bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-planar corrections in orbifold/orientifold $$ \mathcal{N} $$ = 2 superconformal theories from localization
Authors: Beccaria M. , Korchemsky G. P. , Tseytlin A. A.
Published: May 2023

Abstract

We study non-planar corrections in two special $$ \mathcal{N} $$
N
= 2 superconformal SU(N) gauge theories that are planar-equivalent to $$ \mathcal{N} $$
N
= 4 SYM theory: two-nodes quiver model with equal couplings and $$ \mathcal{N} $$
N
= 2 vector multiplet coupled to two hypermultiplets in rank-2 symmetric and antisymmetric representations. We focus on two observables in these theories that admit representation in terms of localization matrix model: free energy on 4-sphere and the expectation value of half-BPS circular Wilson loop. We extend the methods developed in arXiv:2207.11475 to derive a systematical expansion of non-planar corrections to these observables at strong ’t Hooft coupling constant λ. We show that the leading non- planar corrections are given by a power series in λ3/2/N2 with rational coefficients. Sending N and the coupling constant λ to infinity with λ3/2/N2 kept fixed corresponds to the familiar double scaling limit in matrix models. We find that in this limit the observables in the two models are related in a remarkably simple way: the free energies differ by the factor of 2, whereas the Wilson loop expectation values coincide. Surprisingly, these relations hold only at strong coupling, they are not valid in the weak coupling regime. We also discuss a dual string theory interpretation of the leading corrections to the free energy in the double scaling limit suggesting their relation to curvature corrections in type IIB string effective action.
Resurgence, conformal blocks, and the sum over geometries in quantum gravity
Authors: Benjamin Nathan , Collier Scott , Maloney Alexander , Meruliya Viraj
Published: May 2023

Abstract

In two dimensional conformal field theories the limit of large central charge plays the role of a semi-classical limit. Certain universal observables, such as conformal blocks involving the exchange of the identity operator, can be expanded around this classical limit in powers of the central charge c. This expansion is an asymptotic series, so — via the same resurgence analysis familiar from quantum mechanics — necessitates the existence of non-perturbative effects. In the case of identity conformal blocks, these new effects have a simple interpretation: the CFT must possess new primary operators with dimension of order the central charge. This constrains the data of CFTs with large central charge in a way that is similar to (but distinct from) the conformal bootstrap. We study this phenomenon in three ways: numerically, analytically using Zamolodchikov’s recursion relations, and by considering non-unitary minimal models with large (negative) central charge. In the holographic dual to a CFT2, the expansion in powers of c is the perturbative loop expansion in powers of ћ. So our results imply that the graviton loop expansion is an asymptotic series, whose cure requires the inclusion of new saddle points in the gravitational path integral. In certain cases these saddle points have a simple interpretation: they are conical excesses, particle-like states with negative mass which are not in the physical spectrum but nevertheless appear as non-manifold saddle points that control the asymptotic behaviour of the loop expansion. This phenomenon also has an interpretation in SL(2, ℝ) Chern-Simons theory, where the non-perturbative effects are associated with the non-Teichmüller component of the moduli space of flat connections.
Orbit averaging coherent states: holographic three-point functions of AdS giant gravitons
Authors: Holguin Adolfo , Weng Wayne W.
Published: May 2023

Abstract

We study correlation functions of two AdS giant gravitons in AdS5 × S5 and a BPS supergravity mode using holography. In the gauge theory these are described by BPS correlators of Schur polynomials of fully-symmetric representations and a single trace operator. We find full agreement between the semiclassical gravity and gauge theory computations at large N, for both diagonal and off-diagonal structure constants. Our analysis in $$ \mathcal{N} $$
N
= 4 SYM provides a simpler derivation to the results in the literature, and it can be readily generalized to operators describing bound states of AdS giant gravitons as well as bubbling geometries.
Feynman integral reduction using Gröbner bases
Authors: Barakat Mohamed , Brüser Robin , Fieker Claus , Huber Tobias , Piclum Jan
Published: May 2023

Abstract

We investigate the reduction of Feynman integrals to master integrals using Gröbner bases in a rational double-shift algebra Y in which the integration-by-parts (IBP) relations form a left ideal. The problem of reducing a given family of integrals to master integrals can then be solved once and for all by computing the Gröbner basis of the left ideal formed by the IBP relations. We demonstrate this explicitly for several examples. We introduce so-called first-order normal-form IBP relations which we obtain by reducing the shift operators in Y modulo the Gröbner basis of the left ideal of IBP relations. For more complicated cases, where the Gröbner basis is computationally expensive, we develop an ansatz based on linear algebra over a function field to obtain the normal-form IBP relations.
Surface quality investigation in surfactant-based EDM of Inconel 617 using deep cryogenically treated electrodes
Authors: Ishfaq Kashif , Sana Muhammad , Waseem Muhammad Umair , Anwar Saqib , Alfaify Abdullah Yahia , Zia Abdul Wasy
Published: May 2023

