bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of mechanical lung vibrator and high‐frequency chest wall oscillation in patients with cardiac implantable electronic device
Authors: Gwag Hye Bin , Joh Hyun Sung , Kim June Soo , Park Kyoung‐Min , On Young Keun , Park Seung‐Jung
Published: February 2021

Background

Chest physiotherapy (CPT) is a non‐pharmacological therapy to facilitate airway secretion removal. There have been concerns about potential electromagnetic interference (EMI) and lead integrity problems during the use of vibrating CPT devices in patients with cardiac implantable electronic devices (CIEDs).

Hypothesis

Two CPT devices can be used safely in patients with CIED.

Methods

Volunteer patients with CIED underwent device interrogation to check lead integrity and device function before and after application of CPT devices. Mechanical lung vibrator and high‐frequency chest wall oscillation (HFCWO) vests were used while monitoring surface electrocardiograms and intra‐cardiac electrograms.

Results

We prospectively enrolled 46 patients with CIEDs (25 pacemakers, 15 implantable cardioverter‐defibrillators, and six cardiac resynchronization therapy‐defibrillators). There was no noise detection or EMI during CPT in any patient. None of the patients showed clinically significant changes in lead integrity parameters. HFCWO inappropriately accelerated the pacing rate up to the maximal programmed value in five patients with pacemakers and two with cardiac resynchronization therapy‐defibrillators.

Conclusion

CPT may be safely applied to patients with CIED without compromising lead integrity or device function, except for unwanted increase in pacing rate caused by misdetection of chest wall vibration as patients' activity while using HFCWO. Deactivation of the accelerometer‐based activity sensor may be needed when HFCWO is planned for CPT.
Design, Synthesis, and Biological Evaluation of Orally Bioavailable CHK1 Inhibitors Active against Acute Myeloid Leukemia
Authors: Jin Tingting , Wang Peipei , Long Xiubing , Jiang Kailong , Song Pinrao , Wu Wenbiao , Xu Gaoya , Zhou Yubo , Li Jia , Liu Tao
Published: February 2021

Checkpoint kinase 1 (CHK1) is a central component in DNA damage response and has emerged as a target for antitumor therapeutics. Herein, we describe the design, synthesis, and biological evaluation of a novel series of potent diaminopyrimidine CHK1 inhibitors. The compounds exhibited moderate to potent CHK1 inhibition and could suppress the proliferation of malignant hematological cell lines. The optimized compound 13 had a CHK1 IC50 value of 7.73±0.74 nM, and MV‐4‐11 cells were sensitive to it (IC50=0.035±0.007 μM). Furthermore, compound 13 was metabolically stable in mouse liver microsomes in vitro and displayed moderate oral bioavailability in vivo. Moreover, treatment of MV‐4‐11 cells with compound 13 for 2 h led to robust inhibition of CHK1 autophosphorylation on serine 296. Based on these biochemical results, we consider compound 13 to be a promising CHK1 inhibitor and potential anticancer therapeutic agent.
Estimating cardiac active tension from wall motion—An inverse problem of cardiac biomechanics
Authors: Kovacheva Ekaterina , Thämer Laura , Fritz Thomas , Seemann Gunnar , Ochs Marco , Dössel Olaf , Loewe Axel
Published: February 2021

The contraction of the human heart is a complex process as a consequence of the interaction of internal and external forces. In current clinical routine, the resulting deformation can be imaged during an entire heart beat. However, the active tension development cannot be measured in vivo but may provide valuable diagnostic information. In this work, we present a novel numerical method for solving an inverse problem of cardiac biomechanics—estimating the dynamic active tension field, provided the motion of the myocardial wall is known. This ill‐posed non‐linear problem is solved using second order Tikhonov regularization in space and time. We conducted a sensitivity analysis by varying the fiber orientation in the range of measurement accuracy. To achieve RMSE <20% of the maximal tension, the fiber orientation needs to be provided with an accuracy of 10°. Also, variation was added to the deformation data in the range of segmentation accuracy. Here, imposing temporal regularization led to an eightfold decrease in the error down to 12%. Furthermore, non‐contracting regions representing myocardial infarct scars were introduced in the left ventricle and could be identified accurately in the inverse solution (sensitivity >0.95). The results obtained with non‐matching input data are promising and indicate directions for further improvement of the method. In future, this method will be extended to estimate the active tension field based on motion data from clinical images, which could provide important insights in terms of a new diagnostic tool for the identification and treatment of diseased heart tissue.
Strive for ‘beyond compliance’ through collaborative Universal Design
Authors: Freedman Justin E. , Drelick Alicia M.
Published: February 2021

Many students who have been previously identified as having a disability do not access accommodations once enrolled in higher education. Some students do not register with Disability Services. Others register but choose not to disclose their disability status to individual course instructors. Still others, including students in our own research, go so far as to discuss accommodations with instructors but ultimately downplay their need for accommodations or even proactively offer not to use them in an attempt to be more like students without disabilities. The voices of students with disabilities in research consistently demonstrate that the many steps involved in disclosing their disability status create an obstacle to accessing accommodations.
A general model of the thermal constraints on the world’s most destructive locust,Schistocerca gregaria
Authors: Maeno Koutaro Ould , Piou Cyril , Kearney Michael R. , Ould Ely Sidi , Ould Mohamed Sid’Ahmed , Jaavar Mohamed El Hacen , Ould Babah Ebbe Mohamed Abdallahi
Published: February 2021

