bluuebunny/crossref_metadata_2025 huggingface dataset:
Incident Fluence Analysis for 755‐nm Picosecond Laser Treatment of Pigmented Skin Lesions Based on Threshold Fluences for Melanosome Disruption
Authors: Shimojo Yu , Nishimura Takahiro , Hazama Hisanao , Ito Nobuhisa , Awazu Kunio
Published: February 2021

Background and Objectives

In this study, the threshold fluences for disrupting the melanosomes for pigmented skin lesion treatment were determined using a 755‐nm picosecond laser for clinical use. Based on the melanosome disruption thresholds, incident fluences corresponding to the target lesion depths were evaluated in silico for different laser spot sizes.

Study Design/Materials and Methods

Melanosome samples were isolated from porcine eyes as alternative samples for human cutaneous melanosomes. The isolated melanosomes were exposed to 755‐nm picosecond laser pulses to measure the mean particle sizes by dynamic light scattering and confirm their disruption by scanning electron microscopy. The threshold fluences were statistically determined from the relationships between the irradiated fluences and the mean particle sizes. Incident fluences of picosecond laser pulses for the disruption of melanosomes located at different depths in skin tissue were calculated through a light transport simulation using the obtained thresholds.

Results

The threshold fluences of 550‐ and 750‐picosecond laser pulses were determined to be 2.19 and 2.49 J/cm2, respectively. The numerical simulation indicated that appropriate incident fluences of picosecond laser pulses differ depending on the depth distribution of the melanosomes in the skin tissue, and large spot sizes are desirable for disrupting the melanosomes more deeply located within the skin tissue.

Conclusion

The threshold fluences of picosecond laser pulses for melanosome disruption were determined. The incident fluence analysis based on the thresholds for melanosome disruption provides valuable information for the selection of irradiation endpoints for picosecond laser treatment of pigmented skin lesions. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC
Fatigue strength of helical compression springs ‐ comparison of calculation methods according to DIN EN 13906‐1 and Forschungskuratorium Maschinenbau (FKM) guideline “Analytical strength assessment of springs and spring elements”
Authors: Niwinski T.J. , Geilen M.B. , Klein M. , Sharma E. , Schommartz J.O. , Oechsner M.
Published: February 2021

Der Lebensdauernachweis von zyklisch beanspruchten Schraubendruckfedern erfolgt zurzeit mithilfe von Goodman‐Diagrammen der DIN EN 13906‐1. Eine Auslegung gemäß der Richtlinie des Forschungskuratoriums Maschinenbau (FKM) „Rechnerischer Festigkeitsnachweis für Maschinenbauteile“ kann aufgrund zu hoher Zugfestigkeiten der Federstähle nicht erfolgen. Im Rahmen des durch die Industrielle Gemeinschaftsforschung (IGF) geförderten und 2017 abgeschlossenen Forschungsprojekts mit der Nummer 18495 BG, wurde an der TU Darmstadt und der TU Ilmenau ein Nachweisverfahren in Anlehnung an die bestehende Richtlinie des Forschungskuratoriums Maschinenbau entwickelt, welches die federspezifischen Anforderungen berücksichtigt. In der vorliegenden Publikation wird der Berechnungsalgorithmus der neuen Richtlinie des Forschungskuratoriums Maschinenbau „Rechnerischer Festigkeitsnachweis für Federn und Federelemente“ dem Verfahren nach DIN EN 13906‐1 gegenübergestellt und die Berechnungsergebnisse experimentellen Ergebnissen gegenübergestellt.
Analytical approach for the minimum depths of engagement for bolted joints with formed female threads
Authors: Kraemer F. , Klein M. , Oechsner M.
Published: February 2021

Die quasi‐statische Beanspruchbarkeit von Schraubenverbindungen mit gefurchtem Gewinde ist neben dem Scherfestigkeitsverhältnis der eingesetzten Werkstoffe, der Einschraubtiefe, dem Flankenwinkel und der Steigung des Gewindes wesentlich abhängig von der resultierenden Flankenüberdeckung, die durch die Größe des Vorlochdurchmessers bestimmt wird. Zur Bestimmung der erforderlichen Mindesteinschraubtiefe werden Auszugsversuche mit variierter Einschraubtiefe und Gewindeüberdeckung durchgeführt. Basierend auf dem bestehenden Berechnungsansatz nach der VDI‐Richtlinie 2230 (Verein Deutsche Ingenieure) für Verschraubungen in vorgeschnittene Mutterngewinde wird eine analytische Bewertungsmethode abgeleitet, um für Verbindungen mit gefurchtem Mutterngewinde die erforderliche Mindesteinschraubtiefe unter Berücksichtigung der Gewindeausformung des gefurchten Gewindes zu bestimmen.
Small extracellular vesicles‐based cell‐free strategies for therapy
Authors: Guo Yeye , Wang Huaishan , Huang Lili , Ou Lingling , Zhu Jinjin , Liu Shujing , Xu Xiaowei
Published: February 2021