Surface quality governs the physical, mechanical, tribological, physio-chemical, and biological properties of materials. Considering the excellent mechanical characteristics of Inconel 617 and the nature of its intended applications, electric discharge machining is generally engaged. However, there is still a need to uplift the surface quality of machined parts to improve their working life and performance. Therefore, this study revealed the potential of deep cryogenically treated (DCT) electrodes under dielectrics modified with span and tween in the said context using a full factorial experimental design. Experimental findings are deeply investigated by employing 3D surface profilometry, scanning electron, and optical microscopy. Cryogenically treated electrode(s) have demonstrated a better surface quality in comparison to the non-treated electrodes, such as DCT Cu has provided a 25.5% lower roughness value than non-treated Cu. Referring to the role of additives, there exists a reduction of 32.5% in roughness when DCT brass is used instead of typical brass using a mixture of span-20 (S-20) and kerosene as a dielectric. The surface finish given by the cryogenically treated brass is 18.99% better when compared to the average value given by all cryogenically treated electrodes considered in this study. It has also been revealed that tween-based dielectrics gave 83% better surface finish than span-based dielectrics with DCT electrodes.
Price leadership, spying, and secret price changes: a Stackelberg game with imperfect commitment
Authors: Fan Cuihong , Jun Byoung Heon , Wolfstetter Elmar G.
Published: May 2023

We analyze price leadership in a Stackelberg game with incomplete information and imperfect commitment. Sequential play is induced by an information system, represented by a spy, that reports the price of one firm to its rival before the latter chooses its own price. However, the Stackelberg leader may secretly revise its price with some probability. Therefore, the spy’s message is only an imperfect signal. This gives rise to a complex signaling problem where both sender and receiver of messages have private information and the sender has a chance to take another action with some probability. We find partially separating and pooling equilibria that satisfy equilibrium refinements such as the intuitive criterion and support collusive outcomes.
Deep learning regressor model based on nigrosome MRI in Parkinson syndrome effectively predicts striatal dopamine transporter-SPECT uptake
Authors: Bae Yun Jung , Choi Byung Se , Kim Jong-Min , AI Walid Abdullah , Yun Ildong , Song Yoo Sung , Nam Yoonho , Cho Se Jin , Kim Jae Hyoung
Published: May 2023

Purpose

Nigrosome imaging using susceptibility-weighted
imaging (SWI) and dopamine transporter imaging using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single-photon emission computerized tomography (SPECT) can evaluate Parkinsonism. Nigral hyperintensity from nigrosome-1 and striatal dopamine transporter uptake are reduced in Parkinsonism; however, quantification is only possible with SPECT. Here, we aimed to develop a deep-learning-based regressor model that can predict striatal 123I-FP-CIT uptake on nigrosome magnetic resonance imaging (MRI) as a biomarker for Parkinsonism.

Methods

Between February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and 123I-FP-CIT SPECT based on suspected Parkinsonism were included. Two neuroradiologists evaluated the nigral hyperintensity and annotated the centroids of nigrosome-1 structures. We used a convolutional neural network-based regression model to predict striatal specific binding ratios (SBRs) measured via SPECT using the cropped nigrosome images. The correlation between measured and predicted SBRs was evaluated.

Results

We included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39–88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted 123I-FP-CIT SBRs were significantly lower with the loss of nigral hyperintensity (2.31 ± 0.85 vs. 2.44 ± 0.90) than with intact nigral hyperintensity (4.16 ± 1.24 vs. 4.21 ± 1.35, P < 0.01). The sorted measured 123I-FP-CIT SBRs and the corresponding predicted values were significantly and positively correlated (ρc = 0.7443; 95% confidence interval, 0.6216–0.8314; P < 0.01).

Conclusion

A deep learning-based regressor model effectively predicted striatal 123I-FP-CIT SBRs based on nigrosome MRI with high correlation using manually-measured values, enabling nigrosome MRI as a biomarker for nigrostriatal dopaminergic degeneration in Parkinsonism.
Microbial Diversity and Activity of Biofilms from Geothermal Springs in Croatia
Authors: Kostešić Ema , Mitrović Maja , Kajan Katarina , Marković Tamara , Hausmann Bela , Orlić Sandi , Pjevac Petra
Published: May 2023

Hot spring biofilms are stable, highly complex microbial structures. They form at dynamic redox and light gradients and are composed of microorganisms adapted to the extreme temperatures and fluctuating geochemical conditions of geothermal environments. In Croatia, a large number of poorly investigated geothermal springs host biofilm communities. Here, we investigated the microbial community composition of biofilms collected over several seasons at 12 geothermal springs and wells. We found biofilm microbial communities to be temporally stable and highly dominated by Cyanobacteria in all but one high-temperature sampling site (Bizovac well). Of the physiochemical parameters recorded, temperature had the strongest influence on biofilm microbial community composition. Besides Cyanobacteria, the biofilms were mainly inhabited by Chloroflexota, Gammaproteobacteria, and Bacteroidota. In a series of incubations with Cyanobacteria-dominated biofilms from Tuhelj spring and Chloroflexota- and Pseudomonadota-dominated biofilms from Bizovac well, we stimulated either chemoorganotrophic or chemolithotrophic community members, to determine the fraction of microorganisms dependent on organic carbon (in situ predominantly produced via photosynthesis) versus energy derived from geochemical redox gradients (here simulated by addition of thiosulfate). We found surprisingly similar levels of activity in response to all substrates in these two distinct biofilm communities, and observed microbial community composition and hot spring geochemistry to be poor predictors of microbial activity in the study systems.
Stability and safety key factors of the oncolytic protoparvovirus H-1 from manufacturing to human application
Authors: Frehtman Veronika , Wohlfarth Daniel , Müller Marcus , Krebs Ottheinz , Leuchs Barbara
Published: May 2023

