bluuebunny/crossref_metadata_2025 huggingface dataset:
Forced Expiratory Flow (FEF25–75%) as a Clinical Endpoint in Children and Adolescents with Symptomatic Asthma Receiving Tiotropium: A Post Hoc Analysis
Authors: Szefler Stanley J. , Goldstein Stanley , Vogelberg Christian , Bensch George W. , Given John , Jugovic Branko , Engel Michael , Moroni-Zentgraf Petra M. , Sigmund Ralf , Hamelmann Eckard H.
Published: May 2020

Introduction

In pediatric patients with asthma, measurements of forced expiratory volume in 1 s (FEV1) may be normal or may not correlate with symptom severity. Forced expiratory flow at 25–75% of the vital capacity (FEF25–75%) is a potentially more sensitive parameter for assessing peripheral airway function. This post hoc analysis compared FEF25–75% with FEV1 as an endpoint to assess bronchodilator responsiveness in children with asthma.

Methods

Change from baseline in trough FEF25–75% and trough FEV1 following treatment with either tiotropium (5 µg or 2.5 µg) or placebo Respimat® was analyzed in four phase III trials in children (aged 6–11 years) and adolescents (aged 12–17 years) with symptomatic moderate (VivaTinA-asthma® and PensieTinA-asthma®) and mild (CanoTinA-asthma® and RubaTinA-asthma®) asthma. Data from all treatment arms were pooled and correlations between FEF25–75% and FEV1 were calculated and analyzed.

Results

A total of 1590 patients were included in the analysis. Tiotropium Respimat® consistently improved FEF25–75% and FEV1 versus placebo, although in adolescents with severe asthma, the observed improvements were not statistically significant. Improvements in FEF25–75% response with tiotropium versus placebo were largely more pronounced than improvements in FEV1. Statistical assessment of the correlation of FEV1 and FEF25–75% showed moderate-to-high correlations (Pearson’s correlation coefficients 0.73–0.80).

Conclusions

In pediatric patients, FEF25–75% may be a more sensitive measure to detect treatment response, certainly to tiotropium, than FEV1 and should be evaluated as an additional lung function measurement.
Challenging choice of safety factor for design of strip footings on gypsum-rich soils
Authors: Razouki Sabah Said , Kuttah Dina Kamal
Published: May 2020

A fine-grained gypsum-rich clayey soil having a gypsum content of 33% is subjected, in CBR moulds, to modified American association of state highway and transportation officials compaction at optimum moisture content. Two sets of samples were prepared. The first set remained unsoaked, while the second was soaked in fresh water for 120 days. From each CBR sample, three specimens were extracted for unconsolidated undrained triaxial test and the Mohr–Coloumb failure envelopes were obtained for soaked and unsoaked conditions. Soaked samples suffered a significant drop in both cohesion and angle of internal friction. The ultimate bearing capacity of a strip footing was calculated for each of soaked and unsoaked conditions revealing the critical region. For important structures on gypsum-rich soil, the paper shows that the allowable bearing capacity should be based on soaked condition. Based on unsoaked conditions, a safety factor of 8 is required to assure a safety factor of 3 based on soaked condition. For less important structures in regions of hot dry climate with low probability of soaking, safety factors of 4 and 3, based on unsoaked conditions, are required to give safety factors of 1.5 and 1.1 based on soaked conditions, respectively.
How Will Climate Change Affect the Provision and Value of Water from Public Lands in Southern California Through the 21st Century?
Authors: Srivastava Lorie , Hand Michael , Kim John , Sánchez José J. , Lupi Frank , Garnache Cloé , Drapek Raymond J. , Quinn James F.
Published: May 2020

We estimate the ecosystem service value of water supplied by the San Bernardino National Forest in Southern California under climate change projections through the 21st century. We couple water flow projections from a dynamic vegetation model with an economic demand model for residential water originating from the San Bernardino National Forest. Application of the method demonstrates how estimates of consumer welfare changes due to variation in water supply from public lands in Southern California can inform policy and land management decisions. Results suggest variations in welfare changes over time due to alterations in the projected water supply surpluses, shifting demand limited by water supply shortages or surpluses, and price increases. Results are sensitive to future climate projections—in some cases large decreases in welfare due to supply shortages—and to assumptions about the demand model.
Opportunities for Systematically Valuing Ecosystem Service Benefits Produced by Federal Conservation Programs
Authors: Holmes Thomas P.
Published: May 2020

Federal agencies invest taxpayer dollars every year in conservation programs that are focused on improving a suite of ecosystem services produced on private lands. A better understanding of the public benefits generated by federal conservation programs could help improve governmental efficiency and economic welfare by providing science-based evidence for use in policy decision-making regarding targeting of federal conservation investments. Of specific concern here are conservation investments made by the U.S. Department of Agriculture (USDA). While previous research has shown that efficiency gains are possible using cost-benefit analysis for targeting conservation investments, agency-wide implementation of this approach by policy makers has been constrained by the limited availability of location-specific information regarding conservation benefits. Cost-effective opportunities for integrating location-specific ecosystem service valuation research with USDA conservation decision-making include: (1) institutionalizing funding of comparable studies suitable for benefit transfer, (2) utilizing non-traditional data sources for research complementing benefit transfer, and (3) creating a state-of-the-art program for developing and communicating research in ecosystem service valuation exemplifying the highest standards of scientific conduct.
The Constitutionality of §89a IIa of the German Criminal Code and the Concept of a Serious Violent Offense Endangering the State: The German Federal Court of Justice Decision of April 6, 2017—3 StR 326/16
Authors: Zaunseder Anne-Sophie , Heblik Michelle
Published: May 2020

