bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving CPMG liver iron estimates with a ‐corrected proton density estimator
Authors: Doyle Eamon K. , Thornton Samuel , Toy Kristin A. , Powell Andrew J. , Wood John C.
Published: July 2021

Purpose

CPMG spin echo acquisitions are attractive for diagnosing and monitoring liver iron concentration in iron overload disorders due to their time efficiency and potential to reveal unique information about tissue iron distribution. Clinical adoption remains low due to the insensitivity of CPMG‐based estimates to liver iron concentration (LIC) when common fitting techniques are applied. In this work, we demonstrate that the inclusion of a proton density estimator (PDE) derived from the CPMG acquisition increase the sensitivity of CPMG estimates to LIC in both simulated and in‐vivo human data.

Theory and Methods

CPMG acquisitions from 50 clinically indicated MRI studies in patients with iron overload were analyzed with and without PDE constraints. Liver regions of interest were fit to monoexpontial and nonexponential signal decay equations. LIC by served as the reference standard. The observed calibration between CPMG values and LIC were compared to results predicted from a previously validated Monte Carlo model.

Results

The sensitivity of CPMG‐derived triples when a proton density constraint is applied. When compared with ‐LIC estimates, both monoexponential and nonexponential models were unbiased but demonstrated broad 95% confidence intervals particularly for LIC values below 12 mg/g. Absolute error did not increase with LIC.

Conclusion

A proton density constraint can increase the sensitivity of CPMG‐based models to iron. CPMG acquisitions are time‐efficient and could potentially improve the dynamic range of single spin echo techniques as well as providing insight into tissue iron distribution.
Year in Review 2020: Multisystemic impact of cystic fibrosis
Authors: Sharma Preeti B. , Sathe Meghana , Savant Adrienne P.
Published: July 2021

Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Improved outcomes and longevity of persons with CF (PwCF) have increased recognition of the multisystem impact of the disease on the daily lives of PwCF. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served. This review is part of the CF Year in Review 2020 series, focusing on the multi‐system effects of CF. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.
3D Yang-Mills glueballs vs closed effective strings
Authors: Dubovsky Sergei , Hernández-Chifflet Guzmán , Zare Shahrzad
Published: July 2021

Abstract

Recent lattice results strongly support the Axionic String Ansatz (ASA) for quantum numbers of glueballs in 3D Yang-Mills theory. The ASA treats glueballs as closed bosonic strings. The corresponding worldsheet theory is a deformation of the minimal Nambu-Goto theory. In order to understand better the ASA strings and as a first step towards a perturbative calculation of the glueball mass splittings we compare the ASA spectrum to the closed effective string theory. Namely, we model glueballs as excitations around the folded rotating rod solution with a large angular momentum J. The resulting spectrum agrees with the ASA in the regime of validity of the effective theory, i.e., in the vicinity of the leading Regge trajectory. In particular, closed effective string theory correctly predicts that only glueballs of even spin J show up at the leading Regge trajectory. Interestingly though, the closed effective string theory overestimates the number of glueball states far above the leading Regge trajectory.
Chronic exposure to Cytolethal Distending Toxin (CDT) promotes a cGAS-dependent type I interferon response
Authors: Pons Benoît J. , Pettes-Duler Aurélie , Naylies Claire , Taieb Frédéric , Bouchenot Catherine , Hashim Saleha , Rouimi Patrick , Deslande Maxime , Lippi Yannick , Mirey Gladys , Vignard Julien
Published: July 2021

The Cytolethal Distending Toxin (CDT) is a bacterial genotoxin produced by pathogenic bacteria causing major foodborne diseases worldwide. CDT activates the DNA Damage Response and modulates the host immune response, but the precise relationship between these outcomes has not been addressed so far. Here, we show that chronic exposure to CDT in HeLa cells or mouse embryonic fibroblasts promotes a strong type I interferon (IFN) response that depends on the cytoplasmic DNA sensor cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) through the recognition of micronuclei. Indeed, despite active cell cycle checkpoints and in contrast to other DNA damaging agents, cells exposed to CDT reach mitosis where they accumulate massive DNA damage, resulting in chromosome fragmentation and micronucleus formation in daughter cells. These mitotic phenotypes are observed with CDT from various origins and in cancer or normal cell lines. Finally, we show that CDT exposure in immortalized normal colonic epithelial cells is associated to cGAS protein loss and low type I IFN response, implying that CDT immunomodulatory function may vary depending on tissue and cell type. Thus, our results establish a direct link between CDT-induced DNA damage, genetic instability and the cellular immune response that may be relevant in the context of natural infection associated to chronic inflammation or carcinogenesis.
Maximum Correntropy Criterion for Robust TOA-Based Localization in NLOS Environments
Authors: Xiong Wenxin , Schindelhauer Christian , So Hing Cheung , Wang Zhi
Published: July 2021

We investigate the problem of time-of-arrival (TOA)-based localization under possible non-line-of-sight (NLOS) propagation conditions. To robustify the squared-range-based location estimator, we follow the maximum correntropy criterion, essentially the Welsch M-estimator with a redescending influence function which behaves like $$\ell _0$$

