bluuebunny/crossref_metadata_2025 huggingface dataset:
Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial
Authors: Nishiyama Hiroyuki , Yamamoto Yoshiaki , Sassa Naoto , Nishimura Kazuo , Fujimoto Kiyohide , Fukasawa Satoshi , Yokoyama Minato , Enokida Hideki , Takahashi Kenichi , Tanaka Yoshinobu , Imai Kentaro , Shimamoto Takashi , Perini Rodolfo , Frenkl Tara , Bajorin Dean , Bellmunt Joaquim
Published: November 2019

Background

The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan.

Patients and methods

Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points.

Results

Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44–1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32–1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95–3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3–5 events, occurred less frequently with pembrolizumab.

Conclusions

Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.
Stochastic Seismic Waveform Inversion Using Generative Adversarial Networks as a Geological Prior
Authors: Mosser Lukas , Dubrule Olivier , Blunt Martin J.
Published: November 2019

We present an application of deep generative models in the context of partial differential equation constrained inverse problems. We combine a generative adversarial network representing an a priori model that generates geological heterogeneities and their petrophysical properties, with the numerical solution of the partial-differential equation governing the propagation of acoustic waves within the earth’s interior. We perform Bayesian inversion using an approximate Metropolis-adjusted Langevin algorithm to sample from the posterior distribution of earth models given seismic observations. Gradients with respect to the model parameters governing the forward problem are obtained by solving the adjoint of the acoustic wave equation. Gradients of the mismatch with respect to the latent variables are obtained by leveraging the differentiable nature of the deep neural network used to represent the generative model. We show that approximate Metropolis-adjusted Langevin sampling allows an efficient Bayesian inversion of model parameters obtained from a prior represented by a deep generative model, obtaining a diverse set of realizations that reflect the observed seismic response.
Introduction: striving for objectivity in space
Authors: Cheng Tony , Snowdon Paul
Published: November 2019

In this special issue, we put together papers that explore the theme “objectivity, space, and mind” from various angles. In the introduction we minimally discuss what are involved in this theme.
Assessment of meteorological droughts over Saudi Arabia using surface rainfall observations during the period 1978–2017
Authors: Almazroui Mansour
Published: November 2019

This paper discusses the preliminary results of meteorological drought analysis over Saudi Arabia for the period 1978–2017. In conjunction with meteorological observations, datasets from the Climate Prediction Center (CPC), the Merged Analysis of Precipitation (CMAP), the Climatic Research Unit (CRU), and the Tropical Rainfall Measuring Mission (TRMM) are utilized to understand the impact of the spatial distribution of rainfall on drought events. Applying precipitation thresholds allows rainfall classifications such as deficit, scanty, and surplus. Precipitation thresholds are also used to define meteorological droughts in the country, which are categorized as usual, moderate, and severe. It is found that drought events occur in Saudi Arabia due to shortfalls in the dry season, even though there is above normal rainfall in the wet season. There is no case of a shortfall in both the wet and dry seasons causing drought. Saudi Arabian droughts of all categories occurred mostly in the dry season, with fewer in the wet season. Results show that in Saudi Arabia, the last month of the wet season (April) is less prone to drought while the first and last months of the dry season (June and September respectively) are more prone to drought. Spatial distribution of drought climatology is obtained by calculating the Standardized Precipitation Index (SPI) and the Palmer Drought Severity Index (PDSI). Further application-driven studies of projections are needed based on drought indices and climate model output.
Design of converging-diverging nozzles with constant-radius centerbody
Authors: Flock Andreas K. , Gülhan Ali
Published: November 2019

Several flow phenomena, such as recirculating wake flows or noise generation, occur in aerodynamic configurations with backward facing steps. In this context, subsonic nozzles with constant-radius centerbodies exist, which enable fundamental research of these phenomena for $$M < 1$$M<1. For the supersonic regime, however, the existing database and knowledge are limited. Therefore, this work presents a design approach for a converging-diverging nozzle with constant-radius centerbody. For the nozzle throat, Sauer’s method is modified to include a centerbody. The method of characteristics is used for the subsequent supersonic portion. Comparing the analytical calculations to numerical simulations results in very good agreement and therefore underlines the feasibility of the chosen approach. Viscosity reduced the Mach number on the exit plane by 1.0–1.2% and therefore had little influence.
Adaptive Bayesian credible bands in regression with a Gaussian process prior
Authors: Sniekers Suzanne , van der Vaart Aad
Published: November 2019

A credible band is the set of all functions between a lower and an upper bound that are constructed so that the set has prescribed mass under the posterior distribution. In a Bayesian analysis such a band is used to quantify the remaining uncertainty on the unknown function in a similar manner as a confidence band. We investigate the validity of a credible band in the nonparametric regression model with the prior distribution on the function given by a Gaussian process. We show that there are many true regression functions for which the credible band has the correct order of magnitude to be used as a confidence set. We also exhibit functions for which the credible band is misleading.
Prediction of groundwater level in basement complex terrain using artificial neural network: a case of Ijebu-Jesa, southwestern Nigeria
Authors: Adiat K. A. N. , Ajayi O. F. , Akinlalu A. A. , Tijani I. B.
Published: November 2019

