bluuebunny/crossref_metadata_2025 huggingface dataset:
Pentecostalism in Brazil
Authors: Chesnut R. Andrew , Kingsbury Kate
Published: November 2019

Brazil was colonized by the Portuguese in the 1500s, and an integral part of conquest and colonization was missionary activity by Catholic clergy. Brazil, like all of Latin America, was Catholic for over four hundred years. However, in the early 1900s, missionaries from overseas came to Brazil extolling a new faith, known as Pentecostalism, that had its origins in the United States. This creed consisted of a charismatic Protestant movement that focused on baptism in the Holy Spirit. Pentecostal churches, originally founded by outsiders, soon began to burgeon under Brazilian leaders. Pentecostalism mushroomed in a brief span of time, proliferating across the nation and gaining popularity among immiserated urban dwellers. It has proven so popular among Brazilians that it has resulted in the pentecostalization of Christianity, in which the Charismatic Renewal has become the predominant form of Catholicism as the Church has struggled to compete with Pentecostalism over the past few decades.

There are numerous notable denominations that boast millions of members, such as the Four-Square Gospel, the Universal Church of the Kingdom of God, and Assemblies of God. These churches proffer a range of religious products to the urban poor, ranging from Prosperity Theology to faith healing. Impoverished city dwellers, faced with limited opportunities and denied access to basic human needs, nevertheless seek to navigate the difficulties of their daily lives. Faced with somatic diseases and social distress, many seek sacred succor to surmount their troubles. This may lead them to the door of a Pentecostal church, where they are promised miracles and healing in exchange for steadfast piety and generous tithing. Many find empowerment through conversion and catharsis during spirited services, where they imagine that through sacred power they might be freed from material deprivation. Pentecostal leaders, such as Edir Macedo, a billionaire bishop, have acquired not only significant capital but also great influence over their congregants. Such is their sway on the vox populi that political leaders have sought the support of Pentecostal clergy to further their ambitions, such as the recently elected president Jair Bolsonaro, who won thanks to the Evangelical vote.
Lexical Integrity in Morphology
Authors: Bosque Ignacio
Published: November 2019

The Lexical Integrity Hypothesis (LIH) holds that words are syntactic atoms, implying that syntactic processes and principles do not have access to word segments. Interestingly, when this widespread “negative characterization” is turned into its positive version, a standard picture of the Morphology-Syntax borderline is obtained.

The LIH is both a fundamental principle of Morphology and a test bench for morphological theories. As a matter of fact, the LIH is problematic for both lexicalist and anti-lexicalist frameworks, which radically differ in accepting or rejecting Morphology as a component of grammar different from Syntax. Lexicalist theories predict no exceptions to LIH, contrary to fact. From anti-lexicalist theories one might expect a large set of counterexamples to this hypothesis, but the truth is that attested potential exceptions are restricted, as well as confined to very specific grammatical areas. Most of the phenomena taken to be crucial for evaluating the LIH are briefly addressed in this article: argument structure, scope, prefixes, compounds, pronouns, elliptical segments, bracketing paradoxes, and coordinated structures. It is argued that both lexicalist and anti-lexicalist positions crucially depend on the specific interpretations that their proponents are willing to attribute to the very notion of Syntax: a broad one, which basically encompasses constituent structure, binary branching, scope, and compositionality, and a narrow one, which also coverts movement, recursion, deletion, coordination, and other aspects of phrase structure. The objective differences between these conceptions of Syntax are shown to be determinant in the evaluation of LIH’s predictions.
Natural Hazards Governance: An Overview of the Field
Authors: Birkland Thomas A.
Published: November 2019

The field of natural hazards governance has changed substantially since the 1970s as the breadth and severity of natural hazards have grown. These changes have been driven by greater social scientific knowledge around natural hazards and disasters, and by changes in structure of natural hazards governance. The governance of issues relating to natural hazards is challenging because of the considerable complexity inherent in preparing for, responding to, mitigating, or recovering from disasters.
Cerebro: interactive visualization of scRNA-seq data
Authors: Hillje Roman , Pelicci Pier Giuseppe , Luzi Lucilla
Published: November 2019

Despite the growing availability of sophisticated bioinformatic methods for the analysis of single-cell RNA-seq data, few tools exist that allow biologists without extensive bioinformatic expertise to directly visualize and interact with their own data and results. Here, we present Cerebro (cell report browser), a Shiny- and Electron-based standalone desktop application for macOS and Windows which allows investigation and inspection of pre-processed single-cell transcriptomics data without requiring bioinformatic experience of the user. Through an interactive and intuitive graphical interface, users can (i) explore similarities and heterogeneity between samples and cell clusters in two-dimensional or three-dimensional projections such as t-SNE or UMAP, (ii) display the expression level of single genes or gene sets of interest, (iii) browse tables of most expressed genes and marker genes for each sample and cluster and (iv) display trajectories calculated with Monocle 2. We provide three examples prepared from publicly available datasets to show how Cerebro can be used and which are its capabilities. Through a focus on flexibility and direct access to data and results, we think Cerebro offers a collaborative framework for bioinformaticians and experimental biologists that facilitates effective interaction to shorten the gap between analysis and interpretation of the data.