This Article discusses the constitutionality of the recently implemented § 89a IIa of the German Criminal Code (Strafgesetzbuch—StGB) on the basis of the case 3 StR 326/16 decided by the Federal Court of Justice (BGH) on April 6, 2017. First, this Article introduces § 89a IIa of the StGB with a short summary of the events leading to the present anti-terrorist legislation in Germany and the development of the legislation over the past few decades. Second, the facts of the BGH’s case will be outlined, and an overview of the systematic structure of § 89a I, II No. 1, IIa StGB will be provided. Within this framework, the constitutionality of § 89a IIa StGB will be discussed, focusing on the prerequisite of appropriateness, with special attention paid to the requirement of reasonability and the prerequisite of legal certainty pursuant to Article 103(II) Basic Law (Grundgesetz—GG). Finally, § 89a I, II No. 1, IIa StGB will be applied to the BGH’s case after discussing the contentious legal issues regarding these doctrines. This Article concludes by discussing the BGH’s decision, which deems § 89a IIa StGB to be constitutional.
Electing Team Strasbourg: Professional Diversity on the European Court of Human Rights and Why it Matters
Authors: Dzehtsiarou Kanstantsin , Schwartz Alex
Published: May 2020

Reforms to the process for electing judges to the European Court of Human Rights have generally focused on identifying the most qualified individual candidates. This Article argues for a more holistic approach, advancing a theory of why professional diversity on the European Court of Human Rights is an asset in collegial decision making. The results of original interviews with several Strasbourg judges are presented, followed by an empirical analysis of the professional backgrounds of all judges elected to the European Court of Human Rights since 1998. Although the interviews indicate that the judges themselves see the value of professional diversity, the quantitative evidence suggests a trend in the direction of a more professionally homogenous bench. The Article concludes with some suggestions for how the promotion of professional diversity might be appropriately pursued in future reforms to the process for electing Strasbourg judges.
Digital Humanities and the Discontents of Meaning
Authors: Fuller Michael A.
Published: May 2020

The digital humanities offer more than just a set of tools. The application of software to assist in the analysis of large collections of data does not just expand the volume of material we can incorporate in our work, it also expands how we in the humanities understand the nature of meaning. The recent scholarly turn to the expanded modes of analysis made possible by DH is not just the “latest new thing” but gives the scholarly community a way to articulate and respond to long-standing doubts about the epistemological grounding in the practice of the humanities. Even more importantly, I believe that this broadening of inquiry afforded by DH is intrinsic to the humanistic project itself. In this essay, I seek in particular to connect the implicit conceptual substructure behind the architectural logic of the digital humanities to key strains of hermeneutic thought that have established a basis for exploring the question of how we are to understand the vast, variegated world of historical human experience that is the object of our humanistic inquiries across disciplines.
Lost Objects, Hidden Stories: On the Ethnographic Collections Burned in the National Museum of Rio de Janeiro
Authors: Costa Oliveira Thiago Lopes da
Published: May 2020

In this article, I take a close look at the objects collected over the last 200 years from the indigenous people of the Upper Rio Negro, northwest of the Brazilian Amazon, that were part of the ethnographic collection of the National Museum of Rio de Janeiro. Examination of these objects allows us to explore the main characteristics of the ethnographic archive of the museum, as the Upper Rio Negro collections were connected to different topics associated with indigenous societies and histories in Brazil, including enslavement, forced displacement, religious conversion, and indigenous territorial, artifactual, and cultural knowledge. This article also highlights the professional commitment of Brazilian anthropology to amplifying indigenous voices over the course of the history of the discipline, and by doing so, it pays homage to the women and men whose work built the National Museum collections.
Detrital zircon provenance of Triassic sandstone of the Algarve Basin (SW Iberia): evidence of Gondwanan- and Laurussian-type sources of sediment
Authors: Gama Cristina , Pereira M Francisco , Crowley Quentin G , Dias da Silva Ícaro , Silva J Brandão
Published: May 2020