All terrestrial ectotherms are constrained to some degree by their thermal environment and the extent to which they can behaviorally buffer variable thermal conditions. New biophysical modeling methods (NicheMapR) allow the calculation of the body temperature of thermoregulating animals anywhere in the world from first principles, but require detailed observational data for parameterization and testing. Here we describe the thermoregulatory biology of marching bands of the desert locust,Schistocerca gregaria, in the Sahara Desert of Mauritania where extreme heat and strong diurnal fluctuations are a major constraint on activity and physiological processes. Using a thermal infrared camera in the field, we showed that gregarious nymphs altered the microhabitats they used, as well as postural thermoregulatory behaviors, to maintain relatively high body temperature (nearly 40°C). Field and laboratory experiments demonstrated that the preferred body temperature accelerated digestive rates. Migratory bands frequently left foraging sites with full guts before consuming all vegetation and moved to another habitat before emptying their foregut. Thus, the repertoire for behavioral thermoregulation in the desert locust strongly facilitates foraging and digestion rates, which may accelerate developmental rates and increase survival. We used our data to successfully parameterize a general biophysical model of thermoregulatory behavior that could capture hourly body temperature and activity at our remote site using globally available environmental forcing data. This modeling approach provides a stronger basis for forecasting thermal constraints on locust outbreaks under current and future climates.
Serum glucose, lactate dehydrogenase and hypertension are mediators of the effect of body mass index on severity of COVID‐19
Authors: Yan Huadong , Vijay Amrita , Jiang Fanrong , Zheng Nanhong , Hu Yaoren , Ye Honghua , Ollivere Benjamin , Cai Ting , Valdes Ana M , Aithal Guruprasad P.
Published: February 2021

Background

COVID‐19 has a broad clinical spectrum. We investigated the role of serum markers measured on admission on severity as assessed at discharge and investigated those which relate to the effect of BMI on severity.

Methods

Clinical and laboratory data from 610 COVID‐19 cases hospitalized in the province of Zheijang, China were investigated as risk factors for severe COVID‐19 (assessed by respiratory distress) compared to mild or common forms using logistic regression methods. Biochemical markers were correlated with severity using spearman correlations, and a ROC analysis was used to determine the individual contribution of each of the biochemical markers on severity. We carried out formal mediation analyses to investigate the extent of the effect of body mass index (BMI) on COVID‐19 severity mediated by hypertension, glycemia, Lactose Dehydrogenase (LDH) at the time of hospitalization and C‐Reactive Protein levels (CRP), in units of standard deviations.

Results

The individual markers measured on admission contributing most strongly to prediction of COVID‐19 severity as assessed at discharge were LDH, CRP and glucose. The proportion of the effect of BMI on severity of COVID‐19 mediated by CRP, glycemia or hypertension, we find that glucose mediated 79% (p < .0001), LDH mediated 78% (p < .0001), hypertension mediated 66% (p < .0001); however, only 44% (p < .005) was mediated by systemic inflammation (CRP).

Conclusion

Our data indicate that a larger proportion of the effect of BMI on severity of COVID‐19 is mediated by glycemia and LDH levels whereas less than half of it is mediated by systemic inflammation.
Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure
Authors: Bozkurt Biykem , Coats Andrew J.S. , Tsutsui Hiroyuki , Abdelhamid Ca Magdy , Adamopoulos Stamatis , Albert Nancy , Anker Stefan D. , Atherton John , Böhm Michael , Butler Javed , Drazner Mark H. , Michael Felker G. , Filippatos Gerasimos , Fiuzat Mona , Fonarow Gregg C. , Gomez‐Mesa Juan‐Esteban , Heidenreich Paul , Imamura Teruhiko , Jankowska Ewa A. , Januzzi James , Khazanie Prateeti , Kinugawa Koichiro , Lam Carolyn S.P. , Matsue Yuya , Metra Marco , Ohtani Tomohito , Francesco Piepoli Massimo , Ponikowski Piotr , Rosano Giuseppe M.C. , Sakata Yasushi , Seferović Petar , Starling Randall C. , Teerlink John R. , Vardeny Orly , Yamamoto Kazuhiro , Yancy Clyde , Zhang Jian , Zieroth Shelley
Published: February 2021

In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre‐HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41–49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.
When do rock glacier fronts fail? Insights from two case studies in South Tyrol (Italian Alps)
Authors: Kofler Christian , Mair Volkmar , Gruber Stephan , Todisco Maria Cristina , Nettleton Ian , Steger Stefan , Zebisch Marc , Schneiderbauer Stefan , Comiti Francesco
Published: February 2021