Availability and implementation

The Cerebro application, additional documentation, and example datasets are available at https://github.com/romanhaa/Cerebro. Similarly, the cerebroApp R package is available at https://github.com/romanhaa/cerebroApp. All components are released under the MIT License.

Supplementary information

Supplementary data are available at Bioinformatics online.
Incorporating heterogeneous sampling probabilities in continuous phylogeographic inference — Application to H5N1 spread in the Mekong region
Authors: Dellicour Simon , Lemey Philippe , Artois Jean , Lam Tommy T , Fusaro Alice , Monne Isabella , Cattoli Giovanni , Kuznetsov Dmitry , Xenarios Ioannis , Dauphin Gwenaelle , Kalpravidh Wantanee , Von Dobschuetz Sophie , Claes Filip , Newman Scott H , Suchard Marc A , Baele Guy , Gilbert Marius
Published: November 2019

Motivation

The potentially low precision associated with the geographic origin of sampled sequences represents an important limitation for spatially explicit (i.e. continuous) phylogeographic inference of fast-evolving pathogens such as RNA viruses. A substantial proportion of publicly available sequences is geo-referenced at broad spatial scale such as the administrative unit of origin, rather than more precise locations (e.g. geographic coordinates). Most frequently, such sequences are either discarded prior to continuous phylogeographic inference or arbitrarily assigned to the geographic coordinates of the centroid of their administrative area of origin for lack of a better alternative.

Results

We here implement and describe a new approach that allows to incorporate heterogeneous prior sampling probabilities over a geographic area. External data, such as outbreak locations, are used to specify these prior sampling probabilities over a collection of sub-polygons. We apply this new method to the analysis of highly pathogenic avian influenza H5N1 clade data in the Mekong region. Our method allows to properly include, in continuous phylogeographic analyses, H5N1 sequences that are only associated with large administrative areas of origin and assign them with more accurate locations. Finally, we use continuous phylogeographic reconstructions to analyse the dispersal dynamics of different H5N1 clades and investigate the impact of environmental factors on lineage dispersal velocities.

Availability and implementation

Our new method allowing heterogeneous sampling priors for continuous phylogeographic inference is implemented in the open-source multi-platform software package BEAST 1.10.

Supplementary information

Supplementary data are available at Bioinformatics online.
Social context alters retreat- and nest-site selection in a globally invasive gecko, Hemidactylus frenatus
Authors: Muller Benjamin J , Andrews Robin M , Schwarzkopf Lin , Pike David A
Published: November 2019

Microhabitat orientation and structure and the presence of conspecifics may strongly influence the choice of habitat. We studied how these variables influence retreat- and nest-site selection in gravid females of a globally successful invasive species, the Asian house gecko (Hemidactylus frenatus). When provided with various substrates (vertical and horizontal ceramic tiles, vertical and horizontal plywood tiles, horizontal bark over leaf litter, vertical bark over a log, and sand) gravid female geckos preferred to retreat to, and nest in, materials with crevices commonly found in urban habitats. When housed alone, gravid females most frequently retreated to vertical ceramic tile or wooden crevices, and 66.7% nested in vertical ceramic tiles. When housed with two other conspecifics, gravid females most frequently retreated to vertical ceramic tiles, but selected a wider range of nest sites. Overall, gravid geckos housed alone typically nested in the same substrates that they used as diurnal retreats; when housed in groups, however, females oviposited in locations different from those they selected as retreats. Thus, H. frenatus females use a wider range of substrates when conspecifics are present. Invasion success in this species might be driven, in part, by preferences for retreat and nest substrates that are common in human-dominated habitats.
Development and Validation of a Novel Stability-Indicating RP-HPLC Method for Simultaneous Determination of Tezacaftor and Ivacaftor in Fixed Dose Combination
Authors: Singh Narendra , Bansal Parveen , Maithani Mukesh , Chauhan Yashpal
Published: November 2019