Small extracellular vesicles (sEVs) are extracellular nanovesicles that contain bioactive proteins, lipids, RNA, and DNA. A variety of biological process is regulated with sEVs. sEVs are an intercellular messenger regulating recipient cell function and play a role in disease initiation and progression. sEVs derived from certain cells, such as mesenchymal stem cells and immune cells, have the potential for clinical therapy as they possess the characteristics of their parental cells. With better understanding of sEVs biogenesis, their transportation properties, extended circulatory capability, and exceptional biocompatibility, sEVs emerge as a potential therapeutic tool in the clinic. Here, we summarize applications of sEVs‐based therapies in different diseases and current knowledge about the strategies in bioengineered sEVs, as well as the challenges for their use in clinical settings.
Free tensor fascia lata true‐perforator flap transfer for reconstruction of the calcaneal soft tissue defect complicated with osteomyelitis in a patient with alcohol‐induced Charcot foot: A case report and literature review
Authors: Tsuihiji Kanako , Daniel Bassem W. , Kageyama Takashi , Sakai Hayahito , Fuse Yuma , Tsukuura Reiko , Yamamoto Takumi
Published: February 2021

Charcot foot is can result in bone deformities and soft tissue defects. We report a case of alcohol‐induced Charcot (AIC) foot with soft tissue defect including the weight‐bearing zone of the heel and osteomyelitis, which was successfully reconstructed with free tensor fascia lata true‐perforator flap (TFLtp). A 56‐year‐old male suffered from AIC foot with an 18 × 6 cm defect. Based on the preoperative ultrasound, we identified the overlying upper thigh area offering one of the thickest dermis. A TFLtp flap was raised sparing the TFL muscle based on one perforator without including the main trunk of the transverse/ascending branch of the lateral femoral circumflex vessel. The TFLtp flap was transferred to the heel and anastomosed to the posterior tibial artery in an end‐to‐side fashion. The patient complained no postoperative discomfort of the donor site and was able to walk on his foot after 5 weeks. This case report highlights that the TFLtp flap may offer thick dermis, faster surgery due to perforator level dissection and a concealed donor site.
A case study of Covid‐19 epidemic in India via new generalised Caputo type fractional derivatives
Authors: Kumar Pushpendra , Suat Erturk Vedat
Published: February 2021

The first symptomatic infected individuals of coronavirus (Covid‐19) was confirmed in December 2020 in the city of Wuhan, China. In India, the first reported case of Covid‐19 was confirmed on 30 January 2020. Today, coronavirus has been spread out all over the world. In this manuscript, we studied the coronavirus epidemic model with a true data of India by using Predictor‐Corrector scheme. For the proposed model of Covid‐19, the numerical and graphical simulations are performed in a framework of the new generalised Caputo sense non‐integer order derivative. We analysed the existence and uniqueness of solution of the given fractional model by the definition of Chebyshev norm, Banach space, Schauder's second fixed point theorem, Arzel's‐Ascoli theorem, uniform boundedness, equicontinuity and Weissinger's fixed point theorem. A new analysis of the given model with the true data is given to analyse the dynamics of the model in fractional sense. Graphical simulations show the structure of the given classes of the non‐linear model with respect to the time variable. We investigated that the mentioned method is copiously strong and smooth to implement on the systems of non‐linear fractional differential equation systems. The stability results for the projected algorithm is also performed with the applications of some important lemmas. The present study gives the applicability of this new generalised version of Caputo type non‐integer operator in mathematical epidemiology. We compared that the fractional order results are more credible to the integer order results.
Artificial neural network approach for solving fuzzy fractional order initial value problems under gH‐differentiability
Authors: Ezadi Somayeh , Allahviranloo Tofigh
Published: February 2021

This paper aims to solve the celebrated fuzzy fractional differential equations (FFDEs) using an artificial neural network (ANN) technique. To accomplish the aforementioned aim, the error back propagation algorithm and a multilayer feed forward neural architecture are utilized using the unsupervised learning in order to minimize the error function as well as the modification of the parameters such as weights and biases. By combining the initial conditions with the ANN output provides an appropriate approximate solution of the proposed FFDE. Then, two illustrative examples are solved to confirm the applicability of the concept as well as to demonstrate both the precision and effectiveness of the developed method. By comparing with some traditional methods, the obtained results reveal a close match that confirms both accuracy and correctness of the proposed method.
Quantification of intravoxel incoherent motion with optimized b‐values using deep neural network
Authors: Lee Wonil , Kim Byungjai , Park HyunWook
Published: February 2021

Purpose

To develop a framework for quantifying intravoxel incoherent motion (IVIM) parameters, where a neural network for quantification and b‐values for diffusion‐weighted imaging are simultaneously optimized.

Method

A deep neural network (DNN) method is proposed for accurate quantification of IVIM parameters from multiple diffusion‐weighted images. In addition, optimal b‐values are selected to acquire the multiple diffusion‐weighted images. The proposed framework consists of an MRI signal generation part and an IVIM parameter quantification part. Monte‐Carlo (MC) simulations were performed to evaluate the accuracy of the IVIM parameter quantification and the efficacy of b‐value optimization. In order to analyze the effect of noise on the optimized b‐values, simulations were performed with five different noise levels. For in vivo data, diffusion images were acquired with the b‐values from four b‐values selection methods for five healthy volunteers at 3T MRI system.