The fronts of two rock glaciers located in South Tyrol (Italian Alps) failed on 13 August 2014, initiating debris flows in their downslope channels. A multimethod approach including climate, meteorological, and ground temperature data analysis, aerial image correlation, as well as geotechnical testing and modeling, led to the reconstruction of the two events. An integrated investigation of static predisposing factors, slowly changing preparatory factors, and potential triggering events shed light on the most likely reasons for such failures. Our results suggest that the occurrence of front destabilization at the two rock glaciers can only partly be explained by the occurrence of heavy rainfall events. Indeed, antecedent hydrological and thermal ground conditions were characterized by a saturated active layer favored by a snow‐rich winter and extensive precipitation in late spring and summer. Also, the rising trend of air temperature during spring and summer months since 1950s might explain the concurrent marked displacement of the two rock glaciers. Indeed, geotechnical investigations have provided strong indications that one of the investigated rock glacier fronts was at a marginally stable state prior to 2014. As rainfall events more intense than the one that occurred in August 2014 were previously recorded in the same area without resulting failures at the studied rock glaciers, we propose that both predisposing and preparatory destabilizing factors have played a key role in the 2014 rock glacier front failures.
Neuroendocrine neoplasms of the middle ear: Unpredictable tumor behavior and tendency for recurrence
Authors: van der Lans Rik J. L. , Engel Michelle S. D. , Rijken Johannes A. , Hensen Erik F. , Bloemena Elisabeth , van der Torn Marein , Leemans Charles R. , Smit Conrad F. G. M.
Published: February 2021

Background

Middle ear adenomatous neuroendocrine tumors (MEANTs) are rare temporal bone tumors. This study evaluates its clinical behavior and therapy outcome.

Method

Retrospective case review in a tertiary referral center evaluating histopathology, immunohistochemistry, treatment, and outcome.

Results

Nine patients were diagnosed with MEANT. One patient presented with locally invasive tumor and underwent extensive en‐bloc tumor resection with adjuvant radiotherapy. Seven of eight patients with locally non‐aggressive tumor confined to the tympanomastoid space underwent tumor resection. Two patients were disease‐free, five presented recurrence, even after apparent successful surgery. All tumors showed neuroendocrine features. Histopathology and immunohistochemistry did not yield prognostic tumor characteristics.

Conclusion

MEANTs are rare tumors with uncertain biological behavior and subsequent unpredictable clinical course. The preferred treatment is complete surgical tumor resection. They have a high tendency for recurrence, irrespective of negative intermediary surgery. As of yet, there are no prognostic biomarkers, including histopathology and immunohistochemistry.
A novel tissue inhibitor of metalloproteinases‐1/liver/cachexia score predicts prognosis of gastrointestinal cancer patients
Authors: Prokopchuk Olga , Hermann Chris D. , Schoeps Benjamin , Nitsche Ulrich , Prokopchuk Oleksii L. , Knolle Percy , Friess Helmut , Martignoni Marc E. , Krüger Achim
Published: February 2021

Background

Cachexia, a devastating syndrome in cancer patients, critically determines survival and life quality. It is characterized by impaired homeostasis of multiple organs including the liver, involves tissue wasting, and is conventionally diagnosed and classified by weight loss (WL). However, recent studies pointed at the problem that WL is not sufficient for precise classification of cancer patients according to disease severity (i.e. prognosis). Tissue inhibitor of metalloproteinases‐1 (TIMP‐1) is an easily accessible cachexia‐associated biomarker in the blood, known to alter liver homeostasis. Here, we investigated the value of combining blood levels of TIMP‐1 with parameters of liver functionality towards establishment of a cachexia‐associated clinical score, which predicts survival of cancer patients, reflects the clinical manifestation of cachexia, and is easily accessible in the clinic.

Methods

The TIMP‐1/liver cachexia (TLC) score, expressed as numerical value ranging from 0 to 1, was calculated by categorizing the blood levels of TIMP‐1 and parameters of liver functionality (C‐reactive protein, ferritin, gamma‐glutamyl transferase, albumin, and total protein) for each patient as below/above a certain risk threshold. The TLC score was tested in a cohort of colorectal cancer (CRC) patients (n = 82, 35.4% women, 64.6% men, median age: 70 years) and validated in a cohort of pancreatic cancer (PC) patients (n = 84, 54.8% women, 45.2% men, median age: 69 years).

Results

In CRC patients, the TLC score positively correlated with presence of cachexia‐related symptoms (WL, impaired liver function), predicted survival [P < 0.001, hazard ratio (HR): 96.91 (9.85–953.90)], and allowed classification of three prognostically distinct patient subpopulations [low (LO)‐risk, intermediate (IM)‐risk, and high (HI)‐risk groups; LO vs. IM: P = 0.003, LO vs. HI: P < 0.001, IM vs. HI: P = 0.029]. The prognostic power of the cachexia‐associated TLC score [P < 0.001, HR: 7.37 (2.80–19.49)] and its application to define risk groups (LO vs. IM: P = 0.032, LO vs. HI: P < 0.001, IM vs. HI: P = 0.014) was confirmed in a cohort of PC patients. The prognostic power of the TLC score was independent of presence of liver metastases in CRC or PC patients and was superior to clinically established staging classifications.

