bluuebunny/crossref_metadata_2025 huggingface dataset:
Older Refugees in Germany: What Are the Reasons for the Difficulties in Language-learning?
Authors: Al Ajlan Ahmad
Published: June 2019

Learning the German language plays a central role in the integration of refugees in Germany. However, older refugees in particular often face learning difficulties, hindering their efficient integration. Based on qualitative interviews with five low-educated older refugees, five highly educated older refugees and five language teachers, I find that the core of the problem is the meaning that policymakers ascribe to refugees as a homogeneous group and to the need to teach refugees the German language as a temporary phenomenon. Moreover, there is a contradiction in the meaning that the language teachers and the older refugees ascribe to old age. While the language teachers doubt the ability and the readiness of older refugees to learn due to the difficulties that they face, older refugees do not attribute a negative meaning to old age and they do not doubt their ability or their readiness to learn the German language.
The Sexual Clock: Middle-Aged American Women and Sexual Vitality in the 1960s and 1970s
Authors: Paris Leslie
Published: June 2019

In the wake of the “sexual revolution” of the 1960s and 1970s, a new American consensus emerged both that women’s sexual lives remained important past their youth and that women’s sexual pleasure generally increased into middle age. Challenging the idea that older people were (or ought to be) asexual, mainstream pundits suggested ways to retain or even improve one’s sexual vitality into middle age and beyond, and argued that sex itself was both physically and emotionally rejuvenating. New attitudes toward middle-aged women’s sexuality did not entirely supplant a more traditional body project whose focus was physical maintenance, the appearance of youthfulness, and a nostalgic return to the “true” (that is, younger) self. Yet by the 1970s, increasing numbers of middle-aged women began to consider sexual renewal as an avenue for personal and relational growth, sparked by unexpected shifts in midlife, the mainstreaming of feminist critiques of ageism, and a new ethos of self-actualization. The redefinition of sexuality as a lifelong journey enabled middle-aged women to reconsider their intimate relationships and their bodies, rethink their assumptions about age and sexual desirability, and examine their current levels of sexual satisfaction. By defying the notion that aging was inherently shameful and desexualizing for women, sexologists and feminists of the late 1960s and 1970s offered a significant challenge to the “sexual clock” and helped to redefine middle age as a time of continued growth.
The redshift-space momentum power spectrum – II. Measuring the growth rate from the combined 2MTF and 6dFGSv surveys
Authors: Qin Fei , Howlett Cullan , Staveley-Smith Lister
Published: June 2019

Measurements of the growth rate of structure, fσ8, in the low-redshift Universe allow stringent tests of the cosmological model. In this work, we provide new constraints on fσ8 at an effective redshift of z = 0.03 using the combined density and velocity fields measured by the 2MTF and 6dFGSv surveys. We do this by applying a new estimator of the redshift-space density and momentum (density-weighted velocity) power spectra, developed in the first paper of this series, to measured redshifts and peculiar velocities from these data sets. We combine this with models of the density and momentum power spectra in the presence of complex survey geometries and with an ensemble of simulated galaxy catalogues that match the survey selection functions and galaxy bias. We use these simulations to estimate the errors on our measurements and identify possible systematics. In particular, we are able to identify and remove biases caused by the non-Gaussianity of the power spectra by applying the Box-Cox transformation to the power spectra prior to fitting. After thorough validation of our methods we recover a constraint of $f\sigma _8(z_{\mathrm{eff}}=0.03)=0.404^{+0.082}_{-0.081}$ from the combined 2MTF and 6dFGSv data. This measurement is fully consistent with the expectations of general relativity and the Λ cold dark matter cosmological model. It is also comparable and complementary to constraints using different techniques on similar data, affirming the usefulness of our method for extracting cosmology from velocity fields.
The period–luminosity relation of red supergiants with Gaia DR2
Authors: Chatys Filip W , Bedding Timothy R , Murphy Simon J , Kiss László L , Dobie Dougal , Grindlay Jonathan E
Published: June 2019

We revisit the K -band period–luminosity (P–L) relations of Galactic red supergiants using Gaia Data Release 2 parallaxes and up to 70 yr of photometry from AAVSO and ASAS campaigns. In addition, we examine 206 LMC red supergiants using 50 yr of photometric data from the digitized Harvard Astronomical Plate Collection. We identified periods by computing power spectra and calculated the period–luminosity relations of our samples and compared them with the literature. Newly available data tighten the P–L relations substantially. Identified periods form two groups: one with periods of 300–1000 d, corresponding to pulsations, and another with Long Secondary Periods between 1000 and 8000 d. Among the 48 Galactic objects we find shorter periods in 25 stars and long secondary periods in 23 stars. In the LMC sample we identify 85 and 94 red supergiants with shorter and long secondary periods, respectively. The P–L relation of the Galactic red supergiants is in agreement with the red supergiants in both, the Large Magellanic Cloud and the Andromeda galaxy. We find no clear continuity between the known red giant period–luminosity sequences, and the red supergiant sequences investigated here.
Halo acceleration relation
Authors: Tian (田雍) Yong , Ko (高仲明) Chung-Ming
Published: June 2019

