bluuebunny/crossref_metadata_2025 huggingface dataset:
Driving status and health-related quality of life among the oldest old: a population-based examination using data from the AgeCoDe–AgeQualiDe prospective cohort study
Authors: Hajek André , Brettschneider Christian , Lühmann Dagmar , van den Bussche Hendrik , Wiese Birgitt , Mamone Silke , Weyerer Siegfried , Werle Jochen , Leve Verena , Fuchs Angela , Röhr Susanne , Stein Janine , Bickel Horst , Mösch Edelgard , Heser Kathrin , Wagner Michael , Scherer Martin , Maier Wolfgang , Riedel-Heller Steffi G. , Pentzek Michael , König Hans-Helmut
Published: January 2020

Background

It is almost unknown whether the driving status is associated with HRQOL among individuals in highest age.

Aims

Based on a multicenter prospective cohort study, the objective of this study was to examine whether the driving status is associated with health-related quality of life (HRQOL) among the oldest old in Germany.

Methods

Cross-sectional data from follow-up wave 9 (n = 544) were derived from the “Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)” (AgeQualiDe). Average age was 90.3 years (± 2.7; 86 to 101 years). The current driver status (no; yes) was used in our analysis. The EuroQoL EQ-5D questionnaire was used to assess HRQOL in this study.

Results

Regression analysis showed that being a current driver was associated with the absence of problems in ‘self-care’ [OR 0.41 (95%-CI 0.17 to 0.98)], and ‘usual activities’ [OR 0.48 (0.26 to 0.90)], whereas it was not significantly associated with problems in ‘pain/discomfort’ [OR  0.82 (0.47 to 1.45)] and ‘anxiety/depression’ [OR  0.71 (0.36 to 1.39)]. Being a current driver was marginally significantly associated with the absence of problems in ‘mobility’ [OR 0.60 (0.34 to 1.06)]. While being a current driver was not associated with the EQ-VAS in the main model, it was positively associated with the driving status (β = 5.00, p < .05) when functional impairment was removed from the main model.

Discussion

Our findings provide first evidence for an association between driving status and HRQOL among the oldest old.

Conclusions

Future longitudinal studies are required to evaluate a possible causal relationship between driving status and HRQOL in very old individuals.
Dengue meningoencephalitis in a child presenting with focal seizures
Authors: Arishi Haider M. , Ageel Adeeb A. , Al najmi Muneerah I. , Khawaji Tariq K. , Al guridi Hassan I. , Mashhour Abdu H. , Dhayhi Nabeel S. , Eisa Zaki M.
Published: January 2020

We report a 9-year-old female child who presented with fever and focal seizures. The Cerebrospinal Fluid (CSF) analysis was compatible with viral meningoencephalitis and Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on same sample was positive for dengue virus RNA, serotype 2. The dengue IgM in blood sample was positive on the 8th day of the illness. This case demonstrates the emerging neurological manifestations of dengue infection and the first confirmed pediatric meningoencephalitis reported from Saudi Arabia. In areas where it does exist, dengue should be included in the differential diagnosis of cases of viral meningitis or meningoencephalitis.
Tolio: Foot Rot in Grand Canyon River Runners
Authors: Myers Thomas M. , Bigler Carl J. , Maurer Matthew B. , Gaither Marlene E. , Taylor Walter M.
Published: January 2020

Treating skin disorders in wilderness settings is often challenging. In this report we describe common skin conditions affecting the feet of river runners on the Colorado River in Grand Canyon National Park. These conditions are frequently referred to by river runners with a catchall term, “tolio.” Several skin disorders have been identified as components of tolio, with the most prevalent currently being pitted keratolysis. We present a case of pitted keratolysis in a river guide occurring during a multiday river trip, where treatment can be difficult. Prevention is often more important.
The British Academy Brian Barry Prize Essay: Representing the Future: The Interests of Future Persons in Representative Democracy
Authors: Campos Andre Santos
Published: January 2020

As a reaction against contemporary democracy's inherent short-sightedness in solving problems that are likely to affect distant future generations, there has been a recent increase in proposals for different kinds of democratic representation of future persons. This article shows that even though there can be no such thing as political representation of future persons, the relevant affected interests of the as-yet unborn can still be taken into consideration in political decision making. This aim is achieved by focusing on the political representation of children as special cases of semi-future members of the class of the represented.
Assessment irradiation effects on different development stages of Callosobruchus maculatus and on chemical, physical and microbiological quality of cowpea seeds
Authors: Hammad A. , Gabarty A. , Zinhoum R. A.
Published: January 2020

Irradiation is a physical, environmentally friendly treatment which does not leave any residues in the product. It is increasingly used as an alternative to methyl bromide and other chemical fumigants for disinfestation of insect pest in stored grains. In this research, we try to evaluate the effect of low gamma irradiation doses in the range of 50–1200 Gy on the different stages of Callosobruchus maculatus. It was found that no adults emerged after irradiation of eggs at 450 Gy. No emerging adults (F1 generation) have been shown when larvae or pupae were exposed to 650 Gy. Also, no emerging adult has been shown from the parental C. maculatus adults irradiated with 650 Gy. When suppression of F1 generation was used for the measuring effective irradiation dose and phytosanitary efficacy, 650 Gy was required for disinfestation of cowpea seed weevils. The irradiation dose level of 650 Gy was used for the large-scale confirmatory tests applied to 27,754 adults of C. maculatus in cowpea seeds resulting in non F1 adults' production with a confidence level of 93.77%. All the physical and chemical characteristics of cowpea seeds were non-significantly (P ≤ 0.05) affected by the irradiation dose of 650 Gy. Meanwhile, this irradiation dose very slightly reduced the microbial load of cowpea seeds. We recommend the generic dose 650 Gy as the phytosanitary irradiation dose for the cowpea seed weevil.
Justice as Luck Egalitarian Fairness?
Authors: HODGSON LOUIS-PHILIPPE
Published: January 2020