A simple and precise novel stability-indicating method for the simultaneous estimation of tezacaftor and ivacaftor in combined tablet dosage form was developed and validated using reversed-phase high-performance liquid chromatography (RP-HPLC). The method is being reported for the first time and includes an estimation of degradation products produced post-stress conditions without any extraction or derivatization. The chromatographic separation of the drugs was achieved with a Symmetry Shield RP18 Column (100 Å, 5 μm, 4.6 mm × 250 mm) using a mixture of buffer, methanol and acetonitrile (42:27:31 v/v/v) as mobile phase. The buffer used in mobile phase contained 35 mM potassium dihydrogen phosphate, and its pH was adjusted to 7.0 ± 0.02 with 20% orthophosphoric acid. The instrument was set at flow rate of 1.2 mL min−1 at ambient temperature and the wavelength of UV-visible detector at 275 nm. The developed method could be suitable for the quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. Stress testing was performed to prove the specificity. No interference was observed from its stress degradation products. The statistical analysis was done by using F-test and t-test at 95% confidence level.
A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident Tuberculosis and Mortality in Advanced Human Immunodeficiency Virus
Authors: Manabe Yukari C , Andrade Bruno B , Gupte Nikhil , Leong Samantha , Kintali Manisha , Matoga Mitch , Riviere Cynthia , Samaneka Wadzanai , Lama Javier R , Naidoo Kogieleum , Zhao Yue , Johnson W Evan , Ellner Jerrold J , Hosseinipour Mina C , Bisson Gregory P , Salgame Padmini , Gupta Amita
Published: November 2019

Background

People with advanced human immunodeficiency virus (HIV) (CD4 < 50) remain at high risk of tuberculosis (TB) or death despite the initiation of antiretroviral therapy (ART). We aimed to identify immunological profiles that were most predictive of incident TB disease and death.

Methods

The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4 < 50 cells/µL) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n = 257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma.

Results

In total, 52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (interleukin [IL]-1β, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1β, IL-10, sCD14, tumor necrosis factor [TNF]-α, and TNF-β) achieved a sensitivity of 0.90 (95% confidence interval [CI]: .87–.94) and a specificity of 0.71(95% CI: .68–.75) with an area under the curve (AUC) of 0.81 (95% CI: .78–.83) for incident TB.

Conclusion

Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions.

Clinical Trials Registration

NCT01380080
The risk for urinary tract infections with sodium-glucose cotransporter 2 inhibitors: no longer a cause of concern?
Authors: Sarafidis Pantelis A , Ortiz Alberto
Published: November 2019

Sodium–glucose co-transporter-2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in patients with type 2 diabetes, including those with diabetic kidney disease. However, the US Food and Drug Administration and European Medicines Agency warnings about potential adverse effects, such as urosepsis and pyelonephritis, based on post-marketing case reports, may deter physicians from prescribing these drugs. A recent evaluation of two large US-based databases of commercial claims failed to find evidence for an increased risk of urinary tract infection (UTI) or severe UTI in type 2 diabetes patients who were prescribed an SGLT2.
O181 SERUM C-REACTIVE PROTEIN CAN BE AN EARLY PREDICTOR OF LENGHT OF HOSPITAL STAY AFTER MINIMALLY INVASIVE OESOPHAGECTOMY
Authors: Corsi Gabriele , Patel Krashna , Abbassi Omar , Gudkalli Zobia , O’Hara David , Tang Cheuk-Bong , Jayanthi Naga Venkatesh , Zanotti Daniela , Charalabopoulos Alexandros , Lorenzi Bruno
Published: November 2019

Aim

Oesophagectomy is associated with a significant number of potential complications affecting the lenght of the post-operative recovery. Serum C-reactive protein (CRP) is an acute phase protein which has been linked to early detection of post-operative complications, including but not limited to anastomotic leak. The aim of this retrospective study was to investigate the value of CRP elevation in the early post-operative days as a predictor of lenght of Hospital stay after minimally invasive oesophagectomy for cancer.

Background and Methods

The study group included 88 patients undergoing minimally invasive oesophagectomy for cancer from September 2017 to April 2019.

CRP values on post-operative day 1,3,5 and 7 were retrieved and correlated to overall lenght of stay. Post-operative morbidity and mortality were also recorded.

Results

The approach was fully minimally invasive in 65 patients (74%) and hybrid in the remaining 23 (26%). The median length of stay was 11 days (IQR, 6-105 days) with overall mortality of 3.4% (n=3). Gastro-intestinal complications occurred in 15 patients (17%). The overall surgical or endoscopic re-intervention rate was 13.6% (n=12).

The median CRP value was 54.8, 167, 143 and 134 mg/L, respectively on day 1,3,5 and 7.

There was a positive correlation between CRP and length of stay on day 1, 3 and 7. A cut-off value of 167 mg/L on day 3 appeared to be a significant predictor of increased lenght of stay (12.8 vs 23.3 days, p=0.008).