Empirical relationship between geoelectric parameters and groundwater level in boreholes/wells has not been established. Also, prediction of groundwater level from geoelectric parameters had hitherto not been reported. In order to overcome these challenges, the capability of artificial neural network (ANN) to model nonlinear system was explored in this study to predict groundwater level from geoelectric parameters. To achieve the above objectives, the ground water level (GWL) of all the accessible wells in the study area was obtained and this was used as the output parameter for the ANN model. A total of fifty-one (51) parametric vertical electrical soundings (VES) stations were occupied at each of the well location by adopting Schlumberger array configuration with electrode spacing (AB/2) ranging from 1 to 100 m. The VES data were quantitatively interpreted to generate geoelectric parameters believed to be controlling the groundwater flow and storage in the area. These parameters served as input for ANN model. The capability of ANN as a nonlinear modeling system was thereafter applied to produce a model that can predict the GWL from the input parameters. The efficiency of the model was evaluated by estimating the mean square error (MSE) and the regression coefficient (R) for the model. The results established that seasonal variation has little effect on the water fluctuation in the wells. Two aquifer types, weathered and fractured basement aquifer types, were delineated in the area. The results of the ANN model validation showed low MSE of 0.0014286 and the high regression coefficient (R) of 0.98731. This indicates that ANN can be used to predict GWL in a basement complex terrain with reasonably good accuracy. It is concluded that the ANN can effectively predict GWL from geoelectric parameters.
Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis microspora
Authors: Nalin Rathnayake G. R. , Savitri Kumar N. , Jayasinghe Lalith , Araya Hiroshi , Fujimoto Yoshinori
Published: November 2019

An endophytic fungus Pestalotiopsis microspora isolated from the fruits of Manilkara zapota was cultured in potato dextrose broth media. Chromatographic separation of the EtOAc extract of the broth and mycelium led to the isolation of a new azaphilonoid named pitholide E (1), in addition to previously identified pitholide B (2), pitholide D (3), pestalotin (LL-P880α) (4), PC-2 (5), LL-P880β (6), tyrosol (7) and 4-oxo-4H-pyran-3-acetic acid (8). An endophytic fungus P. microspora from M. zapota and the isolation of compounds 1–5, 7 and 8 from P. microspora are reported here for the first time.

Graphic Abstract
Refining RNA solution structures with the integrative use of label-free paramagnetic relaxation enhancement NMR
Authors: Gong Zhou , Yang Shuai , Yang Qing-Fen , Zhu Yue-Ling , Jiang Jing , Tang Chun
Published: November 2019

NMR structure calculation is inherently integrative, and can incorporate new experimental data as restraints. As RNAs have lower proton densities and are more conformational heterogenous than proteins, the refinement of RNA structures can benefit from additional types of restraints. Paramagnetic relaxation enhancement (PRE) provides distance information between a paramagnetic probe and protein or RNA nuclei. However, covalent conjugation of a paramagnetic probe is difficult for RNAs, thus limiting the use of PRE NMR for RNA structure characterization. Here, we show that the solvent PRE can be accurately measured for RNA labile imino protons, simply with the addition of an inert paramagnetic cosolute. Demonstrated on three RNAs that have increasingly complex topologies, we show that the incorporation of the solvent PRE restraints can significantly improve the precision and accuracy of RNA structures. Importantly, the solvent PRE data can be collected for RNAs without isotope enrichment. Thus, the solvent PRE method can work integratively with other biophysical techniques for better characterization of RNA structures.
Recent advances in characterising irradiation damage in tungsten for fusion power
Authors: Das Suchandrima
Published: November 2019

