bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences of living with mental health problems during the COVID-19 pandemic in the UK: a coproduced, participatory qualitative interview study
Authors: Gillard Steven , Dare Ceri , Hardy Jackie , Nyikavaranda Patrick , Rowan Olive Rachel , Shah Prisha , Birken Mary , Foye Una , Ocloo Josephine , Pearce Ellie , Stefanidou Theodora , Pitman Alexandra , Simpson Alan , Johnson Sonia , Lloyd-Evans Brynmor ,   NIHR Mental Health Policy Research Unit Covid coproduction research group, Anderson Katie , Barber Nick , Chhapia Anjie , Chipp Beverley , Jeynes Tamar , Lomani Jo , Machin Karen , Turner Kati
Published: March 2021

Purpose

Research is beginning to quantify the impact of COVID-19 on people with pre-existing mental health conditions. Our paper addresses a lack of in-depth qualitative research exploring their experiences and perceptions of how life has changed at this time.

Methods

We used qualitative interviews (N = 49) to explore experiences of the pandemic for people with pre-existing mental health conditions. In a participatory, coproduced approach, researchers with lived experiences of mental health conditions conducted interviews and analysed data as part of a multi-disciplinary research team.

Results

Existing mental health difficulties were exacerbated for many people. People experienced specific psychological impacts of the pandemic, struggles with social connectedness, and inadequate access to mental health services, while some found new ways to cope and connect to the community. New remote ways to access mental health care, including digital solutions, provided continuity of care for some but presented substantial barriers for others. People from black and ethnic minority (BAME) communities experienced heightened anxiety, stigma and racism associated with the pandemic, further impacting their mental health.

Conclusion

There is a need for evidence-based solutions to achieve accessible and effective mental health care in response to the pandemic, especially remote approaches to care. Further research should explore the long-term impacts of COVID-19 on people with pre-existing mental health conditions. Particular attention should be paid to understanding inequalities of impact on mental health, especially for people from BAME communities.
Creating a human-induced pluripotent stem cell-based NKX2.5 reporter gene assay for developmental toxicity testing
Authors: Lauschke Karin , Treschow Andreas Frederik , Rasmussen Mikkel Aabech , Davidsen Nichlas , Holst Bjørn , Emnéus Jenny , Taxvig Camilla , Vinggaard Anne Marie
Published: March 2021

To test large numbers of chemicals for developmental toxicity, rapid in vitro tests with standardized readouts for automated data acquisition are needed. However, the most widely used assay, the embryonic stem cell test, relies on the counting of beating embryoid bodies by visual inspection, which is laborious and time consuming. We previously developed the PluriBeat assay based on differentiation of human induced pluripotent stem cells (hiPSC) that we demonstrated to be predictive for known teratogens at relevant concentrations using the readout of beating cardiomyocytes. Here, we report the development of a novel assay, which we term the PluriLum assay, where we have introduced a luciferase reporter gene into the locus of NKX2.5 of our hiPSC line. This enabled us to measure luminescence intensities instead of counting beating cardiomyocytes, which is less labor intensive. We established two NKX2.5 reporter cell lines and validated their pluripotency and genetic stability. Moreover, we confirmed that the genetically engineered NKX2.5 reporter cell line differentiated into cardiomyocytes with the same efficiency as the original wild-type line. We then exposed the cells to valproic acid (25–300 μM) and thalidomide (0.1–36 µM) and compared the PluriBeat readout of the cardiomyocytes with the luminescence intensity of the PluriLum assay. The results showed that thalidomide decreased luminescence intensity significantly with a higher potency and efficacy compared to the beating readout. With this, we have developed a novel hiPSC-based assay with a standardized readout that may have the potential for higher throughput screening for developmental toxicity.
Parabolic eigenvarieties via overconvergent cohomology
Authors: Barrera Salazar Daniel , Williams Chris
Published: March 2021

Let$$\mathcal {G}$$Gbe a connected reductive group over$$\mathbf {Q}$$Qsuch that$$G = \mathcal {G}/\mathbf {Q}_p$$G=G/Qpis quasi-split, and let$$Q \subset G$$Q⊂Gbe a parabolic subgroup. We introduce parahoric overconvergent cohomology groups with respect toQ, and prove a classicality theorem showing that the small slope parts of these groups coincide with those of classical cohomology. This allows the use of overconvergent cohomology at parahoric, rather than Iwahoric, level, and provides flexible lifting theorems that appear to be particularly well-adapted to arithmetic applications. WhenQis a Borel, we recover the usual theory of overconvergent cohomology, and our classicality theorem gives a stronger slope bound than in the existing literature. We use our theory to constructQ-parabolic eigenvarieties, which parametrisep-adic families of systems of Hecke eigenvalues that are finite slope atQ, but that allow infinite slope away fromQ.
Underground metabolism facilitates the evolution of novel pathways for vitamin B6 biosynthesis
Authors: Richts Björn , Commichau Fabian M.
Published: March 2021