Conclusion

CRP levels above 167mg/L on post-operative day 3 were associated with a prolonged lenght of hospital stay in our group of patients. Elevated CRP in the early post-operative period could represent a useful tool to predict lenght of stay after minimally invasive oesophagectomy.
The Effect of Rural Credit on Deforestation: Evidence from the Brazilian Amazon
Authors: Assunção Juliano , Gandour Clarissa , Rocha Romero , Rocha Rudi
Published: November 2019

In 2008, the Brazilian government made the concession of rural credit in the Amazon conditional upon stricter requirements as an attempt to curb forest clearings. This article studies the impact of this innovative policy on deforestation. Difference-in-differences estimations based on a panel of municipalities show that the policy change led to a substantial reduction in deforestation, mostly in municipalities where cattle ranching is the leading economic activity. The results suggest that the mechanism underlying these effects was a restriction in access to rural credit, one of the main support mechanisms for agricultural production in Brazil.
Heterogeneous impacts of cash transfers on farm profitability. Evidence from a randomised study in Lesotho
Authors: Prifti Ervin , Daidone Silvio , Pace Noemi , Davis Benjamin
Published: November 2019

We estimate the average treatment effect (ATE) of cash transfers on farm profitability by exploiting a randomised control trial for the evaluation Lesotho’s biggest transfer program. We also explore impact heterogeneity by unpacking the ATE into group-specific parameters. We estimate conditional average treatment effects to describe how treatment effects vary with selected covariates and quantile treatment effects to illustrate the variability of effects at different outcome levels. We find that the program had sizable impacts on farm profitability, but these impacts are spread unevenly in the population. The program benefited more those with greater productive potential and had strong distributional impacts.
Positive linkage between bacterial social traits reveals that homogeneous rather than specialised behavioral repertoires prevail in natural Pseudomonas communities
Authors: Kramer Jos , López Carrasco Miguel Ángel , Kümmerli Rolf
Published: November 2019

Bacteria frequently cooperate by sharing secreted metabolites such as enzymes and siderophores. The expression of such ‘public good’ traits can be interdependent, and studies on laboratory systems have shown that trait linkage affects eco-evolutionary dynamics within bacterial communities. Here, we examine whether linkage among social traits occurs in natural habitats by examining investment levels and correlations between five public goods (biosurfactants, biofilm components, proteases, pyoverdines and toxic compounds) in 315 Pseudomonas isolates from soil and freshwater communities. Our phenotypic assays revealed that (i) social trait expression profiles varied dramatically; (ii) correlations between traits were frequent, exclusively positive and sometimes habitat-specific; and (iii) heterogeneous (specialised) trait repertoires were rarer than homogeneous (unspecialised) repertoires. Our results show that most isolates lie on a continuum between a ‘social’ type producing multiple public goods, and an ‘asocial’ type showing low investment into social traits. This segregation could reflect local adaptation to different microhabitats, or emerge from interactions between different social strategies. In the latter case, our findings suggest that the scope for competition among unspecialised isolates exceeds the scope for mutualistic exchange of different public goods between specialised isolates. Overall, our results indicate that complex interdependencies among social traits shape microbial lifestyles in nature.
Veteran Suicide Risk Factors: A National Sample of Nonveteran and Veteran Men Who Died by Suicide
Authors: Wood David S , Wood Bethany M , Watson Aislinn , Sheffield Devan , Hauter Helena
Published: November 2019

Veteran suicide is a serious public health problem. Some data suggest that veteran suicide risk profiles differ from those of nonveterans. Records for veteran (n = 21,692) and nonveteran (n = 83,430) men who died by suicide were examined from 17 U.S. states using the National Violent Death Reporting System data. Seventeen precipitating factors were examined and combined through meta-analysis of proportions. Many precipitating factors were found to be less frequent for veterans. A smaller number of factors were found to be higher in the veteran population, including physical health problems. A sizable cumulative effect size (1.02) was observed, suggesting that veteran and nonveteran men show meaningful and substantive differences in their risk profiles—differences that should be considered when planning and implementing suicide prevention and intervention efforts. The conspicuous role of physical health problems among veterans who die by suicide is discussed. The article concludes with specific practice recommendations for social workers.
Highlighting growth regulation processes in fish populations by a simplex simulation approach: application to Merluccius hubbsi stocks in the Southwestern Atlantic
Authors: Semmar Nabil , Vaz-dos-Santos André M
Published: November 2019

A new simplex-based simulation approach (Spx) was developed to highlight multidirectional and multi-scale relationships between morphometric variables helping to functionally differentiate biological (fish) groups for better stocks definition and monitoring. Application concerned Merluccius hubbsi sampled in 1968–1972 and 2004 in six Southwestern Atlantic areas. Simulation results highlighted negative trends opposing front to back compartments indicating competition for body biomass distribution. However, top and bottom parts within these compartments were positively correlated indicating cooperative processes in favour of target local growth regulation. Positive and negative trends of growth regulation were also highlighted at lower body scale, notably between smaller components constituting body front compartment. On a geographical scale, average regulation levels of same morphometric variables showed monotonic or alternated variations between successive fish groups. This highlighted target and modulated growth regulations governing biomass distribution in different body parts by geographical-dependent ways. Under dynamical aspect (1968–1972 vs. 2004), growth regulation of mouth tended to increase with time leading to conclude on morphometric responses of M. hubbsi to overfishing pressure. Spx results were confirmed by several traditional approaches which showed less integrative aspect.
Determinants of the population health distribution: an illustration examining body mass index
Authors: Bann David , Fitzsimons Emla , Johnson William
Published: November 2019