Recently, from the new Spitzer Photometry and Accurate Rotation Curves data, McGaugh, Lelli & Schombert reported a tight radial acceleration relation between the observed total acceleration and the acceleration produced by baryons in spiral galaxies. The relation can be fitted by different functions. However, these functions can be discerned if we express the data in the form of a halo acceleration relation. The data reveals a maximum in the halo acceleration. We examined the NFW (cusp) and Burkert (core) profiles in the context of dark matter and different parameter families of the interpolating function in the framework of modified Newtonian dynamics.
Clinical Evaluation of Cingulum Bundle Connectivity for Neurosurgical Hypothesis Development
Authors: Sweet Jennifer A , Beylergil Sinem Balta , Thyagaraj Suraj , Herring Eric Z , Drapekin Jesse E , Gao Keming , Calabrese Joseph R , Miller Jonathan P , McIntyre Cameron C
Published: June 2019

BACKGROUND

The cingulum bundle (CB) has long been a target for psychiatric neurosurgical procedures, but with limited understanding of the brain networks being impacted. Recent advances in human tractography could provide a foundation to better understand the effects of neurosurgical interventions on the CB; however, the reliability of tractography remains in question.

OBJECTIVE

To evaluate the ability of different tractography techniques, derived from typical, human diffusion-weighted imaging (DWI) data, to characterize CB connectivity described in animal models. This will help validate the clinical applicability of tractography, and generate insight on current and future neurosurgical targets for psychiatric disorders.

METHODS

Connectivity of the CB in 15 healthy human subjects was evaluated using DWI-based tractography, and compared to tract-tracing findings from nonhuman primates. Brain regions of interest were defined to coincide with the animal model. Tractography was performed using 3 techniques (FSL probabilistic, Camino probabilistic, and Camino deterministic). Differences in connectivity were assessed, and the CB segment with the greatest connectivity was determined.

RESULTS

Each tractography technique successfully reproduced the animal tracing model with a mean accuracy of 72% (68-75%, P < .05). Additionally, one region of the CB, the rostral dorsal segment, had significantly greater connectivity to associated brain structures than all other CB segments (P < .05).

CONCLUSION

Noninvasive, in vivo human analysis of the CB, using clinically available DWI for tractography, consistently reproduced the results of an animal tract-tracing model. This suggests that tractography of the CB can be used for clinical applications, which may aid in neurosurgical targeting for psychiatric disorders.
Opioid Prescribing Laws Are Not Associated with Short-term Declines in Prescription Opioid Distribution
Authors: Davis Corey S , Piper Brian J , Gertner Alex K , Rotter Jason S
Published: June 2019

Objective

To determine whether the adoption of laws that limit opioid prescribing or dispensing is associated with changes in the volume of opioids distributed in states.

Methods

State-level data on total prescription opioid distribution for 2015–2017 were obtained from the US Drug Enforcement Administration. We included in our analysis states that enacted an opioid prescribing law in either 2016 or 2017. We used as control states those that did not have an opioid prescribing law during the study period. To avoid confounding, we excluded from our analysis states that enacted or modified mandates to use prescription drug monitoring programs (PDMPs) during the study period. To estimate the effect of opioid prescription laws on opioid distribution, we ran ordinary least squares models with indicators for whether an opioid prescription law was in effect in a state-quarter. We included state and quarter fixed effects to control for time trends and time-invariant differences between states.

Results

With the exception of methadone and buprenorphine, the amount of opioids distributed in states fell during the study period. The adoption of opioid prescribing laws was not associated with additional decreases in opioids distributed.

