bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and impact of peripheral parenteral nutrition on nutrient delivery in patients with nutrition risk: A prospective observational study
Authors: Rubino Maria , Jin Jennifer , Gramlich Leah
Published: September 2021

Background

Malnutrition is common in hospitalized patients and strategies to improve energy and protein intake have a positive impact on outcome. Despite early evidence suggesting the usefulness of peripheral parenteral nutrition (PPN), its adoption has been hampered by concerns regarding safety and efficacy. This study addresses this issue.

Methods

This prospective observational study was performed in medical and surgical inpatients in who were screened for nutrition risk and assessed using Subjective Global Assessment (SGA). Data captured included nutrition status, energy and protein requirements, intravenous access, indications for PPN, use of supplemental micronutrients, and disposition of patients on PPN.

Results

Ninety‐eight patients were recruited from two centers over 8 months. The average age was 61.5 years, the mean Charlson Comorbidity Index was 4.21 (±3.09), 52% were male, and 48% were admitted to medicine, whereas 52% were admitted to surgery. Thirty‐three percent of patients were SGA C, 44% were SGA B, and 19% were SGA A. Twenty‐seven percent of patients had cancer. The average length of hospital stay was 22 days. The main indications for PPN were gastrointestinal tract dysfunction (72%) and postsurgical status (16%). PPN provided an average of 1296 kcal (±191) and 46 g of protein (±7). Intravenous access complications in patients receiving PPN did not occur in excess of expected. Almost 40% of patients required transition to central PN.

Conclusions

PPN is a safe, effective way to deliver supplemental protein, energy, and micronutrients to malnourished patients and supports transition to other modes of nutrition care.
CD19 expression in pediatric patients with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia pre‐ and post‐treatment with blinatumomab
Authors: Mejstrikova Ester , Klinger Matthias , Markovic Ana , Zugmaier Gerhard , Locatelli Franco
Published: September 2021

Blinatumomab is a BiTE® (bispecific T‐cell engager) immuno‐oncology therapy, which has demonstrated significant activity in patients with relapsed or refractory B‐cell precursor acute lymphoblastic leukemia (R/R B‐ALL); however, a subset of patients relapse. Monitoring expression of cluster of differentiation (CD)19 in relapsed patients is critical to inform sequencing of subsequent therapies. The expression of CD19 in 59 pediatric patients with R/R B‐ALL was analyzed on the day of diagnosis of R/R B‐ALL and on days 15 and 29 of cycle 1 of blinatumomab. Most patients treated with one cycle of blinatumomab retained expression of CD19, and would therefore be eligible for subsequent anti‐CD19 CAR T‐cell therapy.
Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators
Authors: Geel Jennifer Ann , Challinor Julia , Ranasinghe Neil , Myezo Khumo Hope , Eyal Katherine Claire , Aderounmu Wuraole , Davidson Alan , Pritchard‐Jones Kathy , Howard Scott C. , Bouffet Eric , Hessissen Laila
Published: September 2021

Introduction

Inalignment with the World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC), the International Society of Pediatric Oncology initiated a program to map global pediatric oncology services. As survival rates in Africa are low and data are scant, this continent was mapped first to identify areas with greatest need.

Methods

Beginning November 2018, an electronic survey was sent to all known stakeholders, followed by email communications and internet searches to verify data. Availability of pediatric oncologists, chemotherapy, surgical expertise, and radiotherapy was correlated with geographic region, World Bank income status, Universal Health Coverage, population < 15 and < 24 years, percentage of gross domestic product spent on healthcare, and Human Development Index (HDI).

Results

Responses were received from 48/54 African countries. All three treatment modalities were reportedly available in 9/48 countries, whereas seven countries reported no pediatric oncology services. Negative correlations were detected between provision of all three services and geographic region (P = 0.01), younger median population age (P = 0.002), low‐income country status (P = 0.045), and lower HDI (P < 0.001).

Conclusion

This study provides a comprehensive overview of pediatric oncology care in Africa, emphasizing marked disparities between countries: some have highly specialized services, whereas others have no services. A long‐term strategy to eliminate disparities in African pediatric cancer care should be aligned with the WHO GICC aims and facilitated by SIOP Africa.

Meeting abstracts

SIOP maps pediatric oncology services in Africa to address inequalities in childhood cancer services. Geel J, Ranasinghe N, Davidson A, Challinor J, Howard S, Wollaert S, Myezo K, Renner L, Hessissen L, Bouffet E. 51st Annual Congress of the International Society of Paediatric Oncology (SIOP), Lyon, France, October 2019. Pediatric Blood and Cancer Vol 66 S219‐S219. Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators.
All‐cis poly(p‐phenylene vinylene)s with high molar masses and fast photoisomerization rates obtained through stereoretentive ring‐opening metathesis polymerization of [2,2]paracyclophane dienes with various aryl substituents
Authors: Hsu Ting‐Wei , Kempel Samuel J. , Michaudel Quentin
Published: September 2021