Tungsten is the front-runner candidate for building the plasma-facing armour components for future fusion reactors. However, in-service irradiation by fusion-neutrons and helium will create lattice-defects in the material, compromising its properties and lifetime. Improving the component’s resilience to radiation damage and accurately predicting the lifetime of irradiated components is key for commercial feasibility of the reactor. For this purpose, understanding the creation and evolution of radiation damage is essential. This paper reviews recent advances in characterising radiation damage through experimental and modelling techniques. Tungsten-ion- and helium-ion-implantation are commonly used to mimic the damage created by neutron- and helium-irradiation respectively. Defects (> 1.5 nm) can be directly imaged using transmission electron microscopy while all defects (size-independent), may be indirectly probed by measuring lattice strains induced by them (using diffraction techniques; synchrotron X-rays or high-resolution electron-backscatter). Neutron-irradiation produces mainly ½〈111〉 prismatic loops. Loop-interaction and structural organisation evolves with changing implantation dose and temperature. Helium-irradiation, < 573 K, induces formation of small helium-vacancy clusters, which evolve into bubbles, blisters and “fuzz” structure with changing temperature and dose. Nano-indentation or micro-cantilever bending tests can be used to examine mechanical properties of ion-implanted layers. Both helium- and neutron-implantation defects induce increased hardening often followed by subsequent strain-softening and localised deformation. Such irradiation-induced alterations are detrimental to material ductility and long-term structural integrity of tungsten-based components. Development of physically-based material models that capture the physics of underlying irradiation-induced changes, inspire confidence of reliably using simulations to predict mechanical behaviour and in-service performance of irradiated engineering components in future.
Correlates of short sleep duration among adolescents
Authors: Widome Rachel , Berger Aaron T. , Lenk Kathleen M. , Erickson Darin J. , Laska Melissa N. , Iber Conrad , Kilian Gudrun , Wahlstrom Kyla
Published: November 2019

Introduction

Short sleep duration is exceedingly common among adolescents and has implications for healthy youth development. We sought to document associations between adolescents’ sleep duration and characteristics of their schedules, behaviors, and wellbeing.

Methods

We used data from the baseline wave (9th grade year) of the START study, a cohort of 2134 students in five Minnesota high schools to assess how self‐reported sleep duration was associated with the prevalence of time‐use characteristics (i.e. activity schedules, screen use), sleep‐wake problems (i.e. trouble waking in the morning, falling asleep in class, etc.), and risk of depression.

Results

Shorter sleep duration was associated with various behaviors including greater computer/screen time and screen use after bed, a lower probability of doing homework, participation in sports doing chores on school nights, and reporting that it takes at least 20 min to fall asleep on school days (p < 0.05). Suboptimal sleep duration was also associated with a higher probability of all reported sleep‐wake problems as well as higher risk of depressive symptoms (p < 0.05).

Conclusions

Given that getting an optimal amount of sleep can protect youth from risk and promote healthy youth development, it is critical that we gain a greater understanding of correlates and consequences of short sleep duration in order to develop a sleep‐friendly culture for youth.
Variation in Brain Subcortical Network Topology Between Men with and Without PE: A Diffusion Tensor Imaging Study
Authors: Chen Jianhuai , Yang Jie , Huang Xinfei , Lu Chao , Liu Shaowei , Dai Yutian , Yao Zhijian , Chen Yun , Yu Min
Published: November 2019

Introduction

Premature ejaculation (PE) is a highly prevalent male sexual dysfunction. Previous studies have found abnormal activity in the sympathetic nervous system and penile sensory pathway of PE. Few studies have investigated the neural mechanisms underlying PE.

Aim

The aim of this study was to examine whether the altered cortico-subcortical network topological properties of the brain white matter structural network could be used to differentiate patients with PE from healthy control (HC) subjects.

Methods

Diffusion tensor images data were collected from 32 patients with PE and 35 HC participants. Then, brain white matter structural networks were reconstructed from image acquisition.

Main Outcome Measure

Furthermore, nodal measures were calculated and hub regions were identified using the graph-theoretical methods.

Results

For cortical brain regions, increased strength, global efficiency, and decreased shortest path length were found in the right superior frontal gyrus (medial), and superior frontal gyrus (medial orbital) were found in patients with PE. In addition, patients with PE also showed decreased strength in the right rolandic operculum and decreased shortest path length, and increased global efficiency in the right inferior frontal gyrus (triangular part). For subcortical brain structures, patients with PE were associated with decreased shortest path length and increased global efficiency in the left insula and right caudate nucleus. Finally, the results showed that 9 PE-specific hub regions were identified in patients compared with HCs, including 7 cortical regions and 2 subcortical regions.

Clinical Implications

Our results provide new understanding about the pathology of PE and enhances the understanding of PE pathology.

Strength & Limitations

Our results offer biological markers for understanding the physiopathology of PE. However, our study is a cross-sectional design, longitudinal design studies need to explore the causal relationships between aberrant topological characteristics and PE.

Conclusion

Our results provide new insights into the neural mechanism of PE involving cortico-subcortical network changes, which could serve as a potential biomarker to differentiate individuals with PE from HCs.
Perspectives on Priapism Education in Emergency Medicine
Authors: Dai Jessica C. , Franzen Douglas S. , Lendvay Thomas S. , Ostrowski Kevin A. , Walsh Thomas J.
Published: November 2019

Introduction

Priapism is a urologic emergency managed by both emergency medicine (EM) providers and urologists. Attitudes regarding its management and understanding of education of non-urology trainees in this area are poorly defined.

Aim

The aim of this study was to describe attitudes toward priapism management among multiple stakeholders and define the current state of priapism education among EM residency programs.