ℓ
0

-minimization toward the grossly biased measurements, to derive the formulation. The half-quadratic technique is then applied to settle the resulting optimization problem in an alternating maximization (AM) manner. By construction, the major computational challenge at each AM iteration boils down to handling an easily solvable generalized trust region subproblem. It is worth noting that the implementation of our localization method requires nothing but merely the TOA-based range measurements and sensor positions as prior information. Simulation and experimental results demonstrate the competence of the presented scheme in outperforming several state-of-the-art approaches in terms of positioning accuracy, especially in scenarios, where the percentage of NLOS paths is not large enough.
Predictors of psychiatric comorbidity in cancer patients at the time of their discharge from the hospital
Authors: Roick Julia , Danker Helge , Kersting Anette , Dietrich Arne , Dietz Andreas , Papsdorf Kirsten , Meixensberger Jürgen , Stolzenburg Jens-Uwe , Wirtz Hubert , Singer Susanne
Published: July 2021

Purpose

A cancer diagnosis can have a substantial impact on one’s mental health. The present study investigated the prevalence and predictors of psychiatric comorbidities in cancer patients at the time of their discharge from the hospital.

Methods

Psychiatric comorbidities were assessed shortly before hospital discharge and half a year after hospitalization using a structured clinical interview (SCID), based on the diagnostic and statistical manual of mental disorders (DSM-IV). Frequencies at both time points were estimated using percentages and corresponding 95% confidence intervals. Predictors of mental disorders were identified using binary logistic regression models.

Results

At time of hospital discharge, 39 out of 334 patients (12%) were diagnosed with a psychiatric comorbidity, and 15 (7%) were diagnosed half a year later. Among the diagnoses, adjustment disorders (3%) were most frequent at the time of hospital release, while major depression (3%) was the most frequent 6 months later. Having a mental disorder was associated with unemployment (odds ratio (OR) 3.4, confidence interval (CI) 1.1–10.9, p = 0.04). There was no evidence that school education (OR 2.0, CI 0.4–9.0, p = 0.38), higher education (OR 0.7, CI 0.2–2.4, p = 0.60), income (OR 1.0, CI 1.0–1.0, p = 0.06), tumor stage (OR 1.1, CI 0.4–3.2, p = 0.85), type of disease (OR 0.6, CI 0.2–2.1, p = 0.47), pain (OR 1.0, CI 1.0–1.0, p = 0.15), fatigue (OR 1.0, CI 1.0–1.0, p = 0.77), or physical functioning (OR 1.0, CI 1.0–1.0, p = 0.54) were related to the presence of a psychiatric comorbidity.

Conclusions

Unemployment was associated with at least a threefold increased risk of mental disorder, which highlights the need for special attention to be given to this subgroup of cancer patients.
The J-method for the Gross–Pitaevskii eigenvalue problem
Authors: Altmann Robert , Henning Patrick , Peterseim Daniel
Published: July 2021

This paper studies the J-method of [E. Jarlebring, S. Kvaal, W. Michiels. SIAM J. Sci. Comput. 36-4:A1978-A2001, 2014] for nonlinear eigenvector problems in a general Hilbert space framework. This is the basis for variational discretization techniques and a mesh-independent numerical analysis. A simple modification of the method mimics an energy-decreasing discrete gradient flow. In the case of the Gross–Pitaevskii eigenvalue problem, we prove global convergence towards an eigenfunction for a damped version of the J-method. More importantly, when the iterations are sufficiently close to an eigenfunction, the damping can be switched off and we recover a local linear convergence rate previously known from the discrete setting. This quantitative convergence analysis is closely connected to the J-method’s unique feature of sensitivity with respect to spectral shifts. Contrary to classical gradient flows, this allows both the selective approximation of excited states as well as the amplification of convergence beyond linear rates in the spirit of the Rayleigh quotient iteration for linear eigenvalue problems. These advantageous convergence properties are demonstrated in a series of numerical experiments involving exponentially localized states under disorder potentials and vortex lattices in rotating traps.
Liquid chromatography versus supercritical fluid chromatography coupled to mass spectrometry: a comparative study of performance for multiresidue analysis of pesticides
Authors: Cutillas Víctor , Ferrer Carmen , R. Fernández-Alba Amadeo
Published: July 2021

Abundant studies have been published evaluating different parameters of reverse-phase liquid chromatography (LC) and supercritical fluid chromatography (SFC), both coupled to electrospray (ESI)/mass spectrometry (MS) for pesticide residue analysis. However, there is a lack of a comprehensive comparative study that facilitates deep knowledge about the benefits of using each technique. In the present study, the same mass spectrometer was used coupled to both liquid and supercritical fluid chromatographies with a multiresidue method of 215 compounds, for the analysis of pesticide residues in food samples. Through the injection of the spiked extracts, separate experiments were conducted. A study of the optimum ion source temperature using the different chromatography modes was performed. The results were evaluated in terms of sensitivity with tomato, leek, onion, and orange as representative fruit and vegetable matrices. The compounds which reported the highest area values in each chromatography were evaluated through their substance groups and polarity values. The impact of matrix effects obtained in tomato matrix was similar for both cases; however, SFC clearly showed better results in analyzing matrices with a higher number of natural co-extracted compounds. This can be explained by the combination of two effects: (i) chromatography separation and (ii) ion source efficiency. The chromatographic elution presented different profiles of matrix components, which had diverse impact on the coelution with the analytes, being more beneficial when SFC was used in the matrices studied. The data showed that the best results obtained in SFC are also related to a higher ionization efficiency even when the ESI emitter tip was not optimized for SFC flow. In the present study a comprehensive evaluation of the benefits and drawbacks of these chromatography modes for routine pesticide residue analysis related to target compounds/commodities is provided.