Conclusions

We did not detect an association between adoption of opioid prescribing laws and opioids distributed. States may instead wish to pursue evidence-based efforts to reduce opioid-related harm, with a particular focus on treatment access and harm reduction interventions.
The Apathy Syndrome: How We Are Trained Not to Care about Politics
Authors: Zhelnina Anna
Published: June 2019

The role of emotions in social movements and mobilization has been an important focus of recent research, but the emotional mechanisms producing apathy and non-participation remain under studied. This article explores the thinking and feeling processes involved in the production of apolitical attitudes, paying particular attention to their social and cultural context. Cultural norms of appropriateness and emotional expression can hinder or boost the emotions involved in the mobilizing processes. Based on 60 interviews with young people in two Russian cities, collected during and in the aftermath of the anti-regime protests of 2011–12, I explore the apathy syndrome—a combination of emotional mechanisms and cultural norms that produce political apathy. Personal frustrating experiences develop into long-term cynicism and disbelief in the efficacy of collective action, a process exacerbated by the transmission of apathy in families and educational institutions, as well as by cultural norms of appropriate emotions. Cultural clichés and dissociation from others help people cope with the trap and justify inaction.
The impact of delayed switch to second-line antiretroviral therapy on mortality, depending on failure time definition and CD4 count at failure
Authors: Bell-Gorrod Helen , Fox Matthew P , Boulle Andrew , Prozesky Hans , Wood Robin , Tanser Frank , Davies Mary-Ann , Schomaker Michael
Published: June 2019

Background

Little is known about the functional relationship of delaying second-line treatment initiation for HIV-positive patients and mortality, given a patient’s immune status.

Methods

We included 7255 patients starting antiretroviral therapy between 2004-2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting (IPTW) of marginal structural models. The non-linear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation (TMLE). We adjusted for measured time-varying confounding by CD4 count, viral load and visit frequency.

Results

5-year mortality was estimated as 10.5% (2.2%; 18.8%) for immediate switch and as 26.6% (20.9%; 32.3%) for no switch (49.9% if CD4 count<100 cells/mm3). The hazard of death was estimated to be 0.40 (95%CI: 0.33-0.48) times lower if everyone had been switched immediately compared to never. The shorter the delay in switching, the lower the hazard of death, e.g. delaying 30-60 days reduced the hazard 0.52 (0.41-0.65) times, and 60-120 days 0.56 (0.47-0.66) times.

Conclusions

Early treatment switch is particularly important for patients with low CD4 counts at failure.
Case-control design identifies ecological drivers of endemic coral diseases
Authors: Caldwell Jamie M. , Aeby Greta , Heron Scott F. , Donahue Megan J.
Published: June 2019

Endemic disease transmission is an important ecological process that is challenging to study because of low occurrence rates. Here, we investigate the ecological drivers of two coral diseases -- growth anomalies and tissue loss -- affecting five coral species. We first show that a statistical framework called the case-control study design, commonly used in epidemiology but rarely applied to ecology, provided high predictive accuracy (67-82%) and disease detection rates (60-83%) compared with a traditional statistical approach that yielded high accuracy (98-100%) but low disease detection rates (0-17%). Using this framework, we found evidence that 1) larger corals have higher disease risk; 2) shallow reefs with low herbivorous fish abundance, limited water motion, and located adjacent to watersheds with high fertilizer and pesticide runoff promote low levels of growth anomalies, a chronic coral disease; and 3) wave exposure, stream exposure, depth, and low thermal stress are associated with tissue loss disease risk during interepidemic periods. Variation in risk factors across host-disease pairs suggests that either different pathogens cause the same gross lesions in different species or that the same disease may arise in different species under different ecological conditions.
Dynamic Size-Weight Changes After Object Lifting Reduce the Size-Weight Illusion
Authors: van Polanen Vonne , Davare Marco
Published: June 2019

In the size-weight illusion, the smaller object from two equally weighted objects is typically perceived as being heavier. One explanation is that the mismatch between the weight expectation based on object size and actual sensory feedback influences heaviness perception. In most studies, the size of an object is perceived before its weight. We investigated whether size changes would influence weight perception if both would be perceived simultaneously. We used virtual reality to change the size and weight of an object after lifting and asked participants to judge whether objects became lighter or heavier. We found that simultaneous size-weight changes greatly reduced the size-weight illusion to perceptual biases below discrimination thresholds. In a control experiment in which we used a standard size-weight illusion protocol with sequential lifts of small and large objects in the same virtual reality setup, we found a larger, typical perceptual bias. These results show that the size-weight illusion is smaller when size and weight information is perceived simultaneously. This provides support for the prediction mismatch theory explaining the size-weight illusion. Furthermore, these findings suggest that the lifting phase is a critical time window during which brain mechanisms comparing perceived and expected weight mediate the size-weight illusion.
Stratifying major depressive disorder by polygenic risk for schizophrenia in relation to structural brain measures
Authors: Harris Mathew A. , Shen Xueyi , Cox Simon R. , Gibson Jude , Adams Mark J. , Clarke Toni-Kim , Deary Ian J. , Lawrie Stephen M. , McIntosh Andrew M. , Whalley Heather C.
Published: June 2019

Background

Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.