Results

Experiment results showed that both the optimization of b‐values and the training of DNN were simultaneously performed to quantify IVIM parameters. We found that the accuracies of the perfusion coefficient (Dp) and perfusion fraction (f) were more sensitive to b‐values than the diffusion coefficient (D) was. Furthermore, when the noise level changed, the optimized b‐values also changed. Therefore, noise level has to be considered when optimizing b‐values for IVIM quantification.

Conclusion

The proposed scheme can simultaneously optimize b‐values and train DNN to minimize quantification errors of IVIM parameters. The trained DNN can quantify IVIM parameters from the diffusion‐weighted images obtained with the optimized b‐values.
Non‐Cartesian k‐space trajectory calculation based on concurrent reading of the gradient amplifiers’ output currents
Authors: Rahmer Jürgen , Schmale Ingo , Mazurkewitz Peter , Lips Oliver , Börnert Peter
Published: February 2021

Purpose

Non‐Cartesian imaging sequences involve sampling during rapid variation of the encoding field gradients. The quality of the reconstructed images often suffers from insufficient knowledge of the exact dynamics of the actual fields applied during sampling.

Methods

We propose determination of the accurate field dynamics by measuring the currents at the gradient amplifier outputs using the amplifiers’ internal sensors concurrently with imaging. The actual dynamic field evolution is then determined by convolution with the measured current‐to‐field impulse response function of the gradient coil. Integration of the gradient field evolution allows derivation of the k‐space trajectory for reconstruction.

Results

The current‐based approach is investigated in spiral and ultrashort TE phantom imaging. In comparison with the model‐based product reconstruction as well as a correction approach based on the conventional input waveform‐to‐field impulse response function, it provides slightly improved image quality. The improvement is ascribed to a better representation of eddy current and amplifier nonlinearity effects.

Conclusion

Trajectory calculation based on measured amplifier output currents offers a robust, purely measurement‐based alternative to conventional model‐based approaches. The implementation can mitigate gradient amplifier imperfections with no or little additional hardware effort.
Accelerated radial echo‐planar spectroscopic imaging using golden angle view‐ordering and compressed‐sensing reconstruction with total variation regularization
Authors: Saucedo Andres , Macey Paul M. , Thomas M. Albert
Published: February 2021

Purpose

To implement a novel, accelerated, 2D radial echo‐planar spectroscopic imaging (REPSI) sequence using undersampled radial k‐space trajectories and compressed‐sensing reconstruction, and to compare results with those from an undersampled Cartesian spectroscopic sequence.

Methods

The REPSI sequence was implemented using golden‐angle view‐ordering on a 3T MRI scanner. Radial and Cartesian echo‐planar spectroscopic imaging (EPSI) data were acquired at six acceleration factors, each with time‐equivalent scan durations, and reconstructed using compressed sensing with total variation regularization. Results from prospectively and retrospectively undersampled phantom and in vivo brain data were compared over estimated concentrations and Cramer‐Rao lower‐bound values, normalized RMS errors of reconstructed metabolite maps, and percent absolute differences between fully sampled and reconstructed spectroscopic images.

Results

The REPSI method with compressed sensing is able to tolerate greater reductions in scan time compared with EPSI. The reconstruction and quantitation metrics (i.e., spectral normalized RMS error maps, metabolite map normalized RMS error values [e.g., for total N‐acetyl asparate, REPSI = 9.4% vs EPSI = 16.3%; acceleration factor = 2.5], percent absolute difference maps, and concentration and Cramer‐Rao lower‐bound estimates) showed that accelerated REPSI can reduce the scan time by a factor of 2.5 while retaining image and quantitation quality.

Conclusion

Accelerated MRSI using undersampled radial echo‐planar acquisitions provides greater reconstruction accuracy and more reliable quantitation for a range of acceleration factors compared with time‐equivalent compressed‐sensing reconstructions of undersampled Cartesian EPSI. Compared to the Cartesian approach, radial undersampling with compressed sensing could help reduce 2D spectroscopic imaging acquisition time, and offers a better trade‐off between imaging speed and quality.
An offline multi‐scale unsaturated poromechanics model enabled by self‐designed/self‐improved neural networks
Authors: Heider Yousef , Suh Hyoung Suk , Sun WaiChing
Published: February 2021

Supervised machine learning via artificial neural network (ANN) has gained significant popularity for many geomechanics applications that involves multi‐phase flow and poromechanics. For unsaturated poromechanics problems, the multi‐physics nature and the complexity of the hydraulic laws make it difficult to design the optimal setup, architecture, and hyper‐parameters of the deep neural networks. This paper presents a meta‐modeling approach that utilizes deep reinforcement learning (DRL) to automatically discover optimal neural network settings that maximize a pre‐defined performance metric for the machine learning constitutive laws. This meta‐modeling framework is cast as a Markov Decision Process (MDP) with well‐defined states (subsets of states representing the proposed neural network (NN) settings), actions, and rewards. Following the selection rules, the artificial intelligence (AI) agent, represented in DRL via NN, self‐learns from taking a sequence of actions and receiving feedback signals (rewards) within the selection environment. By utilizing the Monte Carlo Tree Search (MCTS) to update the policy/value networks, the AI agent replaces the human modeler to handle the otherwise time‐consuming trial‐and‐error process that leads to the optimized choices of setup from a high‐dimensional parametric space. This approach is applied to generate two key constitutive laws for the unsaturated poromechanics problems: (1) the path‐dependent retention curve with distinctive wetting and drying paths. (2) The flow in the micropores, governed by an anisotropic permeability tensor. Numerical experiments have shown that the resultant ML‐generated material models can be integrated into a finite element (FE) solver to solve initial‐boundary‐value problems as replacements of the hand‐craft constitutive laws.
What is the impact of post‐radical prostatectomy urinary incontinence on everyday quality of life? Linking Pad usage and International Consultation on Incontinence Questionnaire Short‐Form (ICIQ‐SF) for a COMBined definition (PICOMB definition)
Authors: García Cortés Ángel , Colombás Vives Juan , Gutiérrez Castañé Cristina , Chiva San Román Santiago , Doménech López Pablo , Ancizu Marckert Francisco J. , Hevia Suárez Mateo , Merino Narro Imanol , Velis Campillo José M. , Guillén Grima Francisco , Torres Roca Marcos , Diez‐Caballero y Alonso Fernando , Rosell Costa David , Villacampa Aubá Felipe , Ramón de Fata Chillón Fernando , Andrés Boville Guillermo , Barbas Bernardos Guillermo , Miñana López Bernardino , Robles García José E. , Pascual Piédrola Juan I.
Published: February 2021