Graphical abstract
Fluid overload is associated with increased 90-day mortality in AML patients undergoing induction chemotherapy
Authors: Ballo Olivier , Eladly Fagr , Koschade Sebastian , Büttner Stefan , Stratmann Jan Alexander , Brunnberg Uta , Kreisel Eva-Maria , Frank Franziska , Wagner Sebastian , Steffen Björn , Serve Hubert , Finkelmeier Fabian , Brandts Christian H.
Published: July 2021

Treatment‐related complications contribute substantially to morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Although AML patients are susceptible to fluid overload (FO) (e.g., in the context of chemotherapy protocols, during sepsis treatment or to prevent tumor lysis syndrome), little attention has been paid to its role in AML patients undergoing induction chemotherapy. AML patients receiving induction chemotherapy between 2014 and 2019 were included in this study. FO was defined as ≥5% weight gain on day 7 of induction chemotherapy compared to baseline weight determined on the day of admission. We found FO in 23 (12%) of 187 AML patients undergoing induction chemotherapy. Application of >100 ml crystalloid fluids/kg body weight until day 7 of induction chemotherapy was identified as an independent risk factor for FO. AML patients with FO suffered from a significantly increased 90-day mortality rate and FO was demonstrated as an independent risk factor for 90-day mortality. Our data suggests an individualized, weight-adjusted calculation of crystalloid fluids in order to prevent FO-related morbidity and mortality in AML patients during induction chemotherapy. Prospective trials are required to determine the adequate fluid management in this patient population.
SmartPIV: flow velocity estimates by smartphones for education and field studies
Authors: Cierpka Christian , Otto Henning , Poll Constanze , Hüther Jonas , Jeschke Sebastian , Mäder Patrick
Published: July 2021

In this paper, a smartphone application is presented that was developed to lower the barrier to introduce particle image velocimetry (PIV) in lab courses. The first benefit is that a PIV system using smartphones and a continuous wave (cw-) laser is much cheaper than a conventional system and thus much more affordable for universities. The second benefit is that the design of the menus follows that of modern camera apps, which are intuitively used. Thus, the system is much less complex and costly than typical systems, and our experience showed that students have much less reservations to work with the system and to try different parameters. Last but not least the app can be applied in the field. The relative uncertainty was shown to be less than 8%, which is reasonable for quick velocity estimates. An analysis of the computational time necessary for the data evaluation showed that with the current implementation the app is capable of providing smooth live display vector fields of the flow. This might further increase the use of modern measurement techniques in industry and education.

Graphic abstract
The Olympia anatomic polished cemented stem is associated with a high survivorship, excellent hip-specific functional outcome, and high satisfaction levels: follow-up of 239 consecutive patients beyond 15 years
Authors: Turnbull Gareth S. , Marshall Claire , Nicholson Jamie A. , MacDonald Deborah J. , Clement Nicholas D. , Breusch Steffen J.
Published: July 2021

Introduction

The Olympia femoral stem is a stainless steel, anatomically shaped, polished and three-dimensionally tapered implant designed for use in cemented total hip arthroplasty (THA). The primary aim of this study was to determine the long-term survivorship, radiographic outcome, and patient-reported outcome measures (PROMs) of the Olympia stem.

Patients and methods

Between May 2003 and December 2005, 239 patients (264 THAs) underwent a THA with an Olympia stem in our institution. Patient-reported outcome measures were assessed using the Oxford Hip Score (OHS), EuroQol-5 dimensions (EQ-5D) score, and patient satisfaction at mean 10 years following THA. Patient records and radiographs were then reviewed at a mean of 16.5 years (SD 0.7, 15.3–17.8) following THA to identify occurrence of complications or revision surgery for any cause following surgery. Radiographs were assessed for lucent lines and lysis according to Gruen’s zones

Results

Mean patient age at surgery was 68.0 years (SD 10.9, 31–93 years). There were 156 women (65%, 176 THAs). Osteoarthritis was the indication for THA in 204 patients (85%). All cause stem survivorship at 10 years was 99.2% (95% confidence interval [CI], 97.9%–100%) and at 15 years was 97.5% (94.6%–100%). The 15-year stem survival for aseptic loosening was 100%. Analysis of all-cause THA failure demonstrated a survivorship of 98.5% (96.3%–100%) at 10 years and 95.9% (92.4%–99.4%) at 15 years. There were 9 THAs with non-progressive lucent lines in a single Gruen zone and 3 had lines in two zones, and no patient demonstrated signs for lysis. At a mean of 10-year (SD 0.8, 8.7–11.3) follow-up, mean OHS was 39 (SD 10.3, range 7–48) and 94% of patients reported being very satisfied or satisfied with their THA.