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds of a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression): associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in the 1958 British birth cohort study. Associations of low childhood socio-economic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socio-economic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th to 90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss implications. Risk factors may have larger causal effects among those in worse health, and these effects may not be discovered when health is only examined in average terms. In such scenarios, population-based approaches to intervention may have larger benefits than anticipated when assuming equivalent benefit across the population. Further research is needed to understand why effect estimates differ across the BMI outcome distribution and to investigate whether differential effects exist for other physical and mental health outcomes.
Clinical Diagnostic Testing for Human Cytomegalovirus Infections
Authors: Razonable Raymund R , Inoue Naoki , Pinninti Swetha G , Boppana Suresh B , Lazzarotto Tiziana , Gabrielli Liliana , Simonazzi Giuliana , Pellett Philip E , Schmid D Scott
Published: November 2019

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.
Impact of oral amoxicillin and amoxicillin/clavulanic acid treatment on bacterial diversity and β-lactam resistance in the canine faecal microbiota
Authors: Espinosa-Gongora Carmen , Jessen Lisbeth Rem , Kieler Ida Nordang , Damborg Peter , Bjørnvad Charlotte Reinhard , Gudeta Dereje Dadi , Pires dos Santos Teresa , Sablier-Gallis Frédérique , Sayah-Jeanne Sakina , Corbel Tanguy , Nevière Agathe , Hugon Perrine , Saint-Lu Nathalie , de Gunzburg Jean , Guardabassi Luca
Published: November 2019

Background

Aminopenicillins with or without a β-lactamase inhibitor are widely used in both human and veterinary medicine. However, little is known about their differential impact on the gut microbiota and development of antimicrobial resistance.

Objectives

To investigate changes in the faecal microbiota of dogs treated with amoxicillin or amoxicillin/clavulanic acid.

Methods

Faeces collected from 42 dogs (21 per treatment group) immediately before, during and 1 week after termination of oral treatment with amoxicillin or amoxicillin/clavulanic acid were analysed by culture and 16S rRNA gene sequence analysis.

Results

In both groups, bacterial counts on ampicillin selective agar revealed an increase in the proportion of ampicillin-resistant Escherichia coli during treatment, and an increased occurrence and proportion of ampicillin-resistant enterococci during and after treatment. 16S rRNA gene analysis showed reductions in microbial richness and diversity during treatment followed by a return to pre-treatment conditions approximately 1 week after cessation of amoxicillin or amoxicillin/clavulanic acid treatment. While no significant differences were observed between the effects of amoxicillin and amoxicillin/clavulanic acid on microbial richness and diversity, treatment with amoxicillin/clavulanic acid reduced the abundance of taxa that are considered part of the beneficial microbiota (such as Roseburia, Dialister and Lachnospiraceae) and enriched Escherichia, although the latter result was not corroborated by phenotypic counts.

Conclusions

Our results suggest a limited effect of clavulanic acid on selection of antimicrobial resistance and microbial richness when administered orally in combination with amoxicillin. However, combination with this β-lactamase inhibitor appears to broaden the spectrum of amoxicillin, with potential negative consequences on gut health.
Wide-angle redshift-space distortions at quasi-linear scales: cross-correlation functions from Zel’dovich approximation
Authors: Taruya Atsushi , Saga Shohei , Breton Michel-Andrès , Rasera Yann , Fujita Tomohiro
Published: November 2019

Redshift-space distortions (RSD) in galaxy redshift surveys generally break both the isotropy and homogeneity of galaxy distribution. While the former aspect is particularly highlighted as a probe of growth of structure induced by gravity, the latter aspect, often quoted as wide-angle RSD but ignored in most of the cases, will become important and critical to account for as increasing the statistical precision in next-generation surveys. However, the impact of wide-angle RSD has been mostly studied using linear perturbation theory. In this paper, employing the Zel’dovich approximation, i.e. first-order Lagrangian perturbation theory for gravitational evolution of matter fluctuations, we present a quasi-linear treatment of wide-angle RSD, and compute the cross-correlation function. The present formalism consistently reproduces linear theory results, and can be easily extended to incorporate relativistic corrections (e.g. gravitational redshift).
Properties of reionization-era galaxies from JWST luminosity functions and 21-cm interferometry
Authors: Park Jaehong , Gillet Nicolas , Mesinger Andrei , Greig Bradley
Published: November 2019