InA Conceptual Investigation of Justice, Kyle Johannsen maintains that the strongest version of John Rawls’s theory of justice is one that incorporates the luck egalitarian conception of fairness developed by G.A. Cohen. He also contends that, once the theory is modified in this way, it becomes clear that the original position doesn’t yield principles of justice but rather what Cohen calls ‘rules of regulation.’ I argue that the minimal conception of fairness that Rawls favours is the right one for his purposes, and that bringing in luck egalitarian fairness would render the outcome of the original position indeterminate.
Values for Foxes? A Comment on Kyle Johannsen’sA Conceptual Investigation of Justice
Authors: MACLEOD COLIN M.
Published: January 2020

This paper provides a critical rejoinder to some themes in Kyle Johannsen’sA Conceptual Investigation of Justice. The discussion focuses on Johannsen’s analysis of fundamental value pluralism and identifies a number of challenges to the form of value pluralism defended by Johannsen. I suggest that Johannsen’s analysis fails to explain how conflicts between fundamental values can be resolved, and that there is greater harmony between fundamental values than Johannsen recognizes.
Justice, Pluralism, and the Egalitarian Ethos
Authors: VOIGT KRISTIN
Published: January 2020

One of the central aims of Kyle Johannsen’s monograph,A Conceptual Investigation of Justice, is to defend the idea that we should think of justice as a fundamental value—a value that can come into conflict with other fundamental values. This pluralism is associated in particular with G.A. Cohen’s work and his critique of John Rawls’s theory of justice. In this commentary, I sketch some of the implications of Cohen’s pluralism for a Cohenite ethos of justice.
Ketotic cows display a different serum nonesterified fatty acid composition
Authors: Liu Lei , Shen Taiyu , Yang Wei , Yu Hongjiang , Gao Sansi , Huang Baoyin , Xu Chuang
Published: January 2020

The experiments reported in this research communication aimed to compare the serum nonesterified fatty acid (NEFA) composition in ketotic cows and healthy cows during the perinatal period. NEFAs play significant roles in etiology and pathology of ketosis. We hypothesized that ketotic cows will display a different serum NEFA composition compared to healthy controls, and fatty acid related indicators for ketosis prediction can be screened. Pre-partum healthy cows were recruited, and blood samples were collected on −7, 3, 7, 14 and 21 d postpartum. Cows were further divided into a healthy control group (C group, n = 6) and a ketosis group (K group, n = 6) if blood β-hydroxybutyric acid levels exceeded 1.2 mm during the experiment. NEFA composition was then analyzed by means of Gas Chromatography-Mass Spectrometer (GC-MS). Only C12 : 0% was significantly higher in C group than K group on 7 d pre-partum (P < 0.05), when the cows were not diagnosed with ketosis. Five fatty acids displayed statistical differences in composition between C and K group (P < 0.05), namely C12 : 0, C16 : 0, C17 : 0, C18 : 1n9 and C22 : 1n9. Saturates%, unsaturates%, mono-unsaturates% and saturates/unsaturates were also different between C and K group (P < 0.05). Of note, C18 : 1n9/C12 : 0 and C18 : 1n9/C22 : 1n9 in K group were significantly higher than those in controls on 7 d pre-partum (P < 0.05). It is suggested that the ratios show potential as indicators for prediction of ketosis.
A nutrigenetics approach to study the impact of genetic and lifestyle factors on cardiometabolic traits in various ethnic groups: findings from the GeNuIne Collaboration
Authors: Vimaleswaran Karani S.
Published: January 2020

Several studies on gene–diet interactions (nutrigenetics) have been performed in western populations; however, there are only a few studies to date in lower middle-income countries (LMIC). A large-scale collaborative project called gene–nutrient interactions (GeNuIne) Collaboration, the main objective of which is to investigate the effect of GeNuIne on cardiometabolic traits using population-based studies from various ethnic groups, has been initiated at the University of Reading, UK. While South Asians with higher genetic risk score (GRS) showed a higher risk of obesity in response to a high-carbohydrate diet, South East and Western Asian populations with higher GRS showed an increased risk of central obesity in response to a high-protein diet. The paper also provides a summary of other gene–diet interaction analyses that were performed in LMIC as part of this collaborative project and gives an overview of how these nutrigenetic findings can be translated to personalised and public health approaches for the prevention of cardiometabolic diseases such as obesity, type 2 diabetes and CVD.
Nutrition and gut health: the impact of specific dietary components – it's not just five-a-day
Authors: Rhodes Jonathan M.
Published: January 2020