Poly(p‐phenylene vinylene)s (PPVs) are some of the most widely studied conjugated polymers in academia and industry, but most production methods lack precise control over molar masses and alkene stereochemistry. These critical parameters have a large influence on processability, polymer morphology, and optical properties. Herein, we report the stereoretentive ring‐opening metathesis polymerization (ROMP) of [2.2]paracyclophane dienes bearing either a linear alkyl substituent or a branched alkoxy substituent to form all‐cis PPVs with great solubility in organic solvents. The introduction of 2‐ethylhexyloxy side‐chains permits the preparation of PPV with uncharacteristically high molar masses (up to 108.8 kg/mol) for a polymerization with living characteristics. Exposure to UV light (365 nm) rapidly induces isomerization of all‐cis alkenes leading to the formation of all‐trans PPV. This study proposes an attractive strategy to synthesize soluble all‐cis and all‐trans PPVs with tunable, high molar masses through careful design of the ROMP monomer.
Cancer worry after facial nonmelanoma skin cancer resection and reconstruction: A 1‐year prospective study
Authors: van Hensbergen Lucy J. , Veldhuizen Inge J. , Lee Erica H. , Houterman Saskia , Brinkhuizen Tjinta , van der Hulst René R. W. J. , Hoogbergen Maarten M.
Published: September 2021

Objective

Nonmelanoma skin cancer (NMSC) is one of the most diagnosed cancers in the world, with the number of new occurrences rising every year. Most patients with facial skin cancer experience cancer‐related worry. Yet, little is known about their worry during the period after cancer treatment. This study aimed to assess the long‐term change of cancer worry after surgical treatment in patients with NMSC.

Methods

Patients undergoing surgery for facial NMSC between December 2017 and March 2020 were asked to complete the FACE‐Q Skin Cancer—Cancer Worry scale before (baseline), 3‐month, and 1‐year post‐surgery.

Results

A total of 151 patients completed the baseline and 3‐month, and 99 (65.6%) the 1‐year post‐operative survey. A significant decrease in cancer worry score was seen between baseline and 3‐month post‐surgery (p < 0.001). No difference was found between the 3‐month and 1‐year post‐surgery scores (p = 0.78). Less improvement in cancer worry was seen for patients who had one facial skin cancer in their medical history (p = 0.001) and patients who had a history of facial surgery (p < 0.001).

Conclusion

Post‐surgery patients still experience cancer worry. Therefore, targeted counseling might be of value when coping with cancer‐related concerns. Patients with a history of facial NMSC and patients with a history of facial surgery might benefit from additional counseling.
Adaptive event‐triggered control for MIMO nonlinear systems with asymmetric state constraints based on unified barrier functions
Authors: Wang Sanxia , Xia Jianwei , Park Ju H. , Shen Hao , Chen Guoliang
Published: September 2021

The topic of adaptive event‐triggered control for multi‐input‐multi‐output nonlinear systems with asymmetric state constraints is considered in this article. First, by introducing unified barrier functions method, the initial system is transformed to a non‐constraints system, which brings that the requirement of feasibility conditions could be eliminated and the constraint functions could be relaxed effectively. Then, an adaptive tracking controller is designed by combining some excellent technology, where command filter is utilized to overcome the explosion of complexity, neural network is introduced to approximate unknown nonlinear function, and event‐triggered mechanism is proposed to save communication resources. The designed control scheme can make the outputs of the system to track the target trajectories within a small bounded error range, all signals in the closed‐loop system are bounded, and all states do not escape the state constraints. Finally, practical and comparative examples are given to verify the effectiveness of the method.
Changes in the use of psychotropic drugs during the course of Alzheimer's disease: A large‐scale longitudinal study of French medical records
Authors: Ansart Manon , Epelbaum Stéphane , Houot Marion , Nedelec Thomas , Lekens Béranger , Gantzer Laurène , Dormont Didier , Durrleman Stanley
Published: September 2021

Introduction

We aim to understand how patients with Alzheimer's disease (AD) are treated by identifying in a longitudinal fashion the late‐life changes in patients’ medical history that precede and follow AD diagnosis.

Methods

We use prescription history of 34,782 patients followed between 1996 and 2019 by French general practitioners. We compare patients with an AD diagnosis, patients with mild cognitive impairment (MCI), and patients free of mental disorders. We use a generalized mixed‐effects model to study the longitudinal changes in the prescription of eight drug types for a period 15 years before diagnosis and 10 years after.

Results

In the decades preceding diagnosis, we find that future AD patients are treated significantly more than MCI patients with most psychotropic drugs and that most studied drugs are increasingly prescribed with age. At the time of diagnosis, all psychotropic drugs except benzodiazepines show a significant increase in prescription, while other drugs are significantly less prescribed. In the 10 years after diagnosis, nearly all categories of drugs are less and less prescribed including antidementia drugs.

Discussion

Pre‐diagnosis differences between future AD patients and MCI patients may indicate that subtle cognitive changes are recognized and treated as psychiatric symptoms. The disclosure of AD diagnosis drastically changes patients’ care, priority being given to the management of psychiatric symptoms. The decrease of all prescriptions in the late stages may reflect treatment discontinuation and simplification of therapeutic procedures. This study therefore provides new insights into the medical practices for management of AD.
Antibacterial activity of γFe2O3/TiO2 nanoparticles on toxic cyanobacteria from a lake in Southern Illinois
Authors: Madany Peerzada , Xia Chunjie , Bhattacharjee Linkon , Khan Nafeesa , Li Ruopu , Liu Jia
Published: September 2021