Upcoming observations will probe the first billion years of our Universe in unprecedented detail. Foremost among these are 21-cm interferometry with the Hydrogen Epoch of Reionization Arrays (HERA) and the Square Kilometre Array (SKA), and high-z galaxy observations with the James Webb Space Telescope (JWST). Here, we quantify how observations from these instruments can be used to constrain the astrophysics of high-z galaxies. We generate several mock JWST luminosity functions (LFs) and SKA1 21-cm power spectra, which are consistent with current observations, but assume different properties for the unseen, ultrafaint galaxies driving the epoch of reionization (EoR). Using only JWST data, we predict up to a factor of 2–3 improvement (compared with Hubble Space Telescope, HST) in the fractional uncertainty of the star formation rate to halo mass relation and the turnover magnitude. Most parameters regulating the ultraviolet (UV) galaxy properties can be constrained at the level of ∼10 per cent or better, if either (i) we are able to better characterize systematic lensing uncertainties than currently possible; or (ii) the intrinsic LFs peak at magnitudes brighter than MUV ≲ −13. Otherwise, improvement over HST-based inference is modest. When combining with upcoming 21-cm observations, we are able to significantly mitigate degeneracies, and constrain all of our astrophysical parameters, even for our most pessimistic assumptions about upcoming JWST LFs. The 21-cm observations also result in an order of magnitude improvement in constraints on the EoR history.
Both starvation and outflows drive galaxy quenching
Authors: Trussler James , Maiolino Roberto , Maraston Claudia , Peng Yingjie , Thomas Daniel , Goddard Daniel , Lian Jianhui
Published: November 2019

Star-forming galaxies can in principle be transformed into passive systems by a multitude of processes that quench star formation, such as the halting of gas accretion (starvation) or the rapid removal of gas in AGN-driven outflows. However, it remains unclear which processes are the most significant, primary drivers of the SF-passive bimodality. We address this key issue in galaxy evolution by studying the chemical properties of 80 000 local galaxies in Sloan Digital Sky Survey Data Release 7. In order to distinguish between different quenching mechanisms, we analyse the stellar metallicities of star-forming, green valley, and passive galaxies. We find that the significant difference in stellar metallicity between passive galaxies and their star-forming progenitors implies that for galaxies at all masses, quenching must have involved an extended phase of starvation. However, some form of gas ejection also has to be introduced into our models to best match the observed properties of local passive galaxies, indicating that, while starvation is likely to be the prerequisite for quenching, it is the combination of starvation and outflows that is responsible for quenching the majority of galaxies. Closed-box models indicate that the duration of the quenching phase is 2–3 Gyr, with an e-folding time of 2–4 Gyr, after which further star formation is prevented by an ejective/heating mode. Alternatively, leaky-box models find a longer duration for the quenching phase of 5–7 Gyr and an e-folding time of ∼1 Gyr, with outflows becoming increasingly important with decreasing stellar mass. Finally, our analysis of local green valley galaxies indicates that quenching is slower in the local Universe than at high redshift.
LTBK-08. TOCA 511 & TOCA FC VERSUS STANDARD OF CARE IN PATIENTS WITH RECURRENT HIGH GRADE GLIOMA
Authors: Cloughesy Timothy , Petrecca Kevin , Walbert Tobias , Butowski Nicholas , Salacz Michael , Perry James , Damek Denise , Bota Daniela , Bettegowda Chetan , Zhu Jay-Jiguang , Iwamoto Fabio , Placantonakis Dimitris , Martinez Nina , Elder J Bradley , Kaptain George , Cachia David , Moshel Yaron , Brem Steven , Picconi David , Tran Nam , Nam Do-Hyun , Park Chul-Kee , Landolfi Joseph , Tran David , Ramakrishna Rohan , Fink Karen , Heros Deborah , Zadeh Gelareh , Nicholas Garth , Mehta Vivek , Ian Robins H , Chen Clark , Pitz Marshall , Heth Jason , Nagpal Seema , Pearlman Michael , Ahluwalia Manmeet , Mohile Nimish , Merrell Ryan , Schiff David , Thompson Reid , Davis Raphael , Macdonald David , Kheoh Thian , Kabbinavar Fairooz , Lossos Alexander , Vogelbaum Michael
Published: November 2019

BACKGROUND

Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, retroviral replicating vector encoding a codon optimized, heat stabilized cytosine deaminase that converts Toca FC (extended-release 5-fluorocytosine, 5-FC) into the anticancer agent 5-fluorouracil. Three Ph1 studies in patients with recurrent high grade glioma have demonstrated a tolerable safety profile and encouraging efficacy.

METHODS

Toca 5 is a multi-national, randomized, open-label Ph3 trial (NCT02414165) of Toca 511 & Toca FC versus standard of care (SOC) options that comprises Investigator’s choice of single agent chemotherapy (lomustine, temozolomide) or bevacizumab in patients who have undergone resection for first or second recurrence of glioblastoma or anaplastic astrocytoma. 403 patients were randomized 1:1 to the Toca arm or the SOC arm and stratified by IDH1 status, KPS, and geographic region. Primary endpoint was overall survival (OS), and secondary endpoints were durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. The study used group sequential design including 2 interim analyses and 1 final analysis, and the stratified log-rank test are used for the analysis.

