bluuebunny/crossref_metadata_2025 huggingface dataset:
The mammalian fauna of Kulikovo Pole region (Upper Don River Basin) during the end of Pleistocene – Holocene
Authors: Markova A , Martin T
Published: February 2020

This paper includes information on mammalian faunas from eight localities investigated in the Kulikovo Pole region – the place at the confluence of the Nepryadva and Don River where the famous battle between Tartars and Russians occurred in 1380. The oldest faunal assemblages were recovered from the natural outcrops in the upper floodplains of these streams where only steppe and tundra species from the periglacial interval were encountered. The distribution of Middle Holocene forest-steppe landscapes in the Upper Don basin are correlated with mammalian species that indicate major environmental changes. Mammals identified at several medieval sites reflect steppe, forest and hydrogenous species, and remains of domesticated species (cattle, horse, pig, sheep, goat and dog) reveal the impact of human activities during this time. Thus, the study of mammalian faunas associated with the last ∼14 thousand years BP demonstrates significant environmental and climatic changes from the cold periglacial tundra-steppe conditions at the end of the last glaciation to the establishment of forest-steppe habitats during the Middle and the Late Holocene.
Radial growth projections for spruce on Solovetskiye Islands, the White Sea, for the 21st century
Authors: Matskovsky V , Dolgova E , Morozova P , Semenyak N , Solomina O
Published: February 2020

Climate change projected for the 21st century is expected to affect different forest ecosystems with corresponding ecological, economic, and social impacts. Modeling is extensively used to estimate the impacts of climate change on tree species distributions, but only several studies produced tree growth projections based on climate change scenarios. However, those studies have been based on multiple regression models without considering the basic principles of dendroclimatology – principle of limiting factors and uniformitarian principle. Here we describe the methodology for tree growth projections that takes advantage of the process-based forward model of tree growth, VS-Lite, calibrated and independently validated on tree-ring data and driven by climate projections. We further use this methodology for spruce growth projections on Solovetskiye islands according to two extreme greenhouse gases emissions scenarios. Even according to the conservative one, which is peak-and-decayscenario, tree growth is projected to be significantly higher throughout the 21st century, than in the 20th century. These results are crucial for the strategies of Arctic region development in the near and remote future.
Late Glacial and Holocene in the south of Western Siberia: geochemical indices and pollen data in Kyrtyma Lake sediments
Authors: Ryabogina N E , Afonin A S , Ivanov S N
Published: February 2020

This paper presents some conclusions of a study of a long-term lake sequence in the southwestern part of the Western Siberian Plain. Environment changes in the Holocene were identified according to geochemical indices, accumulation rate, plant macrofossils, and pollen data of sediment in Lake Kyrtyma. As a result, we firstly obtained the data on climatically conditioned changes of the sedimentation in the flat part of Western Siberia over at least the last 15 thousand years. Geochemical changes in the sediment properties clearly revealed climate change over the Late Glacial and the Holocene. Changes in the composition of macrophytes gave little independent information, while the pollen data are perfectly combined with the sedimentation features and serve as a reliable source for the reconstruction of vegetation changes and landscape. The transition to the Holocene was marked at about ∼12–11.2 ka BP, subsequent ongoing warming led to the aridest Holocene phase at ∼7.1–5.5 ka BP. Cooling and the resulting decrease in vaporation began at ∼5.5–4.9 ka BP, but a cardinal shift in sedimentation due to a gradual increase in precipitation was at ∼4.9–2.8 ka BP. The most significant increase in humidification and a cooling began at 2.8 ka BP.
Schiller on Freedom and Aesthetic Value: Part II
Authors: Matherne Samantha , Riggle Nick
Published: February 2020

In his Letters on the Aesthetic Education of Man, Friedrich Schiller draws a striking connection between aesthetic value and individual and political freedom, claiming that, ‘it is only through beauty that man makes his way to freedom’. However, contemporary ways of thinking about freedom and aesthetic value make it difficult to see what the connection could be. Through a careful reconstruction of the Letters, we argue that Schiller’s theory of aesthetic value serves as the key to understanding not only his view of aesthetic engagement, but also his distinctive account of individual and political freedom. Whereas in Part I, we developed a reconstruction of Schiller's view that aesthetic value is the only path to individual freedom, in Part II we analyze how Schiller connects aesthetic value to political freedom. In the end, we show that Schiller defends a non-hedonic, action-oriented, communitarian theory of aesthetic value and a theory of freedom that makes the aesthetic not just supererogatory but fundamental for any fully autonomous life. Although we have lost touch with this way of thinking about aesthetic value and freedom, we submit that it is illuminating for contemporary thinking about both.
Physical performance trajectories and mortality among nursing home residents: results of the SENIOR cohort
Authors: Charles Alexia , Detilleux Johann , Buckinx Fanny , Reginster Jean-Yves , Gruslin Bastien , Bruyère Olivier
Published: February 2020

Background

Previous studies have shown that older people can experience a considerable change in their physical performance (PP) over time.

