated, and the rock fragmentation effect of the HVPD was analyzed.
Chronic pain in people living with dementia: challenges to recognising and managing pain, and personalising intervention by phenotype
Authors: Collins Jemima T , Harwood Rowan H , Cowley Alison , Di Lorito Claudio , Ferguson Eamonn , Minicucci Marcos F , Howe Louise , Masud Tahir , Ogliari Giulia , O’Brien Rebecca , Azevedo Paula S , Walsh David A , Gladman John R F
Published: January 2023

Pain is common in people with dementia, and pain can exacerbate the behavioural and psychological symptoms of dementia. Effective pain management is challenging, not least in people with dementia. Impairments of cognition, communication and abstract thought can make communicating pain unreliable or impossible. It is unclear which biopsychosocial interventions for pain management are effective in people with dementia, and which interventions for behavioural and psychological symptoms of dementia are effective in people with pain. The result is that drugs, physical therapies and psychological therapies might be either underused or overused. People with dementia and pain could be helped by assessment processes that characterise an individual’s pain experience and dementia behaviours in a mechanistic manner, phenotyping. Chronic pain management has moved from a ‘one size fits all’ approach, towards personalised medicine, where interventions recommended for an individual depend upon the key mechanisms underlying their pain, and the relative values they place on benefits and adverse effects. Mechanistic phenotyping through careful personalised evaluation would define the mechanisms driving pain and dementia behaviours in an individual, enabling the formulation of a personalised intervention strategy. Central pain processing mechanisms are particularly likely to be important in people with pain and dementia, and interventions to accommodate and address these may be particularly helpful, not only to relieve pain but also the symptoms of dementia.
A novel prognostic nomogram for older patients with acute-on-chronic liver diseases (AoCLD): a nationwide, multicentre, prospective cohort study
Authors: Zou Ju , Li Hai , Deng Guohong , Wang Xianbo , Zheng Xin , Chen Jinjun , Meng Zhongji , Zheng Yubao , Gao Yanhang , Qian Zhiping , Liu Feng , Lu Xiaobo , Shi Yu , Shang Jia , Huang Yan , Chen Ruochan
Published: January 2023

Background

the incidence of acute-on-chronic liver disease (AoCLD) is increasing.

Objective

to investigate the clinical features and risk factors of AoCLD and construct an effective prognostic nomogram model for older patients with AoCLD.

Methods

data from 3,970 patients included in the CATCH-LIFE study were used, including 2,600 and 1,370 patients in the training and validation sets, respectively. Multivariate Cox regression analyses were performed to identify predictive risk factors in older individuals, and an easy-to-use nomogram was established. Performance was assessed using area under the curve, calibration plots and decision curve analysis (DCA).

Results

of the 3,949 patients with AoCLD, 809 were older with a higher proportion of autoimmune-related abnormalities, hepatitis C viral infection and schistosomiasis. In the older patient group, the incidence of cirrhosis, hepatic encephalopathy (HE), infection, ascites and gastrointestinal bleeding; neutrophil-to-lymphocyte ratio (NLR), aspartate-to-alanine transaminase ratio (AST/ALT), creatinine and blood urea nitrogen levels were higher, whereas incidence of acute-on-chronic liver failure, white blood cell, platelet and haemoglobin levels; albumin, total bilirubin (TB), AST and ALT levels; international normalised ratio (INR), estimated glomerular filtration rate and blood potassium levels were lower than in the younger group. The final nomogram was developed based on the multivariate Cox analysis in training cohort using six risk factors: ascites, HE grades, NLR, TB, INR and AST/ALT. Liver transplantation-free mortality predictions were comparable between the training and validation sets. DCA showed higher net benefit for the nomograph than the treat-all or treat-none strategies, with wider threshold probabilities ranges.