The term vitamin B6 is a designation for the vitamers pyridoxal, pyridoxamine, pyridoxine and the respective phosphate esters pyridoxal-5′-phosphate (PLP), pyridoxamine-5′-phosphate and pyridoxine-5′-phosphate. Animals and humans are unable to synthesise vitamin B6. These organisms have to take up vitamin B6 with their diet. Therefore, vitamin B6 is of commercial interest as a food additive and for applications in the pharmaceutical industry. As yet, two naturally occurring routes for de novo synthesis of PLP are known. Both routes have been genetically engineered to obtain bacteria overproducing vitamin B6. Still, major genetic engineering efforts using the existing pathways are required for developing fermentation processes that could outcompete the chemical synthesis of vitamin B6. Recent suppressor screens using mutants of the Gram-negative and Gram-positive model bacteria Escherichia coli and Bacillus subtilis, respectively, carrying mutations in the native pathways or heterologous genes uncovered novel routes for PLP biosynthesis. These pathways consist of promiscuous enzymes and enzymes that are already involved in vitamin B6 biosynthesis. Thus, E. coli and B. subtilis contain multiple promiscuous enzymes causing a so-called underground metabolism allowing the bacteria to bypass disrupted vitamin B6 biosynthetic pathways. The suppressor screens also show the genomic plasticity of the bacteria to suppress a genetic lesion. We discuss the potential of the serendipitous pathways to serve as a starting point for the development of bacteria overproducing vitamin B6.

Key points

• Known vitamin B6 routes have been genetically engineered.

• Underground metabolism facilitates the emergence of novel vitamin B6 biosynthetic pathways.

• These pathways may be suitable to engineer bacteria overproducing vitamin B6.
Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation
Authors: Salamonowicz-Bodzioch Małgorzata , Frączkiewicz Jowita , Czyżewski Krzysztof , Zając-Spychała Olga , Gorczyńska Ewa , Panasiuk Anna , Ussowicz Marek , Kałwak Krzysztof , Szmit Zofia , Wróbel Grażyna , Kazanowska Bernarda , Chybicka Alicja , Ukielska-Hoffmann Bogna , Wendycz-Domalewska Danuta , Wysocki Mariusz , Dziedzic Magdalena , Wachowiak Jacek , Zaucha-Prażmo Agnieszka , Kowalczyk Jerzy , Goździk Jolanta , Styczyński Jan
Published: March 2021

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.
Theory-assisted optical ray tracing to extract cavitation-bubble shapes from experiment
Authors: Koch Max , Rosselló Juan M. , Lechner Christiane , Lauterborn Werner , Eisener Julian , Mettin Robert
Published: March 2021

Experimental analysis of cavitation bubble dynamics typically uses optical imaging and photographic recording. However, the images are often severely affected by distortions and shadows due to refraction and total reflection of the illuminating light at the liquid–gas interface of the bubble. Optical ray tracing may become a powerful tool for the analysis process by assisting in the comparison of experiments to numerical two-phase flow simulations. The novelty of the present approach consists in digitizing almost the complete experimental arrangement with all its optically relevant elements and objects—including a numerical model of the yet unknown bubble—and numerically photographing the scene via ray tracing. The method is applied to the jetting dynamics of single bubbles collapsing at a solid wall. Here, ray tracing can help in the interpretation of raw experimental data concerning the complex bubble interface deformations and internal structures during the collapse. The precise shape of the highly dynamical bubbles can be inferred, thus ray tracing provides a correction method for velocity values of the liquid jets. Strong evidence is found for the existence of an ultra-short-time, fast jet, exceeding velocities known to date in the field.