Conclusions

The TLC score, a result of straightforward determination of blood parameters, is an objective cachexia‐associated clinical tool for precise survival prediction of gastrointestinal cancer patients.
An experimental and kinetic modeling study of the ignition delay and heat release characteristics of a five component gasoline surrogate and its blends with iso‐butanol within a rapid compression machine
Authors: Michelbach Christian , Tomlin Alison
Published: February 2021

This study investigates the performance of a five component gasoline surrogate (iso‐octane, toluene, n‐heptane, 1‐hexene, and ethanol) in representing the ignition delay time (IDT) behavior of gasoline (reference gasoline PR5801—research octane number 95.4, motor octane number 86.6), at conditions of 675–870 K, 20 bar, and Ф = 1 (stoichiometric) within a rapid compression machine (RCM). Experimentally, the surrogate produces a good representation of the ignition behavior of the gasoline at these conditions, displaying a similar IDT profile. The influence of blending with iso‐butanol on the surrogate's ignition delay behavior is also investigated, at blends from 5% to 70% of iso‐butanol by volume. The surrogate continues to produce a reasonable representation of the experimental IDTs of gasoline and iso‐butanol blends, except under a high degree of iso‐butanol blending (50% iso‐butanol), where the surrogate produced longer IDTs, particularly at temperatures below 740 K. Blends of 5% and 10% iso‐butanol produce IDTs shorter than that of any other blend, including the “neat” surrogate, at temperatures of 740–770 and 830 K, respectively. Kinetic modeling of RCM IDTs is performed using CHEMKIN‐PRO (Reaction Design: San Diego, CA, 2011) and a combined mechanism of the Sarathy et al. butanol isomers mechanism (Progress in Energy and Combustion Science 2014; 44: 40–102) and Lawrence Livermore National Laboratories “Gasoline Surrogate” mechanism (Proceedings of the Combustion Institute 2011; 33(1): 193–200). The model produces good IDT predictions below 740 K but overpredicts reactivity in the negative temperature coefficient region. Heat release rate analysis is conducted for experimental and modeling results to investigate low‐temperature heat release (LTHR) behavior. Simulations largely fail to accurately reproduce this behavior. This analysis, combined with local OH and brute force Δhf sensitivity analyses, indicates the significance of LTHR in the determination of IDTs and provides RCM heat release rates for future model validation.
Hepatitis C Virus RNA Transcript Associates with Prognosis in Non‐human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma
Authors: Tang Bin , Zhu Gangcai , Chen Changhan , Zheng Siyuan , Pu Yuting , Xu Yimin , Huang Huimei , Wang Gang , Huang Donghai , Liu Yong , Zhang Xin
Published: February 2021

Objective/Hypothesis

Hepatitis C virus (HCV) was reported to associate with head and neck squamous cell carcinoma (HNSCC) in many studies. However, its correlation with prognosis of non‐human papillomavirus (HPV) associated HNSCC remains unknown. Here, we sought to investigate clinical significance of HCV RNA transcript in non‐HPV associated HNSCC by analyzing corresponding RNA‐seq data.

Study Design

A retrospective cohort study.

Methods

Four hundred and forty‐eight non‐HPV associated HNSCC patients with aligned RNA‐seq and clinical follow‐up data were included and divided into two groups: low‐HCV and high‐HCV. Means of continuous variables and proportions of categorical variables were compared using independent sample t‐test and chi‐square test, respectively. Survival data were compared using Cox regression analysis, Kaplan–Meier curves, and log‐rank test. Expression of genome‐wide mRNAs and abundance of immune cells were compared using volcano plot and cell signature estimated score analysis.

Results

HCV RNA transcript negatively correlates with pathologic (P = .028) and clinical‐stage (P = .023), clinical N stage (P = .025), and nodal extracapsular spread (P = .042) and is an independent prognosis factor in non‐HPV associated HNSCC (HR = 1.488; 95% CI: 1.004–2.206; P = .048). Elevated expression of HCV improved 5‐year overall survival (43.6% vs. 53.2%; P = .035) in all non‐HPV associated HNSCC patients, the same as in male (46.6% vs. 58.7%; P = .049), clinical M0 stage (42.8% vs. 52.9%; P = .036), white (42.9% vs. 55.9%; P = .010), and histologic grade 1 to 2 subgroups (42.1% vs. 57.2%; P = .043). The expression of several immune‐related genes and abundance of some immune cells significantly changed with the increase of HCV RNA transcript, while HCV‐related oncogenes and tumor suppressor gene did not.

Conclusions

HCV RNA transcript is an independent favorable factor for prognosis of non‐HPV associated HNSCC.

Levels of Evidence

4 Laryngoscope, 131:1774–1781, 2021
Constantly low‐phase‐noise differential VCO based on balanced tunable quasi‐elliptic and constant‐ABW BPF
Authors: Li Zhiyou , Tang Xiaohong , Liu Yong , Lu Di , Cai Zongqi
Published: February 2021

In this article, a parallel‐feedback differential voltage‐controlled oscillator (VCO) with constantly low‐phase noise and frequency tuning range (FTR) of 1.72–2.12 GHz (20.8%) is presented. The presented differential VCO with differential outputs and low‐phase noise is achieved using a four‐pole tunable balanced bandpass filter (BAL‐BPF) with quasi‐elliptic frequency response as a frequency stabilization element. The low‐phase noise is obtained and maintained because of the high in‐band group delay and the constant absolute bandwidth (CABW) of the used tunable BAL‐BPF. For demonstration, an example is designed, fabricated, and measured. The measured oscillation frequency of the differential VCO can be tuned from 1.72–2.12 GHz (20.8%) and the phase noises keep better than −99 dBc/Hz @100 kHz and − 129.1 dBc/Hz @1 MHz over the FTR. In the meantime, the differential oscillating signals are generated at two outputs.
Administration Method of Adjuvant Tegafur-Uracil and Leucovorin Calcium in Patients with Resected Colorectal Cancer: A Phase III Study
Authors: Hata Taishi , Hagihara Kiyotaka , Tsutsui Anna , Akamatsu Hiroki , Ohue Masayuki , Shingai Tatsushi , Tei Mitsuyoshi , Ikenaga Masakazu , Kim Ho Min , Osawa Hideki , Takemoto Hiroyoshi , Konishi Ken , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Murata Kohei , Ohno Yuko , Doki Yuichiro , Eguchi Hidetoshi
Published: February 2021

Lessons Learned

The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy.