The health benefits of fruit, vegetables and dietary fibre have been promoted for many years. Much of the supporting evidence is circumstantial or even contradictory and mechanisms underlying health benefits of specific foods are poorly understood. Colorectal cancer shows marked geographical differences in incidence, probably linked with diet, and explanations for this require knowledge of the complex interactions between diet, microbiota and the gut epithelium. Dietary fibres can act as prebiotics, encouraging growth of saccharolytic bacteria, but other mechanisms are also important. Some but not all soluble fibres have a ‘contrabiotic’ effect inhibiting bacterial adherence to the epithelium. This is particularly a property of pectins (galacturonans) whereas dietary fructans, previously regarded as beneficial prebiotics, can have a proinflammatory effect mediated via toxic effects of high butyrate concentrations. This also suggests that ulcerative colitis could in part result from potentially toxic faecal butyrate concentrations in the presence of a damaged mucus layer. Epithelial adherence of lectins, either dietary lectins as found in legumes, or bacterial lectins such as the galactose-binding lectin expressed by colon cancer-associated Fusobacterium nucleatum, may also be important and could be inhibitable by specific dietary glycans. Conversely, emulsifiers in processed foods may increase bacterial translocation and alter the microbiota thus promoting inflammation or cancer. Focusing on one condition is of limited value although in developing public health messages and growing evidence for impacts of dietary components on all-cause mortality is gaining more attention. We are only just starting to understand the complex interactions between food, the microbiota and health.
gahwat al-murra: the N + DEF-ADJ syntagm and the *at>ahshift in Arabic
Authors: Stokes Phillip W.
Published: January 2020

Multiple varieties of Arabic attest a definite noun + adjective syntagm in which only the adjective is marked morphologically with the article, e.g., Lebanesebēt iz-zġīr“the small house”. The feminine ending*-ahis everywhere realized -(v)t, e.g., Baghdadisint il-māḍye“last year”. Most have assumed that it was originally appositional, and re-analysed as a construct, prompted perhaps by the loss of case (Hopkins 1984; Pat-El 2017). A few scholars (Reckendorf 1921; Retsö 2009) have argued that this syntagm was originally construct. In this article I draw on relevant Arabic data, including parallels with dialectaltanwīn, as well as comparative Semitic evidence, to argue that this syntagm is, diachronically and synchronically, one of apposition and not annexation. I propose that the feminine-athere represents a retention of proto-Arabic*-at, which was protected by the close relationship between a noun and following attribute. I conclude with a discussion of historical and comparative implications.
Five pillars for societal perspective
Authors: Drost Ruben M. W. A. , Paulus Aggie T. G. , Evers Silvia M. A. A.
Published: January 2020

In economic evaluation, the healthcare perspective has gradually given way to use of the societal perspective, as this perspective is often advocated for support in making optimal societal decisions. In practice, economic evaluations conducted from the societal perspective ignore, fail to measure and/or fail to monetize many of the costs that fall outside of the healthcare sector. To limit bias and increase decision-supportive power, researchers could strengthen their evaluations by adhering to a few basic principles. Five “pillars for the societal perspective” are proposed. First, who bears the cost and who does not is irrelevant. Second, it is imperative to consider including costs for sectors outside the healthcare sector. Third, both high frequent costs and costs with high unit prices should be considered. Fourth, double counting should be avoided. And fifth, researchers should reflect on choices related to costs, i.e. cost omission and problems with identifying, measuring, and valuing costs.
Characterization and Rietveld refinements of new dense ceramics Ba3−xSrxTb3−xCexO9 (x = 1 and 1.5) perovskites
Authors: Su Yali , Lu Dayong , Wang Shan
Published: January 2020

Ba3−xSrxTb3−xCexO9 (x = 1 and 1.5) ceramics (BSTC) with a relative density of 93% and a grain size distribution of 0.2–3 µm were prepared by the mixed-oxides reaction route. The crystalline structures, microstructures, valence states, and electrical properties of two ceramics were analyzed using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and electrical measurements. Rietveld analyses of XRPD patterns show that BSTC1 is indexed as a trigonal structure with the space group R-3c, and BSTC3/2 is indexed as an orthorhombic perovskite structure with the space group Pmcn. The EPR, XPS, and electrical conductivity results confirm that Ce and Tb ions in BSTC exist as Ce4+ and mixed-valence states of Tb4+/Tb3+, respectively. At room temperature, the two BSTC ceramics exhibit a similar semiconducting behavior. The relationships between electrical conductivity and temperature/frequency are provided. The defect chemistry is discussed.
Incidental Things in Historiography
Authors: Wimmler Jutta
Published: January 2020

There are some obvious differences between an archaeological and a historiographical approach to things. Put crudely, archaeologists study material ‘things’ while historians study texts. If historians are confronted with things, it is usually through descriptions of them (texts)—thus through the medium of the written word. In the introduction to this issue, the authors propose that the concept ofBeiläufigkeitcan help us ‘to discuss the conditions and processes that are responsible for the variable status of things in a world of objects’. They also propose that a way of approaching the subject is by studying things ‘that were made to be incidental’. One way of applying this to historical scholarship is to look at the way things appear—and disappear—in the historiographical narrative. IfBeiläufigkeitis a fundamental phenomenon of socialization, as they suggest, then it is also a consequence of historical learning: we are taught when things are historically relevant and when they are not. It seems important to question this, especially if we think of historiography as part of a larger discourse that stabilizes and perpetuates hegemonic narratives—such as the narrative of the emergence of the modern West.
Law Reporting and Public Access in the Courts: Is Too Much a Good Thing?
Authors: Magrath Paul
Published: January 2020