Graphic abstract
Quenched local limit theorem for random walks among time-dependent ergodic degenerate weights
Authors: Andres Sebastian , Chiarini Alberto , Slowik Martin
Published: March 2021

We establish a quenched local central limit theorem for the dynamic random conductance model on $${\mathbb {Z}}^d$$

Z

d

only assuming ergodicity with respect to space-time shifts and a moment condition. As a key analytic ingredient we show Hölder continuity estimates for solutions to the heat equation for discrete finite difference operators in divergence form with time-dependent degenerate weights. The proof is based on De Giorgi’s iteration technique. In addition, we also derive a quenched local central limit theorem for the static random conductance model on a class of random graphs with degenerate ergodic weights.
A solution framework for linear PDE-constrained mixed-integer problems
Authors: Gnegel Fabian , Fügenschuh Armin , Hagel Michael , Leyffer Sven , Stiemer Marcus
Published: March 2021

We present a general numerical solution method for control problems with state variables defined by a linear PDE over a finite set of binary or continuous control variables. We show empirically that a naive approach that applies a numerical discretization scheme to the PDEs to derive constraints for a mixed-integer linear program (MILP) leads to systems that are too large to be solved with state-of-the-art solvers for MILPs, especially if we desire an accurate approximation of the state variables. Our framework comprises two techniques to mitigate the rise of computation times with increasing discretization level: First, the linear system is solved for a basis of the control space in a preprocessing step. Second, certain constraints are just imposed on demand via the IBM ILOG CPLEX feature of a lazy constraint callback. These techniques are compared with an approach where the relations obtained by the discretization of the continuous constraints are directly included in the MILP. We demonstrate our approach on two examples: modeling of the spread of wildfire and the mitigation of water contamination. In both examples the computational results demonstrate that the solution time is significantly reduced by our methods. In particular, the dependence of the computation time on the size of the spatial discretization of the PDE is significantly reduced.
Energy flow characteristics of friction-induced nonlinear vibrations in a water-lubricated bearing-shaft coupled system
Authors: Qin Li , Qin Hongling , Xing Jing Tang
Published: March 2021

Based on the energy flow theory of nonlinear dynamical system, the stabilities, bifurcations, possible periodical/chaotic motions of nonlinear water-lubricated bearing-shaft coupled systems are investigated in this paper. It is revealed that the energy flow characteristics around the equlibrium point of system behaving in the three types with different friction-paramters. (a) Energy flow matrix has two negative and one positive energy flow factors, constructing an attractive local zero-energy flow surface, in which free vibrations by initial disturbances show damped modulated oscillations with the system tending its equlibrium state, while forced vibrations by external forces show stable oscillations. (b) Energy flow matrix has one negative and two positive energy flow factors, spaning a divergence local zero-energy flow surface, so that the both free and forced vibrations are divergence oscillations with the system being unstable. (c) Energy flow matrix has a zero-energy flow factor and two opposite factors, which constructes a local zero-energy flow surface dividing the local phase space into stable, unstable and central subspace, and the simulation shows friction self-induced unstable vibrations for both free and forced cases. For a set of friction parameters, the system behaves a periodical oscillation, where the bearing motion tends zero and the shaft motion reaches a stable limit circle in phase space with the instant energy flow tending a constant and the time averaged one tending zero. Numerical simulations have not found any possible chaotic motions of the system. It is discovered that the damping matrices of cases (a), (b) and (c) respectively have positive, negative and zero diagonal elements, resulting in the different dynamic behavour of system, which gives a giderline to design the water-lubricated bearing unit with expected performance by adjusting the friction parameters for applications.

Graphic Abstract
Unsteady Effects on NOx Measurements in Pulse Detonation Combustion
Authors: Hanraths Niclas , Bohon Myles D. , Paschereit Christian Oliver , Djordjevic Neda
Published: March 2021

Emission measurements from unsteady combustion systems such as Pulse Detonation Combustion (PDC) are challenging due to the inherently large variations in pressure, temperature, composition, and flow velocity of the exhaust gas. Comparison of experimental data is additionally complicated by differences in operating conditions and gas sampling setup between different facilities. Qualitative considerations with regard to the sampling process from PDC, based on one-dimensional simulations, indicate a systematic influence of the sampling setup and extraction process on the resulting concentration measurements. Therefore, operating frequency, sample time, fill time, as well as PDC outlet and probe geometry were varied experimentally in order to assess the degree to which each of these parameters impact the resulting measured $${\rm NO}_{\rm x}$$

NO
x

in order to better inform researchers of these effects when making measurements. It was shown that measured $${\rm NO}_{\rm x}$$

NO
x

emissions can vary significantly depending on the choice of these parameters and therefore care must be exercised in order to reduce the influence of the sampling technique when aiming for comparable results.
Assessing population collapse of Drupella spp. (Mollusca: Gastropoda) 2 years after a coral bleaching event in the Republic of Maldives
Authors: Saponari L. , Dehnert I. , Galli P. , Montano S.
Published: March 2021