Conclusions

our analysis will assist clinical predictions and prognoses in older patients with AoCLD.
Hydrostatic Penetration Testing of Protective Glove Materials Using Water and Synthetic Blood to Evaluate Hole Size and Screen Mesh Using an Automated Pressure Delivery System
Authors: Cohen-Gómez Eva , Ruz Mario L , Hoyas-Pablos Eva Mª , Vázquez Francisco
Published: January 2023

There are several international standards that address the resistance of chemical protective clothing materials to the penetration by liquids. The hydrostatic pressure has been documented to discriminate between protective clothing material performance and correlates with visual penetration results that are obtained with human factors validation. The same methodology, based on hydrostatic pressure equipment, is referenced also in other standards addressing penetration resistance of protective clothing and glove materials against synthetic blood or blood-borne pathogens. In this study, we present an automated hydrostatic penetration testing that integrates testing procedures from several standards to evaluate the resistance of materials to penetration by liquids under pressure. The automated control system allows the user to select a specific test method and automatically sets a stepped pressurization protocol to test the material. A pass or a fail result is produced at a certain time and pressure. As an example of application, the penetration of synthetic blood was assessed through gloves made from different materials with ISO 16603, method B, one of the five possible penetration methods and protocols available in the test equipment. The results indicate that the developed system facilitates the application of test methods used to evaluate the barrier effectiveness against liquids of materials used for protective clothing and gloves and show up that the characteristics of the retention grid used have a decisive influence on the test results. In some of the tested glove materials, holes were intentionally performed with needles with different gauges. The capacity of pinhole detection in gloves was evaluated according to the test method selected and compared with results obtained with the classic water leak test method for gloves described in EN ISO 374-2.
A diet supplemented with cholic acid elevates blood pressure accompanied by albuminuria in rats
Authors: Shimoda Tomoko , Shimizu Hidehisa , Iwasaki Wakana , Liu Hongxia , Kamo Yoshie , Tada Koji , Hanai Taketo , Hori Shota , Joe Ga-Hyun , Tanaka Yasutake , Sato Masao , Miyazaki Hitoshi , Ishizuka Satoshi
Published: January 2023

A diet supplemented with cholic acid (CA), the primary 12α-hydroxylated bile acid, can induce hepatic lipid accumulation in rats without obesity. This study examined the effects of a CA-supplemented diet on blood pressure (BP). After acclimation, WKAH/HkmSlc rats (3 weeks old) were divided into two groups and fed with a control AIN-93-based diet or a CA-supplemented diet (0.5 g CA/kg) for 13 weeks. The CA diet increased systolic and diastolic BP as well as hepatic lipid concentrations in the rats. No changes were found in the blood sodium concentration. Urinary albumin concentration increased in CA-fed rats. An increase was observed in the hepatic expression of ATP-binding cassette subfamily B member 1B that correlated BPs and urinary albumin concentration accompanied by an increase in portal taurocholic acid concentration. These results suggest that 12α-hydroxylated bile acids are involved in increased BP and albuminuria via alteration of hepatic function.
Risk of infections in patients with pemphigus treated with rituximab vs. azathioprine or mycophenolate mofetil: a large-scale global cohort study
Authors: Kridin Khalaf , Mruwat Noor , Amber Kyle T , Ludwig Ralf J
Published: January 2023

Background

The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated.

Objectives

To evaluate the risk of infections in patients with pemphigus managed by rituximab vs. first-line corticosteroid-sparing agents [azathioprine and mycophenolate mofetil (MMF)].

Methods

A global population-based cohort study compared patients with pemphigus initiating rituximab (n = 963) vs. azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability.

Results

During the initial 12 months following treatment, patients under rituximab experienced elevated risk of COVID-19 [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.06–3.14; P = 0.028], parasitic diseases (HR 3.22, 95% CI 1.04–9.97; P = 0.032) and cytomegalovirus (CMV) infection (HR 1.63, 95% CI 1.04–2.58; P = 0.033). When evaluating infections developing ≥ 12 months after drug initiation, rituximab was associated with greater risk of pneumonia (HR 1.45, 95% CI 1.00–2.10; P = 0.047), COVID-19 (HR 1.87, 95% CI 1.49–2.33; P < 0.001), osteomyelitis (HR 2.42, 95% CI 1.11–5.31; P = 0.023), herpes simplex virus (HR 2.06, 95% CI 1.03–4.11; P = 0.037) and CMV (HR 1.63, 95% CI 1.07–2.49; P = 0.023) infections.