The oncolytic rodent protoparvovirus H-1PV has been successfully used in phase I/II clinical trials to treat recurrent glioblastoma multiforme and pancreatic cancer. The present work focuses on the stability and environmental safety of the H-1PV drug product from production up to its use in patients. We identified hold-steps in manufacturing for up to 3 months and showed 7-years stability for the optimal product formulation. Stress testing via UV, temperature, and pH also determined that the drug product is stable. De- and rehydration for lyophilization simulation are possible without infectious virus loss. Furthermore, we prove in-use stability for 4 days at room temperature and show no virus adsorption to injection devices, guaranteeing the correct administration dose. Iodixanol in the formulation, resulting in high viscosity, protects H-1PV against UV and some disinfectants. Nonetheless, H-1PV is depleted with rapid heat deactivation, autoclavation, and nanofiltration. Assessment of chemical disinfectants that are currently recommended by the Robert Koch-Institute demonstrated that ethanol-based hand disinfectants are not effective; however, aldehyde-based disinfectants for surfaces and instruments demonstrate sufficient H-1PV deactivation in aqueous formulations by 4 to 6 log10. With these results, we could establish a specific hygiene plan for all involved facilities from manufacturing to patient application. Overall, using 48% Iodixanol in Visipaque/Ringer as a drug formulation stabilizes H-1PV infectivity over years and protects against virus loss from short-term UV, low pH, and temperature exposure.

Key points

• Optimal formulation of drug product protects the H-1PV protoparvovirus against UV, temperatures up to 50 °C, and low pH (> 1.25), stabilizing the virus during manufacturing, storage, transport, and application.

• H-1PV is stable during in-use and does not adsorb to injection devices during patient administration.

• Hygiene plan for H-1PV with physicochemical methods has been established.
Sequential CAR T cell and targeted alpha immunotherapy in disseminated multiple myeloma
Authors: Awuah Dennis , Minnix Megan , Caserta Enrico , Tandoh Theophilus , Adhikarla Vikram , Poku Erasmus , Rockne Russell , Pichiorri Flavia , Shively John E. , Wang Xiuli
Published: May 2023

Multiple myeloma (MM) is still an incurable disorder despite improved antibody and cellular therapies against different MM antigens. Single targeted antigens have so far been ineffective against MM with most patients relapsing after initial response. Hence, sequential immunotherapies directed at different targets are expected to perform better than monotherapy alone. Here, we optimized and established in preclinical studies the therapeutic rationale of using targeted alpha therapy (TAT) directed against CD38 antigen (225Ac-DOTA-daratumumab) with CAR T cell therapy directed at CS1 antigen in a systemic MM model. The sequential therapies compared CAR T therapy followed by TAT to TAT followed by CAR T therapy. CAR T cell monotherapy increased median survival from 49 days (d) in untreated controls to 71d with a modest improvement to 89d for 3.7 kBq of TAT given 14d later. When CAR T was followed by 7.4 kBq of TAT 29d later, sequential therapy increased median survival from 47d in untreated controls to 106d, compared to 68d for CAR T monotherapy. When CAR T therapy was followed by untargeted alpha immunotherapy using 7.4 kBq of 225Ac-DOTA-trastuzumab (anti-HER2) antibody 29d later, there was only a slight improvement in response over CAR T monotherapy demonstrating the role of tumor targeting. TAT (7.4 kBq) followed by CAR T therapy was also effective when CAR T therapy was delayed for 21d vs 14d or 28d post TAT, highlighting the importance of timing sequential therapies. Sequential targeted therapies using CS1 CAR T or 225Ac-DOTA-CD38 TAT in either order shows promise over monotherapies alone.
Risk Factors for Postoperative Complications Following Resection of Colorectal Liver Metastases and the Impact on Long‐Term Survival: A Population‐Based National Cohort Study
Authors: Scherman Peter , Syk Ingvar , Holmberg Erik , Naredi Peter , Rizell Magnus
Published: May 2023

Background

Postoperative complications (POCs) following resection of colorectal liver metastases (CRLM) are common. The objective of this study was to evaluate risk factors for developing complications and their impact on survival considering prognostic factors of the primary tumor, metastatic pattern and treatment in a well‐defined national cohort.

Methods

Patients treated with resection for CRLM that was also radically resected for their primary colorectal cancer (diagnosed in 2009–2013) were identified in Swedish national registers. Liver resections were categorized according to extent of surgery (Category I–IV). Risk factors for developing POCs as well as prognostic impact of POCs were evaluated in multivariable analyses. A subgroup analysis of minor resections was performed to evaluate POCs after laparoscopic surgery.