This article by Paul Magrath considers the role of law reporting not only as a service in support of the administration of justice and legal education, but also in the wider context of open justice, transparency and public legal information. It traces the history of law reporting and considers the pros and cons of the more comprehensive publication of judgments of the senior courts made possible by digitisation and the internet, in comparison with the more selective approach adopted in the past. The article is loosely based on a presentation given at the annual conference of the British and Irish Association of Law Librarians held in Bournemouth in June 2019.
Law Reporting and Public Access in the Courts: Is Too Much a Good Thing?
Authors: Dewey Cole Charles
Published: January 2020

Beginning in the early 1800s, New York has followed a comprehensive model of law-reporting with official law reports. This article by Charles Dewey Cole, Jr. looks at the influence of James Kent in establishing comprehensive law-reporting in New York, reviews the 1938 legislation that created the law reporting bureau and charged the state reporter with reporting almost all appellate court and selective trial court decisions, describes the state reporter's current publication practices and considers both the advantages of and the challenges presented by comprehensive official law-reporting. The article is based on a June 2019 presentation given at the annual conference of the British and Irish Association of Law Librarians in Bournemouth.
Implementing Nano-Learning in the Law Firm
Authors: Karlén Gramming Ann-Christin , Ejemyr Elisabeth , Thunell Elin
Published: January 2020

This article by Ann-Christin Karlén Gramming, Elisabeth Ejemyr and Elin Thunell is based on a presentation delivered at the BIALL Annual Conference in 2019. It focuses on promoting library services through an e-learning system called ‘Nano-learning’. It is an innovative way of promoting the library and its services in a new and engaging manner. It combats information overdose (usually followed by a rapid forgetting curve) by relying on spaced repetition. The system also comes with useful analytics and reporting tools, making it easy to measure and showcase ROI (return on investment) to partners.
QUADRATIC DIFFERENTIAL EQUATIONS: PARTIAL GELFAND–SHILOV SMOOTHING EFFECT AND NULL-CONTROLLABILITY
Authors: Alphonse Paul
Published: January 2020

We study the partial Gelfand–Shilov regularizing effect and the exponential decay for the solutions to evolution equations associated with a class of accretive non-selfadjoint quadratic operators, which fail to be globally hypoelliptic on the whole phase space. By taking advantage of the associated Gevrey regularizing effects, we study the null-controllability of parabolic equations posed on the whole Euclidean space associated with this class of possibly non-globally hypoelliptic quadratic operators. We prove that these parabolic equations are null-controllable in any positive time from thick control subsets. This thickness property is known to be a necessary and sufficient condition for the null-controllability of the heat equation posed on the whole Euclidean space. Our result shows that this geometric condition turns out to be a sufficient one for the null-controllability of a large class of quadratic differential operators.
Is faster better? Political and ethical framings of pace and space
Authors: Amoureux Jack L.
Published: January 2020

Considering the recent ‘temporal turn’ in International Relations scholarship, this article proposes that space and time are concepts that ‘thicken’ one another in several ways, with significant implications for understanding foreign policy and world politics. In the discourse of security and governance, space–time frames work together to facilitate and legitimize certain policies, actions, and reactions, and imply distinct perspectives on ethics. Drawing on the examples of United States (US) drone use, reactions to the event that has become known as ‘Benghazi’, and fears of the global spread of disease, this study investigates how temporal and spatial framings conceptualize effective and ethical security and governance. Arguing that space–time frames take shape from the resonance of political, theoretical, and cultural texts, four frames are elaborated including ‘space–time liberations’, ‘space–time oppressions’, ‘space–time strategics’, and ‘space–time reflexivities’. The article concludes by suggesting that contradictions and tensions between the frames along with postcolonial and decolonial perspectives can be leveraged to interrogate and displace dominant notions of pace and space in the practice and study of world politics, and that this is a form of scholarly and political reflexivity.
Can the Paris Agreement Help Climate Change Litigation and Vice Versa?
Authors: Wegener Lennart
Published: January 2020

Domestic climate change litigation is prospering across the globe to the extent of becoming a transnational phenomenon of growing importance. At the international level the Paris Agreement, although still in its infancy, has been established as the core element of the climate change governance framework. This article explores the still opaque relationship between domestic climate change litigation and the Paris Agreement. It is argued that dynamic interaction between domestic litigation and the Paris Agreement may improve the overall efficacy of both regimes. On the one hand, an examination of the Paris Agreement's architecture and provisions reveals pathways that are already being used or can be explored further in litigation. On the other hand, litigation can assist and complement the Paris Agreement with regard to its implementation and progress towards its overall goals. The result may deliver more than a multi-level perspective on climate change law. As it captures the law in action on different levels, the proposed ‘cross-level’ approach has due regard to the implications of the mutual supportiveness or complementarity of legal tools. It also thereby responds to the concern of whether the law can be of significant benefit in addressing complex global issues like climate change.
Studies of a Lacustrine‐Volcanic Mars Analog Field Site With Mars‐2020‐Like Instruments
Authors: Martin Peter E. , Ehlmann Bethany L. , Thomas Nancy H. , Wiens Roger C. , Hollis Joseph J. R. , Beegle Luther W. , Bhartia Rohit , Clegg Samuel M. , Blaney Diana L.
Published: January 2020