Corallivory causes considerable damage to coral reefs and can exacerbate other disturbances. Among coral predators, Drupella spp. are considered as delayer of coral recovery in the Republic of Maldives, although little information is available on their ecology. Thus, we aimed to assess their population structure, feeding behaviour and spatial distribution around 2 years after a coral bleaching event in 2016. Biological and environmental data were collected using belt and line intercept transects in six shallow reefs in Maldives. The snails occurred in aggregations with a maximum of 62 individuals and exhibited a preference for branching corals. Yet, the gastropods showed a high plasticity in adapting feeding preferences to prey availability. Drupella spp. were homogenously distributed in the study area with an average of 9.04 ± 19.72 ind/200 m2. However, their occurrence was significantly different at the reef scale with the highest densities found in locations with higher coral cover. The impact of Drupella spp. appeared to be minimal with the population suffering from the loss of coral cover. We suggest that monitoring programs collect temporal- and spatial-scale data on non-outbreaking populations or non-aggregating populations to understand the dynamics of predation related to the co-occurrence of anthropogenic and natural impacts.
Electrical conductivity determination of semiconductors by utilizing photography, finite element simulation and resistance measurement
Authors: Wang Rui , Moos Ralf
Published: March 2021

A new method is developed to measure precisely and reliably the electrical conductivity of a block-shaped semiconductor specimen using four-wire technique with electrodes in arbitrary shape and position. No effort for accurate electrode preparation is necessary anymore. This method may be especially applied to measure the conductivity of ceramics at high temperatures, when typical spring-contacts or clamp-contacts are not possible and instead wound wires are used for electrically contacting the specimen. The method comprises the following: An image of the specimen is processed to a 3D model. By applying a finite element simulation on this 3D model, a form factor (also called geometry factor) that considers the effect of the non-infinitesimally small electrodes is calculated. Together with the measured resistance (preferably in four-wire technique), the actual conductivity of the sample is derived. Experimental results confirmed the validity of the proposed method. As a limitation of the method, the conductivity of the specimen should be within the range of 0.01 Sm−1 and 106 Sm−1.
Micro dynamics and macro stability in inventor networks
Authors: Fritsch Michael , Kudic Muhamed
Published: March 2021

From a macro perspective, inventor networks tend to generate remarkably stable structures over time. At the same time, we observe highly dynamic processes at the micro level, in terms of inventor entries and exits as well as formations and terminations of collaborative relationships between them. In order to explain this—at least at the first glance—contradicting pattern, we investigate processes at the intermediate network level. Our analysis draws upon co-patenting data for the entire population of West German inventors in the field of laser technology research from the onset of the technology in the early 1960s over a period of 45 years. Our findings suggest that the key factor for maintaining structural stability of networks is that directly linked partners of inventors with stabilizing properties—so-called ‘key players’—take over this function in a subsequent period. We show that processes at the intermediate network level provide new insights on the co-existence of micro fluidity and macro stability in complex adaptive systems.
Effect of Nanog overexpression on the metastatic potential of a mouse melanoma cell line B16-BL6
Authors: Saito Mikako , Kishi Ryota , Sasai Tomoko , Hatakenaka Tomohiro , Matsuki Nahoko , Minagawa Seiya
Published: March 2021

Nanog, a marker and regulator of the undifferentiated state in embryonic stem cells were anticipated to be an effective enhancer of cancer metastasis. We have developed a Nanog overexpressing mouse melanoma cell line B16-BL6 (BL6). BL6 was well recognized as a cell line with a high metastatic potential. In vitro tests revealed the enhancement of cell proliferation, wound healing activity, and matrix metalloproteinase 9 (MMP9) activity. Nanog-induced up- or down-regulated genes were comprehensively analyzed by transcriptome sequencing using Nanog+BL6 and wild-type BL6. Principally, up-regulated genes were involved in vesicle-aided glucose transport and oxidative phosphorylation, while down-regulated genes were associated with immunosuppression and apoptosis. A marked finding was that TGF-β1 was down-regulated, because TGF-β1 has been well discussed about its suppressive/progressive dual role in cancer. In vivo test showed that the number and volume of metastatic colonies of BL6 to lung were as high as 115 colonies/lung and 5.6 mm3/lung. Under this condition, Nanog overexpression caused a progressive effect (150 colonies/lung, p = 0.25; 9.2 mm3/lung, p = 0.13) rather than a suppressive effect on the metastasis. In this study, the effectiveness of Nanog overexpression in enhancing the metastatic potential of melanoma cell lines has been demonstrated for the first time.
Advancing the Water Footprint into an Instrument to Support Achieving the SDGs – Recommendations from the “Water as a Global Resources” Research Initiative (GRoW)
Authors: Berger Markus , Campos Jazmin , Carolli Mauro , Dantas Ianna , Forin Silvia , Kosatica Ervin , Kramer Annika , Mikosch Natalia , Nouri Hamideh , Schlattmann Anna , Schmidt Falk , Schomberg Anna , Semmling Elsa
Published: March 2021