Objectives

To identify PP trajectories and their association with mortality among nursing home residents who were followed up for 3 years.

Design

Three-year longitudinal observational study.

Setting

Subjects of the SENIOR cohort.

Subjects

Six hundred and four nursing home residents with a mean age of 82.9 ± 9.1 years.

Methods

Baseline characteristics and the date of death were collected from the medical records. PP was assessed annually by the short physical performance battery (SPPB) test. Multiple imputations were performed to manage the missing data. PP trajectory groups were estimated using latent growth curve analysis. Cox proportional hazard regression models were applied to examine the risk of mortality according to the PP trajectory groups.

Results

Three PP trajectory groups were identified: slow decline (N = 96), moderate decline (N = 234) and fast decline (N = 274). After adjustments for potential confounding variables and the baseline SPPB scores, the residents in the fast decline and moderate decline trajectory groups had an increased risk of mortality compared to those in the slow decline trajectory group, with hazard ratio values of 1.78 (95% confidence interval [CI] = 1.34–2.26) and 1.37 (95% CI = 1.10–1.66), respectively.

Conclusions

PP trajectories provide value-added information to baseline geriatric assessments and could be used for predicting 3-year mortality among nursing home residents. It may be important to regularly monitor the SPPB score and signal an alert when a fast decline in PP is detected in older people.
Intrapopulation variation in the behavioral responses of dwarf mongooses to anthropogenic noise
Authors: Eastcott Emma , Kern Julie M , Morris-Drake Amy , Radford Andrew N
Published: February 2020

Anthropogenic noise is an increasingly widespread pollutant, with a rapidly burgeoning literature demonstrating impacts on humans and other animals. However, most studies have simply considered if there is an effect of noise, examining the overall cohort response. Although substantial evidence exists for intraspecific variation in responses to other anthropogenic disturbances, this possibility has received relatively little experimental attention with respect to noise. Here, we used field-based playbacks with dwarf mongooses (Helogale parvula) to test how traffic noise affects vigilance behavior and to examine potential variation between individuals of different age class, sex, and dominance status. Foragers exhibited a stronger immediate reaction and increased their subsequent vigilance (both that on the ground and as a sentinel) in response to traffic-noise playback compared with ambient-sound playback. Traffic-noise playback also resulted in sentinels conducting longer bouts and being more likely to change post height or location than in ambient-sound playback. Moreover, there was evidence of variation in noise responses with respect to age class and dominance status but not sex. In traffic noise, foraging pups were more likely to flee and were slower to resume foraging than adults; they also tended to increase their vigilance more than adults. Dominants were more likely than subordinates to move post during sentinel bouts conducted in traffic-noise trials. Our findings suggest that the vigilance–foraging trade-off is affected by traffic noise but that individuals differ in how they respond. Future work should, therefore, consider intrapopulation response variation to understand fully the population-wide effects of this global pollutant.
Occupancy spectrum distribution: application for coalescence simulation with generic mergers
Authors: Becheler Arnaud , Knowles L Lacey
Published: February 2020

Motivation

As the density of sampled population increases, especially as studies incorporate aspects of the spatial landscape to study evolutionary processes, efficient simulation of genetic data under the coalescent becomes a primary challenge. Beyond the computational demands, coalescence-based simulation strategies have to be reconsidered because traditional assumptions about the dynamics of coalescing lineages within local populations may be violated (e.g. more than two daughter lineages may coalesce to a parent at low population densities). Specifically, to efficiently assign n lineages to m parents, the order relation between n and m strongly affects the relevant algorithm for the coalescent simulator (e.g. only when n<2m, it is reasonable to assume that two lineages, at most, can be assigned to the same parent). Controlling the details of the simulation model as a function of n and m is then crucial to represent accurately and efficiently the assignment process, but current implementations make it difficult to switch between different types of lineage mergers at run-time or even compile-time.