Methods

The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2,370 male and 2,574 female UK Biobank participants.

Results

There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β=.191, q=.043). This was driven by apositiveassociation between SCZ PRS and RACC thickness among MDD cases (β=.098, p=.026), compared to a negative association among controls (β=–.087, p=.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.

Conclusions

Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
Genetic, morphometric, and molecular analyses of interspecies differences in head shape and hybrid developmental defects in the wasp genusNasonia
Authors: Cohen Lorna B , Edwards Rachel , Moody Dyese , Arsala Deanna , Werren Jack H , Lynch Jeremy A
Published: June 2019

Males in the parasitoid wasp genusNasonia(N. vitripennis, N. giraulti, N. longicornis) have distinct, species specific, head shapes. Fertile hybrids among the species are readily produced in the lab allowing genetic analysis of the evolved differences. In addition, the obligate haploidy of males makes these wasps a uniquely powerful model for analyzing the role of complex gene interactions in development and evolution. Previous analyses have shown that complex gene interactions underpin different aspects of the shape differences, and developmental incompatibilities that are specific to the head in F2 haploid hybrid males are also governed by networks of gene interaction. Here we use the genetic tools available inNasoniato extend our understanding of the gene interactions that affect development and morphogenesis in male heads. Using artificial diploid male hybrids, we show that alleles affecting head shape are codominant, leading to uniform, averaged hybrid F1 diploid male heads, while the alleles mediating developmental defects are recessive, and are not visible in the diploid hybrids. We also determine that divergence in time, rather than in morphological disparity is the primary driver of hybrid developmental defects. In addition, we show that doublesex is necessary for the male head shape differences, but is not the only important factor. Finally we demonstrate that we can dissect complex interspecies gene interaction networks using introgression in this system. These advances represent significant progress in the complex web of gene interactions that govern morphological development, and chart the connections between genomic and phenotypic variation.
Misfolded α-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells
Authors: Ugalde C.L , Annesley S.J , Gordon S , Mroczek K , Perugini M.A , Lawson V.A , Fisher P.R , Finkelstein D.I , Hill A.F
Published: June 2019

The misfolding and aggregation of the largely disordered protein, α-synuclein, is a central pathogenic event that occurs in the synucleinopathies; a group of neurodegenerative disorders that includes Parkinson’s disease. While there is a clear link between protein misfolding and neuronal vulnerability, the precise pathogenic mechanisms employed by disease-associated α-synuclein are unresolved. Here, we studied the pathogenicity of misfolded α-synuclein produced using the Protein Misfolding Cyclic Amplification (PMCA) assay. To do this, previous published methods were adapted to allow PMCA-induced protein fibrillization to occur under non-toxic conditions. Insight into potential intracellular targets of misfolded α-synuclein was obtained using an unbiased lipid screen of 15 biologically relevant lipids that identified cardiolipin (CA) as a potential binding partner for PMCA-generated misfolded α-synuclein. To investigate if such an interaction can impact the properties of α-synuclein misfolding, protein fibrillization was carried out in the presence of the lipid. We show CA both accelerates the rate of α-synuclein fibrillization and produces species that harbour enhanced resistance to proteolysis. Because CA is virtually exclusively expressed in the inner mitochondrial membrane, we then assessed the ability of these misfolded species to alter mitochondrial respiration in live non-transgenic SH-SY5Y neuroblastoma cells. Extensive analysis revealed misfolded α-synuclein causes hyperactive mitochondrial respiration without causing any functional deficit. These data give strong support for the mitochondrion as a target for misfolded α-synuclein and reveals persistent, hyperactive respiration as a potential up-stream pathogenic event associated with the synucleinopathies.

Summary statement

Misfolded α-synuclein that was produced using the Protein Misfolding Cyclic Amplification (PMCA) assay was found to associate with cardiolipin and cause hyperactive respiration in neuronal cells.
The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia
Authors: Yang Yunpeng , Lang Nannan , Zhang Huan , Zhang Lu , Chai Changsheng , Jiang Weihong , Gu Yang
Published: June 2019

Small noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and are well known not only for their roles in the control of diverse essential biological processes but also for their value in genetic modification. However, to date, in gram-positive anaerobic solventogenic clostridia (which are a group of important industrial bacteria with exceptional substrate and product diversity), sncRNAs remain minimally explored, leading to a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library ofClostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator of growth and solvent synthesis. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes, through direct or indirect interactions. Notably, modulation of the expression level of either sr8384 or its core target genes significantly increased the growth rate, solvent titer and productivity of the cells, indicating the importance of sr8384-mediated regulatory network inC. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another importantClostridiumspecies,C. beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our work showcases a previously unknown potent and complex role of sncRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes, including pathogenicClostridiumspecies.