On the upcoming Mars‐2020 rover two remote sensing instruments, Mastcam‐Z and SuperCam, and two microscopic proximity science instruments, Scanning for Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) and Planetary Instrument for X‐ray Lithochemistry (PIXL), will collect compositional (mineralogy, chemistry, and organics) data essential for paleoenvironmental reconstruction. The synergies between and limitations of these instruments were evaluated via study of a Mars analog field site in the Mojave desert, using instruments approximating the data that will be returned by Mars‐2020. A ground truth data set was generated for comparison to validate the results. The site consists of a succession of clay‐rich mudstones of lacustrine origin, interbedded tuffs, a carbonate‐silica travertine deposit, and gypsiferous mudstone strata. The major geological units were mapped successfully using simulated Mars‐2020 data. Simulated Mastcam‐Z data identified unit boundaries and Fe‐bearing weathering products. Simulated SuperCam passive shortwave infrared and green Raman data were essential in identifying major mineralogical composition and changes in lacustrine facies at distance; this was possible even with spectrally downsampled passive IR data. Laser‐induced breakdown spectroscopy and simulated PIXL data discriminated and mapped major element chemistry. Simulated PIXL revealed millimeter‐scale zones enriched in zirconium, of interest for age dating. Scanning for SHERLOC‐like data mapped sulfate and carbonate at submillimeter scale; silicates were identified with increased laser pulses/spot or by averaging of hundreds of spectra. Fluorescence scans detected and mapped varied classes of organics in all samples, characterized further with follow‐on spatially targeted deep‐UV Raman spectra. Development of dedicated organics spectral libraries is needed to aid interpretation. Given these observations, the important units in the outcrop would be sampled and cached for sample return.
Implantation of Earth's Atmospheric Ions Into the Nearside and Farside Lunar Soil: Implications to Geodynamo Evolution
Authors: Wei Y. , Zhong J. , Hui H. , Shi Q. , Cui J. , He H. , Zhang H. , Yao Z. , Yue X. , Rong Z. , He F. , Chai L. , Wan W.
Published: January 2020

Earth's present dipolar magnetic field extends into the interplanetary space and interacts with the solar wind, forming a magnetosphere filled up with charged particles mostly originating from the Earth's atmosphere. In the elongated tail of the magnetosphere, the particles were observed to move either Earthward or tailward at different locations, even outside the Moon's orbit. We hypothesize that the lunar soil, on both the nearside and farside, should have been impacted by these particles during the geological history, and the impact was controlled by the size and morphology of the magnetosphere. We predict that the farside soil could also have the features similar to those in the nearside soil, e.g., 15N‐enrichment. Furthermore, we may infer the evolution of the magnetosphere and atmosphere by examining the implanted particles in the lunar soil from both sides. This hypothesis could provide an alternative way to study the evolution of Earth's dynamo and atmosphere.
Constraining Reanalysis Snowfall Over the Arctic Ocean Using CloudSat Observations
Authors: Cabaj A. , Kushner P. J. , Fletcher C. G. , Howell S. , Petty A. A.
Published: January 2020

In the absence of widespread snowfall observations over the Arctic Ocean, reanalysis products provide a wide range of estimates of time‐evolving snowfall rates over Arctic sea ice, and it can be difficult to determine which product is most representative. In this work, Arctic snowfall rates retrieved from 2006 to 2016 CloudSat observations and snowfall products from three reanalyses are assessed. The products can be brought into encouraging agreement over the region on interannual time scales once differences in spatial representativeness and temporal sampling are accounted for. This motivates the use of CloudSat's snowfall product to calibrate reanalysis snowfall. The calibration is carried out for four Arctic quadrants and combined to produce regionally resolved and consistent estimates of interannually varying snowfall. Calibrated reanalysis snowfall inputs are then used to drive the NASA Eulerian Snow On Sea Ice Model, reducing the interproduct spread in the resulting simulated snow depths across the Arctic.
The Use of Ensembles in Space Weather Forecasting
Authors: Guerra J. A. , Murray S. A. , Doornbos E.
Published: January 2020