Conclusions

Within the first 12 months after treatment, patients under rituximab experience an elevated risk of COVID-19, parasitic and CMV infections. Rituximab is associated with pneumonia, osteomyelitis and viral diseases even beyond the first year after therapy. Pneumococcal vaccine and suppressive antiviral therapy should be considered even 1 year following therapy. There is no signal for elevated risk of tuberculosis, hepatitis B virus reactivation, Pneumocystis jiroveci pneumonia and progressive multifocal leukoencephalopathy.
Subthalamic stimulation modulates motor network in Parkinson’s disease: recover, relieve and remodel
Authors: Chu Chunguang , Liu Shang , He Naying , Zeng Zhitong , Wang Jiang , Zhang Zhen , Zeljic Kristina , van der Stelt Odin , Sun Bomin , Yan Fuhua , Liu Chen , Li Dianyou , Zhang Chencheng
Published: January 2023

Aberrant dynamic switches between internal brain states are believed to underlie motor dysfunction in Parkinson’s disease. Deep brain stimulation of the subthalamic nucleus is a well-established treatment for the motor symptoms of Parkinson’s disease, yet it remains poorly understood how subthalamic stimulation modulates the whole-brain intrinsic motor network state dynamics.

To investigate this, we acquired resting-state functional magnetic resonance imaging time-series data from 27 medication-free patients with Parkinson’s disease (mean age: 64.8 years, standard deviation: 7.6) who had deep brain stimulation electrodes implanted in the subthalamic nucleus, in both on and off stimulation states. Sixteen matched healthy individuals were included as a control group. We adopted a powerful data-driven modelling approach, known as a hidden Markov model, to disclose the emergence of recurring activation patterns of interacting motor regions (whole-brain intrinsic motor network states) via the blood oxygen level-dependent signal detected in the resting-state functional magnetic resonance imaging time-series data from all participants. The estimated hidden Markov model disclosed the dynamics of distinct whole-brain motor network states, including frequency of occurrence, state duration, fractional coverage and their transition probabilities.

Notably, the data-driven decoding of whole-brain intrinsic motor network states revealed that subthalamic stimulation reshaped functional network expression and stabilized state transitions. Moreover, subthalamic stimulation improved motor symptoms by modulating key trajectories of state transition within whole-brain intrinsic motor network states. This modulation mechanism of subthalamic stimulation was manifested in three significant effects: recovery, relieving and remodelling effects. Significantly, recovery effects correlated with improvements in tremor and posture symptoms induced by subthalamic stimulation (P < 0.05). Furthermore, subthalamic stimulation was found to restore a relatively low level of fluctuation of functional connectivity in all motor regions to a level closer to that of healthy participants. Also, changes in the fluctuation of functional connectivity between motor regions were associated with improvements in tremor and gait symptoms (P < 0.05).

These findings fill a gap in our knowledge of the role of subthalamic stimulation at the level of neural activity, revealing the regulatory effects of subthalamic stimulation on whole-brain inherent motor network states in Parkinson’s disease. Our results provide mechanistic insight and explanation for how subthalamic stimulation modulates motor symptoms in Parkinson’s disease.
Two women with primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder during pregnancy
Authors: Gambichler Thilo , Scheel Christina H , Kock Katharina , Klapper Wolfram , Doerler Martin , Boms Stefanie
Published: January 2023

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-TCLPD) is a rare subtype of cutaneous T-cell lymphomas of unknown origin. We report for the first time, to the best of our knowledge, on an association of PCSM-TCLPD with pregnancy and briefly discuss the possible pathogenetic link.
Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis
Authors: Solans Belén P , Béranger Agathe , Radtke Kendra , Mohamed Ali , Mirzayev Fuad , Gegia Medea , Linh Nguyen Nhat , Schumacher Samuel G , Nahid Payam , Savic Radojka M
Published: January 2023

Background

Optimal doses of first-line drugs for treatment of drug-susceptible tuberculosis in children and young adolescents remain uncertain. We aimed to determine whether children treated using World Health Organization–recommended or higher doses of first-line drugs achieve successful outcomes and sufficient pharmacokinetic (PK) exposures.

Methods

Titles, abstracts, and full-text articles were screened. We searched PubMed, EMBASE, CENTRAL, and trial registries from 2010 to 2021. We included studies in children aged <18 years being treated for drug-susceptible tuberculosis with rifampicin (RIF), pyrazinamide, isoniazid, and ethambutol. Outcomes were treatment success rates and drug exposures. The protocol for the systematic review was preregistered in PROSPERO (no. CRD42021274222).