Results

POCs were registered for 24% (276/1144) of all patients after CRLM resection. Major resection was a risk factor for POCs in multivariable analysis (IRR 1.76; P = 0.001). Comparing laparoscopic and open resections in the subgroup analysis of small resections, 6% (4/68) in the laparoscopic group developed POCs compared to 18% (51/289) after open resection (IRR 0.32; P = 0.024). POCs were associated with a 27% increased excess mortality rate (EMRR 1.27; P = 0.044). However, primary tumor characteristics, tumor burden in the liver, extrahepatic spread, extent of liver resection and radicality had higher impact on survival.

Conclusion

Minimal invasive resections were associated with a decreased risk of POCs following resection of CRLM which should be considered in surgical strategy. Postoperative complications were associated with a moderate risk for inferior survival.
Fully Robotic Side‐to‐Side Linear‐Stapled Anastomosis During Robotic Ivor Lewis Esophagectomy
Authors: Guerra Francesco , Tribuzi Angela , Giuliani Giuseppe , Di Marino Michele , Coratti Andrea
Published: May 2023

Background

The adoption of robotic surgery for esophageal cancer has been expanding rapidly over the recent years. In the setting of two‐field esophagectomy, different techniques exist for intrathoracic esophagogastric anastomosis, although the superiority of one over another has not been clearly demonstrated. Potential benefits in terms of anastomotic leakage and stenosis have been reported in association with a linear‐stapled anastomosis as compared to the more widespread techniques of circular mechanical and hand‐sewn reconstructions, however, there is still limited reported evidence on its application to robotic surgery. We here report our fully robotic technique of side‐to‐side, semi‐mechanical anastomosis.

Methods

All consecutive patients undergoing fully robotic esophagectomy featuring intrathoracic side‐to‐side stapled anastomosis by a single surgical team were included in this analysis. Operative technique is detailed, and perioperative data are assessed.

Results

A total of 49 patients were included. There were no intraoperative complications and no conversion occurred. The rate of overall postoperative morbidity was 25, 14% being the relative rate of major complications. With anastomotic‐related morbidity in particular, one patient developed minor anastomotic leakage.

Conclusions

Our experience demonstrates that a linear, side‐to‐side fully robotic stapled anastomosis can be created with a high technical success and minimal incidence of anastomosis‐related morbidity.
Outpatient Non‐operative Management of Uncomplicated Acute Appendicitis: A Non‐inferiority Study
Authors: Ceresoli Marco , Fumagalli Chiara , Fugazzola Paola , Zanini Nicola , Magnone Stefano , Ravasi Michela , Bonalumi Jacopo , Morezzi Daniele , Bova Raffaele , Sargenti Benedetta , Schiavone Luca , Lucianetti Alessandro , Catena Fausto , Ansaloni Luca , Braga Marco
Published: May 2023

Introduction

Non‐operative management (NOM) of uncomplicated acute appendicitis is a well‐established alternative to upfront surgery. The administration of intravenous broad‐spectrum antibiotics is usually performed in hospital, and only one study described outpatient NOM. The aim of this multicentre retrospective non‐inferiority study was to evaluate both safety and non‐inferiority of outpatient compared to inpatient NOM in uncomplicated acute appendicitis.

Methods

The study included 668 consecutive patients with uncomplicated acute appendicitis. Patients were treated according to the surgeon’s preference: 364 upfront appendectomy, 157 inpatient NOM (inNOM), and 147 outpatient NOM (outNOM). The primary endpoint was the 30‐day appendectomy rate, with a non‐inferiority limit of 5%. Secondary endpoints were negative appendectomy rate, 30‐day unplanned emergency department (ED) visits, and length of stay.

Results

30‐day appendectomies were 16 (10.9%) in the outNOM group and 23 (14.6%) in the inNOM group (p = 0.327). OutNOM was non‐inferior to inNOM with a risk difference of—3.80% 97.5% CI (− 12.57; 4.97). No difference was found between inNOM and outNOM groups for the number of complicated appendicitis (3 vs. 5) and negative appendectomy (1 vs. 0). Twenty‐six (17.7%) outNOM patients required an unplanned ED visit after a median of 1 (1–4) days. In the outNOM group, the mean cumulative in‐hospital stay was 0.89 (1.94) days compared with 3.94 (2.17) days in the inNOM group (p < 0.001).

Conclusions

Outpatient NOM was non‐inferior to inpatient NOM with regard to the 30‐day appendectomy rate, while a shorter hospital stay was found in the outNOM group. Further, studies are required to confirm these findings.
Impact of sex on the efficacy of immune checkpoint inhibitors in kidney and urothelial cancers: a systematic review and meta-analysis
Authors: Yanagisawa Takafumi , Kawada Tatsushi , Quhal Fahad , Bekku Kensuke , Laukhtina Ekaterina , Rajwa Pawel , von Deimling Markus , Majdoub Muhammad , Chlosta Marcin , Pradere Benjamin , Mori Keiichiro , Kimura Takahiro , Schmidinger Manuela , Karakiewicz Pierre I. , Shariat Shahrokh F.
Published: May 2023

Purpose

To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex.

Methods

Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting.

Results

Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55–0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68–0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females.