Methods

Surveys were developed and distributed online to EM residency leadership, EM residents, and urology providers. Each solicited attitudes and preferences regarding independent priapism management by EM providers. EM residents were further queried about their educational and clinical experiences in priapism management, and EM residency leadership were surveyed about their educational curricula. Responses among all 3 groups were compared using Fisher’s exact tests.

Main Outcome Measure

Quantitative and descriptive responses were solicited regarding EM providers’ management of acute ischemic priapism and current priapism curricula for EM residents.

Results

91 EM residency program directors and assistant program directors (31.6% of programs), 227 EM residents (14.7% of programs), and 94 urologists (6.3% of survey recipients) responded. All geographic regions and all years of EM training were represented. Over 90% of all surveyed groups felt that EM providers should independently manage priapism in practice. 17% of senior EM residents felt “not at all” confident in managing priapism; and 25.5% had never primarily managed this entity in training. 81% of programs had a formalized priapism curriculum, of which 19% included treatment simulation. However, 36% of residents felt that current curricula were insufficient.

Clinical Implications

Widespread approval from both EM providers and urologists support EM-based management for uncomplicated cases of acute ischemic priapism. Current educational curricula for EM trainees may not be sufficient to prepare them to manage this entity in practice.

Strengths & Limitations

This is the first study to examine provider attitudes toward EM-based management of priapism and assess the current state of education in this area with input from all key stakeholders. This survey was limited in its scope and the response rate was lower than desired.

Conclusion

Urologists support independent priapism management by EM providers, but an educational gap remains for EM trainees who do not feel adequately trained to manage this independently in practice.
Red Biocentrism for the Anthropocene
Authors: Boxley Simon
Published: November 2019

If the dawn of the Anthropocene heralds the collapse of the natural and social sciences into a single geostory, then why not also a radical synthesis of the anthropocentrism of Marxist theorising with the biocentrism of Deep Ecology? This article proposes just such a unification for theorising education. First, those on the educational left who wish to develop a fundamental unity between red and green should perhaps unearth the roots of Deep Ecological thinking and delve into the long and manifold history of socialist movements, with the aim of identifying where, between the deep red and deep green, might lie some shared origins in common ground. The flawed but nevertheless distinctive monism of the first philosopher of Marxism, Joseph Dietzgen, offers a philosophy that both prefigures the cosmology of Deep Ecology and suggests means of reconciling the narrative of human toil and ‘progress’ with that of human ‘nestedness’. The task facing the socialist looking to explore such a possibility needs to be located principally at the level of ‘cosmic’, rather than ‘social’ ontology, and this article sketches the outlines of such a unity project. Second, from this synthesis flows a set of implications for education and human growth. As the article explains, themes such as alienation and subjectification that cross-pollinate the theoretical perspectives might serve as central motifs in a red biocentric educational project fit for the Anthropocene. It is not solely environmental education, but approaches to education more broadly that require reconceptualisation for the Anthropocene.
Symbolic Values
Authors: DAVIS RYAN W.
Published: November 2019

When a symbol is a marker of a primary bearer of value and, secondarily, a bearer of value itself, then it has symbolic value. Philosophers have long been suspicious of symbolic values, often regarding them as illusory or irrelevant. I suggest that arguments against symbolic values either overgeneralize or else require premises that can only be supported if the normative significance of some symbolic considerations is presupposed. Humans need symbols to represent identity facts to themselves and others. Symbolic values thereby contribute to individuals’ control over their own agency.
Asymptotic variance for random walk Metropolis chains in high dimensions: logarithmic growth via the Poisson equation
Authors: Mijatović Aleksandar , Vogrinc Jure
Published: November 2019

There are two ways of speeding up Markov chain Monte Carlo algorithms: (a) construct more complex samplers that use gradient and higher-order information about the target and (b) design a control variate to reduce the asymptotic variance. While the efficiency of (a) as a function of dimension has been studied extensively, this paper provides the first results linking the efficiency of (b) with dimension. Specifically, we construct a control variate for a d-dimensional random walk Metropolis chain with an independent, identically distributed target using the solution of the Poisson equation for the scaling limit in [30]. We prove that the asymptotic variance of the corresponding estimator is bounded above by a multiple of

$\log(d)/d$

over the spectral gap of the chain. The proof hinges on large deviations theory, optimal Young’s inequality and Berry–Esseen-type bounds. Extensions of the result to non-product targets are discussed.
Insensitivity of the mean field limit of loss systems under SQ(d) routeing
Authors: Vasantam Thirupathaiah , Mukhopadhyay Arpan , Mazumdar Ravi R.
Published: November 2019