Conclusions

The Olympia stem demonstrated excellent 10-year PROMs and very high rates of stem survivorship at final follow-up beyond 15 years.
Soil carbon and plant richness relationships differ among grassland types, disturbance history and plant functional groups
Authors: Anacker B. L. , Seastedt T. R. , Halward T. M. , Lezberg A. L.
Published: July 2021

Understanding the relationship of soil carbon storage and species diversity in grasslands can provide insights into managing these ecosystems. We studied relationships among soil C and plant species richness within ~ 9700 ha of grasslands in Colorado, US. Using 141 grassland transects, we tested how soil C was related to plant species richness, grassland type, soil texture, and prairie dog presence. Soil C was significantly, positively related to plant species richness, while native perennial graminoid species richness exhibited an even stronger positive relationship. However, the relationship of soil C and plant richness was not found in all three grassland types studied, but instead was unique to the most common grassland type, mixed grass prairie, and absent from both xeric tallgrass and mesic tallgrass prairie. The presence of a single indicator species, Andropogon gerardii, showed a significant, positive relationship with soil carbon. Our best possible model explained 45% of the variance in soil C using species richness, grassland type, and their interaction. Surprisingly, soil C was negatively related to soil clay, suggesting that surface clays amplify evaporation and water runoff rather than protecting soil organic matter from decomposition. Soil C was negatively related to prairie dog presence, suggesting that prairie dogs do not enhance soil carbon sequestration; in fact, prairie dog occupied sites had significantly lower soil C, likely related to loss of topsoil from prairie dog colonies. Our results suggest that management for species richness provides the co-benefit of soil C storage, and high clay and prairie dog disturbance compromises both.
Supervised and unsupervised learning using a fully-plastic all-optical unit of artificial intelligence based on solitonic waveguides
Authors: Bile Alessandro , Moratti Francesca , Tari Hamed , Fazio Eugenio
Published: July 2021

The software implementations of neuronal systems have shown great effectiveness, even if the natural hardware separation between the processing and memory areas in computers slows down the analysis capacity. To overcome these limitations, new hardware configurations are moving towards neuromorphic models, capable of unifying the processing/memory dichotomy. Recently, integrated photonic X-junctions formed by waveguides written by spatial solitons have shown the ability to perform supervised learning. The solitonic technology, compared to the traditional one, offers the advantage of realizing plastic circuitry, a typical characteristic of biological neural networks. This work extensively studies both supervised and unsupervised learning of photonic soliton X-junctions. By exploiting the plasticity of the nonlinear refractive index at the base of the soliton formation, X-junctions can readdress their behaviours forwarding data to different outputs. In this article, we will extend the state-of-the-art: starting from supervised learning, for which all possible cases are now investigated, a material sensitive to the transported signals will be introduced to allow the junction to carry out unsupervised learning. In this way, the junction autonomously recognises the transported signals without the external intervention of the operator. Learning and memory now physically coincide in fact, learning means that the junction slowly switches based on the information sent; any further unknown information sent will find the junction in the modified state which corresponds to the learned information and will be recognised as well (reasoning based on comparison with stored information).
Derivation of Darcy’s law in randomly perforated domains
Authors: Giunti A.
Published: July 2021

We consider the homogenization of a Poisson problem or a Stokes system in a randomly punctured domain with Dirichlet boundary conditions. We assume that the holes are spherical and have random centres and radii. We impose that the average distance between the balls is of size $$\varepsilon $$
ε
and their average radius is $$\varepsilon ^{\alpha }$$

ε
α

, $$\alpha \in (1; 3)$$

α
∈
(
1
;
3
)

. We prove that, as in the periodic case (Allaire, G., Arch. Rational Mech. Anal. 113(113):261–298, 1991), the solutions converge to the solution of Darcy’s law (or its scalar analogue in the case of Poisson). In the same spirit of (Giunti, A., Höfer, R., Ann. Inst. H. Poincare’- An. Nonl. 36(7):1829–1868, 2019; Giunti, A., Höfer, R., Velàzquez, J.J.L., Comm. PDEs 43(9):1377–1412, 2018), we work under minimal conditions on the integrability of the random radii. These ensure that the problem is well-defined but do not rule out the onset of clusters of holes.
Multicenter prospective in vivo study of an endocytoscope system (ECS) for superficial esophageal cancer
Authors: Morita Shuko , Goda Kenichi , Yano Tomonori , Kaise Mitsuru , Kato Mototsugu , Inoue Haruhiro , Niwa Yasumasa , Kodashima Shinya , Miyahara Ryoji , Ochiai Atsushi , Ikegami Masahiro , Hamatani Shigeharu , Shimoda Tadakazu , Ohkura Yasuo , Aida Junko , Nakanishi Yukihiro , Yoshimura Kenichi , Ishikawa Hideki , Takubo Kaiyo , Muto Manabu
Published: July 2021

Background

Endocytoscope systems (ECS) can visualize cellular nuclei of the mucosa of the gastrointestinal tract and are predicted to provide real-time microscopic diagnosis. However, their practical diagnostic performance remains unclear. Therefore, we conducted a multicenter prospective study to evaluate the visualization of superficial esophageal neoplasm in vivo using an ECS, and its diagnostic capability.