Aims

To identify the definition for urinary continence (UC) after radical prostatectomy (RP) which reflects best patients' perception of quality of life (QoL).

Methods

Continence was prospectively assessed in 634 patients, 12 months after RP using the International Consultation on Incontinence Questionnaire Short‐Form (ICIQ‐SF) and the number of pads employed in a 24‐hour period (pad usage). We used the one‐way ANOVA technique with posthoc pairwise comparisons according to Scheffé's method (homogeneous subsets) for assessing the degree of QoL deficit related to urinary incontinence (UI).

Results

The continence prevalence is 64.4%, 74.1%, 88.3%, and 35.8% using “0 pads,” “1 safety pad,” “1 pad,” and “ICIQ score 0” definitions, respectively. Pad usage is moderately strongly associated with ICIQ 1, 2, and 3 (ρ = 0.744, 0.677, and 0.711, respectively; p < 0.001). Concordance between classical UC definitions is acceptable between “0 pads—ICIQ score 0” (K = 0.466), but poor for “1 safety pad” and “1 pad” (K = 0.326 and 0.137, respectively). Patients with “0 pad usage” have better QoL related to urine leakage than patients with “1 safety pad” or “1 pad” (1.41 vs. 2.44 and 3.11, respectively; p < 0.05). There were no significant differences found regarding QoL between patients with ICIQ score 0 and ICIQ score 2 (1.01 vs. 1.63; p = 0.63).

Conclusions

Pad usage and the ICIQ‐SF's answers provide useful information. We propose a combined definition (0 pads and ICIQ score ≤2) as it is the definition with the least impact on daily QoL.
First voided volume: A novel approach to characterize nocturia
Authors: Monaghan Thomas F. , Dmochowski Roger R. , Verbalis Joseph G. , Wein Alan J. , Lazar Jason M. , Birder Lori A. , Everaert Karel , Weiss Jeffrey P. , Bliwise Donald L.
Published: February 2021

Aims

Nocturnal polyuria syndrome (NPS) denotes nocturnal polyuria (NP) in the absence of identifiable contributory factors. The trajectory of nocturnal urine production (NUP; typically expressed as ml/hour) may be useful in delineating between NP patients with versus without NPS, but changes in absolute urine volume, the directly measured substrate for behavioral and pharmacologic interventions targeting nocturnal urine production, have not been well characterized. This study compares the ratio of the first nocturnal voided volume (FNVV) to the nocturnal average voided volume (NAVV) in patients with versus without NPS.

Methods

Secondary analysis of 24‐h voiding diaries from male patients greater than or equal to 18 years of age with two or more nocturnal voids and NP using two different criteria for NP: NUP greater than or equal to 90 ml/h and nocturnal polyuria index (NPi) greater than or equal to 0.33. Patients with diabetes insipidus and CPAP‐adherent obstructive sleep apnea (OSA) were excluded. Patients were divided into 2 groups: secondary NP (OSA, congestive heart failure, and chronic kidney disease) and NPS (absence of edema, diuretic use, and the aforementioned comorbidities). FNVV was defined as the volume of urine accompanying the first nocturic episode. NAVV was defined as nocturnal urine volume/(number of nocturnal voids + 1). The nocturnal urine trajectory ratio (NUTR) was defined as FNVV/NAVV.

Results

At NUP greater than or equal to 90 ml/h, NUTR was significantly greater in patients with (n = 73) versus without (n = 28) NPS (1.10 [0.89–1.33] vs. 0.91 [0.55–1.15], p = .012). At NPi greater than or equal to 0.33, NUTR was likewise significantly greater in patients with (n = 92) versus without (n = 32) NPS (1.09 [0.90–1.33] vs. 0.91 [0.57–1.17], p = .010).