The water footprint has developed into a widely-used concept to examine water use and resulting local impacts caused during agricultural and industrial production. Building on recent advancements in the water footprint concept, it can be an effective steering instrument to support, inter alia, achieving sustainable development goals (SDGs) - SDG 6 in particular. Within the research program “Water as a Global Resource” (GRoW), an initiative of the Federal Ministry for Education and Research, a number of research projects currently apply and enhance the water footprint concept in order to identify areas where water is being used inefficiently and implement practical optimization measures (see imprint for more information). With this paper, we aim to raise awareness on the potential of the water footprint concept to inform decision-making in the public and private sectors towards improved water management and achieving the SDGs.
Reliability-based design and implementation of crow search algorithm for longitudinal dispersion coefficient estimation in rivers
Authors: Ghaemi Alireza , Zhian Tahmineh , Pirzadeh Bahareh , Hashemi Monfared Seyedarman , Mosavi Amir
Published: March 2021

The longitudinal dispersion coefficient (LDC) of river pollutants is considered as one of the prominent water quality parameters. In this regard, numerous research studies have been conducted in recent years, and various equations have been extracted based on hydrodynamic and geometric elements. LDC’s estimated values obtained using different equations reveal a significant uncertainty due to this phenomenon’s complexity. In the present study, the crow search algorithm (CSA) is applied to increase the equation’s precision by employing evolutionary polynomial regression (EPR) to model an extensive amount of geometrical and hydraulic data. The results indicate that the CSA improves the performance of EPR in terms of R2 (0.8), Willmott’s index of agreement (0.93), Nash–Sutcliffe efficiency (0.77), and overall index (0.84). In addition, the reliability analysis of the proposed equation (i.e., CSA) reduced the failure probability (Pf) when the value of the failure state containing 50 to 600 m2/s is increasing for the Pf determination using the Monte Carlo simulation. The best-fitted function for correct failure probability prediction was the power with R2 = 0.98 compared with linear and exponential functions.
A Regularized LSTM Method for Predicting Remaining Useful Life of Rolling Bearings
Authors: Liu Zhao-Hua , Meng Xu-Dong , Wei Hua-Liang , Chen Liang , Lu Bi-Liang , Wang Zhen-Heng , Chen Lei
Published: March 2021

Rotating machinery is important to industrial production. Any failure of rotating machinery, especially the failure of rolling bearings, can lead to equipment shutdown and even more serious incidents. Therefore, accurate residual life prediction plays a crucial role in guaranteeing machine operation safety and reliability and reducing maintenance cost. In order to increase the forecasting precision of the remaining useful life (RUL) of the rolling bearing, an advanced approach combining elastic net with long short-time memory network (LSTM) is proposed, and the new approach is referred to as E-LSTM. The E-LSTM algorithm consists of an elastic mesh and LSTM, taking temporal-spatial correlation into consideration to forecast the RUL through the LSTM. To solve the over-fitting problem of the LSTM neural network during the training process, the elastic net based regularization term is introduced to the LSTM structure. In this way, the change of the output can be well characterized to express the bearing degradation mode. Experimental results from the real-world data demonstrate that the proposed E-LSTM method can obtain higher stability and relevant values that are useful for the RUL forecasting of bearing. Furthermore, these results also indicate that E-LSTM can achieve better performance.
Emergency room comprehensive assessment of demographic, radiological, laboratory and clinical data of patients with COVID-19: determination of its prognostic value for in-hospital mortality
Authors: Gatti Marco , Calandri Marco , Biondo Andrea , Geninatti Carlotta , Piatti Clara , Ruggirello Irene , Santonocito Ambra , Varello Sara , Bergamasco Laura , Bironzo Paolo , Boccuzzi Adriana , Brazzi Luca , Caironi Pietro , Cardinale Luciano , Cavallo Rossana , Riccardini Franco , Limerutti Giorgio , Veltri Andrea , Fonio Paolo , Faletti Riccardo
Published: March 2021