IMPORTANCE

The discovery of sncRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA controlling cellular performance of solventogenicClostridium acetobutylicumand performed detailed functional analysis, which is the most in-depth study of sncRNAs in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of these targets leads to improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sncRNAs in clostridia.
The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver
Authors: Hruschka Natascha , Subijana Maria , Graña-Castro Osvaldo , Del Cano-Ochoa Francisco , Brunet Laia Paré , Sagrera Ana , De Reynies Aurelien , Andreu David , Sutton Joe , Chernukhin Igor , Chin Suet-Feung , Caldas Carlos , Lluch Ana , Burgués Octavio , Bermejo Begoña , Ramón-Maiques Santiago , Carroll Jason S , Prat Aleix , Real Francisco X , Martinelli Paola
Published: June 2019

As the catalogue of oncogenic driver mutations is expanding, it is becoming clear that alterations in a given gene should not be lumped into one single class, since they might have different functions. The transcription factorGATA3is a paradigm of this. Here, we address the functions of the most commonGATA3mutation (X308_Splice) which generates a neoprotein that we designate as neoGATA3, associated with good patient prognosis. Based on extensive analyses of molecular and clinical data from approximately 3000 breast cancer patients, supported by mechanistic studiesin vitro, we show that neoGATA3 interferes with the transcriptional programs controlled by estrogen and progesterone receptors, without fully abrogating them. This has opposite outputs in the pre- or post-menopausal hormonal context, having pro- or anti-proliferative effects, respectively. NeoGATA3 is an example of a context- and stage-dependent driver mutation. Our data call for functional analyses of putative cancer drivers to guide clinical application.
Vital role for Plasmodium berghei Kinesin8B in axoneme assembly during male gamete formation and mosquito transmission
Authors: Depoix D. , Marques S.R. , Ferguson D.J.P. , Chaouch S. , Duguet T. , Sinden R.E. , Grellier P. , Kohl L.
Published: June 2019

Sexual development is an essential phase in the Plasmodium life cycle, where male gametogenesis is an unusual and extraordinarily rapid process. It produces 8 haploid motile microgametes, from a microgametocyte within 15 minutes. Its unique achievement lies in linking the assembly of 8 axonemes in the cytoplasm to the three rounds of intranuclear genome replication, forming motile microgametes, which are expelled in a process called exflagellation. Surprisingly little is known about the actors involved in these processes. We are interested in kinesins, molecular motors that could play potential roles in male gametogenesis. We have undertaken a functional characterization in Plasmodium berghei of kinesin-8B (PbKIN8B) expressed specifically in male gametocytes and gametes. By generating Pbkin8B-gfp parasites, we show that PbKIN8B is specifically expressed during male gametogenesis and is associated with the axoneme. We created a ΔPbkin8B knockout cell line and analysed the consequences of the absence of PbKIN8B on male gametogenesis. We show that the ability to produce sexually differentiated gametocytes is not affected in ΔPbkin8B parasites and that the 3 rounds of genome replication occur normally. Nevertheless, the development to free motile microgametes is halted and the life cycle is interrupted in vivo. Ultrastructural analysis revealed that intranuclear mitoses is unaffected whereas cytoplasmic microtubules, although assembled in doublets and elongated, fail to assemble in the normal axonemal “9+2” structure and become motile. Absence of a functional axoneme prevented microgamete assembly and release from the microgametocyte, severely reducing infection of the mosquito vector. This is the first functional study of a kinesin involved in male gametogenesis. These results reveal a previously unknown role for PbKIN8B in male gametogenesis, providing new insights into Plasmodium flagellar formation.
The role of the endoplasmic reticulum in in vivo cancer FDG kinetics
Authors: Scussolini Mara , Cossu Vanessa , Marini Cecilia , Sambuceti Gianmario , Caviglia Giacomo , Piana Michele
Published: June 2019

A very recent result obtained by means of an in vitro experiment with cancer cultured cells has configured the endoplasmic reticulum as the preferential site for the accumulation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Such a result is coherent with cell biochemistry and is made more significant by the fact that reticular accumulation rate of FDG is dependent upon extracellular glucose availability. The objective of the present paper was to confirm this result in vivo, using small animal models of CT26 cancer tissues. Specifically, assuming that the endoplasmic reticulum plays a specific functional role in the framework of a three-compartment model for FDG kinetics, we are able to explain positron emission tomography dynamic data in a more reliable way than by means of a standard Sokoloff two-compartment system. This result is made more solid from a computational viewpoint by means of some identifiability considerations based on a mathematical analysis of the compartmental equations.
Socioeconomic factors associated with dysentery in children under-five years from developing countries
Authors: Pinzón-Rondón Ángela María , Zarate-Ardila Carol Jisseth , Parra-Correa Laura , Zarate-Ardila Alisson , Lozada-Calderón Paola , Di Cecco Leire
Published: June 2019