Conclusions

The volume of urine produced in the early hours of sleep is central to identification of NPS in patients with nocturia.
A Targeted Nano Drug Delivery System of AS1411 Functionalized Graphene Oxide Based Composites
Authors: Liu Baoqing , Yang Wenzhi , Che Chengchuan , Liu Jinfeng , Si Meiru , Gong Zhijin , Gao Ruixia , Yang Ge
Published: February 2021

A novel method for the preparation of antitumor drug vehicles has been optimized. Biological materials of chitosan oligosaccharide (CO) and γ‐polyglutamic acid (γ‐PGA) have previously been employed as modifiers to covalently modify graphene oxide (GO), which in turn loaded doxorubicin (DOX) to obtain a nano drug delivery systems of graphene oxide based composites (GO‐CO‐γ‐PGA‐DOX). The system was not equipped with the ability of initiative targeting, thus resulting into toxicity and side effects on normal tissues or organs. In order to further improve the targeting property of the system, the nucleic acid aptamer NH2‐AS1411 (APT) of targeted nucleolin (C23) was used to conjugate on GO‐CO‐γ‐PGA to yield the targeted nano drug delivery system APT‐GO‐CO‐γ‐PGA. The structure, composition, dispersion, particle size and morphology properties of the synthesized complex have been studied using multiple characterization methods. Drug loading and release profile data showed that APT‐GO‐CO‐γ‐PGA is provided with high drug loading capacity and is capable of controlled and sustained release of DOX. Cell experimental results indicated that since C23 was overexpressed on the surface of Hela cells but not on the surface of Beas‐2B cells, APT‐GO‐CO‐γ‐PGA‐DOX can target Hela cells and make increase toxicity to Hela cells than Beas‐2B cells, and the IC50 value of APT‐GO‐CO‐γ‐PGA‐DOX was 3.23±0.04 μg/mL. All results proved that APT‐GO‐CO‐γ‐PGA can deliver antitumor drugs in a targeted manner, and achieve the effect of reducing poison, which indicated that the targeted carrier exhibits a broad application prospect in the field of biomedicine.
Bio‐ and oxo‐degradable plastics: Insights on facts and challenges
Authors: Abdelmoez Wael , Dahab Islam , Ragab Esraa M. , Abdelsalam Omnia A. , Mustafa Ahmad
Published: February 2021

The global accumulation of single‐use plastic bags made from nonbiodegradable plastics is the most concerning environmental issue nowadays. The utilization of biodegradable materials is a choice to reduce the environmental impact resulting from the use of plastic products. The utilization of renewable resources to produce fully biodegradable plastics is among the technologies used to overcome petroleum plastic's negative impact. On the other hand, the utilization of oxo‐biodegradable plastics where prodegradant additives are incorporated in conventional plastics to promote their degradation under certain conditions has recently received much attention. This review discusses the types and challenges that face the implementation of biodegradable plastics technology that uses renewable resources. This review also covers the debate addressed in the literature about the biodegradability fate of oxo‐biodegradable plastic in the air, compost, soil, landfill, and marine. A comparative study included the potential published literature in the last 10 years was performed. Based on the discussed evidence in this review, it can be concluded that all literature agrees that the addition of pro‐oxidant/prodegradants can accelerate the degradation of oxo‐plastics to small fragments. However, the complete biodegradation of oxo‐plastics by microorganisms remains in doubt. On the other hand, biopolymers produced from natural resources seem to be the future direction for plastics manufacturing especially single‐use plastic bags.
Simple dispersion of graphene incorporated rubber composite for resistive pressure sensor application
Authors: Marlinda Ab Rahman , Kamaruddin Nurul Hazierah , Fadilah Abd Wahab , Said Mardhiah , Hamizi Nor Aliya , Johan Mohd Rafie
Published: February 2021

We developed a resistive pressure sensor based on stand‐alone film graphene incorporated natural rubber latex (NR/G) composite fabricated in a simple solution casting method. The graphene dispersion had multilayer properties and an average lateral size of ~60 nm successfully incorporated into the NR matrix to form bilayer graphene composite with the I2D/IG calculated ratio of 1.301. The pressure sensor shows high sensitivity (~ 0.2 kPa−1), high cycle stability, and selective response to the applied pressure with a linear relationship of ~6.0 kPa. This work shows that graphene incorporated natural rubber latex pressure sensors with applicable potentials for smart wearable devices to allow pressure detection.
Resilience and its associated factors in brain tumor patients in Karachi, Pakistan: An analytical cross‐sectional study
Authors: Zahid Nida , Martins Russell Seth , Zahid Wajeeha , Khalid Wardah , Azam Iqbal , Bhamani Shireen Shehzad , Ahmad Khabir , Jabbar AdnanAbdul , Shamim Muhammad Shahzad , Khan Rashid Jooma , Javed Gohar , Bari Ehsan , Asad Nargis , Enam Syed Ather
Published: February 2021

Objectives

This study assessed resilience in brain tumor patients at a tertiary care hospital in Pakistan (a lower middle‐income country; LMIC) and explored its relationship with patients' sociodemographic factors, clinical characteristics, social support, and mental health.

Methods

A cross‐sectional survey was conducted amongst adult (≥18 years) patients with brain tumor at the Aga Khan University Hospital, Pakistan. Resilience was assessed by Wagnild and Young's Resilience Scale, and patients' psychosocial characteristics by the Hospital Anxiety and Depression Scale and the Enriched Social Support Instrument.