In order to advance the use of ensembles in forecasting space weather events, the workshop Ensemble Forecasts in Space Weather: Science and Operations took place at the Lorentz Center in Leiden, The Netherlands, on 2–6 September 2019. The aim of this workshop was to bring together space weather scientists from academic institutions and operational centers and experts in ensemble techniques in terrestrial weather forecasting. Ensembles are currently used across all the subfields of space weather; however, there seems to be no community‐wide consensus about how to best utilize them. Therefore, the Testing, Understanding, and Leveraging Ensemble Predictions for Space Weather (TULEPS) working group was created to provide a starting point for the space weather community to the use of ensemble techniques.
Correction: Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment
Authors: Caye Aurélie , Rouault-Pierre Kevin , Strullu Marion , Lainey Elodie , Abarrategi Ander , Fenneteau Odile , Arfeuille Chloé , Osman Jennifer , Cassinat Bruno , Pereira Sabrina , Anjos-Afonso Fernando , Currie Erin , Ariza-McNaughton Linda , Barlogis Vincent , Dalle Jean-Hugues , Baruchel André , Chomienne Christine , Cavé Hélène , Bonnet Dominique
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Correction: CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy
Authors: Kinstrie Ross , Horne Gillian A. , Morrison Heather , Irvine David , Munje Chinmay , Castañeda Eduardo Gómez , Moka Hothri A. , Dunn Karen , Cassels Jennifer E. , Parry Narissa , Clarke Cassie J. , Scott Mary T. , Clark Richard E. , Holyoake Tessa L. , Wheadon Helen , Copland Mhairi
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Prevalence and stability of insufficient sleep measured by actigraphy: a prospective community study
Authors: Ranum Bror M. , Wichstrøm Lars , Pallesen Ståle , Steinsbekk Silje
Published: January 2020

Background

It is well established that reduced sleep has detrimental effects on school-aged children’s functioning, but the prevalence and stability of objectively measured insufficient sleep throughout childhood is unknown.

Methods

A sample of 799 children was followed biennially with 24-h 7-day accelerometer (hip-placed) measurements from ages 6 to 12 years. Insufficient sleep was conceptualized as sleeping <7 h on average (AIS) and as the number of nights with <7 h of sleep (NNIS).

Results

The prevalence of AIS ranged from 1.1% to 13.6%. Of those without AIS, 15.1–64.5% had >1 NNIS. At ages 6–10 years, NNIS was higher on weekend nights, but at age 12 years NNIS was lower on weekends (18.1%) compared to weekdays (23.4%). The stability of AIS was low from ages 6 to 8 years and from 8 to 10 years, but increased from age 10 to 12 years, whereas NNIS evidenced higher stability, increasing sharply through late middle childhood.

Conclusions

The prevalence of AIS was low during the preschool and early school years but increased toward preadolescence. The 2-year stability of insufficient sleep was very low when conceptualized as AIS and moderate when defined as NNIS, hence NNIS might be more sensitive than AIS. Insufficient sleep appears transient in middle childhood and thus might not warrant intervention unless it fosters impairment and endures.
SYK is activated by mutated MYD88 and drives pro-survival signaling in MYD88 driven B-cell lymphomas
Authors: Munshi Manit , Liu Xia , Chen Jiaji G. , Xu Lian , Tsakmaklis Nickolas , Demos Maria G. , Kofides Amanda , Guerrera Maria Luisa , Jimenez Cristina , Chan Gloria G. , Hunter Zachary R. , Palomba M. Lia , Argyropoulos Kimon V. , Meid Kirsten , Keezer Andrew , Gustine Joshua , Dubeau Toni , Castillo Jorge J. , Patterson Christopher J. , Wang Jinhua , Buhrlage Sara J. , Gray Nathanael S. , Treon Steven P. , Yang Guang
Published: January 2020

Activating MYD88 mutations promote pro-survival signaling through BTK and HCK, both targets of ibrutinib. Despite high response rates, complete responses to ibrutinib are lacking, and other MYD88 triggered pro-survival pathways may contribute to primary drug resistance. B-cell receptor (BCR) signaling has been observed in lymphomas driven by mutated MYD88, even without activating the BCR pathway mutations. We identified activated SYK (p-SYK), a component of BCR in complex with MYD88 in MYD88-mutated WM and ABC DLBCL lymphoma cells. Confocal microscopy confirmed co-localization of MYD88 with SYK in MYD88-mutated cells. Knockdown of MYD88 or use of a MYD88 signaling inhibitor abrogated SYK activation, while expression of mutated but not wild-type MYD88 amplified p-SYK in MYD88-mutated and wild-type lymphoma cells. Knockdown of SYK or use of inhibitors targeting SYK blocked p-STAT3 and p-AKT signaling in MYD88-mutated cells. Cell viability analysis showed that combining ibrutinib and SYK inhibitors triggered synthetic killing of MYD88-mutated lymphoma cells. Our findings extend the spectrum of mutated MYD88 pro-survival signaling to include SYK directed BCR cross talk in MYD88-mutated lymphomas. Targeting SYK in combination with ibrutinib produces synthetic lethality, providing a framework for the clinical investigation of ibrutinib with SYK inhibitors in MYD88-mutated lymphomas.
A phase 2 study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in front-line treatment of suboptimal residual ovarian cancer
Authors: Hasegawa Kosei , Shimada Muneaki , Takeuchi Satoshi , Fujiwara Hiroyuki , Imai Yuichi , Iwasa Norihiro , Wada Satoru , Eguchi Hidetaka , Oishi Tetsuro , Sugiyama Toru , Suzuki Mitsuaki , Nishiyama Masahiko , Fujiwara Keiichi
Published: January 2020

Background

We evaluated the efficacy of intraperitoneal (IP) carboplatin in combination with dose-dense paclitaxel (ddTCip) for suboptimal residual ovarian cancer.

Methods

This was a phase 2 study to evaluate ddTCip. Patients with stage II–IV ovarian carcinoma, who underwent primary cytoreductive surgery and had radiologically evaluable disease after surgery, were eligible to participate in this study. IP carboplatin (AUC = 6) was administered on day 1, and intravenous paclitaxel (80 mg/m2) was administered on days 1, 8 and 15. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Interval- debulking surgery followed by the same regimen was allowed when indicated.