Objective

Dysentery represents 10% of all causes of acute diarrhea in the world and recognizing the implied proximal and distal social factors at different levels would impact on every related outcome. Our purpose is to identify mother, household and country characteristics that favor the presence of dysentery in children under 5 years old.

Methods

We conducted a multilevel analysis of data from phase V of the Demographic and Health Survey and the World Bank, which included 38,762 children from 33 countries.

Results

Prevalence of dysentery was 14.74%. GDP per-capita was negative associated (OR= 0.75; 95% CI 0.71-0.78) and Gini index was positive associated (OR= 1.23; 95% CI 1.19-1.28). Additionally, child age (OR= 0.99; 95% CI 0.99-1.00), mother age (OR= 1.01; 95% CI 1.00-1.01), employed mother (OR= 1.11; 95% CI 1.02-1.20), and number of household members (OR= 1.02; 95% CI 1.01-1.03) have significant positive associations with the presence of dysentery, while complete immunization schedule (OR= 0.88; 95% CI 0.81-0.96), duration of breastfeeding (OR= 0.81; 95% CI 0.75-0.89), and type of residence (OR= 0.87; 95% CI 0.79-0.97) have significant negative associations with having the illness. Finally, each of the categories of wealth index showed a significant association with dysentery (p-value < 0.001).

Conclusions

Lower per capita GDP and higher Gini coefficient are associated with the development of dysentery, regardless of characteristics of children, their mother, and household. Future and present public health programs should address these issues in order to impact on the occurrence of this illness.

Author summary

Dysentery represents 10% of all causes of acute diarrheal disease. Diarrhea is the fifth cause of worldwide death in children under five years old. It is particularly important to assess and prevent this condition because the early years of life are critical since it is the period when the brain develops most rapidly and has a high capacity for change. Complications associated with dysentery such as malnutrition and convulsive episodes could have a negative effect in this aspect.

Our purpose is to identify the country proximal and distal socioeconomic factors that favor the presence of dysentery in children under five years old from low and middle-income developing countries in order to impact on the occurrence of this illness and its related outcomes. Studying associated factors with developing dysentery during an episode of acute diarrhea could be the base upon which we can diminish mortality from this illness through national policies to impact on national, community and household aspects.
Burden of tumor mutations, neoepitopes, and other variants are dubious predictors of cancer immunotherapy response and overall survival
Authors: Wood Mary A. , Weeder Benjamin R. , David Julianne K. , Nellore Abhinav , Thompson Reid F.
Published: June 2019

Background

Tumor mutational burden (TMB, the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as a result. However, TMB harbors intrinsic variability across cancer types, and its assessment and interpretation are poorly standardized.

Methods

Using a standardized approach, we quantify the robustness of TMB as a metric and its potential as a predictor of immunotherapy response and survival among a diverse cohort of cancer patients. We also explore the additive predictive potential of RNA-derived variants and neoepitope burden, incorporating several novel metrics of immunogenic potential.

Results

We find that TMB is a partial predictor of immunotherapy response in melanoma and non-small cell lung cancer, but not renal cell carcinoma. We find that TMB is predictive of overall survival in melanoma patients receiving immunotherapy, but not in an immunotherapy-naive population. We also find that it is an unstable metric with potentially problematic repercussions for clinical cohort classification. We finally note minimal additional predictive benefit to assessing neoepitope burden or its bulk derivatives, including RNA-derived sources of neoepitopes.

Conclusions

We find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma.
Habitat selection can reduce effects of extreme climatic events in a long‐lived shorebird
Authors: Bailey Liam D. , Ens Bruno J. , Both Christiaan , Heg Dik , Oosterbeek Kees , van de Pol Martijn
Published: June 2019

Changes in the frequency of extreme climatic events (ECEs) can have profound impacts on individual fitness by degrading habitat quality. Organisms may respond to such changes through habitat selection, favouring those areas less affected by ECEs; however, documenting habitat selection in response to ECEs is difficult in the wild due to the rarity of such events and the long‐term biological data required.