Frequent outbreaks of harmful algal blooms (HABs) have brought adverse impacts on human health, economic viability, and recreational activities in many communities in the United States. Cyanobacteria (or blue‐green algae) blooms are the most common type of HABs in surface water. Current bactericides for controlling the blooms are disadvantageous due to the recycling difficulty. In this study, an innovative magnetic nanomaterial―γFe2O3/TiO2 nanoparticle—was used to inactivate toxic cyanobacteria species found in a lake in Southern Illinois that frequently experienced HABs. Cyanotoxin genes of mcy, nda, cyr, and sxt were used for targeting microcystin‐, nodularin‐, cylindrospermopsin‐, and saxitoxin‐producing cyanobacteria, respectively, by quantitative polymerase chain reaction (PCR) method. It was found that the concentration of chlorophyll a presents a strong correlation (R2 = 0.6024) with the gene copy obtained from 16S rRNA targeted for all cyanobacteria, but not with that from individual toxigenic cyanobacteria. The inactivation efficiencies of the nanomaterials under visible light were as high as 5‐log and 1‐log for cyanobacteria species containing mcyE/ndaF and sxtA genes, respectively, an improvement over the treatment under darkness. These nanomaterials can be recycled by their magnetic properties for reuse. Communities susceptible to HAB outbreaks are expected to benefit from the developed method for mitigating the blooms.

Practitioner points

Lab‐made γFe2O3/TiO2 nanoparticles can be used to inactivate microcystin/nodularin‐ and saxitoxin‐producing cyanobacteria species.

qPCR method can be used for targeting toxic cyanobacteria; Chl a cannot be used as a standalone indicator for HABs.

Better inactivation efficiency under visible light indicated possible application of the technology under sunlight for HAB mitigation from surface water.
Crystal structure re‐determination, spectroscopy, and photoluminescence of π‐YBO3:Eu3+
Authors: Fuchs Birgit , Schröder Franziska , Heymann Gunter , Siegel Renée , Senker Jürgen , Jüstel Thomas , Huppertz Hubert
Published: September 2021

To unambiguously clarify the long‐debated crystal structure of the low‐temperature orthoborate π‐YBO3, single‐crystals of the europium‐doped π‐YBO3:Eu3+ were prepared via a high‐pressure/high‐temperature route at 7.5 GPa and 1400 °C. The structure was solved and refined in the monoclinic space group C2/c (no. 15) in the pseudowollastonite structure type, with the lattice parameters a=11.3407(5), b=6.5501(3), c=9.5798(4) Å, and β=113.08(2)°. This structure determination was corroborated by powder X‐ray diffraction and vibrational spectroscopy. 11B as well as 89Y MAS NMR spectroscopy was used to verify that our results are also accurate for the undoped π‐YBO3 and samples with varying europium content prepared under ambient pressure conditions. Additionally, the luminescence properties of the Eu3+ doped π‐orthoborate were determined in comparison with these ambient‐pressure samples.
The cubic fixed point at large N
Authors: Binder Damon J.
Published: September 2021

Abstract

By considering the renormalization group flow between N coupled Ising models in the UV and the cubic fixed point in the IR, we study the large N behavior of the cubic fixed points in three dimensions. We derive a diagrammatic expansion for the 1/N corrections to correlation functions. Leading large N corrections to conformal dimensions at the cubic fixed point are then evaluated using numeric conformal bootstrap data for the 3d Ising model.
Sunrise integrals with two internal masses and pseudo-threshold kinematics in terms of elliptic polylogarithms
Authors: Campert Lijsbeth G. J. , Moriello Francesco , Kotikov Anatoly
Published: September 2021

Abstract

We consider a set of two-loop sunrise master integrals with two different internal masses at pseudo-threshold kinematics and we solve it in terms of elliptic polylogarithms to all orders of the dimensional regulator.
Understanding the surface integrity of laser surface engineered tungsten carbide
Authors: Hazzan Kafayat Eniola , Pacella Manuela , See Tian Long
Published: September 2021

The study investigated the effect of fibre laser processing (1060 nm, 240-ns pulse duration) on the surface integrity of tungsten carbide (WC). The induced surface damage ranged from crack formation, porosity, balling, to spherical pores; the severity and presence of each were dependent on the laser parameters selected. The influence of fluence (0.05–0.20 J/cm2), frequency (5–100 kHz), feed speed (250–2500 mm/s) and hatch distance (0.02–0.06 mm) on 2D and 3D surface roughness were analysed using the Taguchi technique. Fluence, frequency, and the interaction effect of these were the most influential factors on the surface integrity; from this a linear model was generated to predict the surface roughness. The model performed best at moderate to medium level of processing with an error between 1 and 10 %. The model failed to predict the material response as accurately at higher fluences with percentage errors between 15 and 36 %. In this study, a crack classification system and crack density variable were introduced to estimate the number of cracks and crack type within a 1-mm2 area size. Statistical analysis of variance (ANOVA) found that fluence (63.49%) and frequency (29.38%) had a significant effect on the crack density independently but not the interaction of both. The crack density was minimised at 0.149 J/cm2 and 52.5 kHz. To the author’s knowledge, for the first time, a quantitative analysis of the crack formation mechanism for brittle materials is proposed (post laser processing).
The impact of constant antibiotic prophylaxis in children affected by spinal dysraphism performing clean intermittent catheterization: a 2-year monocentric retrospective analysis
Authors: Mariani Francesco , Ausili Emanuele , Zona Margherita , Grotti Giacomo , Curatola Antonietta , Gatto Antonio , Rendeli Claudia
Published: September 2021

Introduction

Spinal dysraphism (SD) is a general term used to refer to developmental abnormalities of the spine that involves many clinical conditions including myelomeningocele (MMC). In these patients, neurogenic bladder (NB) is a common and predisposing factor for renal damage; the most frequently used approach to manage this situation is based on clean intermittent catheterization (CIC) and anticholinergic drugs. Urinary tract infections (UTIs) are a significant concern for these patients, and antibiotic prophylaxis is frequently used even if it is still a debated topic of literature. The purpose of this paper is to investigate the role and the real effectiveness of antibiotic prophylaxis in the reduction of incidence of UTIs in patients with spina bifida performing CIC.