RESULTS

271 events were observed for this analysis. Median follow-up was 22.8 months, and the Toca arm missed the primary endpoint (OS) compared to the SOC arm (11.1 months median compared to 12.2 months, HR=1.06, p=0.6154). All secondary endpoints showed no meaningful difference between the arms of the trial. The safety, tolerability and adverse event profile of Toca 511 and Toca FC was as expected for this patient population, with low incidences of Grade 3–4 adverse events. Pre-planned subgroup analyses showed compelling OS improvement in patients with secondary recurrence, and favorable trends in IDH1 mutant and AA population. Detailed data will be presented at the time of the conference.
LTBK-12. EORTC 26951, RANDOMIZED STUDY OF ADJUVANT PCV AFTER 59.4 GY RADIOTHERAPY: VERY LONG TERM FOLLOW-UP
Authors: van den Bent Martin , Hoang-Xuan Khe , Brandes Alba , Kros Johan , Kouwenhoven M C M , Taphoorn Martin , Delattre Jean-Yves , Bernsen Hans , Frenay Marc , Synhaeve Nathalie , Weller Michael , Enting Roelien , French Pim , Dinjens Winand , Golfinopoulos Vassilis , Gorlia Thierry
Published: November 2019

BACKGROUND

Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma (AOD). A mature follow-up presented in 2012 showed survival benefit of the addition of PCV, in particular in 1p/19q co-deleted tumors and tumors with MGMT promoter methylation. We now present very long term follow-up.

MATERIALS AND METHODS

Patients were eligible if locally diagnosed with a newly diagnosed AOD. They were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression free survival (PFS). 1p/19q status (FISH) was determined in 300 patient. Kaplan- Meier technique and Cox modeling were used for long term survival analysis. Primary analyses were adjusted for known prognostic factors. For other analyses no adjustment was performed.

RESULTS

With 368 patients included, a median follow-up of 18.4 years and 307 (83%) survival events, median and 20-year survival after RT/PCV versus RT alone were 42.3 mo and 16.8% vs 30.6 months and 10.1% (HR 0.78; 95% CI (0.63, 0.98), adjusted p=0.06). Eighty patients were 1p/19q codel of which 26 (33%) were still alive, in this subgroup median and 20-year survival after RT/PCV versus RT alone were 14 years and 37.1% versus 9.3 years and 13.6% (HR 0.60, 95% CI (0.35, 1.03), unadjusted p=0.06). Twenty year PFS in 1p/19q codel was 31.3% in RT/PCV treated patients and 10.8% in RT only treated patients (HR 0.49, 95% CI (0.29, 0.83), unadjusted p=0.007). In the 1p/19q codel subgroup age, WHO PS and necrosis at pathology were identified to be of independent prognostic value for OS.

CONCLUSION

This long term analysis confirms the earlier conclusions and provides data on long term survival in this patient group. In 1p/19q codel patients treated with RT/PCV, the 20-year PFS and OS rates are 31% and 37% respectively.
European institutional integration, trade unions and income inequality
Authors: Tober Tobias
Published: November 2019

What are the distributional implications of European institutional integration? This article argues that European institutional integration exerts a moderating effect on the relationship between trade union strength and income inequality—particularly inequality at the top—within countries of the European Union (EU). I contend that European institutional integration reduces the bargaining power of trade unions due to rising market competition and decreasing union control over the supply of labor. Thus, the effectiveness of trade unions in reducing inequality should decline with progressing European institutional integration. On the basis of a long-term within-country analysis of the EU15, I will show that the effect of trade unions on inequality varies strongly with European institutional integration. Consistent with the theoretical argument, the inequality-reducing effect of trade unions becomes substantially lower the more a country integrates in the EU.
Detection of Drug-Induced Torsades de Pointes Arrhythmia Mechanisms Using hiPSC-CM Syncytial Monolayers in a High-Throughput Screening Voltage Sensitive Dye Assay
Authors: da Rocha Andre Monteiro , Creech Jeffery , Thonn Ethan , Mironov Sergey , Herron Todd J
Published: November 2019