In this paper, we study a large multi-server loss model under the SQ(d) routeing scheme when the service time distributions are general with finite mean. Previous works have addressed the exponential service time case when the number of servers goes to infinity, giving rise to a mean field model. The fixed point of the limiting mean field equations (MFEs) was seen to be insensitive to the service time distribution in simulations, but no proof was available. While insensitivity is well known for loss systems, the models, even with state-dependent inputs, belong to the class of linear Markov models. In the context of SQ(d) routeing, the resulting model belongs to the class of nonlinear Markov processes (processes whose generator itself depends on the distribution) for which traditional arguments do not directly apply. Showing insensitivity to the general service time distributions has thus remained an open problem. Obtaining the MFEs in this case poses a challenge due to the resulting Markov description of the system being in positive orthant as opposed to a finite chain in the exponential case. In this paper, we first obtain the MFEs and then show that the MFEs have a unique fixed point that coincides with the fixed point in the exponential case, thus establishing insensitivity. The approach is via a measure-valued Markov process representation and the martingale problem to establish the mean field limit.
Two-player zero-sum stochastic differential games with random horizon
Authors: Ferreira M. , Pinheiro D. , Pinheiro S.
Published: November 2019

We consider a two-player zero-sum stochastic differential game with a random planning horizon and diffusive state variable dynamics. The random planning horizon is a function of a non-negative continuous random variable, which is assumed to be independent of the Brownian motion driving the state variable dynamics. We study this game using a combination of dynamic programming and viscosity solution techniques. Under some mild assumptions, we prove that the value of the game exists and is the unique viscosity solution of a certain nonlinear partial differential equation of Hamilton–Jacobi–Bellman–Isaacs type.
Antimicrobial stewardship staffing: How much is enough?
Authors: Greene Matthew H. , Nesbitt Whitney J. , Nelson George E.
Published: November 2019

Antimicrobial stewardship improves patient care and reduces antimicrobial resistance, inappropriate use, and adverse outcomes. Despite high-profile mandates for antimicrobial stewardship programs across the healthcare continuum, descriptive data, and recommendations for dedicated resources, including appropriate physician, pharmacist, data analytics, and administrative staffing support, are not robust. This review summarizes the current literature on antimicrobial stewardship staffing and calls for the development of minimum staffing recommendations.
Co-infection of malaria and HIV infection in severely undernourished children in the Democratic Republic of the Congo: a cross-sectional study
Authors: Jacques MuziaziaLupemba , Mahamane Salissou MaibougeTanko , Kaswiyi Lufuluabo , Guan Fei , Lei Jiahui
Published: November 2019

Purpose

This study aims to determine the prevalence of malaria and HIV seropositivity among children with undernutrition in the Democratic Republic of the Congo.

Methods

A cross-sectional study of undernourished children aged between 12 and 60 months in Kalembe-Lembe hospital was carried out. Blood samples were collected for the analyses of malaria parasite, haemoglobin and haematocrit levels. HIV serostatus was determined with rapid HIV antibody tests and enzyme-linked immunosorbent assay. Logistic regression analyses were used to identify clinical predictors of HIV seropositivity.

Results

Of 225 children, 88.9% had malaria; the parasite loads were 16 000 para per μL (38.0%); 24 400 para per μL (56.8%), P < 0.001 and malaria and associated HIV infection accounted for 29.2%. In children aged >12 months, HIV seroprevalence was 29.3%; 86.0% had undernutrition and malaria, 6.8% had undernutrition and HIV and 4.3% had undernutrition, HIV and malaria (P < 0.001). The occurrence of at least three or more symptoms was highly specific (96.4–100.0%) for HIV seropositivity (P < 0.05). The overall mortality rate was 18.4%, higher in children with malaria and HIV (39.6% vs 12.2%, P < 0.001) and those with lower weight gain (4.3 vs 7.5 g kg−1 day−1, P < 0.001).

Conclusions

There was high prevalence of malaria and HIV and mortality among severely undernourished children with malaria and HIV.
Association of sociodemographic factors and internet query data with pertussis infections in Shandong, China
Authors: Zhang Yuzhou , Bambrick Hilary , Mengersen Kerrie , Tong Shilu , Feng Lei , Zhang Li , Liu Guifang , Xu Aiqiang , Hu Wenbiao
Published: November 2019

This study explored how internet queries vary in facilitating monitoring of pertussis, and the effects of sociodemographic characteristics on such variation by city in Shandong province, China. We collected weekly pertussis notifications, Baidu Index (BI) data and yearly sociodemographic data at the city level between 1 January 2009 and 31 December 2017. Spearman's correlation was performed for temporal risk indices, generalised linear models and regression tree models were developed to identify the hierarchical effects and the threshold between sociodemographic factors and internet query data with pertussis surveillance. The BI was correlated with pertussis notifications, with a strongly spatial variation among cities in temporal risk indices (composite temporal risk metric (CTRM) range: 0.59–1.24). The percentage of urban population (relative risk (RR): 1.05, 95% confidence interval (CI) 1.03–1.07), the proportion of highly educated population (RR: 1.27, 95% CI 1.16–1.39) and the internet access rate (RR: 1.04, 95% CI 1.02–1.05) were correlated with CTRM. Higher RRs in the three identified sociodemographic factors were associated with higher stratified CTRM. The percentage of highly educated population was the most important determinant in the BI with pertussis surveillance. The findings may lead to spatially-specific criteria to inform development of an early warning system of pertussis infections using internet query data.
Survey of rice weed management and public and private consultant characteristics in Southern Brazil
Authors: Fruet Bruno de Lima , Merotto Aldo , Ulguim André da Rosa
Published: November 2019