Methods

We collected data of all patients performing CIC, who did their last follow-up visit in the period between January 2019 and January 2021, followed at the children multidisciplinary Spina Bifida Center of A. Gemelli Hospital in Rome. Data collected included age at referral, gender, type of SD lesion, serum creatinine and cystatin C levels, the use of anticholinergic medications, antibiotic prophylaxis and type of prophylaxis (oral/endovesical), age of starting prophylaxis with its duration/adherence, number of CIC/day and its duration, episodes of UTIs in the 2 years prior to the last follow-up, and presence and grade of vesical-ureteric reflux (VUR) on cystourethrogram.

Results

A total of 121 patients with SD performing CIC was included in the study; 66 (54%) presented ≥ 1 episode of UTIs in the last two years and 55 (46%) none. During the study period, 85 (70%) patients received antibiotic prophylaxis (ABP group) and 36 (30%) did not (NABP group): no statistically significative difference in terms of UTI development was observed between the two groups (p = 0.17). We also evaluated compliance to the therapy; 71 patients (59%) took antibiotic prophylaxis constantly (CABP group) and 50 (41%) did not do antibiotic prophylaxis constantly or did not do antibiotic prophylaxis at all (NCABP group): we observed a statistically significative difference in terms of UTIs with a 2.2 times higher risk of development at least one episode of UTIs in NCABP group.

Conclusion

In conclusion, antibiotic prophylaxis performed constantly, without interruption, is associated with a lower risk of developing urinary tract infections and consequently to develop renal failure in adulthood.
Analysis of the interannual variability in satellite gravity solutions: detection of climate modes fingerprints in water mass displacements across continents and oceans
Authors: Pfeffer Julia , Cazenave Anny , Barnoud Anne
Published: September 2021

This study analyzes the interannual variability of the water mass transport measured by satellite gravity missions in regard to eight major climate modes known to influence the Earth’s climate from regional to global scales. Using sparsity promoting techniques (i.e., LASSO), we automatically select the most relevant predictors of the climate variability among the eight candidates considered. The El Niño–Southern Oscillation, Southern Annular Mode and Arctic Oscillation are shown to account for a large part the interannual variability of the water mass transport observed in extratropical ocean basins (up to 40%) and shallow seas (up to 70%). A combination of three Pacific and one Atlantic modes is needed to account for most (up to 60%) of the interannual variability of the terrestrial water storage observed in the North Amazon, Parana and Zambezi basins. With our technique, the impact of climate modes on water mass changes can be tracked across distinct water reservoirs (oceans, continents and ice-covered regions) and we show that a combination of climate modes is necessary to explain at best the natural variability in water mass transport. The climate modes predictions based on LASSO inversions can be used to reduce the inter-annual variability in satellite gravity measurements and detect processes unrelated with the natural variability of climate but with similar spatio-temporal signatures. However, significant residuals in the satellite gravity measurements remain unexplained at inter-annual time scales and more complex models solving the water mass balance should be employed to better predict the variability of water mass distributions.
Sleep disturbances in craniopharyngioma: a challenging diagnosis
Authors: Cordani Ramona , Veneruso Marco , Napoli Flavia , Milanaccio Claudia , Verrico Antonio , Consales Alessandro , Cataldi Matteo , Fava Daniela , Di Iorgi Natascia , Maghnie Mohamad , Mancardi Maria Margherita , Nobili Lino
Published: September 2021

Craniopharyngiomas are rare solid or mixed solid and cystic tumors that arise from Rathke’s pouch remnants along the pituitary-hypothalamic axis, from the sella turcica to the brain third ventricle. Both the tumor and its treatment can lead to significant neurological and endocrinological complications. Due to the essential role of the hypothalamus in the complex neurophysiologic process of sleep, tumors involving the hypothalamic area may be responsible for disturbances in sleep–wake regulation with alterations in the circadian rhythm, sleep fragmentation, and increased daytime sleepiness. We report two cases of patients with craniopharyngioma, who came to our attention due to the occurrence of episodes characterized by psychomotor slowing and afinalistic limb movements, temporal and spatial disorientation, psychomotor agitation, and oneiric stupor like episodes. A comprehensive clinical data collection and a targeted diagnostic work-up led to a diagnosis of severe sleep disorder characterized by hypersomnia, altered sleep–wake rhythm, and sleep-related breathing disorder. In addition, the polysomnography revealed peculiar alterations in the sleep structure. The diagnostic work-up lead to an accurate differential diagnosis between epileptic seizures and episodes expressions of sleep disturbances. These clinical features can be challenging to diagnose and can lead to misdiagnosis and inappropriate treatment. Diagnosis of sleep disorders is crucial, considering the impact of sleep on general health, cognition, and neuropsychological functioning. These findings support the need to incorporate a comprehensive sleep evaluation in childhood brain tumor involving the suprasellar/hypothalamic region.
Prevalence and clinical features of autosomal dominant and recessive TMC1-associated hearing loss
Authors: Nishio Shin-ya , Usami Shin-ichi
Published: September 2021