Results

With the described occupancy spectrum and algorithm that generates the support of the joint probability distribution of the occupancy spectrum; computation is much faster than realizing the whole assignment process under the coalescent. Using general definitions of lineage merges, which also makes the codebase reusable, we implement several variants of coalescent mergers, including an approximation where low probability spectrums are discarded. Comparison of runtimes and performance of the different C++ highly reusable coalescence mergers (binary, multiple, hybrids) are given, and we illustrate their potential utility with example applications.

Availability and implementation

All components are integrated into Quetzal, an open-source C++ library for coalescence available at https://becheler.github.io/pages/quetzal.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
A catalogue of new incidence estimates of monogenic neurodevelopmental disorders caused by de novo variants
Authors: López-Rivera Javier A , Pérez-Palma Eduardo , Symonds Joseph , Lindy Amanda S , McKnight Dianalee A , Leu Costin , Zuberi Sameer , Brunklaus Andreas , Møller Rikke S , Lal Dennis
Published: February 2020

A large fraction of rare and severe neurodevelopmental disorders are caused by sporadic de novo variants. Epidemiological disease estimates are not available for the vast majority of these de novo monogenic neurodevelopmental disorders because of phenotypic heterogeneity and the absence of large-scale genomic screens. Yet, knowledge of disease incidence is important for clinicians and researchers to guide health policy planning. Here, we adjusted a statistical method based on genetic data to predict, for the first time, the incidences of 101 known de novo variant-associated neurodevelopmental disorders as well as 3106 putative monogenic disorders. Two corroboration analyses supported the validity of the calculated estimates. First, greater predicted gene-disorder incidences positively correlated with larger numbers of pathogenic variants collected from patient variant databases (Kendall’s τ = 0.093, P-value = 6.9 × 10−6). Second, for six of seven (86%) de novo variant associated monogenic disorders for which epidemiological estimates were available (SCN1A, SLC2A1, SALL1, TBX5, KCNQ2, and CDKL5), the predicted incidence estimates matched the reported estimates. We conclude that in the absence of epidemiological data, our catalogue of 3207 incidence estimates for disorders caused by de novo variants can guide patient advocacy groups, clinicians, researchers, and policymakers in strategic decision-making.
Racial/Ethnic Disparities in the Incidences of Bronchiolitis Requiring Hospitalization
Authors: Inagaki Kengo , Blackshear Chad , Burns Paul A , Hobbs Charlotte V
Published: February 2020

Background

Race/ethnicity is currently not considered a risk factor for bronchiolitis, except for indigenous populations in Western countries. A better understanding of the potential impact of race/ethnicity can inform programs, policies, and practices related to bronchiolitis.

Methods

We performed a population-based, longitudinal, observational study using the State Inpatient Database from New York State in the United States. Infants born between 2009 and 2013 at term without comorbidities were followed for the first 2 years of life, up to 2015. We calculated the cumulative incidences among different race/ethnicity groups, and evaluated the risks by developing logistic regression models.

Results

Of 877 465 healthy, term infants, 10 356 infants were hospitalized with bronchiolitis. The overall cumulative incidence was 11.8 per 1000 births. The cumulative incidences in non-Hispanic White, non-Hispanic Black, Hispanic, and Asian infants were 8.6, 15.4, 19.1, and 6.5 per 1000 births, respectively. In a multivariable analysis adjusting for socioeconomic status, the risks remained substantially high among non-Hispanic Black (odds ratio, 1.42; 95% confidence interval [CI], 1.34–1.51) and Hispanic infants (odds ratio, 1.77; 95% CI, 1.67–1.87), whereas being of Asian race was protective (odds ratio, .62; 95% CI, .56–.69).

Conclusions

The risks of bronchiolitis hospitalization in the first 2 years of life were substantially different by race/ethnicity, with Hispanic and Black infants having the highest rates of hospitalization. Further research is needed to develop and implement culturally appropriate public health interventions to reduce racial and ethnic health disparities in bronchiolitis.
The Relationship Between the Human Immunodeficiency Virus-1 Transmission Network and the HIV Care Continuum in Los Angeles County
Authors: Hassan Adiba , De Gruttola Victor , Hu Yunyin W , Sheng Zhijuan , Poortinga Kathleen , Wertheim Joel O
Published: February 2020

Background

Public health action combating human immunodeficiency virus (HIV) includes facilitating navigation through the HIV continuum of care: timely diagnosis followed by linkage to care and initiation of antiretroviral therapy to suppress viral replication. Molecular epidemiology can identify rapidly growing HIV genetic transmission clusters. How progression through the care continuum relates to transmission clusters has not been previously characterized.