Identification of common weeds is fundamental in determining adequate recommendations for management practices. The aim of this study was to identify the patterns of weed management adopted by rice farmers and the perspectives of consultants who work in flooded rice areas in Rio Grande do Sul (RS) State, Brazil. Fifty-three public and 50 private consultants who worked with rice in RS in 2017 and 2018 were interviewed. Data were analyzed by descriptive statistics. Both weedy rice and Echinochloa sp. occurred and escaped more often from chemical control because they remained in the field until harvest in 59% of the area. According to consultants, the main reasons for reduced weed control were related to herbicide resistance and late herbicide application. Fifty-six percent of farmers used imidazolinone herbicides at rates that were greater than those indicated on the label for POST application. The consultants’ main challenges were weed escapes, resistance management, and guidelines on herbicide rates. Survey results show that the use of herbicide rates above label recommendations and consultants’ work on control of weed escapes are directly related to the high occurrence of herbicide resistance.
Imaging the Fault Damage Zone of the San Jacinto Fault Near Anza With Ambient Noise Tomography Using a Dense Nodal Array
Authors: Wang Yadong , Allam Amir , Lin Fan‐Chi
Published: November 2019

We apply the double‐beamforming tomography to a monthlong temporary dense seismic array to obtain high‐resolution images of the San Jacinto Fault's damage zone. We obtain Rayleigh waves between 0.3‐ and 0.8‐s periods via vertical‐vertical noise cross correlation, apply double beamforming to obtain phase velocities, and apply a piecewise 1‐D least squares inversion to obtain shear velocities in the top 300 m. We observe a ~200‐m‐wide low‐velocity zone that narrows with depth, which we interpret as the main damage zone in addition to two other ~100‐m‐wide subsidiary zones corresponding to secondary damaged structures, agreeing with the distribution of fault zone trapped waves produced by local earthquakes. The primary damage zone asymmetry indicates that materials on the northeast side of the fault are stiffer at seismogenic depth and suggests that large San Jacinto earthquakes tend to nucleate to the southeast and propagate to the northwest.
Orographic Controls on Subdaily Rainfall Statistics and Flood Frequency in the Colorado Front Range, USA
Authors: Rossi Matthew W. , Anderson Robert S. , Anderson Suzanne P. , Tucker Gregory E.
Published: November 2019

Generalizable relationships for how subdaily rainfall statistics imprint into runoff statistics are lacking. We use the Colorado Front Range, known for destructive rainfall‐triggered floods and landslides, to assess whether orographic patterns in runoff generation are a direct consequence of rainstorm climatology. Climatological analysis relies on a dense network of tipping‐bucket rain gauges and gridded precipitation frequency estimates from the National Oceanic and Atmospheric Administration to evaluate relationships among subdaily rainfall statistics, topography, and flood frequency throughout the South Platte River basin. We find that event‐scale rainfall statistics only weakly depend on elevation, suggesting that orographic gradients in runoff “extremes” are not simply a consequence of rainfall patterns. In contrast, bedrock exposure strongly varies with elevation in a way that plausibly explains enhanced runoff generation at lower elevations via reduced water storage capacity. These findings are suggestive of feedbacks between bedrock river evolution and hillslope hydrology not typically included in models of landscape evolution.
Venus Cloud Winds and Mean Albedo Variability From Atmospheric Waves
Authors: Hueso R.
Published: November 2019

Venus's atmosphere presents an enigmatic global circulation with winds that rotate around the planet 60 times faster than the slow rotation of the surface. For decades the connection between the atmospheric super rotation and atmospheric waves has been suspected. However, the characterization of how these atmospheric waves originate, interact with the global circulation, and dissipate has been difficult. Recent results from the Akatsuki mission (Imai et al., 2019, https://doi.org/10.1029/2019JE006065) show explicitly the emergence of planetary‐scale Kelvin and Rossby waves at the upper cloud tops and how they transform from one type of wave to other giving new insights in the atmospheric super rotation.
Overexpression of SlOFP20 affects floral organ and pollen development
Authors: Zhou Shengen , Hu Zongli , Li Fenfen , Tian Shibing , Zhu Zhiguo , Li Anzhou , Chen Guoping
Published: November 2019