Detrital zircon populations from six samples of upper Triassic sandstone (Algarve Basin) were analysed, yielding mostly Precambrian ages. zircon age populations of the Triassic sandstone sampled from the western and central sectors of the basin are distinct, suggesting local recycling and/or lateral changes in their sources. Our findings and the available detrital zircon ages from the Palaeozoic terranes of SW Iberia, Nova Scotia and NW Morocco were jointly examined using the Kolmogorov–Smirnov test and multidimensional scaling diagrams. The obtained results enable direct discrimination of competing Laurussian-type and Gondwanan-type sediment sources, involving recycling and mixing relationships. The detrital zircon populations of the Algarve Triassic sandstone are very different from those of the lower–upper Carboniferous Mértola and Mira formations (South Portuguese Zone), upper Devonian – lower Carboniferous Horta da Torre, Represa and Santa Iria formations (Pulo do Lobo Zone), and the late Carboniferous Santa Susana and early Permian Viar basins, which are ruled out as potential sources. The detrital zircon populations of Triassic sandstone from the central sector and those from the Ossa–Morena Zone Ediacaran–Cambrian siliciclastic rocks, upper Devonian – Carboniferous Ronquillo, Tercenas, Phyllite-Quartzite and Brejeira formations (South Portuguese Zone), and Frasnian siliciclastic rocks of the Pulo do Lobo Zone are not statistically distinguishable. Thus, sedimentation in the central sector was influenced by Gondwanan- and Laurussian-type putative sources exposed in SW Iberia, in contrast to the western sector, where Meguma Terrane and Sehoul Block Cambrian siliciclastic rocks allegedly constituted the main (Laurussian-type) sources. These findings provide insights into the denudation of distinctive source terranes distributed along the late Palaeozoic suture zone that juxtaposed the Laurussian and Gondwanan margins.
Framingham risk score is associated with hearing outcomes in patients with idiopathic sudden sensorineural hearing loss
Authors: Chang Y-S , Park S , Lee M K , Rah Y C , Choi J
Published: May 2020

Objective

To assess the Framingham risk score as a prognostic tool for idiopathic sudden sensorineural hearing loss patients.

Methods

Medical records were reviewed for unilateral idiopathic sudden sensorineural hearing loss patients between January 2010 and October 2017. The 10-year risk of developing cardiovascular disease was calculated. Patients were subdivided into groups: group 1 – Framingham risk score of less than 10 per cent (n= 28); group 2 – score of 10 to less than 20 per cent (n= 6); and group 3 – score of 20 per cent or higher (n= 5).

Results

Initial pure tone average and Framingham risk score were not significantly associated (p= 0.32). Thirteen patients in group 1 recovered completely (46.4 per cent), but none in groups 2 and 3 showed complete recovery. Initial pure tone average and Framingham risk score were significantly associated in multivariable linear regression analysis (R2= 0.36). The regression coefficient was 0.33 (p= 0.003) for initial pure tone average and −0.67 (p= 0.005) for Framingham risk score.

Conclusion

Framingham risk score may be useful in predicting outcomes for idiopathic sudden sensorineural hearing loss patients, as those with a higher score showed poorer hearing recovery.
Behavioural changes and potential consequences of cetacean exposure to purse seine vessels in the Istanbul Strait, Turkey
Authors: Olaya Meza Cristóbal , Akkaya Aylin , Affinito Flavio , Öztürk Bayram , Öztürk Ayaka Amaha
Published: May 2020

Marine traffic has both short- and long-term effects on cetacean behaviour, yet fishing vessels present a unique situation as they disturb cetaceans whilst potentially offering alternative foraging opportunities. The Istanbul Strait is a key area for the study of anthropogenic disturbance on cetaceans due to heavy human pressure in a narrow space where at least three cetacean species are regularly encountered. The present study investigated changes in behaviour of bottlenose dolphins, common dolphins and harbour porpoises in relation to the presence of purse seiners using Markov chains analysis. The results revealed increased foraging in bottlenose and common dolphins' behavioural budgets and a decrease in the time spent foraging by harbour porpoises. Moreover, a loglinear model was used to analyse the effect of possible confounding variables on observed behaviours. The only variables found to be affecting behaviour were the previous recorded behaviour, seiner presence and marine traffic density. Consequently, the presence of purse seine vessels leads bottlenose and common dolphins to change their behaviour and are related with a decrease of energy intake in porpoises. The results of this study reveal that there is an effect of purse seine vessel presence on the cetaceans found in the Istanbul Strait with potentially significant impacts on their behaviour, therefore we suggest more research is needed in the area to identify the long-term impacts of these observed behavioural changes.
A Multi-Priority Controller for Industrial Macro-Micro Manipulation
Authors: Uzunoğlu Emre , Tatlicioğlu Enver , Dede Mehmet İ. Can
Published: May 2020

In this study, a control algorithm is proposed and evaluated for a special type of kinematically redundant manipulator. This manipulator is comprised of two mechanisms, macro and micro mechanisms, with distinct acceleration and work space characteristics. A control algorithm is devised to minimize the task completion duration and the overall actuator effort with respect to the conventional manipulator. A general framework multi-priority controller for macro-micro manipulators is introduced by utilizing virtual dynamics, which is introduced in null-space projection to achieve secondary tasks. The proposed controller is evaluated on a simulation model based on a previously constructed macro-micro manipulator for planar laser cutting. Task completion duration and the total actuator effort are investigated and the results are compared.
Performance Evaluation of Maritime Search and Rescue Missions Using Automatic Identification System Data
Authors: Zhou Fan , Chen Hua , Zhang Peng
Published: May 2020

In maritime search and rescue (SAR), commanders need to understand the task execution efficiency of each SAR unit in real time to improve the overall efficiency of SAR efforts. This study proposes a method to evaluate the progress of maritime SAR missions using automatic identification system (AIS) data. First, the positioning accuracy of the AIS data was improved according to the relationship between position, speed, and course. Second, the historical track of the SAR ship was used to generate the SAR completion area based on a line buffer algorithm. The SAR completion area and SAR mission area were then superimposed to determine the overall progress of the SAR mission. The proposed method has been deployed within the SAR software on-board Haixun01 (China's largest and most advanced large-scale cruise rescue ship) since 2017 and has played an important role in devising SAR strategies and tracking mission progress, during several SAR actions.
COVID-19: Pandemic Risk, Resilience and Possibilities for Aging Research
Authors: Wister Andrew , Speechley Mark
Published: May 2020