Methods

We performed a retrospective study on HIV surveillance data from 5226 adult cases in Los Angeles County diagnosed from 2010 through 2014. Genetic transmission clusters were constructed using HIV-TRACE. Cox proportional hazard models were used to estimate the impact of transmission cluster growth on the time intervals between care continuum events. Gamma frailty models incorporated the effect of heterogeneity associated with genetic transmission clusters.

Results

In contrast to our expectations, there were no differences in time to the care continuum events among individuals in clusters with different growth dynamics. However, upon achieving viral suppression, individuals in high growth clusters were slower to experience viral rebound (hazard ratio 0.83, P = .011) compared with individuals in low growth clusters. Heterogeneity associated with cluster membership in the timing to each event in the care continuum was highly significant (P < .001), with and without adjustment for transmission risk and demographics.

Conclusions

Individuals within the same transmission cluster have more similar trajectories through the HIV care continuum than those across transmission clusters. These findings suggest molecular epidemiology can assist public health officials in identifying clusters of individuals who may benefit from assistance in navigating the HIV care continuum.
Faecal glucocorticoid metabolites as a measure of adrenocortical activity in polar bears (Ursus maritimus)
Authors: Hein Anna , Palme Rupert , Baumgartner Katrin , von Fersen Lorenzo , Woelfing Benno , Greenwood Alex D , Bechshoft Thea , Siebert Ursula
Published: February 2020

Analysis of faecal glucocorticoid metabolites (FGMs) is frequently applied to assess adrenocortical activity in animal conservation and welfare studies. Faecal sample collection is non-invasive and feasible under field conditions. FGM levels are also less prone to circadian rhythms, episodic fluctuations and short acute stressors than glucocorticoid (GC) levels obtained from other matrices, for example blood or saliva. To investigate the suitability of FGM measurement in polar bears (Ursus maritimus), a species listed as Vulnerable by the IUCN (International Union for Conservation of Nature), a cortisol enzyme immunoassay (EIA) was biologically validated by demonstrating a significant increase in FGMs after five zoo-to-zoo transports. In addition to validating the method, the study also documented an average delay of 7 h until the first occurrence of food colorants in the monitored polar bears, which provides essential information for future studies. After validation, the assay was applied to measure FGM concentrations of five polar bears over a 1-year period. Several pre-defined potentially stressful events were recorded in an event log to measure their effect on FGM concentrations. A mixed model analysis revealed significant increases in FGM concentrations after social tension and environmental changes, whereas season and sex had no significant effect. The study demonstrates that the applied cortisol EIA is suitable for measuring FGM levels in polar bears and that using a carefully validated assay for FGM analysis in combination with a detailed sampling protocol can serve as a valuable tool for evaluating mid- to long-term stress in polar bears. FGM levels can be used to monitor stress in captive polar bears in order to optimize housing conditions but also to elucidate stress responses in wild populations for targeted conservation measures.
The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions
Authors: Motiejūnaitė Justina , Akiyama Eiichi , Cohen-Solal Alain , Maggioni Aldo Pietro , Mueller Christian , Choi Dong-Ju , Kavoliūnienė Aušra , Čelutkienė Jelena , Parenica Jiri , Lassus Johan , Kajimoto Katsuya , Sato Naoki , Miró Òscar , Peacock W Frank , Matsue Yuya , Voors Adriaan A , Lam Carolyn S P , Ezekowitz Justin A , Ahmed Ali , Fonarow Gregg C , Gayat Etienne , Regitz-Zagrosek Vera , Mebazaa Alexandre
Published: February 2020

Aims

Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world.

Methods and results

We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79–0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67–0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89–0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001).

Conclusion

Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF.
Meningococcal Disease-Associated Prophage-Like Elements Are Present in Neisseria gonorrhoeae and Some Commensal Neisseria Species
Authors: Al Suwayyid Barakat A , Rankine-Wilson Leah , Speers David J , Wise Michael J , Coombs Geoffrey W , Kahler Charlene M
Published: February 2020