Results

A total of 117 patients were considered eligible for this study prior to surgery and temporarily registered. Of the 117 patients, 76 patients met the inclusion criteria and were enrolled in this study. Fifty-nine (83.1%) patients had objective clinical responses. Median PFS and OS were 18.3 and 55.5 months, respectively. Sixty-four (84.2%) patients had grade 3/4 neutropenia, 43 (56.5%) patients had anaemia and 17 (22.4%) patients had thrombocytopenia. Port-related adverse events occurred in nine (11.8%) patients.

Conclusions

Front-line chemotherapy with ddTCip therapy appears safe and effective, even for patients with suboptimal residual ovarian cancer.

Trial registration

UMIN Clinical Trials Registry (ID: UMIN000001713) on February 16th, 2009.
Elucidating target specificity of the taccalonolide covalent microtubule stabilizers employing a combinatorial chemical approach
Authors: Du Lin , Yee Samantha S. , Ramachandran Karthik , Risinger April L.
Published: January 2020

The taccalonolide microtubule stabilizers covalently bind β-tubulin and overcome clinically relevant taxane resistance mechanisms. Evaluations of the target specificity and detailed drug–target interactions of taccalonolides, however, have been limited in part by their irreversible target engagement. In this study, we report the synthesis of fluorogenic taccalonolide probes that maintain the native biological properties of the potent taccalonolide, AJ. These carefully optimized, cell-permeable probes outperform commercial taxane-based probes and enable direct visualization of taccalonolides in both live and fixed cells with dramatic microtubule colocalization. The specificity of taccalonolide binding to β-tubulin is demonstrated by immunoblotting, which allows for determination of the relative contribution of key tubulin residues and taccalonolide moieties for drug–target interactions by activity-based protein profiling utilizing site-directed mutagenesis and computational modeling. This combinatorial approach provides a generally applicable strategy for investigating the binding specificity and molecular interactions of covalent binding drugs in a cellular environment.
Preclinical development of a miR-132 inhibitor for heart failure treatment
Authors: Foinquinos Ariana , Batkai Sandor , Genschel Celina , Viereck Janika , Rump Steffen , Gyöngyösi Mariann , Traxler Denise , Riesenhuber Martin , Spannbauer Andreas , Lukovic Dominika , Weber Natalie , Zlabinger Katrin , Hašimbegović Ena , Winkler Johannes , Fiedler Jan , Dangwal Seema , Fischer Martin , de la Roche Jeanne , Wojciechowski Daniel , Kraft Theresia , Garamvölgyi Rita , Neitzel Sonja , Chatterjee Shambhabi , Yin Xiaoke , Bär Christian , Mayr Manuel , Xiao Ke , Thum Thomas
Published: January 2020

Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators and essential drivers of disease progression. We previously demonstrated that miR-132 is both necessary and sufficient to drive the pathological cardiomyocytes growth, a hallmark of adverse cardiac remodelling. Therefore, miR-132 may serve as a target for HF therapy. Here we report further mechanistic insight of the mode of action and translational evidence for an optimized, synthetic locked nucleic acid antisense oligonucleotide inhibitor (antimiR-132). We reveal the compound’s therapeutic efficacy in various models, including a clinically highly relevant pig model of HF. We demonstrate favourable pharmacokinetics, safety, tolerability, dose-dependent PK/PD relationships and high clinical potential for the antimiR-132 treatment scheme.
Quasiparticle tunnel electroresistance in superconducting junctions
Authors: Rouco V. , Hage R. El , Sander A. , Grandal J. , Seurre K. , Palermo X. , Briatico J. , Collin S. , Trastoy J. , Bouzehouane K. , Buzdin A. I. , Singh G. , Bergeal N. , Feuillet-Palma C. , Lesueur J. , Leon C. , Varela M. , Santamaría J. , Villegas Javier E.
Published: January 2020

The term tunnel electroresistance (TER) denotes a fast, non-volatile, reversible resistance switching triggered by voltage pulses in ferroelectric tunnel junctions. It is explained by subtle mechanisms connected to the voltage-induced reversal of the ferroelectric polarization. Here we demonstrate that effects functionally indistinguishable from the TER can be produced in a simpler junction scheme—a direct contact between a metal and an oxide—through a different mechanism: a reversible redox reaction that modifies the oxide’s ground-state. This is shown in junctions based on a cuprate superconductor, whose ground-state is sensitive to the oxygen stoichiometry and can be tracked in operando via changes in the conductance spectra. Furthermore, we find that electrochemistry is the governing mechanism even if a ferroelectric is placed between the metal and the oxide. Finally, we extend the concept of electroresistance to the tunnelling of superconducting quasiparticles, for which the switching effects are much stronger than for normal electrons. Besides providing crucial understanding, our results provide a basis for non-volatile Josephson memory devices.
Network-based diffusion analysis reveals context-specific dominance of dance communication in foraging honeybees
Authors: Hasenjager Matthew J. , Hoppitt William , Leadbeater Ellouise
Published: January 2020