The COVID-19 global crisis is reshaping Canadian society in unexpected and profound ways. The significantly higher morbidity and mortality risks by age suggest that this is largely a “gero-pandemic,” which has thrust the field of aging onto center stage. This editorial emphasizes that vulnerable older adults are also those most affected by COVID-19 in terms of infection risk, negative health effects, and the potential deleterious outcomes on a range of social, psychological, and economic contexts – from ageism to social isolation. We also contend that the pathogenic analysis of this pandemic needs to be balanced with a salutogenic approach that examines the positive adaptation of people, systems and society, termed COVID-19 resilience. This begs the question: how and why do some older adults and communities adapt and thrive better than others? This examination will lead to the identification and response to research and data gaps, challenges, and innovative opportunities as we plan for a future in which COVID-19 has become another endemic infection in the growing list of emerging and re-emerging pathogens.
Beliefs Unworthy of Respect in a Democratic Society: A View from the Employment Tribunal
Authors: Hambler Andrew
Published: May 2020

There have been a number of tribunal decisions on the admissibility of discrimination claims concerning ‘belief’ as a protected characteristic under the Equality Act 2010. Some have favoured the claimant, establishing, inter alia, that opposition to fox hunting and hare-coursing, a belief in the ‘higher purpose’ of public service broadcasting and a commitment to vegetarianism constitute ‘philosophical beliefs’ for the purposes of the Equality Act. Others do not, such that a belief in wearing a poppy or, in contrast with an earlier decision, a commitment to vegetarianism do not qualify. The admissibility of these claims tended to turn on the extent to which the belief in question was considered cogent or was sufficiently weighty and substantial. In Forstater v CGD Europe & Anor, whether or not a belief fell into the protected category focused on the rather different issue of whether or not it was worthy of respect because of its compatibility (or otherwise) with the dignity and rights of others.
Palivizumab compliance in congenital heart disease patients: factors related to compliance and altered lower respiratory tract infection viruses after palivizumab prophylaxis
Authors: Sel Kutay , Aypar Ebru , Dönmez Yasemin Nuran , Aliyev Emil , Aykan Hakan Hayrettin , Karagöz Tevfik , Alehan Dursun
Published: May 2020

Background:

Lower respiratory tract infections caused by respiratory syncytial virus can be severe during infancy, which requires admission to the hospital. These infections may be more severe especially in patients with congenital heart disease. Passive immunisation with palivizumab, a monoclonal antibody, is recommended in high-risk infants. We tried to determine the compliance rates, factors affecting compliance, and also other microorganisms responsible for lower respiratory tract infections after palivizumab prophylaxis in these patients.

Methods:

We evaluated patients’ compliance to prophylaxis with palivizumab in two consecutive respiratory syncytial virus seasons from pharmacy records. We also investigated factors affecting compliance and the frequency of hospitalisations for lower respiratory tract infections. We investigated the causative microorganisms detected in hospitalised patients.

Results:

In this study, 86.7% of the desired number of injections was achieved in 176 patients in two seasons. Out of these, 117 patients (66.4%) received all the doses they were prescribed. Although not statistically significant, compliance to prophylaxis was higher in male patients, cyanotic patients, those who started under 1 year old, and who lived in the city centre. Human metapneumovirus, parainfluenza type 3, and bocavirus were detected in the hospitalised patients.

Conclusion:

Patients with congenital heart disease can survive the period of infancy with less problem by making palivizumab prophylaxis more effective, and awareness about non- respiratory syncytial virus factors may be a guide for the development of new treatments.
Efficacy and safety of dasotraline in adults with binge-eating disorder: a randomized, placebo-controlled, fixed-dose clinical trial
Authors: Grilo Carlos M. , McElroy Susan L. , Hudson James I. , Tsai Joyce , Navia Bradford , Goldman Robert , Deng Ling , Kent Justine , Loebel Antony
Published: May 2020

Objective

The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED).

Methods

Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses of dasotraline (4 and 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating (BE) days per week at week 12. Secondary efficacy endpoints included week 12 change on the BE CGI-Severity Scale (BE-CGI-S) and the Yale-Brown Obsessive–Compulsive Scale Modified for BE (YBOCS-BE).

Results

At week 12, treatment with dasotraline was associated with significant improvement in number of BE days per week on the dose of 6 mg/d (N = 162) vs placebo (N = 162; −3.47 vs −2.92;P = .0045), but not 4 mg/d (N = 161; −3.21). Improvement vs placebo was observed for dasotraline 6 and 4 mg/d, respectively, on the BE-CGI-S (effect size [ES]: 0.37 and 0.27) and on the YBOCS-BE total score (ES: 0.43 and 0.29). The most common adverse events on dasotraline were insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in blood pressure and pulse were minimal.