Neisseria spp. possess four genogroups of filamentous prophages, termed Nf1 to 4. A filamentous bacteriophage from the Nf1 genogroup termed meningococcal disease-associated phage (MDA φ) is associated with clonal complexes of Neisseria meningitidis that cause invasive meningococcal disease. Recently, we recovered an isolate of Neisseria gonorrhoeae (ExNg63) from a rare case of gonococcal meningitis, and found that it possessed a region with 90% similarity to Nf1 prophages, specifically, the meningococcal MDA φ. This led to the hypothesis that the Nf1 prophage may be more widely distributed amongst the genus Neisseria. An analysis of 92 reference genomes revealed the presence of intact Nf1 prophages in the commensal species, Neisseria lactamica and Neisseria cinerea in addition to the pathogen N. gonorrhoeae. In N. gonorrhoeae, Nf1 prophages had a restricted distribution but were present in all representatives of MLST ST1918. Of the 160 phage integration sites identified, only one common insertion site was found between one isolate of N. gonorrhoeae and N. meningitidis. There was an absence of any obvious conservation of the receptor for prophage entry, PilE, suggesting that the phage may have been obtained by natural transformation. An examination of the restriction modification systems and mutated mismatch repair systems with prophage presence suggested that there was no obvious preference for these hosts. A timed phylogeny inferred that N. meningitidis was the donor of the Nf1 prophages in N. lactamica and N. gonorrhoeae. Further work is required to determine whether Nf1 prophages are active and can act as accessory colonization factors in these species.
The great Chinese surprise: the rupture with the United States is real and is happening
Authors: Yang Xiangfeng
Published: February 2020

Ample evidence exists that China was caught off guard by the Trump administration's onslaught of punishing acts—the trade war being a prime, but far from the only, example. This article, in addition to contextualizing their earlier optimism about the relations with the United States under President Trump, examines why Chinese leaders and analysts were surprised by the turn of events. It argues that three main factors contributed to the lapse of judgment. First, Chinese officials and analysts grossly misunderstood Donald Trump the individual. By overemphasizing his pragmatism while downplaying his unpredictability, they ended up underprepared for the policies he unleashed. Second, some ingrained Chinese beliefs, manifested in the analogies of the pendulum swing and the ‘bickering couple’, as well as the narrative of the ‘ballast’, lulled officials and scholars into undue optimism about the stability of the broader relationship. Third, analytical and methodological problems as well as political considerations prevented them from fully grasping the strategic shift against China in the US.
Association Between Maternal Human Papillomavirus Infection and Adverse Pregnancy Outcomes: Systematic Review and Meta-Analysis
Authors: Niyibizi Joseph , Zanré Nadège , Mayrand Marie-Hélène , Trottier Helen
Published: February 2020

Background

Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes.

Methods

We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies.

Results

From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19–1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11–3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08–1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01–1.37), low birth weight (aOR, 1.91; 95% CI, 1.33–2.76), and fetal death (aOR, 2.23; 95% CI, 1.14–4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40–3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80–1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained.

Conclusions

We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases.
Frequency of capsid substitutions associated with GS-6207 in vitro resistance in HIV-1 from antiretroviral-naive and -experienced patients
Authors: Marcelin Anne-Geneviève , Charpentier Charlotte , Jary Aude , Perrier Marine , Margot Nicolas , Callebaut Christian , Calvez Vincent , Descamps Diane
Published: February 2020

Background

GS-6207 is a first-in-class HIV capsid inhibitor, targeting several functions of the HIV capsid in the viral cycle, including viral particle assembly, capsid formation and nuclear entry. GS-6207 has demonstrated picomolar potency in vitro, activity confirmed by high potency in a Phase 1 clinical study, with a long-acting antiretroviral profile with potential dosing every 6 months. In vitro resistance selections previously conducted with increasing doses of GS-6207 have identified capsid variants with reduced susceptibility to GS-6207.

Objectives

To study the prevalence of capsid mutations associated with in vitro resistance to GS-6207 in people living with HIV (PLWH).

Methods

Plasma samples from ART-naive or -experienced PLWH, including PI-experienced people, were sequenced and analysed for the presence of capsid variants identified during in vitro resistance selection: L56I, M66I, Q67H, K70N, N74D, N74S and T107N.

Results

Among the samples from the 1500 patients studied, none of the seven GS-6207 resistance mutations identified during in vitro selection experiments was detected, regardless of HIV subtype or PLWH treatment history.

Conclusions

Out of the seven HIV capsid substitutions previously selected in vitro and shown to confer phenotypic resistance to GS-6207, none of these seven mutations was observed in this large dataset, suggesting that neither PLWH with previous PI failure nor PLWH with emergence of PI resistance mutations are anticipated to impact GS-6207 activity in these diverse HIV-infected populations.
Diversity minimization through part combination – a Portuguese railway infrastructure case study
Authors: Rechena Diogo , Sousa Luís , Infante Virgínia , Henriques Elsa
Published: February 2020