Mortality risk in COVID-19 patients is determined by several factors. The aim of our study was to adopt an integrated approach based on clinical, laboratory and chest x-ray (CXR) findings collected at the patient’s admission to Emergency Room (ER) to identify prognostic factors. Retrospective study on 346 consecutive patients admitted to the ER of two North-Western Italy hospitals between March 9 and April 10, 2020 with clinical suspicion of COVID-19 confirmed by reverse transcriptase-polymerase reaction chain test (RT-PCR), CXR performed within 24 h (analyzed with two different scores) and recorded prognosis. Clinical and laboratory data were collected. Statistical analysis on the features of 83 in-hospital dead vs 263 recovered patients was performed with univariate (uBLR), multivariate binary logistic regression (mBLR) and ROC curve analysis. uBLR identified significant differences for several variables, most of them intertwined by multiple correlations. mBLR recognized as significant independent predictors for in-hospital mortality age > 75 years, C-reactive protein (CRP) > 60 mg/L, PaO2/FiO2 ratio (P/F) < 250 and CXR “Brixia score” > 7. Among the patients with at least two predictors, the in-hospital mortality rate was 58% against 6% for others [p < 0.0001; RR = 7.6 (4.4–13)]. Patients over 75 years had three other predictors in 35% cases against 10% for others [p < 0.0001, RR = 3.5 (1.9–6.4)]. The greatest risk of death from COVID-19 was age above 75 years, worsened by elevated CRP and CXR score and reduced P/F. Prompt determination of these data at admission to the emergency department could improve COVID-19 pretreatment risk stratification.
Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis
Authors:   On Behalf of Endo ERN (MTG1), Nowotny Hanna , Ahmed S. Faisal , Bensing Sophie , Beun Johan G. , Brösamle Manuela , Chifu Irina , Claahsen van der Grinten Hedi , Clemente Maria , Falhammar Henrik , Hahner Stefanie , Husebye Eystein , Kristensen Jette , Loli Paola , Lajic Svetlana , Reisch Nicole
Published: March 2021

Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
Urologic, lymphedema, pelvic pain and gastrointestinal symptoms increase after radiotherapy in patients with primary uterine tumors: a prospective longitudinal Swedish cohort study
Authors: Holmqvist A. , Axelsson A. , Mikivier R. , Redelius K. , Odelram Wiréen U. , Uppugunduri S.
Published: March 2021

Purpose

Radiotherapy (RT) causes an inflammatory reaction of the tissue which leads to fibrosis and reduced functioning of the pelvic organs. Few studies have shown significant relationships between side effects and RT in uterine tumors. Here, the urological, lymphedema, pelvic pain and gastrointestinal (GI) symptoms were studied before and after RT in patients with primary uterine tumors using the EORTC QLQ-EN24, specifically designed for uterine cancer patients.

Methods

This prospective cohort study comprised patients with primary uterine tumors who received pelvic radiotherapy (RT). A total of 43 patients were included from May 2014 to February 2019. Patients completed the questionnaires for global health status and functioning before the start of RT and at 3 and 12 months after RT.

Results

We found a significant worsening of the urological symptoms 3 months after RT which persisted up to 12 months after RT compared to baseline values prior to start of RT (p = 0.007). An exacerbation of the urinary symptoms was seen in patients with vaginal brachytherapy/boost compared to patients with pelvic RT at 12 months after RT (p = 0.053). The severity of lymphedema symptoms increased from RT start to 12 months after RT (p = 0.019) and the pelvic pain were higher at 3 months after RT compared to before RT (p = 0.004). Also, the level of GI symptoms was significantly higher 12 months after RT compared to the RT start (p < 0.001).

Conclusions

The urologic, lymphedema, pelvic pain and GI symptoms all increase after RT.
Agricultural diversification in West Africa: an archaeobotanical study of the site of Sadia (Dogon Country, Mali)
Authors: Champion Louis , Fuller Dorian Q. , Ozainne Sylvain , Huysecom Éric , Mayor Anne
Published: March 2021