Results

Of 304 studies identified, 46 were eligible for full-text review, and 12 and 18 articles were included for the efficacy and PK analyses, respectively. Of 1830 children included in the efficacy analysis, 82% had favorable outcomes (range, 25%–95%). At World Health Organization–recommended doses, exposures to RIF, pyrazinamide, and ethambutol were lower in children than in adults. Children ≤6 years old have 35% lower areas under the concentration-time curve (AUCs) than older children (mean of 14.4 [95% CI 9.9–18.8] vs 22.0 [13.8–30.1] μg·h/mL) and children with human immunodeficiency virus (HIV) had 35% lower RIF AUCs than HIV-negative children (17.3 [11.4–23.2] vs 26.5 [21.3–31.7] μg·h/mL). Heterogeneity and small sample sizes were major limitations.

Conclusions

There is large variability in outcomes, with an average of 82% favorable outcomes. Drug exposures are lower in children than in adults. Younger children and/or those with HIV are underexposed to RIF. Standardization of PK pediatric studies and individual patient data analysis with safety assessment are needed to inform optimal dosing.
From ‘the land of the rising sun’ to ‘the countries of the sun’: Mishima Yukio in Greece and Italy
Authors: Zhang Xiaoxi
Published: January 2023

The famous Japanese author Mishima Yukio is known to have been keenly interested in ancient Greek culture. In this article, I seek to explain how his visit to Greece and Italy in the spring of 1952 intensified his philhellenism. To such an end, I will rely on Mishima’s travelogue titled Apollo’s Cup, which was published in the fall of that same year. I will pay close attention to Mishima’s encounters with the ancient ruins in Athens and with the sculptures of Antinous in the Vatican City, because they were the highlights of Mishima’s trip. I will argue that Mishima’s philhellenism was driven by his personal needs at the time and heightened by his fascination for the materiality of ancient Greece, since the ‘placeness’ of ancient Greece allowed Mishima not only to position and approach ancient Greece but also to idealize ancient Greece.
Somapacitan in children born small for gestational age: a multi-centre, open-label, controlled phase 2 study
Authors: Juul Anders , Backeljauw Philippe , Højby Michael , Kawai Masanobu , Kildemoes Rasmus Juul , Linglart Agnès , Zuckerman-Levin Nehama , Horikawa Reiko
Published: January 2023

Objective

Investigate efficacy, safety, and tolerability of 3 once-weekly somapacitan doses compared with daily growth hormone (GH) administration in short children born small for gestational age (SGA).

Design

Randomised, multi-centre, open-label, controlled phase 2 study comprising a 26-week main phase and a 4-year extension (NCT03878446). The study was conducted at 38 sites across 12 countries. 26-week main phase results are presented here.

Sixty-two GH treatment-naïve, prepubertal short children born SGA were randomised and exposed; 61 completed the main phase. Three somapacitan doses (0.16 [n = 12], 0.20 [n = 13], 0.24 [n = 12] mg/kg/week) and 2 daily GH doses (0.035 [n = 12], 0.067 [n = 13] mg/kg/day) were administered subcutaneously.

Results

After 26 weeks of treatment, the estimated mean annualised height velocity (HV) was 8.9, 11.0, and 11.3 cm/year for somapacitan 0.16, 0.20, and 0.24 mg/kg/week, respectively, compared to 10.3 and 11.9 cm/year for daily GH 0.035 and 0.067 mg/kg/day. Changes from baseline in HV standard deviation score (SDS), height SDS, and insulin-like growth factor I (IGF-I) SDS showed similar dose-dependent responses. Exposure-response modelling indicated the greatest efficacy correlated with the highest somapacitan exposure. Similar safety and tolerability were demonstrated for all weekly somapacitan and daily GH doses.