Conclusion

Treatment with dasotraline 6 mg/d (but not 4 mg/d) was associated with significantly greater reduction in BE days per week. Both doses of dasotraline were generally safe and well-tolerated and resulted in global improvement on the BE-CGI-S, as well as improvement in BE related obsessional thoughts and compulsive behaviors on the YBOCS-BE. These results confirm the findings of a previous flexible dose study.
Nick Martin and the ‘Boulder Workshops’
Authors: Hewitt John K.
Published: May 2020

The author provides a personal perspective on Nick Martin’s contributions to behavioral genetics and his role in the workshops on statistical genetics held annually in Boulder. Highlighted are Prof. Martin’s seminal work on multivariate behavioral genetics, his career-long commitment to the value of the study of twins, and his enthusiastic support of the didactic mission of the ‘Boulder workshops’. These contributions and activities continue unabated as we celebrate Prof. Martin’s 70th birthday.
The Genetics of Endometriosis
Authors: Montgomery Grant W.
Published: May 2020

Mapping genetic risk factors for endometriosis continues from early studies on women’s health initiated by Nick Martin and Susan Treloar. Their initial recruitment of endometriosis cases and family members received a major boost and became a flagship project within the Cooperative Research Centre (CRC) for the Discovery of Common Human Disease. We extended the study through a formal collaboration with Professor Stephen Kennedy and his group in Oxford. Our first joint scientific meeting was held in Brisbane and was sadly memorable as the day the planes were flown into the Twin Towers in New York. Our initial collaboration expanded into the International Endometriosis Genetics Consortium (IEGC). The IEGC now has 15 groups around the world, and the most recent meta-analysis will be published this year.
Stratospheric Ozone Changes From Explosive Tropical Volcanoes: Modeling and Ice Core Constraints
Authors: Ming Alison , Winton V. Holly L. , Keeble James , Abraham Nathan L. , Dalvi Mohit C. , Griffiths Paul , Caillon Nicolas , Jones Anna E. , Mulvaney Robert , Savarino Joël , Frey Markus M. , Yang Xin
Published: May 2020

Major tropical volcanic eruptions have emitted large quantities of stratospheric sulfate and are potential sources of stratospheric chlorine although this is less well constrained by observations. This study combines model and ice core analysis to investigate past changes in total column ozone. Historic eruptions are good analogs for future eruptions as stratospheric chlorine levels have been decreasing since the year 2000. We perturb the preindustrial atmosphere of a chemistry‐climate model with high and low emissions of sulfate and chlorine. The sign of the resulting Antarctic ozone change is highly sensitive to the background stratospheric chlorine loading. In the first year, the response is dynamical, with ozone increases over Antarctica. In the high HCl (2 Tg emission) experiment, the injected chlorine is slowly transported to the polar regions with subsequent chemical ozone depletion. These model results are then compared to measurements of the stable nitrogen isotopic ratio,
, from a low snow accumulation Antarctic ice core from Dronning Maud Land (recovered in 2016–2017). We expect ozone depletion to lead to increased surface ultraviolet (UV) radiation, enhanced air‐snow nitrate photochemistry and enrichment in
in the ice core. We focus on the possible ozone depletion event that followed the largest volcanic eruption in the past 1,000 years, Samalas in 1257. The characteristic sulfate signal from this volcano is present in the ice core but the variability in
dominates any signal arising from changes in ultraviolet from ozone depletion. Prolonged complete ozone removal following this eruption is unlikely to have occurred over Antarctica.
North Indian Ocean Circulation Since the Last Deglaciation as Inferred From New Elemental Ratio Records for Benthic Foraminifera Hoeglundina elegans
Authors: Ma Ruifang , Sépulcre Sophie , Bassinot Franck , Haurine Frédéric , Tisnérat‐Laborde Nadine , Colin Christophe
Published: May 2020

The evolution of intermediate circulation in the northern Indian Ocean since the last deglaciation has been reconstructed from two marine cores located at intermediate depths off the southern tip of India (MD77‐191) and in the northern Bay of Bengal (BoB) (MD77‐176). Benthic foraminiferal δ13C, seawater carbonate ion concentration ([CO32−]) estimated from the Sr/Ca, and paleotemperature reconstructed on the basis of the Mg/Li of aragonite benthic species Hoeglundina elegans were used to trace the evolution of past intermediate‐deepwater masses and to constrain ocean‐atmosphere exchanges during the two‐stage increase in atmospheric CO2 across the last deglaciation. The intermediate water [CO32−] was mainly affected by changes in the ocean alkalinity inventory, associated with the modulation of atmospheric CO2 on glacial‐interglacial timescales. Higher benthic foraminiferal δ13C, depleted [CO32−], and decreased benthic‐planktonic 14C age offsets at intermediate water depths suggest a release of deep‐sea CO2 to the atmosphere through the Antarctic Intermediate Water (AAIW) in the Southern Ocean during the 17–15.2 and 12.6–10.5 cal kyr BP time intervals. In addition, the decreased H. elegans Mg/Li record seems to reflect an increased contribution of cold water mass during the 17–15.2 and 12.6–11.9 cal kyr BP intervals and throughout the Holocene. In contrast, two warm events occurred in the 15–13.3 and 11–10.3 cal kyr BP time intervals. During the late Holocene, a decrease in the intermediate water [CO32−] indicates a contribution to atmospheric CO2 rise since 8 cal kyr BP, due to the depleted global ocean alkalinity and/or the variations in surface productivity (at least for MD77‐191).
From Blowing Wind to Running Water: Unifying Sediment Transport
Authors: P�htz Thomas , Clark Abram , Valyrakis Manousos , Dur�n Orencio
Published: May 2020