Sea level rise and changing weather patterns over the past decades have led to an increase in the frequency of coastal flooding events, with serious consequences for ground nesting shorebirds. Shorebirds therefore present a useful natural study system to understand habitat selection as a response to ECEs. We used a 32‐year study of the Eurasian oystercatcher (Haematopus ostralegus) to investigate whether habitat selection can lead to an increase in nest elevation and minimize the impacts of coastal flooding.

The mean nest elevation of H. ostralegus has increased during the last three decades. We hypothesized that this change has been driven by changes in H. ostralegus territory settlement patterns over time. We compared various possible habitat selection cues to understand what information H. ostralegus might use to inform territory settlement.

There was a clear relationship between elevation and territory settlement in H. ostralegus. In early years, settlements were more likely at low elevations but in more recent years the likelihood of settlement was similar between high and low elevation areas. Territory settlement was associated with conspecific fledgling output and conspecific density. Settlement was more likely in areas of high density and areas with high fledgling output.

This study shows that habitat selection can minimize the effects of increasingly frequent ECEs. However, it seems unlikely that the changes we observe will fully alleviate the consequences of anthropogenic climate change. Rates of nest elevation increase were insufficient to track current increases in maximum high tide (0.5 vs. 0.8 cm/year). Furthermore, habitat selection cues that rely on information from previous breeding seasons (e.g. conspecific fledgling output) may become ineffective as ECEs become more frequent and environmental predictability is diminished.
Estimating interactions between individuals from concurrent animal movements
Authors: Schlägel Ulrike E. , Signer Johannes , Herde Antje , Eden Sophie , Jeltsch Florian , Eccard Jana A. , Dammhahn Melanie
Published: June 2019

Animal movements arise from complex interactions of individuals with their environment, including both conspecific and heterospecific individuals. Animals may be attracted to each other for mating, social foraging, or information gain, or may keep at a distance from others to avoid aggressive encounters related to, e.g., interference competition, territoriality, or predation. With modern tracking technology, more datasets are emerging that allow to investigate fine‐scale interactions between free‐ranging individuals from movement data, however, few methods exist to disentangle fine‐scale behavioural responses of interacting individuals when these are highly individual‐specific.

In a framework of step‐selection functions, we related movements decisions of individuals to dynamic occurrence distributions of other individuals obtained through kriging of their movement paths. Using simulated data, we tested the method's ability to identify various combinations of attraction, avoidance, and neutrality between individuals, including asymmetric (i.e. non‐mutual) behaviours. Additionally, we analysed radio‐telemetry data from concurrently tracked small rodents (bank vole, Myodes glareolus) to test whether our method could detect biologically plausible behaviours.

We found that our method was able to successfully detect and distinguish between fine‐scale interactions (attraction, avoidance, neutrality), even when these were asymmetric between individuals. The method worked best when confounding factors were taken into account in the step‐selection function. However, even when failing to do so (e.g. due to missing information), interactions could be reasonably identified. In bank voles, responses depended strongly on the sexes of the involved individuals and matched expectations.

Our approach can be combined with conventional uses of step‐selection functions to tease apart the various drivers of movement, e.g. the influence of the physical and the social environment. In addition, the method is particularly useful in studying interactions when responses are highly individual‐specific, i.e. vary between and towards different individuals, making our method suitable for both single‐species and multi‐species analyses (e.g. in the context of predation or competition).
A novel procedure for measuring functional traits of herbaceous species through field spectroscopy
Authors: Van Cleemput Elisa , Roberts Dar A. , Honnay Olivier , Somers Ben
Published: June 2019

Collecting species‐level information on plant functional traits is highly relevant for understanding ecosystem functioning under global change. Measuring optical properties of plant species is a promising approach to retrieve such data, but standardized protocols are essential. Due to fine‐scale heterogeneity of many vegetation types, measuring the spectral response, as a proxy for functional traits, of individual plant species remains challenging using conventional approaches.

Here we present a novel method for measuring the reflectance of individual species in situ. The procedure consists of measuring monospecific arrangements of plant individuals on a black, light absorbing table, preserving structural plant properties while avoiding the admixture of other species, soil or non‐photosynthetically active vegetation. To evaluate the feasibility of the approach, a case study was conducted on forbs, where we collected and compared the reflectance of 16 herbaceous species at different phenological stages, both using common field spectroscopy and by following our novel procedure.

Our procedure accurately represented spectral and functional differences between species. Spectral shape, and to a lesser extent, amplitude differences between species were preserved (SAM: Mantel r = 0.69 and p = 0.001; Manhattan distance: Mantel r = 0.42 and p = 0.002). Moreover, the method was able to capture the pattern of functional traits present among the sampled species (Procrustes r = 0.81 and p = 0.001).