Conclusions

OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.
On the characterization of bias errors in defocusing-based 3D particle tracking velocimetry for microfluidics
Authors: Coutinho Gonçalo , Moita Ana , Ribeiro Ana , Moreira António , Rossi Massimiliano
Published: May 2023

In this work, we provide a systematic theoretical and experimental characterization of bias errors in defocusing particle tracking (DPT) methods based on a single calibration function, with respect to microfluidic applications, in which it is not possible to use calibration targets inside the measurement volume. This approach is widely used in microfluidic experiments, but bias errors are often neglected and to date only few works reported empirical procedures to compensate for that. A systematic characterization of the impact of such error in DPT measurements is still lacking. We show that the field curvature aberration and the refractive index mismatch are the main sources of bias error in these applications. We present a correction methodology for the bias error based on the determination of a reference surface, and in addition we propose a procedure based on a reference measurement of a Poiseuille flow to determine the reference surface on microfluidic channels with constant cross section. We discuss the impact of the refractive index mismatch and how to correctly compensate for it. We validated our methodology and quantified the bias errors on 10 different experimental setups, using different working fluids, materials, geometries, and microscope objective lenses ranging from 5$$\times$$
×
to 40$$\times$$
×
magnification. Our results indicate that the impact of this type of bias errors is in general not predictable and must be evaluated case by case. The proposed methodology allows to estimate and minimize the bias error in most microfluidic setups and is suitable for any single-camera DPT approach.
Separation control with elliptical air-jet vortex generators
Authors: Ramaswamy Deepak Prem , Schreyer Anne-Marie
Published: May 2023

The flow organisation of air-jet vortex generators (AJVGs) of elliptical cross sections and their control effectiveness on a$$24^{\circ }$$24∘-compression-ramp-induced shock-wave/boundary-layer interaction was analysed on the basis of experiments at$$M_{\infty } = 2.52$$M∞=2.52and$$Re_{\theta _c} = 8225$$Reθc=8225. We investigated a circular orifice and two elliptical orifices of aspect ratios 0.5 and 2; all characterised by the same hydraulic diameter. Measurements of separation lengths from oil-flow visualisation and PIV reveal that elliptical AJVGs achieve a$$25\%$$25%reduction in total separation length, which constitutes a strong improvement over the$$17\%$$17%reduction achieved with the commonly used circular AJVGs. The jet-induced structures from elliptical AJVGs penetrate on average$$25\%$$25%farther into the boundary layer. However, the lateral spread is limited to a maximum value equal to the inter-jet spacing in the control array, which highlights the onset of jet/jet interactions between adjacent jets in the array. A consequence of these interactions is better flow entrainment for the elliptical cases, as observed in the mean boundary-layer velocity profiles and an improved turbulent mixing (indicated by an increase in Reynolds-shear-stress magnitude).
Computational framework for complex flow and transport in heterogeneous porous media
Authors: Icardi Matteo , Pescimoro Eugenio , Municchi Federico , Hidalgo Juan J.
Published: May 2023

We present a flexible scalable open-source computational framework, named , based on the finite-volume library OpenFOAM®, for flow and transport problems in highly heterogeneous geological media and other porous materials. The framework combines geostatistical pre- and post-processing tools with specialised partial differential equations solvers. Random fields, for permeability and other physical properties, are generated by means of continuous or thresholded Gaussian random fields with various covariance/variogram functions. The generation process is based on an explicit spectral Fourier decomposition of the field which, although more computationally intensive than Fast Fourier Transform methods, allows a more flexible choice of statistical parameters and can be used for general geometries and grids. Flow and transport equations are solved for single-phase and variable density problems, with and without the Boussinesq approximation, and for a wide range of density, viscosity, and dispersion models, including dual-continuum (dual permeability or dual porosity) formulations. The mathematical models are here presented in details and the numerical strategies to deal with heterogeneities, equation coupling, and boundary conditions are discussed and benchmarked for the heterogeneous Henry and Horton–Rogers–Lapwood problems, and other test cases. We show that our framework is capable of dealing with large permeability variances, viscous instabilities, and large-scale three-dimensional transport problems.
COVID-19- Experiences and support needs of children and young people with Hydrocephalus and parents in the United Kingdom
Authors: Collaço Nicole , Campion Anna , McNicholas Roisin , Darlington Anne-Sophie
Published: May 2023

Purpose

Little is known about the impact of COVID-19 on children and young people (CYP) with hydrocephalus and their families. This study explored the experiences and support needs of CYP with hydrocephalus and parents who have a child with hydrocephalus during the COVID-19 pandemic.

Methods

CYP with hydrocephalus and parents of CYP with hydrocephalus in the United Kingdom completed an online survey with open and closed questions exploring experiences, information, support needs and decision making processes. Qualitative thematic content analysis and descriptive quantitative analyses were undertaken.

Results

CYP aged 12-32 years (n=25) and parents of CYP aged 0-20 years (n=69) responded. Parents (63.5%) and CYP (40.9%) worried about the virus, and both were vigilant for virus symptoms (86.5% and 57.1%). Parents (71.2%) and CYP (59.1%) worried about their child/feeling more isolated during the virus outbreak. Parents felt concerned about having to take their child to hospital with a suspected shunt problem during the virus outbreak (64.0%). Qualitative findings reported the following themes: (1) Healthcare and treatment provision: delays and challenges to access and availability of care (2) Impact of COVID-19/lockdown on daily lives and routines, and (3) Provision of information and support for parents and CYP with hydrocephalus.