TheOVATEgene was initially identified in tomato and serves as a key regulator of fruit shape. There are 31 OFP members in the tomato genome. However, their roles in tomato growth and reproductive development are largely unknown. Here, we cloned theOFPtranscription factorSlOFP20. Tomato plants overexpressingSlOFP20displayed several phenotypic defects, including an altered floral architecture and fruit shape and reduced male fertility.SlOFP20overexpression altered the expression levels of some brassinosteroid (BR)-associated genes, implying that SlOFP20 may play a negative role in the BR response, similar to its ortholog OsOFP19 in rice. Moreover, the transcript accumulation of gibberellin (GA)-related genes was significantly affected in the transgenic lines. SlOFP20 may play an important role in the crosstalk between BR and GA. The pollen germination assay suggested that the pollen germination rate ofSlOFP20-OE plants was distinctly lower than that of WT plants. In addition, the tomato pollen-associated genesSlCRK1,SlPMEI,LePRK3,SlPRALF, andLAT52were all suppressed in the transgenic lines. Our data imply thatSlOFP20may affect floral organ and pollen development by modulating BR and GA signaling in tomato.
Early dorsomedial tissue interactions regulate gyrification of distal neocortex
Authors: Chizhikov Victor V. , Iskusnykh Igor Y. , Steshina Ekaterina Y. , Fattakhov Nikolai , Lindgren Anne G. , Shetty Ashwin S. , Roy Achira , Tole Shubha , Millen Kathleen J.
Published: November 2019

The extent of neocortical gyrification is an important determinant of a species’ cognitive abilities, yet the mechanisms regulating cortical gyrification are poorly understood. We uncover long-range regulation of this process originating at the telencephalic dorsal midline, where levels of secreted Bmps are maintained by factors in both the neuroepithelium and the overlying mesenchyme. In the mouse, the combined loss of transcription factors Lmx1a and Lmx1b, selectively expressed in the midline neuroepithelium and the mesenchyme respectively, causes dorsal midline Bmp signaling to drop at early neural tube stages. This alters the spatial and temporal Wnt signaling profile of the dorsal midline cortical hem, which in turn causes gyrification of the distal neocortex. Our study uncovers early mesenchymal-neuroepithelial interactions that have long-range effects on neocortical gyrification and shows that lissencephaly in mice is actively maintained via redundant genetic regulation of dorsal midline development and signaling.
The MoSeS dynamic omnigami paradigm for smart shape and composition programmable 2D materials
Authors: Berry Joel , Ristić Simeon , Zhou Songsong , Park Jiwoong , Srolovitz David J.
Published: November 2019

The properties of 2D materials can be broadly tuned through alloying and phase and strain engineering. Shape programmable materials offer tremendous functionality, but sub-micron objects are typically unachievable with conventional thin films. Here we propose a new approach, combining phase/strain engineering with shape programming, to form 3D objects by patterned alloying of 2D transition metal dichalcogenide (TMD) monolayers. Conjugately, monolayers can be compositionally patterned using non-flat substrates. For concreteness, we focus on the TMD alloy MoSe$${}_{2c}$$2cS$${}_{2(1-c)}$$2(1−c); i.e., MoSeS. These 2D materials down-scale shape/composition programming to nanoscale objects/patterns, provide control of both bending and stretching deformations, are reversibly actuatable with electric fields, and possess the extraordinary and diverse properties of TMDs. Utilizing a first principles-informed continuum model, we demonstrate how a variety of shapes/composition patterns can be programmed and reversibly modulated across length scales. The vast space of possible designs and scales enables novel material properties and thus new applications spanning flexible electronics/optics, catalysis, responsive coatings, and soft robotics.
Multiple conformations facilitate PilT function in the type IV pilus
Authors: McCallum Matthew , Benlekbir Samir , Nguyen Sheryl , Tammam Stephanie , Rubinstein John L. , Burrows Lori L. , Howell P. Lynne
Published: November 2019

Type IV pilus-like systems are protein complexes that polymerize pilin fibres. They are critical for virulence in many bacterial pathogens. Pilin polymerization and depolymerization are powered by motor ATPases of the PilT/VirB11-like family. This family is thought to operate with C2 symmetry; however, most of these ATPases crystallize with either C3 or C6 symmetric conformations. The relevance of these conformations is unclear. Here, we determine the X-ray structures of PilT in four unique conformations and use these structures to classify the conformation of available PilT/VirB11-like family member structures. Single particle electron cryomicroscopy (cryoEM) structures of PilT reveal condition-dependent preferences for C2,C3, and C6 conformations. The physiologic importance of these conformations is validated by coevolution analysis and functional studies of point mutants, identifying a rare gain-of-function mutation that favours the C2 conformation. With these data, we propose a comprehensive model of PilT function with broad implications for PilT/VirB11-like family members.
Early coauthorship with top scientists predicts success in academic careers
Authors: Li Weihua , Aste Tomaso , Caccioli Fabio , Livan Giacomo
Published: November 2019