The honeybee (Apis mellifera) dance communication system is a marvel of collective behaviour, but the added value it brings to colony foraging efficiency is poorly understood. In temperate environments, preventing communication of foraging locations rarely decreases colony food intake, potentially because simultaneous transmission of olfactory information also plays a major role in foraging. Here, we employ social network analyses that quantify information flow across multiple temporally varying networks (each representing a different interaction type) to evaluate the relative contributions of dance communication and hive-based olfactory information transfer to honeybee recruitment events. We show that virtually all successful recruits to novel locations rely upon dance information rather than olfactory cues that could otherwise guide them to the same resource. Conversely, during reactivation to known sites, dances are relatively less important, as foragers are primarily guided by olfactory information. By disentangling the contributions of multiple information networks, the contexts in which dance communication truly matters amid a complex system full of redundancy can now be identified.
Structural basis of proton-coupled potassium transport in the KUP family
Authors: Tascón Igor , Sousa Joana S. , Corey Robin A. , Mills Deryck J. , Griwatz David , Aumüller Nadine , Mikusevic Vedrana , Stansfeld Phillip J. , Vonck Janet , Hänelt Inga
Published: January 2020

Potassium homeostasis is vital for all organisms, but is challenging in single-celled organisms like bacteria and yeast and immobile organisms like plants that constantly need to adapt to changing external conditions. KUP transporters facilitate potassium uptake by the co-transport of protons. Here, we uncover the molecular basis for transport in this widely distributed family. We identify the potassium importer KimA from Bacillus subtilis as a member of the KUP family, demonstrate that it functions as a K+/H+ symporter and report a 3.7 Å cryo-EM structure of the KimA homodimer in an inward-occluded, trans-inhibited conformation. By introducing point mutations, we identify key residues for potassium and proton binding, which are conserved among other KUP proteins.
Global meta-analysis shows pervasive phosphorus limitation of aboveground plant production in natural terrestrial ecosystems
Authors: Hou Enqing , Luo Yiqi , Kuang Yuanwen , Chen Chengrong , Lu Xiankai , Jiang Lifen , Luo Xianzhen , Wen Dazhi
Published: January 2020

Phosphorus (P) limitation of aboveground plant production is usually assumed to occur in tropical regions but rarely elsewhere. Here we report that such P limitation is more widespread and much stronger than previously estimated. In our global meta-analysis, almost half (46.2%) of 652 P-addition field experiments reveal a significant P limitation on aboveground plant production. Globally, P additions increase aboveground plant production by 34.9% in natural terrestrial ecosystems, which is 7.0–15.9% higher than previously suggested. In croplands, by contrast, P additions increase aboveground plant production by only 13.9%, probably because of historical fertilizations. The magnitude of P limitation also differs among climate zones and regions, and is driven by climate, ecosystem properties, and fertilization regimes. In addition to confirming that P limitation is widespread in tropical regions, our study demonstrates that P limitation often occurs in other regions. This suggests that previous studies have underestimated the importance of altered P supply on aboveground plant production in natural terrestrial ecosystems.
Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis
Authors: Zhang Wei , Xiang Xin-Xin , Chen Junyi , Yang Chen , Pan Yu-Liang , Cheng Jin-Pei , Meng Qingbin , Li Xin
Published: January 2020

The discovery of modern medicine relies on the sustainable development of synthetic methodologies to meet the needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class of organofluoro molecules with potential applications in pharmaceutical, agricultural and material science. Herein, we developed an organophotocatalytic direct difluoromethylation of heterocycles using O2 as a green oxidant. The C–H oxidative difluoromethylation obviates the need for pre-functionalization of the substrates, metals and additives. The operationally straightforward method enriches the efficient synthesis of many difluoromethylated heterocycles in moderate to excellent yields. The direct difluoromethylation of pharmaceutical moleculars demonstrates the practicability of this methodology to late-stage drug development. Moreover, 2′-deoxy-5-difluoromethyluridine (F2TDR) exhibits promising activity against some cancer cell lines, indicating that the difluoromethylation methodology might provide assistance for drug discovery.
Neuronal ensemble-specific DNA methylation strengthens engram stability
Authors: Gulmez Karaca Kubra , Kupke Janina , Brito David V. C. , Zeuch Benjamin , Thome Christian , Weichenhan Dieter , Lutsik Pavlo , Plass Christoph , Oliveira Ana M. M.
Published: January 2020

Memories are encoded by memory traces or engrams, represented within subsets of neurons that are synchronously activated during learning. However, the molecular mechanisms that drive engram stabilization during consolidation and consequently ensure its reactivation by memory recall are not fully understood. In this study we manipulate, during memory consolidation, the levels of the de novo DNA methyltransferase 3a2 (Dnmt3a2) selectively within dentate gyrus neurons activated by fear conditioning. We found that Dnmt3a2 upregulation enhances memory performance in mice and improves the fidelity of reconstitution of the original neuronal ensemble upon memory retrieval. Moreover, similar manipulation in a sparse, non-engram subset of neurons does not bias engram allocation or modulate memory strength. We further show that neuronal Dnmt3a2 overexpression changes the DNA methylation profile of synaptic plasticity-related genes. Our data implicates DNA methylation selectively within neuronal ensembles as a mechanism of stabilizing engrams during consolidation that supports successful memory retrieval.