Laboratory experiments and grain-scale computer simulations during the past decade have led to a more universal understanding of flow-driven sediment transport across flows in oil, water, and air.
Long Live the Laurentian Great Lakes
Authors: Morton Mary
Published: May 2020

Living in Geologic Time: Billion-year-old rifting events set the stage for Earth’s greatest lakes.
Proteomic analysis reveals a biosignature of decreased synaptic protein in cerebrospinal fluid of major depressive disorder
Authors: Al Shweiki MHD Rami , Oeckl Patrick , Steinacker Petra , Barschke Peggy , Dorner-Ciossek Cornelia , Hengerer Bastian , Schönfeldt-Lecuona Carlos , Otto Markus
Published: May 2020

Major depressive disorder (MDD) is a leading cause of morbidity with a lifetime prevalence of 10%. There is increasing evidence suggesting synaptic dysfunction and impaired integrity of certain brain circuits in MDD. Here we investigate the cerebrospinal fluid proteome of psychiatric patients focusing on MDD by deep proteomic profiling approach combined with a further validation step using targeted mass spectrometry. We demonstrate profound CSF proteomic changes during on-going depression episodes in MDD patients (n = 40) in comparison to controls (n = 27), schizophrenia spectrum disorder (n = 13), and bipolar disorder patients (n = 11). The discovery analysis with isobaric tags for relative and absolute quantitation (iTRAQ) reveals changes in proteins associated with synaptic transmission, myelination, and Wnt signaling in CSF of MDD. The multiple reaction monitoring (MRM) validation analysis confirms significantly decreased levels of eight proteins including the membrane synaptic proteins neurexin 3 (NRXN3), contactin-associated protein-like 4 (CNTNAP4), and glutamate ionotropic receptor AMPA type subunit 4 (GRIA4) in the CSF of MDD patients in comparison to the controls. Overall, the study demonstrates proteins that constitute an MDD biosignature for further validation studies and provides insight into the pathophysiology of MDD and other psychiatric disorders.
Temporomandibular joint function, periodontal health, and oral microbiome in early rheumatoid arthritis and at-risk individuals: a prospective cohort study protocol
Authors: Kroese J. M. , Volgenant C.M.C. , van Schaardenburg D. , Loos B. G. , Crielaard W. , Lobbezoo F.
Published: May 2020

Objectives/aims

Rheumatoid arthritis (RA) is an autoimmune disease affecting the joints, including the temporomandibular joint (TMJ). Early diagnosis and treatment can alleviate symptoms and prevent progression. Predictors for disease outcome in individuals at risk for RA are therefore valuable. While limited information is available on the prevalence of TMJ involvement in early RA, previous studies suggest that RA, periodontitis and the oral microbiome are interrelated. Predictive factors for RA development may thus be present in the oral cavity. Our two aims are: (1) to assess the prevalence of TMJ involvement in early RA, and (2) to investigate the predictive value of oral factors in RA development.

Materials and methods

We will include 150 individuals in this multi-center, prospective cohort study: 50 patients with early RA, 50 at-risk individuals, and 50 healthy controls. At baseline, the TMJ, periodontal health, and the oral microbiome will be examined. The general health will be followed over time, on four occasions up to 3 years.

Discussion

Our results will provide insight into the prevalence and clinical characterization of TMJ involvement in early RA. For at-risk individuals, oral factors can be studied as possible predictors for the development of RA.
Association of tumour and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with DCB and OS to nivolumab treatment in NSCLC patients pre-treated with chemotherapy
Authors: Niemeijer Anna-Larissa Nadia , Sahba Sara , Smit Egbert Frederik , Lissenberg-Witte Birgit Ilja , de Langen Adrianus Johannes , Thunnissen Erik
Published: May 2020

Background

Immune checkpoint inhibitors are most beneficial in patients with high tumour PD-L1 expression. However, the use of PD-L1 expression is not straightforward. We investigated PD-L1 expression and immune cell (IC) infiltrates in non-small-cell lung cancer (NSCLC) patients treated with nivolumab.

Methods

Tumour tissue specimens of 139 NSCLC patients were scored for tumour/stromal PD-L1 and various IC expression markers, and associated with durable clinical benefit (DCB) and overall survival (OS).

Results

Median OS was higher for patients with high stromal infiltration of CD8+ ICs (9.0 months) compared with patients with low and intermediate infiltration (both 5.0 months, p = 0.035) and for patients with high infiltration of stromal CD4+ ICs (9.0 months) compared with patients with low and intermediate infiltration (both 5.0 months, p = 0.010) and this was confirmed in the validation cohort. Post hoc analyses showed that biopsies taken after the last line of chemotherapy (ACT) were predictive for DCB and OS, whereas samples obtained before the last line of chemotherapy (BCT) were not.