Background

Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting.

Methods

Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival.

Results

In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6–84.4–74.5–85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%).

Conclusion

Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.
Analysis of fentanyl pharmacokinetics, and its sedative effects and tolerance in critically ill children
Authors: Lim Sin Yin , Miller Jamie L. , Henry Emilie , Heltsley Rebecca , Woo Sukyung , Johnson Peter N.
Published: February 2021

Introduction

Fentanyl pharmacokinetic and pharmacodynamic data are limited in mechanically ventilated children. This study aimed to assess the fentanyl pharmacokinetics (PK), the sedation outcome, and the development of tolerance in children receiving fentanyl continuous infusion.

Methods

This study included children admitted to the pediatric or cardiovascular intensive care unit between January 1 and October 31, 2016, who were >30 days to <18 years of age, receiving ventilatory support via endotracheal tube or tracheostomy, and receiving a fentanyl infusion. Population PK analysis was performed using a nonlinear mixed‐effects model. The relationship between initial sedation outcome using State Behavioral Scale (SBS) and fentanyl exposure was assessed, and the observations consistent with tolerance were described.

Results

Seventeen children, with a median age of 0.83 years (range: 0.1–12) and weight of 8.7 kg (range: 3.4–52), were included. The fentanyl PK was adequately described by a weight‐based allometry model with the power of 0.75 for clearance (CL=89.8 L/hr/70 kg) and distributional CL, and 1 for volumes of distribution. In infants <6.6 months, age was an additional factor for CL (31.4 L/h/70 kg) to account for age‐related maturation. Seven of twelve nonparalyzed patients achieved goal sedation, defined as >80% of SBS scores ≤0 per 24 h, on the first day of fentanyl infusion with a median plasma concentration of 1.29 ng/ml (interquartile range: 0.78–2.05). Eight of the nine tolerant patients developed tolerance within a day of reaching goal sedation.

Conclusion

Different weight‐based fentanyl dosing rates may be required for infants and children of different ages to achieve similar plasma concentrations. Using SBS scores may guide the dosing titration of fentanyl that resulted in plasma concentrations within the therapeutic range of 1–3 ng/ml. For those who developed tolerance to fentanyl and/or a sedative, it was noted one day after goal sedation was achieved.
Two‐Step Fabrication of Durable, Flexible, and Fluorine‐Free Superhydrophobic SiO2‐Silane@Fabric for Self‐Cleaning Application
Authors: Pal Sukanta , Mondal Sourav , Das Ajit , Mondal Debasish , Maity Jayanta
Published: February 2021

In this present research, a superhydrophobic cotton fabric exhibiting a water contact angle of 155.2° has been prepared via dip‐coating technique involving silica nanoparticle deposition followed by silane hydrophobization. Interestingly, the mirror‐like phenomenon was also observed at the interface between was and modified cotton fabric. The surface morphology and microstructure of the modified fabrics were characterized by scanning electron microscope (SEM) and energy dispersive x‐ray spectroscopy (EDX). Fourier transform infrared spectroscopy (FTIR) was performed for functional group detection on a modified cotton surface. For practical applications, the washing durability was characterized by measuring contact angle values before and after washing cycles. Besides this, the durability of the superhydrophobic cotton fabric was measured under different harsh environmental conditions such as highly acidic, neutral, and highly basic environment. After each measurement, water contact angles and sliding angles were measured for dynamic stabilities. Again the modified coated cotton fabric showed strong resistance to the various organic solvents. Along with the above studies, the physical and mechanical durability of the coated fabric was also measured for both industrial and household importance.
Chromic Properties of Carboxyphenyl Viologen Induced by Complexation in Cucurbit[7]uril
Authors: Luo Dan , Guang Long‐Yu , Lin Rong‐Guang , Zhang Ning‐Ning , Liu Mei‐Chen , Lin Rui‐Lian , Sun Wen‐Qi , Liu Jing‐Xin
Published: February 2021

Upon encapsulation in cucurbit[7]uril, carboxyphenyl viologen exhibited dramatically enhanced photochromism, while its alkaline form exhibited enhanced thermochromism. ESR experiments and reorientation energy calculation indicate that these chromic behaviors are caused by the electron transfer from the host to the guest.
Back to the future: The effect of returning family successions on firm performance
Authors: Amore Mario Daniele , Bennedsen Morten , Le Breton‐Miller Isabelle , Miller Danny
Published: February 2021

Research Summary

We study successions from a non‐family CEO back to a family CEO, which we label “Type‐R" successions. In our sample of 489 Italian family firms experiencing the departure of non‐family CEOs, these successions represent 42% of all cases. Our difference‐in‐differences results indicate that family firms undertaking Type‐R successions experience an 18% superiority in profitability. Exploring the heterogeneity underlying this result, we find that Type‐R successions produce weaker results in contexts that are highly volatile and that rely on innovative inputs before succession. Finally, in studying the drivers of the performance increase, we find that Type‐R successions reduce labor costs and spur efficiency. Collectively, our evidence suggests that Type‐R successions improve performance by leveraging family assets while avoiding dysfunctional nepotism and other parochial family priorities.