Methods

The study target was histologically confirmed squamous cell carcinoma (SCC) and high-grade intraepithelial neoplasia (HGIN). An integrated ECS was used to obtain ECS images. In each patient, three ECS images of cancerous and corresponding noncancerous regions were selected for evaluation. A pathological review board of five certified pathologists made the final diagnosis of the images. The primary endpoint was the sensitivity of ECS diagnosis by pathologists.

Results

ECS images of 68 patients were assessed: 42 lesions were mucosal SCC, 13 were submucosal SCC, and 13 were HGIN. The rate of assessable images was 96% (95% CI 87.6–99.1). The sensitivity of ECS diagnosis by pathologists was 88% (95% CI 77.2–94.5).

Conclusions

ECS can provide high-quality images of cancerous lesions and a high diagnostic accuracy by pathologists, and could be useful for real-time endoscopic histological diagnosis of SCC and HGIN.

Trial registration

The UMIN Clinical Trials Registry Identification Number: 000004218
Patients with higher vitamin D levels show stronger improvement of self-reported depressive symptoms in psychogeriatric day-care setting
Authors: Zech Linda D. , Scherf-Clavel Maike , Daniels Christine , Schwab Michael , Deckert Jürgen , Unterecker Stefan , Herr Alexandra S.
Published: July 2021

Depression is a common psychiatric disorder among geriatric patients that decreases the quality of life and increases morbidity and mortality. Vitamin D as a neuro-steroid hormone might play a role in the onset and treatment of depression. In the present study, the association between depressive symptoms and vitamin D concentration in serum was evaluated. 140 patients of a psychogeriatric day-care unit were included. The geriatric depression scale (GDS) and the Hamilton depression rating scale (HDRS) were assessed at the beginning and end of treatment, GDS scores additionally 6 weeks after discharge from the day-care unit. Vitamin D levels were measured at the beginning of the treatment, routinely. Patients with levels below 30 µg/L were treated with 1000 IU vitamin D per day. There was no association between the severity of depressive symptoms and the concentration of vitamin D at the beginning of the treatment. Patients with higher vitamin D levels showed a stronger decline of depressive symptoms measured by the GDS during their stay in the day-care unit. We provide evidence that vitamin D serum levels might influence antidepressant therapy response in a geriatric population. Prospective studies are necessary to determine which patients may profit from add-on vitamin D therapy.
Timing of non-pharmaceutical interventions to mitigate COVID-19 transmission and their effects on mobility: a cross-country analysis
Authors: Summan Amit , Nandi Arindam
Published: July 2021

In the early stages of a pandemic, non-pharmaceutical interventions (NPIs) that encourage physical distancing and reduce contact can decrease and delay disease transmission. Although NPIs have been implemented globally during the COVID-19 pandemic, their intensity and timing have varied widely. This paper analyzed the country-level determinants and effects of NPIs during the early stages of the pandemic (January 1st to April 29th, 2020). We examined countries that had implemented NPIs within 30 or 45 days since first case detection, as well as countries in which 30 or 45 days had passed since first case detection. The health and socioeconomic factors associated with delay in implementation of three NPIs—national school closure, national lockdown, and global travel ban—were analyzed using fractional logit and probit models, and beta regression models. The probability of implementation of national school closure, national lockdown, and strict national lockdown by a country was analyzed using a probit model. The effects of these three interventions on mobility changes were analyzed with propensity score matching methods using Google’s social mobility reports. Countries with larger populations and better health preparedness measures had greater delays in implementation. Countries with greater population density, higher income, more democratic political systems, and later arrival of first cases were more likely to implement NPIs within 30 or 45 days of first case detection. Implementation of lockdowns significantly reduced physical mobility. Mobility was further reduced when lockdowns were enforced with curfews or fines, or when they were more strictly defined. National school closures did not significantly change mobility.
Estimation and computations for Gaussian mixtures with uniform noise under separation constraints
Authors: Coretto Pietro
Published: July 2021

In this paper we study a finite Gaussian mixture model with an additional uniform component that has the role to catch points in the tails of the data distribution. An adaptive constraint enforces a certain level of separation between the Gaussian mixture components and the uniform component representing noise and outliers in the tail of the distribution. The latter makes the proposed tool particularly useful for robust estimation and outlier identification. A constrained ML estimator is introduced for which existence and consistency is shown. One of the attractive features of the methodology is that the noise level is estimated from data. We also develop an EM-type algorithm with proven convergence. Based on numerical evidence we show how the methods developed in this paper are useful for several fundamental data analysis tasks: outlier identification, robust location-scale estimation, clustering, and density estimation.
Italy and the Comprehensive Agreement on Investments: disappointment over the process
Authors: Ghiretti Francesca
Published: July 2021