Conclusions

Based on the totality of data on improvements in height-based parameters combined with exposure-response analyses, somapacitan 0.24 mg/kg/week appears most efficacious, providing similar efficacy, safety, and tolerability as daily GH 0.067 mg/kg/day in short children born SGA after 26 weeks of treatment.
Institutions, Holdup, and Automation
Authors: Presidente Giorgio
Published: January 2023

What drives investment in automation technologies? This paper documents a positive relationship between labor-friendly institutions and investment in industrial robots in a sample of advanced and developing economies. Institutions explain a substantial share of cross-country variation in automation. The relationship between institutions and robots is stronger in sunk cost-intensive industries, where producers are vulnerable to holdup. The result suggests that one reason for producers to invest in automation is to thwart rent appropriation by labor.
Measuring the Impact of a Blood Supply Shortage Using Data Science
Authors: Bahar Burak , Gehrie Eric A , Mo Yunchuan D , Jacquot Cyril , Delaney Meghan
Published: January 2023

Background

Transfusion medicine is the only section of the clinical laboratory that performs diagnostic testing and dispenses a drug (blood) on the basis of those results. However, not all of the testing that informs the clinical decision to prescribe a blood transfusion is performed in the blood bank. To form a holistic assessment of blood bank responsiveness to clinical needs, it is important to be able to merge blood bank data with datapoints from the hematology laboratory and the electronic medical record.

Methods

We built an interactive visualization of the time from hemoglobin result availability to initiation of red blood cell (RBC) transfusion and monitored the result over a 2-year period that coincided with several severe blood shortages. The visualization runs entirely on free software and was designed to be feasibly deployed on a variety of hospital information technology platforms without the need for significant data science expertise.

Results

Patient factors, such as hemoglobin concentration, blood type, and presence of minor blood group antibodies influenced the time to initiation of transfusion. Time to transfusion initiation did not appear to be significantly affected by periods of blood shortage.

Conclusion

Overall, we demonstrate a proof of concept that complex, but clinically important, blood bank quality metrics can be generated with the support of a free, user-friendly system that aggregates data from multiple sources.
Technology Platforms and Approaches for Building and Evaluating Machine Learning Methods in Healthcare
Authors: Mooney Sean D
Published: January 2023

Background

Artificial intelligence (AI) methods are becoming increasingly commonly implemented in healthcare as decision support, business intelligence tools, or, in some cases, Food and Drug Administration–approved clinical decision-makers. Advanced lab-based diagnostic tools are increasingly becoming AI driven. The path from data to machine learning methods is an active area for research and quality improvement, and there are few established best practices. With data being generated at an unprecedented rate, there is a need for processes that enable data science investigation that protect patient privacy and minimize other business risks. New approaches for data sharing are being utilized that lower these risks.

Content

In this short review, clinical and translational AI governance is introduced along with approaches for securely building, sharing, and validating accurate and fair models. This is a constantly evolving field, and there is much interest in collecting data using standards, sharing data, building new models, evaluating models, sharing models, and, of course, implementing models into practice.

AI is an active area of research and development broadly for healthcare and laboratory testing. Robust data governance and machine learning methodological governance are required. New approaches for data sharing are enabling the development of models and their evaluation. Evaluation of methods is difficult, particularly when the evaluation is performed by the team developing the method, and should ideally be prospective. New technologies have enabled standardization of platforms for moving analytics and data science methods.
Risk Analysis for Quality Control Part 3: Practical Application of the Precision Quality Control Model
Authors: Schmidt Robert L , Moore Ryleigh A , Walker Brandon S , Rudolf Joseph W
Published: January 2023

Background

We developed a theoretical framework (Precision Quality Control [PQC]) to minimize the cost of quality, but it is not known whether the method can be applied in practice.

Methods

We used data for 2 analytes, cadmium and carbohydrate-deficient transferrin (CDT), and applied the PQC framework to find the optimal control limits. These analytes were selected because they differed with respect to sigma values that are major determinants of control limits. We explored different ways to visualize the results: (a) risk trade-off (false-positive risk vs false-negative risk), (b) cost–risk trade-off (false-positive cost vs false-negative risk), and (c) cost minimization.

Results

We were able to use the PQC limit to produce 3 different visualizations to suggest control limits. The risk-based analysis was the simplest to apply, but the most difficult to interpret. The cost vs risk method was easy to apply but was still difficult to interpret. The cost minimization method was easy to interpret but required users to declare a willingness to pay that may be difficult to estimate.