The new method is promising for building databases of plant traits based on spectral libraries. It might, moreover, form a standardized procedure for field campaigns, especially in the context of mixed grasslands and forb systems where relatively small plants dominate the ecosystem.
Post‐burning germination responses of woody invaders in a fire‐prone ecosystem
Authors: Moreschi Eleonor Graciela , Funes Guillermo , Zeballos Sebastián R. , Tecco Paula A.
Published: June 2019

It has been frequently recognised that there is a positive feedback between plant invasion and fire underlying invasion success in fire‐prone ecosystems. Accordingly, the response of woody alien species germination to fire may have direct implications on their invasiveness in those ecosystems, particularly when fruit ripening occurs in the fire season. Here, we experimentally evaluated the germination response of some of the main woody invaders of the Chaco Serrano dry woodlands (Gleditsia triacanthos, Cotoneaster glaucophyllus, Ligustrum lucidum, Pyracantha angustifolia and Melia azedarach), which fruit in the seasons of highest fire frequency. Seeds were subjected to heat‐shock treatments that simulated a range of heat intensities, and the species were classified according to their germination response as heat sensitive, tolerant or stimulated. Since Gleditsia triacanthos has indehiscent fruits that fall from the plant and might be exposed to flames, its germination response was also assessed of seeds exposed to fruit burning. Germination responses to heat varied among the invasive species. G. triacanthos seeds experienced increased germination under very low and low heat indexes; it was therefore classified as heat stimulated. The other four species showed no change in germination under very low heat indexes and were therefore considered heat tolerant. However, all species were sensitive to high heat as indicated by their significant decline in germination. G. triacanthos would have limited capacity to recruit from seeds following flaming combustion of its fruits. The prevalence of heat‐tolerant rather than heat‐stimulated germination responses suggests that the occurrence of frequent and seasonal fires in this subtropical savanna system might delay rather than boost the expansion of these invasive species in the system. Yet, the presence of heat‐stimulated germination in one of the studied species warns against generalisation, even within the same ecosystem, and further supports the idiosyncratic nature of invasion success.

Abstract in Spanish is available with online material.
Rationalization and Reflection Differentially Modulate Prior Attitudes Toward the Purity Domain
Authors: Hannikainen Ivar R. , Rosas Alejandro
Published: June 2019

Outside Western, predominantly secular‐liberal environments, norms restricting bodily and sexual conduct are widespread. Moralization in the so‐called purity domain has been treated as evidence that some putative violations are victimless. However, respondents themselves disagree: They often report that private yet indecent acts incur self‐harm, or harm to one's family and the wider community—a result which we replicate in Study 1. We then distinguish two cognitive processes that could generate a link between harmfulness and immorality, and recreate them in Studies 2 and 3: Colombian and British participants were randomly assigned to either reflect (decide whether acts are harmful and reconsider their initial moral judgments) or rationalize (decide whether acts are immoral and reconsider their initial harmfulness beliefs). In both countries, reflection promoted opposition to unjust, but not impure, behavior. Additionally, in both countries, ruminating on the moral status of impure acts elevated beliefs in the acts' harmfulness. We conclude by suggesting that rationalization aggravates, while reflection mitigates, intergroup disagreement regarding putative violations of purity and decency.
Maternal odor shapes rapid face categorization in the infant brain
Authors: Leleu Arnaud , Rekow Diane , Poncet Fanny , Schaal Benoist , Durand Karine , Rossion Bruno , Baudouin Jean‐Yves
Published: June 2019

To successfully interact with a rich and ambiguous visual environment, the human brain learns to differentiate visual stimuli and to produce the same response to subsets of these stimuli despite their physical difference. Although this visual categorization function is traditionally investigated from a unisensory perspective, its early development is inherently constrained by multisensory inputs. In particular, an early‐maturing sensory system such as olfaction is ideally suited to support the immature visual system in infancy by providing stability and familiarity to a rapidly changing visual environment. Here, we test the hypothesis that rapid visual categorization of salient visual signals for the young infant brain, human faces, is shaped by another highly relevant human‐related input from the olfactory system, the mother's body odor. We observe that a right‐hemispheric neural signature of single‐glance face categorization from natural images is significantly enhanced in the maternal versus a control odor context in individual 4‐month‐old infant brains. A lack of difference between odor conditions for the common brain response elicited by both face and non‐face images rules out a mere enhancement of arousal or visual attention in the maternal odor context. These observations show that face‐selective neural activity in infancy is mediated by the presence of a (maternal) body odor, providing strong support for multisensory inputs driving category acquisition in the developing human brain and having important implications for our understanding of human perceptual development.