TMC1 is a causative gene for both autosomal dominant non-syndromic hearing loss (DFNA36) and autosomal recessive non-syndromic hearing loss (DFNB7/11). To date, 125 pathogenic variants in TMC1 have been reported. Most of the TMC1 variants are responsible for autosomal recessive hearing loss, with only 8 variants reported as causative for DFNA36. Here, we reported the prevalence of TMC1-associated hearing loss in a large non-syndromic hearing loss cohort of about 12,000 subjects. As a result, we identified 26 probands with TMC1-associated hearing loss, with the estimated prevalence of TMC1-associated hearing loss in the Japanese hearing loss cohort being 0.17% among all patients. Among the 26 probands with TMC1-associated hearing loss, 15 cases were identified from autosomal dominant hearing loss families. Based on the audiometric data from the probands, family members and previously reported cases, we evaluated hearing deterioration for DFNA36 patients. In addition, we performed haplotype analysis for 11 unrelated autosomal dominant hearing loss families carrying the same variant TMC1: NM_138691:c.1627G > A:p.Asp543Asn. The results clearly indicated that the same haplotype was present despite the families being unrelated, supporting the contention that this variant occurred by founder mutation.
Differential genetic diagnoses of adult post-lingual hearing loss according to the audiogram pattern and novel candidate gene evaluation
Authors: Rim John Hoon , Noh Byunghwa , Koh Young Ik , Joo Sun Young , Oh Kyung Seok , Kim Kyumin , Kim Jung Ah , Kim Da Hye , Kim Hye-Youn , Yoo Jee Eun , Lee Seung-Tae , Bok Jin Woong , Lee Min Goo , Jung Jinsei , Choi Jae Young , Gee Heon Yung
Published: September 2021

Ski-slope hearing loss (HL), which refers to increased auditory threshold at high frequencies, is common in adults. However, genetic contributions to this post-lingual HL remain largely unknown. Here, we prospectively investigated deafness-associated and novel candidate genes causing ski-slope HL. We analyzed 192 families with post-lingual HL via gene panel and/or exome sequencing. With an overall molecular diagnostic rate of 35.4% (68/192) in post-lingual HL, ski-slope HL showed a lower diagnostic rate (30.7%) compared with other conditions (40.7%). In patients who showed HL onset before the age of 40, genetic diagnostic probability was significantly lower for ski-slope HL than for other conditions. Further analysis of 51 genetically undiagnosed patients in the ski-slope HL group identified three variants in delta-like ligand 1 (DLL1), a Notch ligand, which presented in vitro gain-of-function effects on Notch downstream signaling. In conclusion, genetic diagnostic rates in post-lingual HL varied according to audiogram patterns with age-of-onset as a confounding factor. DLL1 was identified as a candidate gene causing ski-slope HL.
Magma chamber stratification of the 1815 Tambora caldera-forming eruption
Authors: Suhendro Indranova , Toramaru Atsushi , Miyamoto Tomoharu , Miyabuchi Yasuo , Yamamoto Takahiro
Published: September 2021

The eruption of the Tambora volcano in 1815 was initiated by two precursory Plinian falls and formed two generations of pyroclastic density current (PDC) deposits. In this study, we found slight changes in phenocrysts (modal mineralogy, content, and size), bulk-rock and feldspar microlite chemical compositions, and bubble and microlite number densities through the stratigraphic position. Plinian fall units are characterized by a lower phenocryst abundance (avg. of 5.1%), smaller phenocryst size (avg. of 0.06 mm2), and higher silica content (bulk-rock, 58–58.5 wt.%). The PDC deposits are characterized by a relatively higher crystal abundance (avg. of 12.1%), larger phenocryst sizes (avg. of 0.13 mm2), and lower silica content (bulk-rock, 56.7–57.9 wt.%). Therefore, the deposit stratigraphy and analyses suggest that phenocryst stratification in the magma chamber was established prior to the 1815 eruption and was thus responsible for yielding a slight contrast in bulk compositions. Feldspar microlite moves toward slightly more albitic compositions from Plinian falls to the PDCs, suggesting a slight decrease in the initial melt temperature from the upper to the lower magma chamber portion. Because the Plinian eruptions extracted the hottest magma, the degree of supercooling became low, and consequently yielded microlite-poor juveniles. By contrast, the PDCs experienced a larger degree of supercooling because the temperature was relatively low, thus yielding microlite-rich juveniles. Moreover, such temperature stratification coupled with the evidence of homogeneous melt composition (58.5–58.9 wt.% SiO2) and the minor evidence of crystal mush (at most 27%) might suggest that the Tambora case is still in the early stage of magmatic evolution under cooling from the surrounding rocks.
Metabolic control analysis of L-tryptophan producing Escherichia coli applying targeted perturbation with shikimate
Authors: Schoppel Kristin , Trachtmann Natalia , Mittermeier Fabian , Sprenger Georg A. , Weuster-Botz Dirk
Published: September 2021