Results

A total of 250 patients were included (mean age: 44 years; 68% males), with majority (97.6%) having high social support and only 4.4% and 2% having symptomatic depression and anxiety, respectively. On multivariable linear regression adjusted for covariates, lower resilience was associated with not being involved in household decision‐making (Adjusted Beta Coefficient: 4.58 [95% Confidence Interval:−7.59, −1.56]), not currently working (−2.80 [−4.61, −0.99]), undergoing multiple neurosurgical interventions such as tumor biopsies or resections (−8.64 [−13.11, −4.16]), receiving chemotherapy (−5.17 [−9.51, −0.83]) or combination adjuvant therapy (−2.91 [−5.14, −0.67]), low social support (−7.77 [−13.73, 1.81]), mild depression (−13.00 [‐17.00,‐8.99]) or symptomatic depression (−19.79 [−24.69, −14.89]), and mild anxiety (−4.24 [−7.98, −0.50]).

Conclusion

Our study highlights the function of familial/household role and working status in mediating resilience, and demonstrates the well‐known protective effect of resilience for mental health in brain tumor patients in Pakistan, a South‐Asian LMIC. These findings are of clinical relevance with regards to the development of culture‐specific evidence‐based resilience‐building interventions that may help patients with brain tumors to cope with the psychological distress of cancer.
Experimental and Simulation Study on the Ignition Criterion of JHL‐3 under Non‐Shock Loading
Authors: Qin Jingui , Liang Wen , Chen Rong , Lu Fangyun
Published: February 2021

The non‐shock ignition of explosives can bring huge accidental disasters, so it is meaningful to study the conditions under which explosives ignite. The safety performance of JHL‐3, a polymer‐bonded explosive (PBX), under low amplitude and long pulse load has been analyzed based on experiment and simulation from a macro perspective, and the load criterion for ignition of JHL‐3 is given. First, JHL‐3 was loaded under confining pressure by the modified separated Hopkinson pressure bar. By observing whether the explosives ignite at different pulses whose width and amplitude can be changed by changing the length and initial speed of the striker, we find that the greater the loading pressure, the shorter the loading time required for the ignition of JHL‐3. According to the experimental results, the relationship between the amplitude and width of the loading pulse at which the JHL‐3 is ignited is fitted. Then, load JHL‐3 of different densities under the same conditions to analyze the influence of density on the ignition sensitivity of JHL‐3. The experimental results show that the sensitivity is highest when the density is between 1.7–1.75 g/cm3. Finally, based on the Uintah Computational Framework (UCF), the experiment is simulated by the coupling algorithm (MPMICE) of material point method (MPM) and implicit continuous‐fluid Eulerian (ICE). JHL‐3 is modeled by the Visco‐Scram model, and the WSB model is used as a reaction model to simulate the combustion behavior of the explosive after ignition. The simulation results closely match the experimental results, further verifying the accuracy of the ignition criterion. The ignition criterion can predict the ignition of explosives under non‐shock loading conditions, which has a guiding effect on the storage, transportation, and packaging of explosives.
Bayesian predictive model to assess BRCA2 mutational status according to clinical history: Early onset, metastatic phenotype or family history of breast/ovary cancer
Authors: Leon Priscilla , Cancel‐Tassin Geraldine , Bourdon Violaine , Buecher Bruno , Oudard Stephane , Brureau Laurent , Jouffe Lionel , Blanchet Pascal , Stoppa‐Lyonnet Dominique , Coulet Florence , Sobol Hagay , Cussenot Olivier
Published: February 2021

Background

Mutations of the BRCA2 gene are the most frequent alterations found in germline DNA from men with prostate cancer (PrCa), but clinical parameters that could better orientate for BRCA2 mutation screening need to be established.

Methods

Germline DNA from 325 PrCa patients (median age at diagnosis: 57 years old) was screened for BRCA2 mutation. The mutation frequency was compared between three subgroups: patients with an age at diagnosis at 55 years old and under (Group I); a personal or family history of breast, uterine or ovarian cancer (Group II); or a metastatic disease (Group III). Frequency of BRCA2 mutations was established for each combination of phenotypes, and compared between patients meeting or not the criteria for each subgroup using Fisher's exact test. Mutual information, direct effect, elasticity and contribution to the mutational status of each phenotype, taking into account overlap between subgroups, were also estimated using Bayesian algorithms.

Results

The proportion of BRCA2 mutation was 5.9% in Group I, 10.9% in Group II and 6.9% in Group III. The frequency of BRCA2 mutation was significantly higher among patients of Group II (p = .006), and reached 15.6% among patients of this group who presented a metastatic disease. Mutual information, direct effect, elasticity and contribution to the mutational status were the highest for phenotype II. Fifteen (71.4%) of the 21 BRCA2 mutation carriers had an aggressive form of the disease. Four (19%) of them died from PrCa after a median follow‐up duration of 64.5 months.