We examined the long-term impact of coauthorship with established, highly-cited scientists on the careers of junior researchers in four scientific disciplines. Here, using matched pair analysis, we find that junior researchers who coauthor work with top scientists enjoy a persistent competitive advantage throughout the rest of their careers, compared to peers with similar early career profiles but without top coauthors. Such early coauthorship predicts a higher probability of repeatedly coauthoring work with top-cited scientists, and, ultimately, a higher probability of becoming one. Junior researchers affiliated with less prestigious institutions show the most benefits from coauthorship with a top scientist. As a consequence, we argue that such institutions may hold vast amounts of untapped potential, which may be realised by improving access to top scientists.
Enantiodivergence by minimal modification of an acyclic chiral secondary aminocatalyst
Authors: Dai Jun , Wang Zhuang , Deng Yuhua , Zhu Lei , Peng Fangzhi , Lan Yu , Shao Zhihui
Published: November 2019

The development of enantiodivergent catalysis for the preparation of both enantiomers of a chiral compound is of importance in pharmaceutical and bioorganic chemistry. With the design of a class of reactive and stereoselective organocatalysts, acyclic chiral secondary amines, a method for achieving the enantiodivergence is developed simply by changing the secondary N-i-Bu- to N-Me-group within the catalyst architecture while maintaining the same absolute configuration of the catalysts, which modulates the catalyst conformation. This catalyst-controlled enantiodivergent method not only enables challenging asymmetric transformations to occur in an enantiodivergent manner but also features a high level of stereocontrol and broad scope that is demonstrated in eight different reactions (90 examples), all delivering both enantiomers of a range of structurally diverse products including hitherto less accessible, yet important, compounds in good yields with high stereoselectivities.
Floodplain inundation spectrum across the United States
Authors: Scott Durelle T. , Gomez-Velez Jesus D. , Jones C. Nathan , Harvey Judson W.
Published: November 2019

Floodplain inundation poses both risks and benefits to society. In this study, we characterize floodplain inundation across the United States using 5800 stream gages. We find that between 4% and 12.6% of a river’s annual flow moves through its floodplains. Flood duration and magnitude is greater in large rivers, whereas the frequency of events is greater in small streams. However, the relative exchange of floodwater between the channel and floodplain is similar across small streams and large rivers, with the exception of the water-limited arid river basins. When summed up across the entire river network, 90% of that exchange occurs in small streams on an annual basis. Our detailed characterization of inundation hydrology provides a unique perspective that the regulatory, management, and research communities can use to help balance both the risks and benefits associated with flooding.
Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors
Authors: Lee Jongha , Cho Hye Rim , Cha Gi Doo , Seo Hyunseon , Lee Seunghyun , Park Chul-Kee , Kim Jin Wook , Qiao Shutao , Wang Liu , Kang Dayoung , Kang Taegyu , Ichikawa Tomotsugu , Kim Jonghoon , Lee Hakyong , Lee Woongchan , Kim Sanghoek , Lee Soon-Tae , Lu Nanshu , Hyeon Taeghwan , Choi Seung Hong , Kim Dae-Hyeong
Published: November 2019

Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.
Deciphering signalling network in broad spectrum Near Isogenic Lines of rice resistant to Magnaporthe oryzae
Authors: Jain Priyanka , Dubey Himanshu , Singh Pankaj Kumar , Solanke Amolkumar U. , Singh Ashok K. , Sharma T. R.
Published: November 2019

Disease resistance (R) genes like Pi9, Pita, Pi21, Pi54 are playing important role for broad spectrum blast resistance in rice. Development of near isogenic lines (NILs) using these type of broad spectrum genes and understanding their signalling networks is essential to cope up with highly evolving Magnaporthe oryzae strains for longer duration. Here, transcriptional-level changes were studied in three near-isogenic lines (PB1 + Pi1, PB1 + Pi9 and PB1 + Pi54) of rice resistant to blast infection, to find the loci that are unique to resistant lines developed in the background of Pusa Basmati 1 (PB1). The pathway analysis of loci, unique to resistant NILs compared to susceptible control revealed that plant secondary metabolite synthesis was the common mechanism among all NILs to counter against M. oryzae infection. Comparative transcriptome analysis helped to find out common clusters of co-expressed significant differentially expressed loci (SDEL) in both PB1 + Pi9 and PB1 + Pi54 NILs. SDELs from these clusters were involved in the synthesis and degradation of starch; synthesis and elongation of fatty acids; hydrolysis of phospholipids; synthesis of phenylpropanoid; and metabolism of ethylene and jasmonic acid. Through detailed analysis of loci specific to each resistant NIL, we identified a network of signalling pathways mediated by each blast resistance gene. The study also offers insights into transcriptomic dynamics, points to a set of important candidate genes that serve as module to regulate the changes in resistant NILs. We suggest that pyramiding of the blast resistance gene Pi9 with Pi54 will lead to maximum broad spectrum resistance to M. oryzae.