L-tryptophan production from glycerol with Escherichia coli was analysed by perturbation studies and metabolic control analysis. The insertion of a non-natural shikimate transporter into the genome of an Escherichia coli L-tryptophan production strain enabled targeted perturbation within the product pathway with shikimate during parallelised short-term perturbation experiments with cells withdrawn from a 15 L fed-batch production process. Expression of the shikimate/H+-symporter gene (shiA) from Corynebacterium glutamicum did not alter process performance within the estimation error. Metabolic analyses and subsequent extensive data evaluation were performed based on the data of the parallel analysis reactors and the production process. Extracellular rates and intracellular metabolite concentrations displayed evident deflections in cell metabolism and particularly in chorismate biosynthesis due to the perturbations with shikimate. Intracellular flux distributions were estimated using a thermodynamics-based flux analysis method, which integrates thermodynamic constraints and intracellular metabolite concentrations to restrain the solution space. Feasible flux distributions, Gibbs reaction energies and concentration ranges were computed simultaneously for the genome-wide metabolic model, with minimum bias in relation to the direction of metabolic reactions. Metabolic control analysis was applied to estimate elasticities and flux control coefficients, predicting controlling sites for L-tryptophan biosynthesis. The addition of shikimate led to enhanced deviations in chorismate biosynthesis, revealing a so far not observed control of 3-dehydroquinate synthase on L-tryptophan formation. The relative expression of the identified target genes was analysed with RT-qPCR. Transcriptome analysis revealed disparities in gene expression and the localisation of target genes to further improve the microbial L-tryptophan producer by metabolic engineering.
Evaluation of the Diametrical Core Deformation and Discing Analyses for In-Situ Stress Estimation and Application to the 4.9 km Deep Rock Core from the Basel Geothermal Borehole, Switzerland
Authors: Ziegler Martin , Valley Benoît
Published: September 2021

The in situ state of rock mass stresses is a key design parameter, e.g., for deep engineered geothermal systems. However, knowledge of the stress state at great depths is sparse mostly because of the lack of possible in situ tests in deep boreholes. Among different options, core-based in situ stress estimation may provide valuable stress information though core-based techniques have not yet become a standard. In this study we focus on the Diametrical Core Deformation Analysis (DCDA) technique using monzogranitic to monzonitic rock drill cores from 4.9 km depth of the Basel-1 borehole in Switzerland. With DCDA the maximum and minimum horizontal stress (SHmax and Shmin) directions, and the horizontal differential stress magnitudes (∆S) can be estimated from rock cores extracted from vertical boreholes. Our study has three goals: first, to assess photogrammetric core scanning to conduct DCDA; second, to compare DCDA results with borehole breakout and stress-induced core discing fracture (CDF) data sets; and third, to investigate the impact of rock elastic anisotropy on ∆S. Our study reveals that photogrammetric scanning can be used to extract reliable core diametrical data and CDF traces. Locally aligned core pieces showed similar SHmax orientations, conform to borehole breakout results. However, the variability of core diametrical differences was large for the Basel-1 core pieces, which leads to a large spread of ∆S. Finally, we demonstrate that core elastic anisotropy must be considered, requiring robust estimates of rock elastic moduli, to receive valuable stress information from DCDA analyses.
Extracellular cystine influences human preadipocyte differentiation and correlates with fat mass in healthy adults
Authors: Elkafrawy Hagar , Mehanna Radwa , Ali Fayrouz , Barghash Ayman , Dessouky Iman , Jernerén Fredrik , Turner Cheryl , Refsum Helga , Elshorbagy Amany
Published: September 2021

Plasma cysteine is associated with human obesity, but it is unknown whether this is mediated by reduced, disulfide (cystine and mixed-disulfides) or protein-bound (bCys) fractions. We investigated which cysteine fractions are associated with adiposity in vivo and if a relevant fraction influences human adipogenesis in vitro. In the current study, plasma cysteine fractions were correlated with body fat mass in 35 adults. Strong positive correlations with fat mass were observed for cystine and mixed disulfides (r ≥ 0.61, P < 0.001), but not the quantitatively major form, bCys. Primary human preadipocytes were differentiated in media containing cystine concentrations varying from 10–50 μM, a range similar to that in plasma. Increasing extracellular cystine (10–50 μM) enhanced mRNA expression of PPARG2 (to sixfold), PPARG1, PLIN1, SCD1 and CDO1 (P = 0.042– < 0.001). Adipocyte lipid accumulation and lipid-droplet size showed dose-dependent increases from lowest to highest cystine concentrations (P < 0.001), and the malonedialdehyde/total antioxidant capacity increased, suggesting increased oxidative stress. In conclusion, increased cystine concentrations, within the physiological range, are positively associated with both fat mass in healthy adults and human adipogenic differentiation in vitro. The potential role of cystine as a modifiable factor regulating human adipocyte turnover and metabolism deserves further study.
Productivity and the pandemic: short-term disruptions and long-term implications
Authors: de Vries Klaas , Erumban Abdul , van Ark Bart
Published: September 2021