While narratives of the spread of agriculture are central to interpretation of African history, hard evidence of past crops and cultivation practices are still few. This research aims at filling this gap and better understanding the evolution of agriculture and foodways in West Africa. It reports evidence from systematic flotation samples taken at the settlement mounds of Sadia (Mali), dating from 4 phases (phase 0=before first–third century AD; phase 1=mid eighth–tenth c. AD; phase 2=tenth–eleventh c. AD; phase 3=twelfth–late thirteenth c. AD). Flotation of 2200 l of soil provided plant macro-remains from 146 archaeological samples. As on most West African sites, the most dominant plant is pearl millet (Pennisetum glaucum). But from the tenth century AD, sorghum (Sorghum bicolor) and African rice (Oryza glaberrima) appear in small quantities, and fonio (Digitaria exilis) and barnyard millet/hungry rice (Echinochloa sp.), sometimes considered weeds rather than staple crops, are found in large quantities. Some samples also show remains of tree fruits from savannah parklands, such as baobab (Adansonia digitata), marula (Sclerocarya birrea), jujube (Ziziphus sp.), shea butter (Vittelaria paradoxa) and African grapes (Lannea microcarpa). Fonio and Echinochloa sp. cultivation appears here to be a later addition that helped to diversify agriculture and buffer against failures that might affect the monoculture of pearl millet. This diversification at the end of the 1st millennium AD matches with other evidence found in West Africa.
Do Investor–State Disputes (Still) Harm FDI?
Authors: Kerner Andrew , Pelc Krzysztof J.
Published: March 2021

What are the consequences of being sued for violating bilateral investment treaties? The conventional wisdom is that investor–state disputes (ISDS) tarnish countries' compliance records, and harm foreign direct investment in the process. This article re-examines this belief in light of recent trends in ISDS. The regime has witnessed a proliferation of claims, a growing proportion of which allege breaches of provisions like fair and equitable treatment and indirect expropriation. Combined with a decrease in the rate of success of such claims, the authors argue that the average ISDS claim now contains less information than it once did. If this is the case, investors should be less likely to update their expectations and reduce investments. This study examines 812 investor–state disputes from 1987 to the present day, and finds consistent evidence for this across two different datasets relating to firms' risk perceptions. Consequences of investor–state claims on foreign direct investment are only apparent in cases that allege direct expropriation. Even among these, the effects are smaller today than they were in the past. In sum, the reputational effects of ISDS claims appear to have been eroded by the developments of the last two decades. ISDS just isn't what it used to be.
Inverse cascade and magnetic vortices in kinetic Alfvén-wave turbulence
Authors: Miloshevich G. , Laveder D. , Passot T. , Sulem P. L.
Published: March 2021

A Hamiltonian two-field gyrofluid model for kinetic Alfvén waves (KAWs) in a magnetized electron–proton plasma, retaining ion finite-Larmor-radius corrections and parallel magnetic field fluctuations, is used to study the inverse cascades that develop when turbulence is randomly driven at sub-ion scales. In the directions perpendicular to the ambient field, the dynamics of the cascade turns out to be non-local and the ratio

$\chi _f$

of the wave period to the characteristic nonlinear time at the driving scale affects some of its properties. For example, at small values of

$\chi _f$

, parametric decay instability of the modes driven by the forcing can develop, enhancing for a while inverse transfers. The balanced state, obtained at early time when the two counter-propagating waves are equally driven, also becomes unstable at small

$\chi _f$

, leading to an inverse cascade. For

$\beta _e$

smaller than a few units, the cascade slows down when reaching the low-dispersion spectral range. For higher

$\beta _e$

, the ratio of the KAW to the Alfvén frequencies displays a local minimum. At the corresponding transverse wavenumber, a condensate is formed, and the cascade towards larger scales is then inhibited. Depending on the parameters, a parallel inverse cascade can develop, enhancing the elongation of the ion-scale magnetic vortices that generically form.
The genetic basis of major depression
Authors: Kendall K. M. , Van Assche E. , Andlauer T. F. M. , Choi K. W. , Luykx J. J. , Schulte E. C. , Lu Y.
Published: March 2021

Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.
Psychosocial working conditions and the risk of diagnosed depression: a Swedish register-based study
Authors: Almroth Melody , Hemmingsson Tomas , Sörberg Wallin Alma , Kjellberg Katarina , Burström Bo , Falkstedt Daniel
Published: March 2021

Background

High job demands, low job control, and their combination (job strain) may increase workers' risk of depression. Previous research is limited by small populations, not controlling for previous depression, and relying on the same informant for reporting exposure and outcome. This study aims to examine the relationship between objectively measured workplace factors and the risk of developing clinical depression among the Swedish working population while controlling for previous psychiatric diagnoses and sociodemographic factors.

Methods

Control, demands, and job strain were measured using the Swedish Job Exposure Matrix (JEM) measuring psychosocial workload linked to around 3 million individuals based on their occupational titles in 2005. Cox regression models were built to estimate associations between these factors and diagnoses of depression recorded in patient registers.