With increasing market needs for product and service variety, companies struggle to provide diversity in cost-effective ways. Through standardization of components with a low perceived added value, companies can take advantage of economies of scale while maintaining product diversity. Railway infrastructure managers face similar challenges of providing economically sustainable services while dealing with the costs of maintaining the system diversity. Typically, unintended design diversity stems from design practices in which existing solutions are not reused for new problems and new solutions are rarely planned considering the dynamics of requirement changes. In this paper we provide a methodology to assess how to standardize different designs to minimize design diversity and to assess design divergence in a product family. The developed methodology is able to take into account any set of standardization compatibility constraints that the user can define. The methodology was applied in the context of a small-scale railway infrastructure manager using a dataset of 223 unique designs of functionally similar components from its electrification system. Depending on the activated compatibility constraints, results indicate that over 60% of components can be reduced to a set of 86 unique designs.
Statistical tolerance analysis applied on overconstrained mechanisms with form deviations
Authors: Gouyou Doriane , Teissandier Denis , Delos Vincent , Ledoux Yann
Published: February 2020

One method for modeling geometric variations in hyperstatic (i.e. overconstrained) systems is to use sets of constraints. Different models have been developed in this way, e.g. domains, T-maps, and polytopes. In general, if the intersection of the contact constraints between two parts potentially in contact is nonempty, the parts can be assembled without interference, and their relative positions determined. In this study, the polytope method is used with a statistical approach to define the behavior of an assembly. In the first part, geometric variations including form deviations of individual parts are defined. The relations between these variations resulting from the architecture of a mechanism are then defined. In the second part, contact constraints are introduced and the general method to conform the constraints into double description polytopes is presented. The general process to simulate the compliance of the mechanism with respect to functional conditions is described. A failure rate is obtained for a simulated population of manufactured parts using the Monte Carlo method. In the third part, an application to a flange is described, an example from an industrial case study. We show how to take advantage of double description of polytopes when simulating the assembly and the misalignment of the two parts that make up the flange. Finally, we present our conclusions and prospects for future studies.
Cutting Through the Fog: Financial Literacy and Financial Investment Choices
Authors: Nieddu Marco , Pandolfi Lorenzo
Published: February 2020

This paper examines the impact of financial literacy on the individual propensity to invest in financial assets. In a laboratory experiment with a two-by-two design, we study how the certainty equivalent of a risky lottery changes when varying the lottery framing and the participants’ financial literacy level. We find that presenting the lottery as a financial asset—whose payoffs need to be computed from a given return rate—rather than as a simple coin toss reduces the average value participants assign to the lottery by approximately 20% and lowers their understanding of the lottery’s structure. Enhancing financial literacy by explaining the basic financial concepts involved in the description of the financial-asset lottery, offsets the negative effects of the financial framing: it improves respondents’ understanding of the lottery and increases the certainty equivalent. Our results—which can be rationalized by ambiguity aversion—shed new light on the linkages between financial literacy and financial investment behavior. Additionally, they highlight the importance of promoting financial education to stimulate households’ financial market participation.
Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer
Authors: Olson Jared , Mehra Sonia , Hersh Adam L , Thorell Emily A , Stoddard Gregory J , Maese Luke , Barnette Phillip E , Lemons Richard S , Pavia Andrew T , Knackstedt Elizabeth D
Published: February 2020

Background

Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline.

Methods

We performed a quasi-experimental, pre–post study of discharge FN treatment at a stand-alone children’s hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014).

Results

In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03–.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17–.93]) compared to the preintervention time period.

Conclusions

Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.
Inferring the role of pit membranes in solute transport from solute exclusion studies in living conifer stems
Authors: Yang Dongmei , Wei Kailu , Li Junhui , Peng Guoquan , Tyree Melvin T
Published: February 2020

The functional role of pits between living and dead cells has been inferred from anatomical studies but amassing physiological evidence has been challenging. Centrifugation methods were used to strip water from xylem conduits, permitting a more quantitative gravimetric determination of the water and solid contents of cell walls than is possible by more traditional methods. Quantitative anatomical evidence was used to evaluate the water volume in xylem conduits and the water content of living cells. Quantitative perfusion of stems with polyethylene glycol of different molecular weight was used to determine the solute-free space. We measured the portioning of water and solute-free space among anatomical components in stems and demonstrated that lignin impeded the free movement of solutes with molecular weight >300. Hence, movement of large solutes from living cells to xylem conduits is necessarily confined to pit structures that permit transmembrane solute transport via primary walls without lignin. The functional role of pits was additionally indicated by combining data in this paper with previous studies of unusual osmotic relationships in woody species that lack pits between dead wood fibers and vessels. The absence of pits, combined with the evidence of exclusion of solutes of molecular weight >300, explains the unexpected osmotic properties.
The SUrvey for Pulsars and Extragalactic Radio Bursts – IV. Discovery and polarimetry of a 12.1-s radio pulsar
Authors: Morello V , Keane E F , Enoto T , Guillot S , Ho W C G , Jameson A , Kramer M , Stappers B W , Bailes M , Barr E D , Bhandari S , Caleb M , Flynn C M L , Jankowski F , Johnston S , van Straten W , Arzoumanian Z , Bogdanov S , Gendreau K C , Malacaria C , Ray P S , Remillard R A
Published: February 2020