We validated 3 distinct hiPSC-CM cell lines—each of different purity and a voltage sensitive dye (VSD)-based high-throughput proarrhythmia screening assay as a noncore site in the recently completed CiPA Myocyte Phase II Validation Study. Blinded validation was performed using 12 drugs linked to low, intermediate, or high risk for causing Torsades de Pointes (TdP). Commercially sourced hiPSC-CMs were obtained either from Cellular Dynamics International (CDI, Madison, Wisconsin, iCell Cardiomyoyctes2) or Takara Bio (CLS, Cellartis Cardiomyocytes). A third hiPSC-CM cell line (MCH, Michigan) was generated in house. Each cell type had distinct baseline electrophysiological function (spontaneous beat rate, action potential duration, and conduction velocity) and drug responsiveness. Use of VSD and optical mapping enabled the detection of conduction slowing of sodium channel blockers (quinidine, disopyramide, and mexiletine) and drug-induced TdP-like activation patterns (rotors) for some high- and intermediate-risk compounds. Low-risk compounds did not induce rotors in any cell type tested. These results further validate the utility of hiPSC-CMs for predictive proarrhythmia screening and the utility of VSD technology to detect drug-induced APD prolongation, arrhythmias (rotors), and conduction slowing. Importantly, results indicate that different ratios of cardiomyocytes and noncardiomyocytes have important impact on drug response that may be considered during risk assessment of new drugs. Finally, we present the first blinded CiPA hiPSC-CM validation results to simultaneously detect drug-induced conduction slowing, action potential duration prolongation, action potential triangulation, and drug-induced rotors in a proarrhythmia assay.
Approaches to the law applicable to proprietary effects of transactions in securities taken in uniform law: a lesson for the EU
Authors: Müller Michael F
Published: November 2019

The modern practice of securities trading has led to almost insurmountable tensions with classical conflict-of-laws doctrine. The Hague Securities Convention set out to provide for a new and uniform solution. In a recent communication from the Commission, the topic has resurfaced on the European agenda. Against this background, this article poses the question of whether the discussion around the Convention can serve as a lesson for the European Union (EU). It is submitted that neither the status quo of EU law is satisfactory nor does the adoption of the Convention offer a fully convincing solution but that the problem should be targeted at its root: the outdated concept of some national substantive laws in intermediated securities.
Journals in Aging, Geriatrics, and Gerontology: A Survey
Authors: Wolff Robert J. , Bowser Hannah L.
Published: November 2019

Aging, geriatrics, gerontology, and related areas are important areas of research as the population of older people increases in relationship to the total population. Researchers in these fields would benefit from guidance regarding sources for publishing and finding relevant scholarly journals and articles. Multiple database sites of journals were searched to provide a list of relevant publications. This list was expanded via perusal of published citation lists and searches in general search engines. A total of 243 journals were identified and examined. Of those journals, 198 journals are currently publishing and 45 journals have ceased publication. In terms of publication medium, 39% of the currently publishing journals are online-only, 4% are print-only and 59% of the journals publish both online and in print. Journals with aging in the title represent 36%, geriatrics 30% and gerontology 23%. Less than 10% have been identified as predatory journals. An expected increase in journals in the broad field of aging is indicated by the 49% of listed titles beginning in 2000 or later. This recent increase in available journals provides a need for the information listed in this paper.
Drivers of Frailty from Adulthood into Old Age: Results from a 27-year Longitudinal Population-Based Study in Sweden
Authors: Raymond Emma , Reynolds Chandra A. , Dahl Aslan Anna K. , Finkel Deborah , Ericsson Malin , Hägg Sara , Pedersen Nancy L. , Jylhävä Juulia
Published: November 2019

Background

Frailty is a strong predictor of adverse aging outcomes. However, the longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the predictors of the level and rate of change in FI.

Methods

An age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N=1,842; aged 29-102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave.

Results

A bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the rate of increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one’s co-twin during childhood, smoking, poor social support and low physical activity were associated with a higher level of FI at age 65, with underweight having the largest effect size. When tested as time-varying predictors, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65.

Conclusions

Predictors for the level and rate of change in frailty are largely actionable and could provide targets for intervention. Underweight increased the risk of higher FI trajectory until age 65, whereas being overweight or obese were associated with slower progression of frailty towards the oldest ages.
Accurate influenza forecasts using type-specific incidence data for small geographical units
Authors: Turtle James , Riley Pete , Ben-Nun Michal , Riley Steven
Published: November 2019

Influenza incidence forecasting is used to facilitate better health system planning and could potentially be used to allow at-risk individuals to modify their behavior. For example, the US Centers for Disease Control and Prevention (CDC) runs an annual competition to forecast influenza-like illness (ILI) at the regional and national levels in the US, based on a standard discretized incidence scale. Here, we use a suite of forecasting models to analyze type-specific incidence at the smaller spatial scale of clusters of nearby counties. We used data from point-of-care (POC) diagnostic machines over three seasons, in 10 clusters, capturing: 57 counties; 1,061,891 total specimens; and 173,909 specimens positive for Influenza A. Total specimens were closely correlated with comparable CDC ILI data. Mechanistic models were substantially more accurate when forecasting influenza A positive POC data than total specimen POC data, especially at longer lead times. Also, models that fit individual counties separately were better able to forecast clusters than were models that directly fit to aggregated cluster data. Public health authorities may wish to consider developing forecasting pipelines for type-specific POC data in addition to ILI data. Simple mechanistic models will likely improve forecast accuracy when applied at small spatial scales to pathogen-specific data before being scaled to larger geographical units and broader syndromic data. Highly local forecasts may enable new public health messaging to encourage at-risk individuals to temporarily reduce their social mixing.