The formal conclusion of the Comprehensive Agreement on Investments (CAI) has drawn much criticism. Criticisms for member states did not always recognise the same critical points. The case of Italy presents an instance in which the issue rather than laying in the content of the agreement was identified in the process. Not only had Italy been marginalised in the process of negotiation that led to the conclusion of the CAI, but also exponents from the government claim that leading negotiators, amongst which France and Germany, ignored Italy’s doubts about the deal when these were raised. Beyond politics, the paper shows that the Italian business community displays a response to the agreement in line with that of the rest of the EU in its positive assessment of the outcome.
Subpollen particle release from different species of the invasive allergenic genus Ambrosia: the effect of rainwater composition and wind speed
Authors: Caronni Sarah , Gentili Rodolfo , Montagnani Chiara , Citterio Sandra
Published: July 2021

Allergen-containing subpollen particles (SPPs) are micrometric or sub-micrometric particles (0.12–5 µm) released from pollen. They are able to reach the lower airways, causing allergenic reactions. SPP release occurs through the pore of intact grains or by rupture of the whole grain. In this paper the results of two laboratory experiments investigating the dynamics of SPP release for three alien species of Ambrosia genus are shown. Rainwater composition and wind speed were considered, by simulating different conditions, in accordance with a fully orthogonal experimental design. The principle response variable was the total percentage of SPPs-releasing pollen grains; also the percentage of intact grains releasing SPPs through the pore and of broken SPPs-releasing grains were considered. Both osmotic and mechanical shock caused the discharge of SPPs but different results were observed. The highest number of releasing grains was recorded in case of acid solution and 20 knots wind speed. Moreover, wind and rainfalls caused SPPs release through different mechanisms. Wind mainly provoked a mechanical shock leading to grain rupture, whereas rainfall caused mainly SPPs release through the pore of intact grains. Comparing species, the effect of wind and at least in some cases also that of rainwater appeared to be less relevant for Ambrosia trifida than for Ambrosia psilostachya and Ambrosia artemisiifolia. The obtained results suggest a species-specific response of Ambrosia species to wind speed and rainwater that lead to a different release of SPPs and then to a species-specific impact on allergy according to the characteristics of their growth environment.
Community seed network in an era of climate change: dynamics of maize diversity in Yucatán, Mexico
Authors: Fenzi Marianna , Rogé Paul , Cruz-Estrada Angel , Tuxill John , Jarvis Devra
Published: July 2021

Local seed systems remain the fundamental source of seeds for many crops in developing countries. Climate resilience for small holder farmers continues to depend largely on locally available seeds of traditional crop varieties. High rainfall events can have as significant an impact on crop production as increased temperatures and drought. This article analyzes the dynamics of maize diversity over 3 years in a farming community of Yucatán state, Mexico, where elevated levels of precipitation forced farmers in 2012 to reduce maize diversity in their plots. We study how farmers maintained their agroecosystem resilience through seed networks, examining the drivers influencing maize diversity and seed provisioning in the year preceding and following the 2012 climatic disturbance (2011–2013). We found that, under these challenging circumstances, farmers focused their efforts on their most reliable landraces, disregarding hybrids. We show that farmers were able to recover and restore the diversity usually cultivated in the community in the year following the critical climate event. The maize dynamic assessed in this study demonstrates the importance of community level conservation of crop diversity. Understanding farmer management strategies of agrobiodiversity, especially during a challenging climatic period, is necessary to promote a more tailored response to climate change in traditional farming systems.
Origins and minimization of intermodulation distortion in a pseudo-differential CMOS beamforming receiver
Authors: Shabanzadeh Negar , Akbar Rehman , Pärssinen Aarno , Rahkonen Timo
Published: July 2021

This paper studies how nonlinear distortion is generated in the combination of an inverter-based low-noise amplifier and a passive mixer. The dominant nonlinearity appears to be the quadratic $$V_{gs}V_{ds}$$

V

gs

V

ds

mixing term in the passive mixer that first causes low-frequency IM2 and then upconverts it to IM3. Adding a common-mode feedback (CMFB) cancels the IM2 in a pseudo-differential structure, and hence also reduces the IM3 caused by the cascaded second order nonlinearities significantly. The effect of CMFB gain, bandwidth and linearity were analyzed, and it is concluded that from the linearity point of view, the feedback circuit does not have to be very wideband since the dominant distortion products originate from baseband. Finally, the paper takes a look at the spurious tones rising in the mixing, and how to extend the analysis to include the actual frequency translation effect.
Estimated pulse wave velocity (ePWV) as a potential gatekeeper for MRI-assessed PWV: a linear and deep neural network based approach in 2254 participants of the Netherlands Epidemiology of Obesity study
Authors: van Hout Max J. , Dekkers Ilona A. , Lin Ling , Westenberg Jos J. , Schalij Martin J. , Jukema J. Wouter , Widya Ralph L. , Boone Sebastiaan C. , de Mutsert Renée , Rosendaal Frits R. , Scholte Arthur J. , Lamb Hildo J.
Published: July 2021