We report the discovery of PSR J2251−3711, a radio pulsar with a spin period of 12.1 s, the second longest currently known. Its timing parameters imply a characteristic age of 15 Myr, a surface magnetic field of 1.3 × 1013 G, and a spin-down luminosity of 2.9 × 1029 erg s−1. Its dispersion measure of 12.12(1) pc cm−3 leads to distance estimates of 0.5 and 1.3 kpc according to the NE2001 and YMW16 Galactic free electron density models, respectively. Some of its single pulses show an uninterrupted 180-deg sweep of the phase-resolved polarization position angle, with an S-shape reminiscent of the rotating vector model prediction. However, the fact that this sweep occurs at different phases from one pulse to another is remarkable and without straightforward explanation. Although PSR J2251−3711 lies in the region of the $P-\dot{P}$ parameter space occupied by the X-ray isolated neutron stars (XINS), there is no evidence for an X-ray counterpart in our Swift XRT observation; this places a 99 per cent-confidence upper bound on its unabsorbed bolometric thermal luminosity of $1.1 \times 10^{31}~(d / 1~\mathrm{kpc})^2~\mathrm{erg\, s}^{-1}$ for an assumed temperature of 85 eV, where d is the distance to the pulsar. Further observations are needed to determine whether it is a rotation-powered pulsar with a true age of at least several Myr, or a much younger object such as an XINS or a recently cooled magnetar. Extreme specimens like PSR J2251−3711 help bridge populations in the so-called neutron star zoo in an attempt to understand their origins and evolution.
The infrared view of dust and molecules around V4334 Sgr (Sakurai’s object): a 20-yr retrospective
Authors: Evans A , Gehrz R D , Woodward C E , Banerjee D P K , Geballe T R , Clayton G C , Sarre P J , Starrfield S , Hinkle K , Joyce R R , Lykou Foteini , Helton L A , Eyres S P S , Worters H , Montiel E J , Liimets T , Zijlstra A , Richter M , Krautter J
Published: February 2020

We present an analysis of the evolution of circumstellar dust and molecules in the environment of the very late thermal pulse object V4334 Sgr (Sakurai’s object) over an ∼20-yr period, drawing on ground-, airborne-, and space-based infrared photometry and spectroscopy. The dust emission, which started in 1997, resembles a blackbody that cooled from ∼1200 K in 1998 August to ∼180 K in 2016 July. The dust mass, assuming amorphous carbon, was ∼5 × 10−10 M⊙ in 1998 August, and we estimate that the total dust mass was ∼2 × 10−5 M⊙ by ∼2016. The appearance of a near-infrared excess in 2008 suggests that a new episode of (or renewed) mass-loss began then. We infer lower limits on the bolometric luminosity of the embedded star from that of the dust shell, which rose to ∼16 000 L⊙ before declining to ∼3000 L⊙. There is evidence for weak 6–7 μm absorption, which we attribute to hydrogenated amorphous carbon formed in material ejected by Sakurai’s object during a mass ejection phase that preceded the 1997 event. We detect small hydrocarbon and other molecules in the spectra, and trace the column densities in hydrogen cyanide (HCN) and acetylene (C2H2). We use the former to determine the 12C/13C ratio to be 6.4 ± 0.7, 14 times smaller than the Solar system value.
Cis- and Trans-Regulatory Variations in the Domestication of the Chili Pepper Fruit
Authors: Díaz-Valenzuela Erik , Sawers Ruairidh H , Cibrián-Jaramillo Angélica
Published: February 2020