Results

Lower job control was associated with an increased risk of developing depression (HR 1.43, 95% CI 1.39–1.48 and HR 1.27, 95% CI 1.24–1.30 for men and women with the lowest control, respectively), and this showed a dose–response relationship among men. Having high job demands was associated with a slight decrease in depression risk for men and women. High strain and passive jobs (both low control jobs) were associated with an increased risk of depression among men, and passive jobs were associated with an increased risk among women.

Conclusion

High job control appears important for reducing the risk of developing depression even when accounting for previous psychiatric diagnoses and sociodemographic factors. This is an important finding concerning strategies to improve occupational and in turn mental health.
New Developments in the Comprehensive Inner Magnetosphere‐Ionosphere Model
Authors: Fok M.‐C. , Kang S.‐B. , Ferradas C. P. , Buzulukova N. Y. , Glocer A. , Komar C. M.
Published: March 2021

A Comprehensive Inner Magnetosphere‐Ionosphere (CIMI) model was developed to study the dynamic variations of the radiation belts, ring current, and plasmasphere as well as the couplings between these populations and with the ionosphere. The CIMI model has been used in multiple studies to simulate a number of magnetic storms and reproduce many observable features that involve cross‐region and cross‐energy processes. This model has been continuously validated and improved. In this study, we report on two major recent advancements in CIMI. The first improvement is transforming coordinates in both configuration and velocity space into uniform grids. Numerical schemes, especially those of high order, are generally more stable on such uniform grids. The second advancement is to solve both advection and diffusion in the CIMI equation in a single coordinate system. Previously, the phase space distribution was expressed in terms of the first two adiabatic invariants when solving for particle drift, whereas particle distributions were transformed into energy and pitch angle for calculating wave diffusion. In the new approach in CIMI, particles and distribution functions are identified by their momentum. This change avoids interpolation errors inherent in the mapping of the phase space distribution when switching back and forth between advective and diffusive transport. We describe the detailed implementation of these recent advancements in the CIMI model, and demonstrate how the newly improved model provides better predictions of the ring current and radiation belt dynamics.
Global Prediction of Soil Saturated Hydraulic Conductivity Using Random Forest in a Covariate‐Based GeoTransfer Function (CoGTF) Framework
Authors: Gupta Surya , Lehmann Peter , Bonetti Sara , Papritz Andreas , Or Dani
Published: March 2021

Saturated hydraulic conductivity (Ksat) is a key soil hydraulic parameter for representing infiltration and drainage in land surface models. For large scale applications, Ksat is often estimated from pedotransfer functions (PTFs) based on easy‐to‐measure soil properties like soil texture and bulk density. The reliance of PTFs on data from uniform arable lands and the omission of soil structure limits the applicability of texture‐based predictions of Ksat in vegetated lands. To include effects of terrain, climate, and vegetation in the derivation of a new global Ksat map at 1 km resolution, we harness technological advances in machine learning and availability of remotely sensed surrogate information. For model training and testing, a global compilation of 6,814 geo‐referenced Ksat measurements from the literature was used. The accuracy assessment based on spatial cross‐validation shows a concordance correlation coefficient (CCC) of 0.16 and a root mean square error (RMSE) of 1.18 for log10 Ksat values in cm/day (CCC = 0.79 and RMSE = 0.72 for non‐spatial cross‐validation). The generated maps of Ksat represent spatial patterns of soil formation processes more distinctly than previous global maps of Ksat based on easy‐to‐measure soil properties. The validation of the model indicates that Ksat could be modeled without bias using Covariate‐based GeoTransfer Functions (CoGTFs) that harness spatially distributed surface and climate attributes, compared to soil information based PTFs. The relatively poor performance of all models in the validation (low CCC and high RMSE) highlights the need for the collection of additional Ksat values to train the model for regions with sparse data.
Rastreando c�mo se mueve el pl�stico en el oc�ano costero
Authors: Wheeling Kate
Published: March 2021

Investigadores utilizaron un tanque de olas para estudiar el movimiento de part�culas de pl�stico de forma experimental y comprender el papel de la densidad de part�culas en el comportamiento de deriva.
Sialylated human milk oligosaccharides program cognitive development through a non-genomic transmission mode
Authors: Hauser Jonas , Pisa Edoardo , Arias Vásquez Alejandro , Tomasi Flavio , Traversa Alice , Chiodi Valentina , Martin Francois-Pierre , Sprenger Norbert , Lukjancenko Oksana , Zollinger Alix , Metairon Sylviane , Schneider Nora , Steiner Pascal , Martire Alberto , Caputo Viviana , Macrì Simone
Published: March 2021

Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6′SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6′SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6′SL-deficient milk. To test whether lactational 6′SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6′SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6′SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.