Managerial Summary

How does CEO succession affect family business performance? In this article, we study an unexplored yet common succession pattern in mature family firms—the appointment of a family member following the tenure of an outside CEO. Surprisingly, we find that when, after a period of professional leadership, a family CEO returns to lead the company; the firm exhibits an 18% advantage in profitability. This result is more prevalent in stable industries, where traditional family assets prove especially valuable. A key takeaway of our study is that family leadership can enhance performance in companies that have already professionalized their governance, and thus have learned to reconcile meritocratic principles with family‐based assets.
Microenvironment‐Protected Exosome‐Hydrogel for Facilitating Endometrial Regeneration, Fertility Restoration, and Live Birth of Offspring
Authors: Lin Jiaying , Wang Zhen , Huang Jialyu , Tang Shengluan , Saiding Qimanguli , Zhu Qianqian , Cui Wenguo
Published: February 2021

Thin endometrium is a primary cause of failed embryo transfer, resulting in long‐term infertility and negative family outcomes. While hormonal treatments have greatly improved fertility results for some women, these responses remain unsatisfactory due to damage and infection of the complex endometrial microenvironment. In this study, a multifunctional microenvironment‐protected exosome‐hydrogel is designed for facilitating endometrial regeneration and fertility restoration via in situ microinjection and endometrial regeneration. This exosome hydrogel is formulated via Ag+‐S dynamic coordination and fusion with adipose stem cell‐derived exosomes (ADSC‐exo), yielding an injectable preparation that is sufficient to mitigate infection risk while also possessing the antigenic contents and paracrine signaling activity of the ADSC source cells, enabling regeneration of the endometrial microenvironment. In vitro, this exosome‐hydrogel exerts an outstanding neovascularization‐promoting effect, increased human umbilical vein endothelial cell proliferation and tube formation for 1.87 and 2.2 folds. In vivo, microenvironment‐protected exosome‐hydrogel also reveals to promote neovascularization and tissue regeneration while suppressing local tissue fibrosis. Importantly, regenerated endometrial tissue is more receptive to give embryos and birth to a healthy newborn. This microenvironment‐protected exosome‐hydrogel system offers a convenient, safe, and noninvasive approach for repairing thin endometrium and fertility restoration.
Cerebral amyloid angiopathy distribution in older people: A cautionary note
Authors: Alakbarzade Vafa , French Jonathan MR , Howlett David R , Attems Johannes , Francis Paul T , Stratton Sarah , Clark Camilla N , Pereira Anthony C , Hainsworth Atticus H
Published: February 2021

Introduction

Radiolabeled ligands for fibrillar amyloid beta (Aβ) peptides are used in positron emission tomography (PET) for dementia diagnosis. Current ligands do not discriminate parenchymal amyloid plaques from cerebral amyloid angiopathy (CAA).

Methods

We undertook neuropathological examination of 65 older people (81.6 ± 7.96 (mean ± SD) years, 27F/38M): 15 with neuropathological diagnosis of AD, 25 with neuropathological diagnosis of other neurodegenerative dementias (Lewy body dementia and Parkinson disease dementia), and 25 without significant neurodegenerative pathology.

Results

We observed CAA in non‐Alzheimer's dementia (non‐AD dementia) and control brains, of comparable extent to those with neuropathologically confirmed AD. Aβ‐positive vessel density did not differ significantly between non‐AD dementia and control groups. Across all subjects there was a highly significant correlation between vessel Aβ40 density and vessel Aβ42 density (Spearman rho = 0.855, P < .001). CAA was absent or sparse in subcortical white matter across all patient groups.

Conclusion

Our data indicate that CAA can be abundant in non‐AD brains and raise a cautionary note regarding interpretation of amyloid PET imaging.
Efficacy of grape seed hydro‐alcoholic extract in the treatment of experimentally Pasteurella multocida infected rabbits
Authors: El‐Sheikh Sawsan M. A. , Youssef Fatma M. , Mohamed Haidi I. , El‐Saber Batiha Gaber , Albrakati Ashraf , Galal Azza A. A.
Published: February 2021

Pasteurellosis is one of the rabbit's most bacterial severe diseases and leads to considerable financial damages in large production systems worldwide. Antibiotic use in animals may lead to antibiotic residues in animal products, including meat. Therefore, this study was designed to evaluate the potential role of grape seed extract (GSE) in treating Pasteurella multocida infection in rabbits. For this purpose, 45 weaned male New Zealand rabbits were divided into three groups; control, infected and infected‐GSE treated. Experimental P. multocida infection in rabbits induced a remarkable decrease in body weight, body weight gain, as well as microcytic hypochromic anaemia, leucocytosis, neutrophilia and lymphocytopenia. Also, a significant increase in the hepatic and renal injury biomarkers, in interleukin‐6, total globulin, α, β and γ globulins, as well as a marked reduction in total protein and albumin, were recorded in the P. multocida‐infected rabbits. Treatment of infected rabbits with GSE modulated most of these altered parameters. This study endorses the administration of GSE for the treatment of Pasteurellosis in rabbits. Further studies are required to identify the possible additional effects, appropriate doses and duration of the GSE therapy in rabbits Pasteurellosis.
Bladder wall necrosis and septic peritonitis in two Icelandic mares after parturition and mating
Authors: Weltrich Nina , Barsnick Rosa
Published: February 2021