The process of domestication requires the rapid transformation of the wild morphology into the cultivated forms that humans select for. This process often takes place through changes in the regulation of genes, yet, there is no definite pattern on the role of cis- and trans-acting regulatory variations in the domestication of the fruit among crops. Using allele-specific expression and network analyses, we characterized the regulatory patterns and the inheritance of gene expression in wild and cultivated accessions of chili pepper, a crop with remarkable fruit morphological variation. We propose that gene expression differences associated to the cultivated form are best explained by cis-regulatory hubs acting through trans-regulatory cascades. We show that in cultivated chili, the expression of genes associated with fruit morphology is partially recessive with respect to those in the wild relative, consistent with the hybrid fruit phenotype. Decreased expression of fruit maturation and growth genes in cultivated chili suggest that selection for loss-of-function took place in its domestication. Trans-regulatory changes underlie the majority of the genes showing regulatory divergence and had larger effect sizes on gene expression than cis-regulatory variants. Network analysis of selected cis-regulated genes, including ARP9 and MED25, indicated their interaction with many transcription factors involved in organ growth and fruit ripening. Differentially expressed genes linked to cis-regulatory variants and their interactions with downstream trans-acting genes have the potential to drive the morphological differences observed between wild and cultivated fruits and provide an attractive mechanism of morphological transformation during the domestication of the chili pepper.
High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts
Authors: Roux Alexandre , Pallud Johan , Saffroy Raphaël , Edjlali-Goujon Myriam , Debily Marie-Anne , Boddaert Nathalie , Sanson Marc , Puget Stéphanie , Knafo Steven , Adam Clovis , Faillot Thierry , Cazals-Hatem Dominique , Mandonnet Emmanuel , Polivka Marc , Dorfmüller Georges , Dauta Aurélie , Desplanques Mathilde , Gareton Albane , Pages Mélanie , Tauziede-Espariat Arnault , Grill Jacques , Bourdeaut Franck , Doz François , Dhermain Frédéric , Mokhtari Karima , Chretien Fabrice , Figarella-Branger Dominique , Varlet Pascale
Published: February 2020

Background

Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs).

Methods

We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification.

Results

Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance.

Conclusions

HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.
Transcallosal Interforniceal Approach for a Large Choroid Plexus Tumor in a 4-Month-Old Boy: 2-Dimensional Operative Video
Authors: Ravindra Vijay M , Aldave Guillermo
Published: February 2020

Tumors in the third ventricle constitute a challenge for the neurosurgeon, regardless of the chosen approach. The additional risk of severe blood loss in the pediatric population, specially for choroid plexus tumors, which are the most common ventricular tumors in children, adds a significant challenge in these cases. Therefore, a careful selection of the approach in addition to surgical technique is crucial for a favorable outcome.

In this video, we discuss the approach selected for the treatment of a large choroid plexus tumor in a 4-mo-old male and highlight the surgical technique chosen for this case, a transcallosal interforniceal approach.
1
Appropriate consent for the video authorization and the procedure was obtained from the parent of the patient. Images in video from Rhoton AL Jr, The Cerebrum, Neurosurgery, 2007, 61, suppl_1, SHC-37-SHC-119, by permission of the Congress of Neurological Surgeons.
Maternal and neonatal outcomes associated with biologic exposure before and during pregnancy in women with inflammatory systemic diseases: a systematic review and meta-analysis of observational studies
Authors: Tsao Nicole W , Rebic Nevena , Lynd Larry D , De Vera Mary A
Published: February 2020

Objective

To determine the association between exposure to biologics in pregnant women with inflammatory systemic diseases and maternal and neonatal outcomes through a meta-analysis of findings from studies identified in a systematic review.

Methods

We conducted a systematic review of Medline, Embase, and Cochrane Database of Systematic Reviews to identify observational studies assessing the perinatal impacts of biologic in women with inflammatory systemic disease. Findings were meta-analysed across included studies with random-effects models. Crude risk estimates and, where possible, adjusted risk estimates were pooled to determine the impact on results when confounding is addressed.

Results

Overall, 24 studies were included in the meta-analysis. Meta-analyses of crude risk estimates resulted in pooled odds ratios (OR) for the association of biologic use during pregnancy and the following respective outcomes: congenital anomalies (1.30, 95% CI: 1.02, 1.67), preterm birth (OR 1.61, 95% CI: 1.37, 1.89), and low birth weight (OR 1.68, 95% CI: 1.21, 2.31). However, in pooled analyses of adjusted risk estimates we observed that the association between biologics use during pregnancy in disease-matched exposed and unexposed pregnant women was no longer statistically significant for congenital anomalies (adjusted OR 1.18, 95% CI: 0.88, 1.57).

Conclusion

Pooled results from studies reporting adjusted risk estimates showed no increased risk of congenital anomalies associated with biologics use, suggesting that increased rates of adverse outcomes may be due to disease activity itself or other confounders.