This paper analyses quarterly estimates of productivity growth at industry level for three advanced economies, France, the UK and the US, for 2020. We use detailed industry-level data to distinguish reallocations of working hours between industries from pure within-industry productivity gains or losses. We find that all three countries showed positive growth rates of aggregate output per hour in 2020 over 2019. However, after removing the effects from the reallocation of hours between low and high productivity industries, only the US still performed positively in terms of within-industry productivity growth. In contrast, the two European economies showed negative within-industry productivity growth rates in 2020. While above-average digital-intensive industries outperformed below-average ones in both France and the UK, the US showed higher productivity growth in both groups compared to the European countries. Industries with medium-intensive levels of shares of employees working from home prior to the pandemic made larger productivity gains in 2020 than industries with the highest pre-pandemic work-from-home shares. Overall, after taking into account the productivity collapse in the hospitality and culture sector during 2020, productivity growth shows no clear deviation from the slowing pre-pandemic productivity trend. Future trends in productivity growth will depend on whether the favourable productivity gains (or smaller losses) in industries with above-average digital intensity will outweigh negative effects from the pandemic, in particular scarring effects on labour markets and business dynamics.
Vaccine-masked spread of SARS-CoV2 in an elderly care home, and how to prevent a spill-over into the general population
Authors: Weigl Josef A. I. , Werlang Thorsten , Wessendorf Michael , Helbing Holger
Published: September 2021

Aim

The vaccination campaign against SARS-CoV2 in Germany started at the peak of the second wave. An outbreak in an elderly care home occurred in our county at the time of the second vaccination. We describe a package of measures to control the outbreak and to prevent a spill over into the general population.

Subjects and methods

After outbreak confirmation, a package of measures such as quarantine of the elderly care home, staff and visitors, and their households was implemented. By sequential testing, quarantine measures were lifted. Surveillance of staff and residents by rapid antigen test and symptom monitoring was used in parallel.

Results

The outbreak was on-going for around 17 days until it was noticed by a symptomatic external staff member as index case. A total of 23 out of 96 residents (24.0%) and nine out of 114 staff (7.9%) were infected. Three residents died. Effective first-dose vaccine coverage was 85.4% in residents, 27.4% in internal, and 10.5% in external staff. Given the long latency period, the use of household quarantine prevented a spill over into the public. Already 16 days after notification of the index case the outbreak could be declared over.

Conclusions

Interferences between vaccination coverage and outbreak characteristics in regard to an extended latency period were observed. Household quarantine of case as well as contact households is of increased importance in the era of vaccination to prevent further spread into the general population until population-based control measures and lockdowns can be lifted.
Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells
Authors: Ghelli Luserna Di Rorà Andrea , Ghetti Martina , Ledda Lorenzo , Ferrari Anna , Bocconcelli Matteo , Padella Antonella , Napolitano Roberta , Fontana Maria Chiara , Liverani Chiara , Imbrogno Enrica , Bochicchio Maria Teresa , Paganelli Matteo , Robustelli Valentina , Sanogo Seydou , Cerchione Claudio , Fumagalli Monica , Rondoni Michela , Imovilli Annalisa , Musuraca Gerardo , Martinelli Giovanni , Simonetti Giorgia
Published: September 2021

Doxorubicin (Dox) is one of the most commonly used anthracyclines for the treatment of solid and hematological tumors such as B−/T cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase II enzyme functionality, thus inducing structural damages during DNA replication and causes direct damages intercalating into DNA double helix. Eukaryotic cells respond to DNA damages by activating the ATM-CHK2 and/or ATR-CHK1 pathway, whose function is to regulate cell cycle progression, to promote damage repair, and to control apoptosis. We evaluated the efficacy of a new drug schedule combining Dox and specific ATR (VE-821) or CHK1 (prexasertib, PX) inhibitors in the treatment of human B−/T cell precursor ALL cell lines and primary ALL leukemic cells. We found that ALL cell lines respond to Dox activating the G2/M cell cycle checkpoint. Exposure of Dox-pretreated ALL cell lines to VE-821 or PX enhanced Dox cytotoxic effect. This phenomenon was associated with the abrogation of the G2/M cell cycle checkpoint with changes in the expression pCDK1 and cyclin B1, and cell entry in mitosis, followed by the induction of apoptosis. Indeed, the inhibition of the G2/M checkpoint led to a significant increment of normal and aberrant mitotic cells, including those showing tripolar spindles, metaphases with lagging chromosomes, and massive chromosomes fragmentation. In conclusion, we found that the ATR-CHK1 pathway is involved in the response to Dox-induced DNA damages and we demonstrated that our new in vitro drug schedule that combines Dox followed by ATR/CHK1 inhibitors can increase Dox cytotoxicity against ALL cells, while using lower drug doses.

Graphical abstract

• Doxorubicin activates the G2/M cell cycle checkpoint in acute lymphoblastic leukemia (ALL) cells.

• ALL cells respond to doxorubicin-induced DNA damages by activating the ATR-CHK1 pathway.

• The inhibition of the ATR-CHK1 pathway synergizes with doxorubicin in the induction of cytotoxicity in ALL cells.