Conclusions

Our results showed that a higher frequency of BRCA2 mutation carriers is observed, not only among PrCa patients with young onset or a metastatic disease, but also with a personal or a familial history of breast cancer.
Terrorism, migrant crisis and attitudes towards immigrants from outside of the European Union
Authors: Baláž Vladimír , Nežinský Eduard , Williams Allan M.
Published: February 2021

This paper analyses how terrorist attacks and high inflows of immigrants impact public attitudes towards immigrants from outside the European Union (EU). It makes an original contribution by analysing both effects in tandem, using an extended longitudinal framework to assess both shorter and longer term impacts and taking into account the role of uncertainty. Ordered probit regression models are applied to data from nine consecutive Eurobarometer (EB) surveys to examine impacts of 25 terrorist attacks in Western Europe in 2014–2018. Attacks with higher number of deaths significantly increase negative attitudes to immigrants although the effect fades over time. However, the 2015 migration crisis had a significant, greater and more sustained impact on attitudes towards immigrants than terrorist attacks. The differences in attitudes to migrants in the EU15 countries and post‐communist countries provide support for the assumptions of the intergroup contact theory rather than the group threat theory.
Opportunities and challenges for applying model‐informed drug development approaches to gene therapies
Authors: Belov Artur , Schultz Kimberly , Forshee Richard , Tegenge Million A.
Published: February 2021

As part of the US Food and Drug Administration (FDA)’s Prescription Drug User Fee Act (PDUFA) VI commitments, the Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER) are conducting a model‐informed drug development (MIDD) pilot program. Sponsor(s) who apply and are selected will be granted meetings that aim to facilitate the application of MIDD approaches throughout the product development lifecycle and the regulatory process. Due to their complex mechanisms of action and limited clinical experience, cell and gene therapies have the potential to benefit from the application of MIDD methods, which may facilitate their safety and efficacy evaluations. Leveraging data that are generated from all stages of drug development into appropriate modeling and simulation techniques that inform decisions remains challenging. Additional discussions regarding the application of quantitative modeling approaches to drug development decisions, such as through the MIDD pilot program, may be crucial for both the sponsor(s) and regulatory review teams. Here, we share some perspectives on the opportunities and challenges for utilizing MIDD approaches for product review, which we hope will encourage investigators to publish their experiences and application of MIDD in gene therapy product development.
Potential impact of COVID‐19 on ongoing clinical trials: a simulation study with the neurological Yale Global Tic Severity Scale based on the CANNA‐TICS study
Authors: Lasch Florian , Guizzaro Lorenzo , Aguirre Dávila Lukas , Müller‐Vahl Kirsten , Koch Armin
Published: February 2021

The COVID‐19 pandemic has manifold impacts on clinical trials. In response, drug regulatory agencies and public health bodies have issued guidance on how to assess potential impacts on ongoing clinical trials and stress the importance of a risk‐assessment as a pre‐requisite for modifications to the clinical trial conduct. This article presents a simulation study to assess the impact on the power of an ongoing clinical trial without the need to unblind trial data and compromise trial integrity. In the context of the CANNA‐TICS trial, investigating the effect of nabiximols on reducing the total tic score of the Yale Global Tic Severity Scale (YGTSS‐TTS) in patients with chronic tic disorders and Tourette syndrome, the impact of the two COVID‐19 related intercurrent events handled by a treatment policy strategy is investigated using a multiplicative and additive data generating model. The empirical power is examined for the analysis of the YGTSS‐TTS as a continuous and dichotomized endpoint using analysis techniques adjusted and unadjusted for the occurrence of the intercurrent event. In the investigated scenarios, the simulation studies showed that substantial power losses are possible, potentially making sample size increases necessary to retain sufficient power. However, we were also able to identify scenarios with only limited loss of power. By adjusting for the occurrence of the intercurrent event, the power loss could be diminished to different degrees in most scenarios. In summary, the presented risk assessment approach may support decisions on trial modifications like sample size increases, while maintaining trial integrity.
Molint 1.0: A framework for the computation of molecular integrals and their derivatives for density‐fitted methods
Authors: Bozkaya Uğur
Published: February 2021

The efficient computation of molecular integrals and their derivatives is a crucial step in molecular property evaluation in modern quantum chemistry. In this study, an application programming interface (API) framework, denoted Molint, for the computation of molecular integrals and their first derivatives, over contracted Gaussian functions, for the density‐fitted methods is reported. The Molint is free software and it includes overlap, dipole, kinetic, potential, 2‐index, and 3‐index integrals, and their first derivatives. Furthermore, the Molint provides a smooth approach to build the Fock matrix and evaluate analytic gradients for the density‐fitted methods. The Molint is a C++/Fortran hybrid code, which can take advantage of shared‐memory parallel programming techniques. Our results demonstrate that the Molint is an efficient and user‐friendly API for the computation of molecular integrals and their first derivatives.
C‐reactive protein as an effector molecule in Covid‐19 pathogenesis
Authors: Mosquera‐Sulbaran Jesús A. , Pedreañez Adriana , Carrero Yenddy , Callejas Diana
Published: February 2021

The current pandemic caused by SARS‐CoV‐2 virus infection is known as Covid‐19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C‐reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI‐PubMed database to find articles related to Covid‐19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid‐19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro‐inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid‐19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid‐19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.
Robust controllers design for constrained nonlinear parameter varying descriptor systems
Authors: Righi Ines , Aouaouda Sabrina , Chadli Mohammed , Khelil Khaled
Published: February 2021