This report describes bladder wall necrosis and secondary septic peritonitis in two adult Icelandic mares due to traumatic etiology. Mare 1 was mated naturally a few days prior to presentation, and Mare 2 had foaled one week before admission. Both horses presented with signs of peritonitis due to necrosis of their bladder wall detected on cystoscopy. Treatment included antibiotics, anti‐inflammatories and abdominal lavage. Both cases had a poor outcome. Mare 1 was euthanised due to a small intestinal obstruction caused by abdominal adhesions. Mare 2 initially improved clinically but was euthanised due to subsequent bladder rupture very unexpectedly at five weeks after parturition. Based on this experience, the authors recommend a modified therapy for future cases, and want to point out these very rare cases of bladder wall necrosis to equine practitioners.
Cross-Domain Security Asset Management for Healthcare
Authors: Stirano Federico , Lubrano Francesco , Vitali Giacomo , Bertone Fabrizio , Varavallo Giuseppe , Petrucci Paolo
Published: February 2021

Healthcare is one of the most peculiar between all Critical Infrastructures due to its context and role in the society. The characteristics of openness and pervasive usage of IT systems and connected devices make it particularly exposed to both physical threats, such as theft and unauthorized access to restricted areas, and cyber attacks, like the notorious wannacry ransomware that abruptly disrupted the British National Health System in May 2017. Even the recent COVID-19 pandemic period has been negatively characterized by an increase of both physical and cyber incidents that specifically targeted hospitals and undermined an essential public service like healthcare. Effective security solutions are necessary in order to protect and enhance the resiliency of the Critical Infrastructures. This paper presents the work being developed in the context of the SAFECARE H2020 project, that specifically considers the requirements for security of hospitals. A particular focus is given to the asset management that consider cross-domain aspects of security, like the physical location and virtual connections that link different components of a hospital. This allows advanced knowledge that enables to infer and forewarn of possible elaborated cyber-physical kill chains. This is particularly important and useful during crisis, as allows to have a holistic overview of the status of the hospital and the potential impacts of one or more incidents to the critical assets. The description and simulation of an attack scenario is also given, together with the description of the messages exchanged by the security systems and the information made available to security operators.
Towards a Global CIs’ Cyber-Physical Security Management and Joint Coordination Approach
Authors: Mantzana Vasiliki , Georgiou Eftichia , Gazi Anna , Gkotsis Ilias , Chasiotis Ioannis , Eftychidis Georgios
Published: February 2021

Critical Infrastructures (CIs) face numerous cyber-physical threats that can affect citizens’ lives and habits, increase their feeling of insecurity, and influence the seamless services provision. During such incidents, but also in general for the security of CIs several internal and external stakeholders are involved, having different needs and requirements, trying to cooperate, respond and recover. Although CIs security management process is well analyzed in the literature there is a need to set a common ground among different CIs, thus reducing administration/coordination overhead and rendering the decision making and crisis management process more efficient. In this direction, this paper considers three different CIs (airport facilities, gas infrastructures, and hospitals); presents the current and emerging physical and cyber security related regulations and standards, operations, organisational and technical measure and; finally, through the discussion on gaps and best practices identified, proposes a global, cyber-physical security management and joint coordination approach. The proposed approach recommends among others that the adoption of a Holistic Security Operation Centre (HSOC) in each CI and a National Coordination Centre (NCC), supervising them, which will facilitate the communication and cooperation between the different CI operators and stakeholders, in case of an incident, that may have cascading effects to interconnected Infrastructures. The findings presented and the conclusions drawn are linked with three EU funded research projects (SATIE, SecureGas and SAFECARE), that aim to improve physical and cyber security of CIs in a seamless and cost-effective way.
Inferring Anomaly Situation from Multiple Data Sources in Cyber Physical Systems
Authors: Baldoni Sara , Celozzi Giuseppe , Neri Alessandro , Carli Marco , Battisti Federica
Published: February 2021

Cyber physical systems are becoming ubiquitous devices in many fields thus creating the need for effective security measures. We propose to exploit their intrinsic dependency on the environment in which they are deployed to detect and mitigate anomalies. To do so, sensor measurements, network metrics, and contextual information are fused in a unified security architecture. In this paper, the model of the proposed framework is presented and a first proof of concept involving a telecommunication infrastructure case study is provided.
Limits of JT gravity
Authors: Grumiller Daniel , Hartong Jelle , Prohazka Stefan , Salzer Jakob
Published: February 2021

Abstract

We construct various limits of JT gravity, including Newton-Cartan and Carrollian versions of dilaton gravity in two dimensions as well as a theory on the three-dimensional light cone. In the BF formulation our boundary conditions relate boundary connection with boundary scalar, yielding as boundary action the particle action on a group manifold or some Hamiltonian reduction thereof. After recovering in our formulation the Schwarzian for JT, we show that AdS-Carroll gravity yields a twisted warped boundary action. We comment on numerous applications and generalizations.
Aktuelle Therapie der chronischen Hepatitis C bei Kindern und Jugendlichen
Authors: Wirth S. , Schreiber-Dietrich Dagmar , Dietrich Christoph F.
Published: February 2021

Zur Behandlung der chronischen Hepatitis C wurden in den letzten Jahren direkt wirkende antivirale Medikamente (DAA) zugelassen und sind bei Erwachsenen etabliert. Sie machten die interferonbasierten Therapien obsolet. Auch für Kinder und Jugendliche stehen seit Kurzem einige DAA zur Verfügung, die überwiegend ab dem Alter von 3 Jahren eingesetzt werden können.