Conclusions

Stromal infiltration of ICs can predict response to PD-1-directed immunotherapy in NSCLC patients. Interestingly, we found differences in the predictive value of IC markers between the ACT and BCT biopsies, suggesting that chemotherapy might influence the immune microenvironment.
Seismic ground vibrations give advanced early-warning of subglacial floods
Authors: Eibl Eva P. S. , Bean Christopher J. , Einarsson Bergur , Pàlsson Finnur , Vogfjörd Kristin S.
Published: May 2020

Glacier runoff and melt from volcanic and geothermal activity accumulates in glacier dammed lakes in glaciated areas around the world. These lakes eventually drain, creating hazardous subglacial floods that are usually only confirmed after they exit the glacier and reach local river systems, which can be many tens of kilometres from the flood source. Once in the river systems, they travel rapidly to populated areas. Such delayed detection represents a potentially lethal shortcoming in early-warning. Here we demonstrate how to advance early-warning potential through the analysis of four such floods in a glaciated region of Iceland. By comparing exceptional multidisciplinary hydrological, GPS and seismic ground vibration (tremor) data, we show that array analysis of seismic tremor can be used for early location and tracking of the subglacial flood front. Furthermore the timing and size of the impending flood can be estimated, prior to it entering the river system. Advanced warnings of between 20 to 34 hours are achieved for large (peak discharge of more than 3000 m3/s, accumulation time of ~ 5.25 years) to small floods (peak discharges from 210 to 380 m3/s, accumulation times of ~ 1.3 years) respectively.
Extreme differences between human germline and tumor mutation densities are driven by ancestral human-specific deviations
Authors: Heredia-Genestar José María , Marquès-Bonet Tomàs , Juan David , Navarro Arcadi
Published: May 2020

Mutations do not accumulate uniformly across the genome. Human germline and tumor mutation density correlate poorly, and each is associated with different genomic features. Here, we use non-human great ape (NHGA) germlines to determine human germline- and tumor-specific deviations from an ancestral-like great ape genome-wide mutational landscape. Strikingly, we find that the distribution of mutation densities in tumors presents a stronger correlation with NHGA than with human germlines. This effect is driven by human-specific differences in the distribution of mutations at non-CpG sites. We propose that ancestral human demographic events, together with the human-specific mutation slowdown, disrupted the human genome-wide distribution of mutation densities. Tumors partially recover this distribution by accumulating preneoplastic-like somatic mutations. Our results highlight the potential utility of using NHGA population data, rather than human controls, to establish the expected mutational background of healthy somatic cells.
HOX13-dependent chromatin accessibility underlies the transition towards the digit development program
Authors: Desanlis Ines , Kherdjemil Yacine , Mayran Alexandre , Bouklouch Yasser , Gentile Claudia , Sheth Rushikesh , Zeller Rolf , Drouin Jacques , Kmita Marie
Published: May 2020

Hox genes encode transcription factors (TFs) that establish morphological diversity in the developing embryo. The similar DNA-binding motifs of the various HOX TFs contrast with the wide-range of HOX-dependent genetic programs. The influence of the chromatin context on HOX binding specificity remains elusive. Here, we used the developing limb as a model system to compare the binding specificity of HOXA13 and HOXD13 (HOX13 hereafter), which are required for digit formation, and HOXA11, involved in forearm/leg development. We find that upon ectopic expression in distal limb buds, HOXA11 binds sites normally HOX13-specific. Importantly, these sites are loci whose chromatin accessibility relies on HOX13. Moreover, we show that chromatin accessibility specific to the distal limb requires HOX13 function. Based on these results, we propose that HOX13 TFs pioneer the distal limb-specific chromatin accessibility landscape for the proper implementation of the distal limb developmental program.
The mutational impact of culturing human pluripotent and adult stem cells
Authors: Kuijk Ewart , Jager Myrthe , van der Roest Bastiaan , Locati Mauro D. , Van Hoeck Arne , Korzelius Jerome , Janssen Roel , Besselink Nicolle , Boymans Sander , van Boxtel Ruben , Cuppen Edwin
Published: May 2020

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies.
Allele-aware chromosome-level genome assembly and efficient transgene-free genome editing for the autotetraploid cultivated alfalfa
Authors: Chen Haitao , Zeng Yan , Yang Yongzhi , Huang Lingli , Tang Bolin , Zhang He , Hao Fei , Liu Wei , Li Youhan , Liu Yanbin , Zhang Xiaoshuang , Zhang Ru , Zhang Yesheng , Li Yongxin , Wang Kun , He Hua , Wang Zhongkai , Fan Guangyi , Yang Hui , Bao Aike , Shang Zhanhuan , Chen Jianghua , Wang Wen , Qiu Qiang
Published: May 2020

Artificially improving traits of cultivated alfalfa (Medicago sativaL.), one of the most important forage crops, is challenging due to the lack of a reference genome and an efficient genome editing protocol, which mainly result from its autotetraploidy and self-incompatibility. Here, we generate an allele-aware chromosome-level genome assembly for the cultivated alfalfa consisting of 32 allelic chromosomes by integrating high-fidelity single-molecule sequencing and Hi-C data. We further establish an efficient CRISPR/Cas9-based genome editing protocol on the basis of this genome assembly and precisely introduce tetra-allelic mutations into null mutants that display obvious phenotype changes. The mutated alleles and phenotypes of null mutants can be stably inherited in generations in a transgene-free manner by cross pollination, which may help in bypassing the debate about transgenic plants. The presented genome and CRISPR/Cas9-based transgene-free genome editing protocol provide key foundations for accelerating research and molecular breeding of this important forage crop.
Unstable twin in body-centered cubic tungsten nanocrystals
Authors: Wang Xiang , Wang Jiangwei , He Yang , Wang Chongmin , Zhong Li , Mao Scott X.
Published: May 2020