This article proposes a method for designing robust controller laws for a class of uncertain nonlinear parameter varying (NLPV) descriptor systems under input saturation and external disturbances. Both static and dynamic output feedback controllers are proposed. To synthesize the fuzzy controllers, the stability conditions are derived using polytopic parameter‐dependent (PD) nonquadratic Lyapunov functions with respect to the given saturation constraint on the control input. First, the designed conditions are established in terms of linear matrix inequalities (LMIs) and gain performance is used to attenuate the effect of the external disturbance signals. Then, the estimation of the largest domain of attraction (DoA) for the system is formulated and solved as an optimization problem. Two examples are used to illustrate the effectiveness of the proposed design methods.
Input–output gain analysis of positive periodic systems
Authors: Zhu Bohao , Lam James , Ebihara Yoshio
Published: February 2021

This paper investigates the input‐output gains, includingℓ1‐ andℓ∞‐gains andL1‐ andL∞‐gains, of discrete‐time and continuous‐time positive periodic systems. For the discrete‐time case, the input–output gain can be characterized by linear inequalities. For the continuous‐time case, the input–output gain characterization problem turns into the existence problem of a positive periodic vector function. Based on some necessary and sufficient input–output gain conditions, we find theℓ1‐ (L1‐) gain of discrete‐time (continuous‐time) positive periodic systems is equivalent to the ofℓ∞‐ (L∞‐) gain of the associated dual systems. Finally, two numerical examples are given to illustrate the results.
Discretized quasi‐time‐dependent control for continuous‐time switched linear systems with persistent dwell‐time
Authors: Tong Yanhui , Sun Weichao , Li Xiaohang
Published: February 2021

This article is concerned with the dynamic output‐feedbackcontrol problem for continuous‐time switched linear systems with persistent dwell‐time (PDT). Considering the quasi‐periodic property of PDT switching, a discretized quasi‐time‐dependent (QTD) control scheme is proposed by means of a multiple discretized QTD Lyapunov function approach. This control scheme is devoted to designing discretized controllers for continuous‐time switched systems straightforwardly. Firstly, the stability and‐gain of switched systems with PDT is analyzed utilizing multiple QTD Lyapunov functions. Then, by constructing the quadratic discretized version of these functions, a synthesis condition for the discretized QTDcontroller is established. In order to formulate the synthesis condition in terms of LMIs, we employ the controller state reset strategy in the derivation, which means that the controller state is reset to that of the plant at each switching instant. Finally, a numerical example is given to illustrate the effectiveness of the proposed control scheme.
Predicting mean annual and mean monthly streamflow in Colorado ungauged basins
Authors: Eurich Abby , Kampf Stephanie K. , Hammond John C. , Ross Matt , Willi Katie , Vorster Anthony G. , Pulver Bryce
Published: February 2021

River managers often need estimates of streamflow for ungauged streams. These estimates can be used in water rights acquisitions, in‐stream flow management, habitat assessment, water quality planning, and stream hazard identification. This publication describes new regression models for predicting mean annual and mean monthly streamflow in Colorado. Unlike previous regional regression studies, the new models incorporate snow persistence (SP), the fraction of time a watershed remains snow covered. Models were developed using streamflow data from 131 watersheds with drainage areas <1,500 km2, no transbasin diversions, and <10% urban area. In addition to SP, topographic, climate, geologic, and hydrologic region variables were used in model predictions. All new models had very good performance, with <6% absolute bias and stronger performance compared to current regional regression models in StreamStats. The mean annual model had the strongest performance, with Nash‐Sutcliffe efficiency coefficient (NSE) of 0.93 and <2% absolute bias. Mean monthly models had best performance during snowmelt runoff months (May‐Jul; NSE ≥0.79; absolute % bias ≤ 4) and weaker performance during low flow months (Aug‐Apr; NSE ≥ 0.59; % bias ≤ 5). Tests of the mean annual model using decadal average streamflow from 1910s to 2000s show very good performance (NSE > 0.75), but predictions were biased low by 14–28% in wetter decades. All equations and coefficients needed to run the models are presented in the publication appendix, and the associated data release includes the spatial data and model code, which can be applied using R or within an R‐based Shiny web app.
Physicochemical drivers of managed river and agricultural drainage channel macroinvertebrate communities
Authors: Gething Kieran J.
Published: February 2021

Artificial channels are common features in lowland agricultural catchments, and are a potentially significant habitat for aquatic species. Recent studies have suggested communities in managed rivers and artificial channels are broadly similar, but with some compositional differences. However, because relatively few studies have considered how artificial channels may contribute to supporting aquatic communities, their physicochemical condition and suitability for aquatic fauna remain poorly characterised. Therefore, this study explores the role of physicochemical variables in driving macroinvertebrate community differences between intensively managed rivers and artificial channels in a highly arable catchment. Aquatic macroinvertebrates were sampled in intensively managed rivers and artificial channels. Physicochemical water quality variables were also recorded, and used to identify macroinvertebrate community responses. Both intensively managed rivers and artificial channels had spatiotemporally stable communities, with no significant differences in richness, abundance, effective diversity or Berger–Parker dominance detected between sampling months or channel types. Macroinvertebrate composition in intensively managed rivers and artificial channels was significantly different, and driven by the relative abundance of taxa present, not the number of taxa unique to each channel type. Compositional differences between intensively managed rivers and artificial channels were partially driven by conductivity, dissolved oxygen and temperature. Identifying remaining sources of compositional variance may support tailored management strategies that accentuate compositional differences between rivers and artificial channels, increasing overall diversity in intensively farmed arable catchments.