Conclusion

The impact of COVID-19 and national measures to control the spread of the virus- no contact with anyone outside the household significantly impacted the daily lives and routines of CYP with hydrocephalus and parents. Social engagements were missed, families faced challenges to their work life, education and access to health care and support, which subsequently contributed negatively to their mental wellbeing. CYP and parents highlighted a need for clear, timely and targeted information to address their concerns.
Atlantic decadal-to-bidecadal variability in a version of the Kiel Climate Model
Authors: Sun Jing , Latif Mojib , Park Wonsun
Published: May 2023

Atlantic decadal-to-bidecadal variability (ADV) is described from a multimillennial control integration of a version of the Kiel Climate Model (KCM). The KCM’s ADV is the second most energetic mode of long-term North Atlantic variability in that simulation, whereas the Atlantic multidecadal variability (AMV) is the leading mode that has been described in a previous study. The KCM’s ADV can be regarded as a mixed oceanic gyre-overturning circulation mode that is forced by the North Atlantic Oscillation. The extratropical North Atlantic sea surface temperature (SST) anomalies associated with the model’s ADV initially exhibit a tripolar structure in the meridional direction, which is linked to the gyre circulation. After some years, the SST-anomaly pattern turns into a monopolar pattern located in the subpolar North Atlantic. This transition is related to the overturning circulation. The AMV and the ADV co-exist and share some similarities. Both modes of variability rely on the upper-ocean heat transport into the subpolar North Atlantic. They differ in the importance of the gyre and overturning circulations. In the ADV, gyre and overturning-heat transports into the subpolar North Atlantic are equally important in contrast to the AMV where the overturning contribution dominates.
Robot-assisted laparoscopic varicocelectomy in a pediatric population
Authors: Reinhardt Susanne , Thorup Jorgen , Joergensen Peter Hjorth , Fode Mikkel
Published: May 2023

Purpose

To present our experience with robot-assisted laparoscopic varicocelectomy in a pediatric population.

Methods

We reviewed 49 consecutive cases performed by the same experienced surgeon. One-to-four veins were ligated at the internal ring of the inguinal canal, while the testicular artery and lymphatics were spared. Information on patient characteristics, surgical time, complications, and recurrences were collected.

Results

Median patient age was 14 (range 10–17) years. Forty-eight had left-sided varicoceles and one had a bilateral varicocele. Forty-five were grade 3. All patients were referred due to discomfort/pain and 20 also had reduced testicular size. The median operating time from skin incision was 48 min (31–89 min) and the median console time was 18 min (7–55 min). Forty-seven patients were discharged the same day. Two patients experienced pain and problems urinating, respectively. These issues had resolved by the first post-operative day. There were no other complications, but at 6 months, eight recurrences were noted (16%). Scrotal complaints had subsided in all patients. Catch-up growth of the affected testicles was seen in 19/20 cases.

Conclusion

Robot-assisted laparoscopic varicocelectomy is feasible and safe in a pediatric population but with a relatively high recurrence rate.
A machine learning method for distinguishing detrital zircon provenance
Authors: Zhong S. H. , Liu Y. , Li S. Z. , Bindeman I. N. , Cawood P. A. , Seltmann R. , Niu J. H. , Guo G. H. , Liu J. Q.
Published: May 2023

Zircon geochemistry provides a sensitive monitor of its parental magma composition. However, due to the complexity of the uptake of trace elements during zircon growth, identifying source magmas remains challenging, particularly for detrital grains whose petrological context is lost. We use a machine learning-based approach to explore the classifiers for zircon provenance, based on 3794 published, high-quality zircon trace element analyses compiled from I-, S-, and A-type granites. Three supervised machine learning algorithms, namely, Support Vector Machine (SVM), Random Forest (RF), and Multilayer Perceptron (MLP) were used and trained with 11 features, including 7 trace elements (Ce, Eu, Ho, Nb, Ta, Th, and U) and 4 derived trace element ratios (Th/U, U/Yb, Ce/Ce*, and Eu/Eu*). Our results show that all three trained machine learning methods perform very well with accuracy varying from 0.86 to 0.89, and that input–output relationships captured by different ML methods are nearly consistent and can be explained by the known petrological processes. The application of our trained machine learning classifiers to detrital zircon studies will enhance the interpretability of zircon assemblages of different origins. It also helps develop interpretations, approaches, and tools that will benefit, for example, the study of continental crust evolution and mineral exploration.
Altitude-induced effects on neuromuscular, metabolic and perceptual responses before, during and after a high-intensity resistance training session
Authors: Márquez Gonzalo , Colomer David , Benavente Cristina , Morenilla Luis , Alix-Fages Carlos , Padial Paulino , Feriche Belén
Published: May 2023

Purpose

We tested if an acute ascending to 2320 m above sea level (asl) affects corticospinal excitability (CSE) and intracortical inhibition (SICI) measured with transcranial magnetic stimulation (TMS) at rest, before, during and after a traditional hypertrophy-oriented resistance training (RT) session. We also explored whether blood lactate concentration (BLa), ratings of perceived exertion (RPE), perceived muscular pain and total training volume differed when the RT session was performed at hypoxia (H) or normoxia (N).