Conclusions

The PQC method can be used to find control limits that minimize the cost of quality.
Feeding thermally processed spray-dried egg whites, singly or in combination with 15-acetyldeoxynivalenol or peroxidized soybean oil on growth performance, digestibility, intestinal morphology, and oxidative status in nursery pigs
Authors: Wilson Victoria C , McCormick Susan P , Kerr Brian J
Published: January 2023

Two experiments (EXP) determined the susceptibility of spray-dried egg white (SDEW) to oxidation (heating at 100 °C for 72 h; thermally processed, TP) and whether feeding TP–SDEW, 15-acetyldeoxynivalenol (15-ADON), or peroxidized soybean oil (PSO), singularly or in combination, would affect pig performance, intestinal morphology, digestibility, and markers of oxidative stress in nursery pigs. In EXP 1, 32 pigs (7.14 kg body weight, BW) were placed individually into pens and fed diets containing either 12% SDEW, 6% TP–SDEW plus 6% SDEW, or 12% TP–SDEW. Performance was measured at the end of the 24-d feeding period with biological samples harvested following euthanasia. In EXP 2, 64 pigs (10.6 kg BW) were placed individually into pens and fed diets containing 7.5% soybean oil or PSO, 10% SDEW or TP–SDEW, and diets without or with 3 mg 15-ADON/kg diet in a 2 × 2 × 2 factorial arrangement. Performance was measured at the end of the 28-d feeding period with biological samples harvested following euthanasia. In EXP 1, dietary treatment did not affect pig performance, apparent ileal digestibility of amino acids (AAs), apparent total tract digestibility (ATTD) of gross energy (GE) or nitrogen (N), ileal crypt depth, or villi height:crypt depth ratio (P > 0.05). The effects of feeding TP–SDEW on protein damage in the plasma and liver (P < 0.05) were variable. In EXP 2, there were no three-way interactions and only one two-way interactions among dietary treatments on parameters evaluated. There was no effect of feeding TP–SDEW on ATTD of GE or N, intestinal morphology, or on oxidative markers in the plasma, liver, or ileum (P > 0.05). There was no effect of feeding diets containing added 15-ADON on ATTD of GE, ileal AA digestibility, intestinal morphology, oxidative markers in the plasma, liver, or ileum, or pig performance (P > 0.05). Feeding pigs diets containing PSO resulted in reduced ATTD of GE and N, plasma vitamin E concentration, and pig performance (P < 0.01) but did not affect intestinal morphology or oxidative markers in the liver or ileum (P > 0.05). In conclusion, it was difficult to induce protein oxidation in SDEW and when achieved there were limited effects on performance, digestibility, intestinal morphology, and oxidative status. Furthermore, singly adding 15-A-DON to a diet had no effect on the animal. At last, adding PSO reduces animal performance, but has limited effect on digestibility, intestinal morphology, and oxidative status in nursery pigs.
Global Patterns of Insect Resistance to Transgenic Bt Crops: The First 25 Years
Authors: Tabashnik Bruce E , Fabrick Jeffrey A , Carrière Yves
Published: January 2023

Crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) have improved pest management and reduced reliance on insecticide sprays. However, evolution of practical resistance by some pests has reduced the efficacy of Bt crops. We analyzed global resistance monitoring data for 24 pest species based on the first 25 yr of cultivation of Bt crops including corn, cotton, soybean, and sugarcane. Each of the 73 cases examined represents the response of one pest species in one country to one Bt toxin produced by one or more Bt crops. The cases of practical resistance rose from 3 in 2005 to 26 in 2020. Practical resistance has been documented in some populations of 11 pest species (nine lepidopterans and two coleopterans), collectively affecting nine widely used crystalline (Cry) Bt toxins in seven countries. Conversely, 30 cases reflect no decrease in susceptibility to Bt crops in populations of 16 pest species in 10 countries. The remaining 17 cases provide early warnings of resistance, which entail genetically based decreases in susceptibility without evidence of reduced field efficacy. The early warnings involve four Cry toxins and the Bt vegetative insecticidal protein Vip3Aa. Factors expected to favor sustained susceptibility include abundant refuges of non-Bt host plants, recessive inheritance of resistance, low resistance allele frequency, fitness costs, incomplete resistance, and redundant killing by multi-toxin Bt crops. Also, sufficiently abundant refuges can overcome some unfavorable conditions for other factors. These insights may help to increase the sustainability of current and future transgenic insecticidal crops.