Twinning is commonly activated in plastic deformation of low stacking-fault face-centered cubic (Fcc) metals but rarely found in body-centered cubic (Bcc) metals under room temperature and slow strain rates. Here, by conducting in situ transmission electron microscopy (TEM) at atomic scale, we discover that, in stark contrast to those in most Fcc metals, a majority of deformation twins in Bcc metals are unstable and undergo spontaneously detwinning upon unloading. Such unexpected instability of Bcc twins is found to be closely related to the prevalence of the inclined twin boundaries—a peculiar structure where twin boundaries are not parallel to the twinning plane, and the degree of instability is in direct proportion to the fraction of the inclined twin boundary. This work provides significant insights into the structure and stability of deformation twins in Bcc metals.
Ultrathin high-κ antimony oxide single crystals
Authors: Yang Kena , Zhang Tao , Wei Bin , Bai Yijia , Jia Shuangfeng , Cao Guanghui , Jiang Renhui , Zhang Chunbo , Gao Enlai , Chang Xuejiao , Li Juntao , Li Simo , Zhu Daming , Tai Renzhong , Zhou Hua , Wang Jianbo , Zeng Mengqi , Wang Zhongchang , Fu Lei
Published: May 2020

Ultrathin oxides have been reported to possess excellent properties in electronic, magnetic, optical, and catalytic fields. However, the current and primary approaches toward the preparation of ultrathin oxides are only applicable to amorphous or polycrystalline oxide nanosheets or films. Here, we successfully synthesize high-quality ultrathin antimony oxide single crystals via a substrate-buffer-controlled chemical vapor deposition strategy. The as-obtained ultrathin antimony oxide single crystals exhibit high dielectric constant (~100) and large breakdown voltage (~5.7 GV m−1). Such a strategy can also be utilized to fabricate other ultrathin oxides, opening up an avenue in broadening the applicaitons of ultrathin oxides in many emerging fields.
Component response rate variation underlies the stability of highly complex finite systems
Authors: Duthie A. Bradley
Published: May 2020

The stability of a complex system generally decreases with increasing system size and interconnectivity, a counterintuitive result of widespread importance across the physical, life, and social sciences. Despite recent interest in the relationship between system properties and stability, the effect of variation in response rate across system components remains unconsidered. Here I vary the component response rates (γ) of randomly generated complex systems. I use numerical simulations to show that when component response rates vary, the potential for system stability increases. These results are robust to common network structures, including small-world and scale-free networks, and cascade food webs. Variation in γ is especially important for stability in highly complex systems, in which the probability of stability would otherwise be negligible. At such extremes of simulated system complexity, the largest stable complex systems would be unstable if not for variation in γ. My results therefore reveal a previously unconsidered aspect of system stability that is likely to be pervasive across all realistic complex systems.
The pressure to communicate efficiently continues to shape language use later in life
Authors: Long Madeleine , Rohde Hannah , Rubio-Fernandez Paula
Published: May 2020

Language use is shaped by a pressure to communicate efficiently, yet the tendency towards redundancy is said to increase in older age. The longstanding assumption is that saying more than is necessary is inefficient and may be driven by age-related decline in inhibition (i.e. the ability to filter out irrelevant information). However, recent work proposes an alternative account of efficiency: In certain contexts, redundancy facilitates communication (e.g., when the colour or size of an object is perceptually salient and its mention aids the listener’s search). A critical question follows: Are older adults indiscriminately redundant, or do they modulate their use of redundant information to facilitate communication? We tested efficiency and cognitive capacities in 200 adults aged 19–82. Irrespective of age, adults with better attention switching skills were redundant in efficient ways, demonstrating that the pressure to communicate efficiently continues to shape language use later in life.
Comparison of Three Histological Techniques for Fat Emboli Detection in Lung Cetacean’s Tissue
Authors: Arregui Marina , Fernández Antonio , Paz-Sánchez Yania , Santana Ángelo , Sacchini Simona , Sierra Eva , Arbelo Manuel , de Quirós Yara Bernaldo
Published: May 2020

Fat embolism is the mechanical blockage of blood vessels by circulating fat particles. It is frequently related to traumas involving soft tissues and fat-containing bones. Different techniques have been used for decades to demonstrate histologically fat emboli, being the extremely toxic post-fixation with osmium tetroxide one of the most used techniques in the last decades. In the present study, the osmium tetroxide technique was compared qualitatively and quantitatively, for the first time, with chromic acid and Oil Red O frozen techniques  for histological fat emboli detection in the lungs of eight sperm whales that died due to ship strikes. This was also the first time that chromic acid technique was tested in cetaceans. Results showed that the three techniques were valuable for the histological detection of fat embolism in cetaceans, even when tissues presented advanced autolysis and had been stored in formaldehyde for years. Although quantitative differences could not be established, the Oil Red O frozen technique showed the lowest quality for fat emboli staining. On the contrary, the chromic acid technique was proven to be a good alternative to osmium tetroxide due to its slightly lower toxicity, its equivalent or even superior capacity of fat emboli detection, and its significantly lower economic cost.