Methods

Twelve resistance-trained men performed eight sets of 10 repetitions at 70% of one repetition maximum of a bar biceps curl at N (SpO2 = 98.0 ± 0.9%) and H (at 2320 asl, SpO2 = 94.0 ± 1.9%) in random order. Before each session, a subjective well-being questionnaire, the resting motor threshold (rMT) and a single pulse recruitment curve were measured. Before, during and after the RT session, BLa, RPE, muscle pain, CSE and SICI were measured.

Results

Before the RT session only the rMT differed between H (− 5.3%) and N (ES = 0.38). RPE, muscle pain and BLa increased through the RT session and were greater at H than N (12%, 54% and 15%, respectively) despite a similar training volume (1618 ± 468 kg vs. 1638 ± 509 kg). CSE was reduced during the RT session (~ 27%) but recovered ten minutes after, regardless of the environmental condition. SICI did not change after any RT session.

Conclusions

The data suggest that acute exposure to moderate hypoxia slightly increased the excitability of the most excitable structures of the corticospinal tract but did not influence intracortical or corticospinal responses to a single RT session.
Postoperative drainage management and wound complications following resection of lower limb soft tissue tumors: a retrospective cohort study
Authors: Gerken A. L. H. , Jawny P. , Weigl H. , Yang C. , Hardt J. , Menge F. , Hohenberger P. , Weiß C. , Reißfelder C. , Jakob J.
Published: May 2023

Purpose

Postoperative wound complications are common in patients undergoing resection of lower extremity soft tissue tumors. Postoperative drainage therapy ensures adequate wound healing but may delay or complicate it. The aim of this study is to evaluate the incidence of postoperative wound complications and delayed or prolonged drainage treatment and to propose a standardized definition and severity grading of complex postoperative courses.

Methods

A monocentric retrospective analysis of 80 patients who had undergone primary resection of lower extremity soft tissue tumors was performed. A new classification was developed, which takes into account postoperative drainage characteristics and wound complications. Based on this classification, risk factors and the prognostic value of daily drainage volumes were evaluated.

Results

According to this new definition, regular postoperative course grade 0 (no wound complication and timely drainage removal) occurred in 26 patients (32.5%), grade A (minor wound complications or delayed drainage removal) in 12 (15.0%), grade B (major wound complication or prolonged drainage therapy) in 31 (38.8%), and grade C (reoperation) in 11 (13.7%) patients. Tumor-specific characteristics, such as tumor size (p = 0.0004), proximal tumor location (p = 0.0484), and tumor depth (p = 0.0138) were identified as risk factors for complex postoperative courses (grades B and C). Drainage volume on postoperative day 4 was a suitable predictor for complex courses (cutoff of 70 ml/d).

Conclusion

The proposed definition incorporates wound complications and drainage management while also being clinically relevant and easy to apply. It may serve as a standardized endpoint for assessing the postoperative course after resection of lower extremity soft tissue tumors.
Parafoveal syntactic processing from word N + 2 during reading: the case of gender-specific German articles
Authors: Schwalm Laura , Radach Ralph
Published: May 2023

Previous research has suggested that some syntactic information such as word class can be processed parafoveally during reading. However, it is still unclear to what extent early syntactic cueing within noun phrases can facilitate word processing during dynamic reading. Two experiments (total N = 72) were designed to address this question using a gaze-contingent boundary change paradigm to manipulate the syntactic fit within a nominal phrase. Either the article (Experiment 1) or the noun (Experiment 2) was manipulated in the parafovea, resulting in a syntactic mismatch, depending on the condition. Results indicated a substantial elevation of viewing times on both parts of the noun phrase when conflicting syntactic information had been present in the parafovea. In Experiment 1, the article was also fixated more often in the syntactic mismatch condition. These results provide direct evidence of parafoveal syntactic processing. Based on the early time-course of this effect, it can be concluded that grammatical gender is used to generate constraints for the processing of upcoming nouns. To our knowledge, these results also provide the first evidence that syntactic information can be extracted from a parafoveal word N + 2.
Exome sequencing of choreoacanthocytosis reveals novel mutations in VPS13A and co-mutation in modifier gene(s)
Authors: Chaudhari Sima , Ware Akshay Pramod , Jasti Dushyanth Babu , Gorthi Sankar Prasad , Acharya Lavanya Prakash , Bhat Manoj , Mallya Sandeep , Satyamoorthy Kapaettu
Published: May 2023