• The inhibition of ATR-CHK1 pathway induces aberrant chromosome segregation and mitotic spindle defects in doxorubicin-pretreated ALL cells.
University students’ behavioral intention and gender differences toward the acceptance of shifting regular field training courses to e-training courses
Authors: Alghamdi Abdullah M. , Alsuhaymi Dhaifallah S. , Alghamdi Fahad A. , Farhan Ahmed Mohamed , Shehata Saleh M. , Sakoury Mona Mostafa
Published: September 2021

During the COVID-19 lockdown, all the courses at Imam Abdulrahman Bin Faisal University (IAU) were delivered fully online, including field-training courses. Since there was no previous experience in offering field-training courses in a distance format, the current study aims to identify factors that could impact students’ behavioral intention to accept the e-training approach in teaching field training courses at IAU. In order to gather the data, the researchers designed a questionnaire based on the UTAUT model and they ensured the face, content, and construct validity of the questionnaire by sending it to five experts in the relevant field and by using exploratory factor analysis. Also, all the questionnaire’s items were reliable since the Cronbach’s alpha values were above 0.77 for all the items. A total of 397 participants provided valid responses. The result of this study indicated that Effort Expectancy (EE), Facilitating Condition (FC), Performance Expectancy (PE), and Social Influence (SI), respectively were the primary predictors for students’ intention to use e-training. These factors explained 32.1% of the variance in students’ behavioral intentions. As far as students’ gender is concerned, there were significant differences between students’ PE, FC, and SI. Based on these results, policymakers at IAU will have a clear image of the most essential factors that colleges should target to increase students’ acceptance of e-training.
Preventing Environmental Disasters in Investment under Uncertainty
Authors: Kort Peter , Lavrutich Maria , Nunes Cláudia , Oliveira Carlos
Published: September 2021

The paper considers a firm that has the option to invest in a project with an unknown profitability, which is affected by general market uncertainty. The project has the adverse effect that it can cause environmental damage. In case the firm has the option to undertake preventive investment at the time of market entry, we get that preventive investment is significant when (i) the project revenue is large, (ii) the environmental incidents potentially cause a huge reduction of firm value, and (iii) when preventive investment substantially decreases the probability of environmental damage occurrence. The optimality of such a preventive investment results in a significant delay of the project investment. When the firm has the possibility to invest in the project first and do the preventive investment later, this will accelerate the project investment and will result in a larger preventive investment when it indeed will decide to do that one later.
Investor asset valuation under a wealth tax and a capital income tax
Authors: Bjerksund Petter , Schjelderup Guttorm
Published: September 2021

We study how a capital income tax and a wealth tax affect an investor's valuation of a company's stock in an efficient international capital market. Using a one-period model, a model of infinite horizon where the asset generates a future cash flow that is a martingale, and a finite horizon model where we abandon the martingale assumption, we find that a wealth tax and/or a capital income tax do not lead investors to value an investment differently from untaxed investors. Investors who seek a higher pre-tax rate of return due to capital taxes harm their own wealth.
Epistemic austerity: limits to entitlement
Authors: Ohlhorst Jakob
Published: September 2021

Epistemic entitlement is a species of internalist warrant that can be had without any evidential support. Unfortunately, for this kind of warrant the so-called problem of demarcation arises, a form of epistemic relativism. I first present entitlement theory and examine what the problem of demarcation is exactly, rejecting that it is either based on bizarreness or disagreement in favour of the thesis that the problem of demarcation is based on epistemic arbitrariness. Second, I argue that arbitrariness generates a problem for entitlement because it undermines epistemic warrant. Third, I draw out some of the consequences that arbitrariness has for an entitlement epistemology, notably that it threatens to generalise to all our beliefs. Finally, I examine how different solutions to the problem of demarcation fare with respect to the danger of arbitrariness. I argue that none of the considered options succeeds in dealing with the risks of arbitrariness.
On the Importance of Considering Multinuclear Metal Sites in Homogeneous Catalysis Modeling
Authors: Matsuzawa Akinobu , Harvey Jeremy N. , Himo Fahmi
Published: September 2021

In this short review, we provide an account of a number of computational studies of catalytic reaction mechanisms carried out in our groups. We focus in particular on studies in which we came to realize during the course of the investigation that the active catalytic species was a bimetallic complex, rather a monometallic one as previously assumed. In some cases, this realization was in part prompted by experimental observations, but careful exploration based on computation of the speciation of the metal precursor also provided a powerful guide: it is often possible to predict that bimetallic species (intermediates or transition states) lie lower in free energy than a priori competitive monometallic species. In this sense, we argue that in organometallic catalysis, the rule whereby “two is better than one” turns out to be relevant much more often than one might expect.
The Fishyscapes Benchmark: Measuring Blind Spots in Semantic Segmentation
Authors: Blum Hermann , Sarlin Paul-Edouard , Nieto Juan , Siegwart Roland , Cadena Cesar
Published: September 2021

Deep learning has enabled impressive progress in the accuracy of semantic segmentation. Yet, the ability to estimate uncertainty and detect failure is key for safety-critical applications like autonomous driving. Existing uncertainty estimates have mostly been evaluated on simple tasks, and it is unclear whether these methods generalize to more complex scenarios. We present Fishyscapes, the first public benchmark for anomaly detection in a real-world task of semantic segmentation for urban driving. It evaluates pixel-wise uncertainty estimates towards the detection of anomalous objects. We adapt state-of-the-art methods to recent semantic segmentation models and compare uncertainty estimation approaches based on softmax confidence, Bayesian learning, density estimation, image resynthesis, as well as supervised anomaly detection methods. Our results show that anomaly detection is far from solved even for ordinary situations, while our benchmark allows measuring advancements beyond the state-of-the-art. Results, data and submission information can be found athttps://fishyscapes.com/.