Die chronische Hepatitis C wird bei Kindern überwiegend vertikal übertragen und ist selten. Sie ist zwar zunächst eine wenig aktive und progrediente Erkrankung, kann aber im Erwachsenenalter in eine Leberzirrhose mit der Folge eines hepatozellulären Karzinoms übergehen. Die Diagnose ist mit der Bestimmung des Anti-HCV (IgM/IgG) und der HCV-RNA im Serum mit Genotypisierung leicht zu stellen. Die DAA werden oral appliziert und ausgesprochen gut toleriert. Drei Wirkstoffkombinationen stehen aktuell zur Verfügung, und 2021 wird eine weitere zugelassen. Die Heilungschancen sind mit über 95 % ausgesprochen gut und anhaltend.

Im eigenen Krankengut wurden 25 Jungen und Mädchen überwiegend mit Genotyp 1 im Alter von 4 bis 17 Jahren mit DAA behandelt. Unabhängig von der Höhe der HCV-RNA im Serum waren alle bereits nach 4 Wochen HCV-RNA negativ und erzielten einen dauerhaften Erfolg.

Die wesentliche Aufgabe ist nun, alle Kinder und Jugendlichen mit einer chronischen Hepatitis C zu identifizieren. Bei der äußerst guten Heilungschance kann davon ausgegangen werden, dass das Eradikationsziel in dieser Altersgruppe in absehbarer Zeit erreicht werden kann.
SUDEP kompakt – praxisrelevante Erkenntnisse und Empfehlungen zum plötzlichen, unerwarteten Tod bei Epilepsie
Authors: Surges Rainer , Conrad Stefan , Hamer Hajo M. , Schulze-Bonhage Andreas , Staack Anke M. , Steinhoff Bernhard J. , Strzelczyk Adam , Trinka Eugen
Published: February 2021

„Sudden unexpected death in epilepsy“ (SUDEP) ist der plötzliche, unerwartete Tod eines Epilepsiepatienten, der unter „gutartigen“ Umständen und ohne typische Todesursachen auftritt. SUDEP betrifft alle Epilepsiepatienten. Das individuelle Risiko hängt vor allem von Merkmalen der Epilepsie und Anfälle sowie von Lebensumständen ab. Fokale zu bilateral bzw. generalisierte tonisch-klonische Anfälle (TKA), nächtliche Anfälle und fehlende nächtliche Überwachung erhöhen das Risiko. In den meisten SUDEP-Fällen kommt es nach TKA zu einer fatalen Kaskade mit Apnoe, Hypoxämie und Asystolie. Wahrscheinlich könnten zwei Drittel der SUDEP-Fälle bei nicht überwachten Epilepsiepatienten mit TKA verhindert werden. Mobile Geräte („wearables“) können nächtliche TKA erkennen und Hilfspersonen benachrichtigen. Eine SUDEP-Aufklärung wird von den meisten Patienten und Angehörigen gewünscht, beeinflusst Therapieadhärenz und Verhalten günstig und hat keine negativen Auswirkungen auf Stimmung oder Lebensqualität.

Empfehlungen der Kommission „Patientensicherheit“ der Deutschen Gesellschaft für Epileptologie: Therapieziel ist Anfallsfreiheit. Wenn dies nicht möglich ist, soll versucht werden, zumindest TKA zu kontrollieren. Alle Epilepsiepatienten und ihre Angehörigen sollen über SUDEP und Risikofaktoren aufgeklärt werden. Patienten und Angehörige sollen über Maßnahmen informiert werden, die einem erhöhten Risiko bzw. einem drohenden SUDEP entgegenwirken. Die Aufklärung soll in einem persönlichen Gespräch erfolgen, bei Diagnosestellung oder später. Die Aufklärung sollte dokumentiert werden. Wearables zur Detektion von TKA können empfohlen werden. Bei persistierenden TKA sollen Therapieversuche zur Anfallskontrolle fortgeführt werden. Nach SUDEP sollten Hinterbliebene kontaktiert werden.
Search for a moving target in a competitive environment
Authors: Duvocelle Benoit , Flesch János , Shi Hui Min , Vermeulen Dries
Published: February 2021

We consider a discrete-time dynamic search game in which a number of players compete to find an invisible object that is moving according to a time-varying Markov chain. We examine the subgame perfect equilibria of these games. The main result of the paper is that the set of subgame perfect equilibria is exactly the set of greedy strategy profiles, i.e. those strategy profiles in which the players always choose an action that maximizes their probability of immediately finding the object. We discuss various variations and extensions of the model.