Pulse wave velocity (PWV) assessed by magnetic resonance imaging (MRI) is a prognostic marker for cardiovascular events. Prediction modelling could enable indirect PWV assessment based on clinical and anthropometric data. The aim was to calculate estimated-PWV (ePWV) based on clinical and anthropometric measures using linear ridge regression as well as a Deep Neural Network (DNN) and to determine the cut-off which provides optimal discriminative performance between lower and higher PWV values. In total 2254 participants from the Netherlands Epidemiology of Obesity study were included (age 45–65 years, 51% male). Both a basic and expanded prediction model were developed. PWV was estimated using linear ridge regression and DNN. External validation was performed in 114 participants (age 30–70 years, 54% female). Performance was compared between models and estimation accuracy was evaluated by ROC-curves. A cut-off for optimal discriminative performance was determined using Youden’s index. The basic ridge regression model provided an adjusted R2 of 0.33 and bias of < 0.001, the expanded model did not add predictive performance. Basic and expanded DNN models showed similar model performance. Optimal discriminative performance was found for PWV < 6.7 m/s. In external validation expanded ridge regression provided the best performance of the four models (adjusted R2: 0.29). All models showed good discriminative performance for PWV < 6.7 m/s (AUC range 0.81–0.89). ePWV showed good discriminative performance with regard to differentiating individuals with lower PWV values (< 6.7 m/s) from those with higher values, and could function as gatekeeper in selecting patients who benefit from further MRI-based PWV assessment.
High-temperature decomposition of amorphous and crystalline cellulose: reactive molecular simulations
Authors: Paajanen Antti , Rinta-Paavola Aleksi , Vaari Jukka
Published: July 2021

We study the thermal decomposition of cellulose using molecular simulations based on the ReaxFF reactive force field. Our analysis focuses on the mechanism and kinetics of chain scission, and their sensitivity on the condensed phase environment. For this purpose, we simulate the thermal decomposition of amorphous and partially crystalline cellulose at various heating rates. We find that thermal degradation begins with depolymerization via glycosidic bond cleavage, and that the order of events corresponds to a randomly initiated chain reaction. Depolymerization is followed by ring fragmentation reactions that lead to the formation of a number of light oxygenates. Water is formed mainly in intermolecular dehydration reactions at a later stage. The reaction rate of glycosidic bond cleavage follows a sigmoidal reaction model, with an apparent activation energy of 166 ± 4 kJ/mol. Neither the condensed phase environment nor the heating programme have appreciable effects on the reactions. We make several observations that are compatible with mechanisms proposed for cellulose fast pyrolysis. However, due to the absence of anhydrosugar forming reactions, the simulations offer limited insight for conditions of industrial interest. It remains unclear whether this is a natural consequence of the reaction conditions, or a shortcoming of the force field or its parameter set.

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Dementia risk in the general population: large-scale external validation of prediction models in the AGES-Reykjavik study
Authors: Vonk Jet M. J. , Greving Jacoba P. , Gudnason Vilmundur , Launer Lenore J. , Geerlings Mirjam I.
Published: July 2021

We aimed to evaluate the external performance of prediction models for all-cause dementia or AD in the general population, which can aid selection of high-risk individuals for clinical trials and prevention. We identified 17 out of 36 eligible published prognostic models for external validation in the population-based AGES-Reykjavik Study. Predictive performance was assessed with c statistics and calibration plots. All five models with a c statistic > .75 (.76–.81) contained cognitive testing as a predictor, while all models with lower c statistics (.67–.75) did not. Calibration ranged from good to poor across all models, including systematic risk overestimation or overestimation for particularly the highest risk group. Models that overestimate risk may be acceptable for exclusion purposes, but lack the ability to accurately identify individuals at higher dementia risk. Both updating existing models or developing new models aimed at identifying high-risk individuals, as well as more external validation studies of dementia prediction models are warranted.
Socioeconomic inequalities in dementia risk among a French population-based cohort: quantifying the role of cardiovascular health and vascular events
Authors: Letellier Noémie , Ilango Sindana D. , Mortamais Marion , Tzourio Christophe , Gabelle Audrey , Empana Jean-Philippe , Samieri Cécilia , Berr Claudine , Benmarhnia Tarik
Published: July 2021

This study aimed to investigate the role of cardiovascular health (CVH) and vascular events as potential contributors to socioeconomic inequalities in dementia using causal mediation analyses. We used data from the Three-City Cohort, a French population-based study with 12 years of follow-up, with active search of dementia cases and validated diagnosis. Individual socioeconomic status was assessed using education, occupation and income. A CVH score as defined by the American Heart Association and incident vascular events were considered separately as mediators. We performed multi-level Cox proportional and Aalen additive hazard regression models to estimate the total effects of socioeconomic status on dementia risk. To estimate natural direct and indirect effects through CVH and vascular events, we applied two distinct weighting methods to quantify the role of CVH and vascular events: Inverse Odds Ratio Weighting (IORW) and Marginal Structural Models (MSM) respectively. Among 5581 participants, the risk of dementia was higher among participants with primary education (HR 1.60, 95%CI 1.44–1.78), blue-collar workers (HR 1.62, 95%CI 1.43–1.84) and with lower income (HR 1.23, 95%CI 1.09–1.29). Using additive models, 571 (95% CI 288–782) and 634 (95% CI 246–1020) additional cases of dementia per 100 000 person and year were estimated for primary education and blue-collar occupation, respectively. Using IORW, the CVH score mediate the relationship between education or income, and dementia (proportion mediated 17% and 26%, respectively). Yet, considering vascular events as mediator, MSM generated indirect effects that were smaller and more imprecise. Socioeconomic inequalities in dementia risk were observed but marginally explained by CVH or vascular events mediators.
Place matters: geographical context, place belonging and the production of locality in Mediterranean Noirs
Authors: Gabellieri Nicola
Published: July 2021