Choreoacanthocytosis, one of the forms of neuroacanthocytosis, is caused by mutations in vacuolar protein sorting-associated protein A (VPS13A), and is often misdiagnosed with other form of neuroacanthocytosis with discrete genetic defects. The phenotypic variations among the patients with VPS13A mutations significantly obfuscates the understanding of the disease and treatment strategies. In this study, two unrelated cases were identified, exhibiting the core phenotype of neuroacanthocytosis but with considerable clinical heterogeneity. Case 1 presented with an additional Parkinsonism phenotype, whereas seizures were evident in case 2. To decipher the genetic basis, whole exome sequencing followed by validation with Sanger sequencing was performed. A known homozygous pathogenic nonsense mutation (c.799C > T; p.R267X) in exon 11 of the VPS13A gene was identified in case 1 that resulted in a truncated protein. A novel missense mutation (c.9263T > G; p.M3088R) in exon 69 of VPS13A identified in case 2 was predicted as pathogenic. In silico analysis of the p.M3088R mutation at the C-terminus of VPS13A suggests a loss of interaction with TOMM40 and may disrupt mitochondrial localization. We also observed an increase in mitochondrial DNA copy numbers in case 2. Mutation analysis revealed benign heterozygous variants in interacting partners of VPS13A such as VAPA in case 1. Our study confirmed the cases as ChAc and identified the novel homozygous variant of VPS13A (c.9263T > G; p.M3088R) within the mutation spectrum of VPS13A-associated ChAc. Furthermore, mutations in VPS13A and co-mutations in its potential interacting partner(s) might contribute to the diverse clinical manifestations of ChAc, which requires further study.
Adopting the Rumsfeld approach to understanding the action of levodopa and apomorphine in Parkinson’s disease
Authors: Jenner P. , Falup-Pecurariu C. , Leta V. , Verin M. , Auffret M. , Bhidayasiri Roongroj , Weiss D. , Borovečki F. , Jost W. H.
Published: May 2023

Dopaminergic therapies dominate the treatment of the motor and non-motor symptoms of Parkinson’s disease (PD) but there have been no major advances in therapy in many decades. Two of the oldest drugs used appear more effective than others—levodopa and apomorphine—but the reasons for this are seldom discussed and this may be one cause for a lack of progress. This short review questions current thinking on drug action and looks at whether adopting the philosophy of ex-US Secretary of State Donald Rumsfeld reveals ‘unknown’ aspects of the actions of levodopa and apomorphine that provide clues for a way forward. It appears that both levodopa and apomorphine have a more complex pharmacology than classical views would suggest. In addition, there are unexpected facets to the mechanisms through which levodopa acts that are either forgotten as ‘known unknowns’ or ignored as ‘unknown unknowns’. The conclusion reached is that we may not know as much as we think about drug action in PD and there is a case for looking beyond the obvious.
Single-cell RNA sequencing and kidney organoid differentiation
Authors: Uchimura Kohei
Published: May 2023

Since 2015, Japanese researchers have made great progress in developing a method to differentiate human pluripotent stem cells (hPSCs) into kidney organoids. Protocols have been established to produce increasingly complex three-dimensional (3D) structures, which are used as a human kidney disease model and adapted for high-throughput screening. During this period, single-cell RNA sequencing (scRNA-seq) technology was developed to perform a comprehensive analysis at the single-cell level. We have performed a comprehensive analysis using scRNA-seq to define how kidney organoids can be applied to understand kidney development and pathology. The structure of kidney organoids is complex and contains many cell types of varying maturity. Since only a few proteins and mRNAs can be identified by immunostaining and other techniques, we performed scRNA-seq, which is an unbiased technology that can comprehensively categorize all cell types present in organoids. The aim of this study is to review the problems of kidney organoids based on scRNA-seq and the efforts to address the problems and predict future applications with this powerful technique.
Evaluation of Hydrotalcites Produced in Seawater for Remediation of Metalliferous Acid Mine Drainage and Submarine Placement
Authors: Suliartini Ni Made Sri , Joll Cynthia A. , Douglas Grant B.
Published: May 2023

Uncontrolled release of acid mine drainage (AMD) causes widespread detrimental impacts on the receiving environment. Thus, effective treatment to neutralise AMD effluent pH and capture a suite of metals is required. In-situ hydrotalcite (HTC) precipitation is an emerging technology for AMD remediation. HTC has an inherent capacity to accommodate a range of cations and anions during in situ formation, offering a method of broad-spectrum contaminant removal. This study explored the feasibility of using seawater as an Mg source and synthetic AMD in HTC formation. The HTC was formed from a stoichiometric combination of synthetic AMD and seawater. While three initial stoichiometric M2+:M3+ ratios of 2:1, 3:1, and 4:1 were investigated, only HTC with an M2+:M3+ ratio of 2:1 was generated, as confirmed by both mineralogical and geochemical analyses. Importantly, the HTC was demonstrated to effectively remove a suite of metals present in AMD such as Cu, Zn, Al, and Mn with removal rates of between 99.97 to 99.99%. The HTC precipitate contained ≈6.6% Cu and 4.1% Zn, and thus shows the potential, if required, for future metal recovery. Since submarine placement is often used in metal mining and processing operations proximal to the coast, the stability of the HTC precipitate in seawater was also investigated. Importantly, only 0.2% of the Cu and 1.1% of the Zn within the HTC were subsequently leaching in decreasing increments into seawater over 30 days with decreasing increments after the initial seven days. This indicates robust element retention and confirms the potential of HTC for AMD remediation with direct submarine placement.