Scholars have been investigating detective stories and crime fiction mostly as literary works reflecting the societies that produced them and the movement from modernism to postmodernism. However, these genres have generally been neglected by literary geographers. In the attempt to fill such an epistemological vacuum, this paper examines and compare the function and importance of geography in both classic and late 20th century detective stories. Arthur Conan Doyle’s and Agatha Christie’s detective stories are compared to Mediterranean noir books by Manuel Montalbán, Andrea Camilleri and Jean Claude Izzo. While space is shown to be at the center of the investigations in the former two authors, the latter rather focus on place, that is space invested by the authors with meaning and feelings of identity and belonging. From this perspective, the article argues that detective investigations have become a narrative medium allowing the readership to explore the writer’s representation/construction of his own territorial context, or place-setting, which functions as a co-protagonist of the novel. In conclusion, the paper suggests that the emerging role of place in some of the later popular crime fiction can be interpreted as the result of writer’s sentiment of belonging and, according to Appadurai’s theory, as a literary and geographical discourse aimed at the production of locality.
Evolution under domestication of correlated characters in populations of Stenocereus stellatus (Pfeiff.) Riccob., under different forms of management in central Mexico: genetic diversity, damage, and defense mechanisms
Authors: Patiño-López Verónica , Bravo-Avilez David , Vargas-Mendoza Carlos F. , Blancas José , Rendón-Aguilar Beatriz
Published: July 2021

Across the process of domestication, human selection produces changes in target attributes as well as changes that are not necessarily desired by humans due to pleiotropic or linked genes. In this paper we addressed, correlated changes between genetic diversity, damage level, defense mechanisms (resistance and tolerance), and fitness due to the domestication process ofStenocereus pruinosus(Otto ex Pfeiff.)Buxbaum and Stenocereus stellatus(Pfeiff.) Riccobono, an endemic columnar cactus of south-central Mexico. One hundred eighty individuals ofS. stellatusfrom wild, in situ managed, and cultivated populations of Valle de Tehuacán and Mixteca Baja, Puebla, were sampled, and attributes including damage level, defense mechanisms and fitness (number of fruits) were measured. The DNA of 176 individuals was extracted to amplify and analyze five microsatellites in order to estimate genetic diversity and structure. As expected, cultivated populations showed a significantly higher damage level, as well as lower resistance and genetic diversity. Depending on the form of management, correlations between genetic diversity and the rest of the attributes exhibited different patterns. In wild populations, genetic diversity was positively correlated with damage and negatively with resistance; in situ managed populations exhibited the opposite pattern, and in cultivated populations, no correlations were found between these attributes. We propose a hypothetic model of human selection to explain the variation in these correlations. No differences in genetic diversity and tolerance were detected between regions; however, the populations of Valle de Tehuacán exhibited more damage and more resistance. In both regions, populations showed a positive correlation between fitness and resistance and a negative correlation between damage and resistance, suggesting the existence of a defense mechanism to ensure fitness. Also, non-regional differentiation suggests an eventual gene flow due to pollinators, human movement of branches, or a common ancestry before the domestication process.
The adjuvant activity of two urea derivatives on cytokinins: an example of serendipitous dual effect
Authors: Brunoni Federica , Rolli Enrico , Polverini Eugenia , Spíchal Lukáš , Ricci Ada
Published: July 2021

The aim of this study was to investigate the action spectrum of two urea derivatives, the 1,3-di(benzo[d]oxazol-5-yl)urea (5-BDPU) and the 1,3-di(benzo[d]oxazol-6-yl)urea (6-BDPU). In order to evaluate a possible adjuvant activity on cytokinins the compounds alone or in the simultaneous presence of different cytokinins were assayed either on in vitro﻿ typical cytokinin-related bioassays, or on in planta interaction with cytokinin signal transduction pathway. The compounds ability to activate the cytokinin receptor CRE1/AHK4 was studied either by a heterologous bacterial assay or by a competitive binding assay and docking simulations were performed with the crystal structure of the same receptor. Then, owing to their chemical structure which resembles that of urea-type cytokinins, the ability of 5- and 6-BDPU to inhibit the activity of cytokinin oxidase/dehydrogenase of Zea mays (ZmCKX1) was investigated and docking simulations were performed as well. Accordingly to the experimental results, we speculate that BDPUs could show a dual activity: the blocking of the conformational re-adaption of CRE1/AHK4 receptor maintaining the cytokinin inside its binding pocket, thus possibly enhancing its kinase action; the inhibition of cytokinin oxidase/dehydrogenase activity thus possibly preventing its cleavage of natural cytokinins with isoprenoid side chain.

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