bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Development of Hypersensitivity and Hyperalgesia After Repeated Application of Platelet-Rich Plasma in Rats: An Experimental Study
Authors: Ince Bilsev , Yıldırım Mehmet Emin Cem , Kilinc Ibrahim , Oltulu Pembe , Dadaci Mehmet
Published: April 2019

Background

Hyperalgesia, defined as hypersensitivity to pain, refers to sensitization of nociceptors to normal levels of pain.

Objectives

We aimed to determine whether hyperalgesia occurs due to the development of sensitization following repeated applications of platelet-rich plasma (PRP), and to ascertain the mechanism responsible for inducing hyperalgesia.

Methods

This study, performed between 2016 and 2017, involved 32 rats. A 2 cm × 2 cm area was shaved on the back of 10 experimental and 10 sham control animals. In the experimental animals this area was divided into 4 equal squares of 1 cm × 1 cm, and these squares were numbered 1 (no treatment; only the needle was inserted), 2 (0.2 mL, saline), 3 (0.2 mL, nonactivated PRP), and 4 (0.2 mL, activated PRP). The response of the animals to painful stimuli in these areas was investigated with Von Frey filaments, immediately before application and 4 weeks after the last application. Skin biopsies were taken, and growth factors were evaluated pathologically and biochemically.

Results

Hyperalgesia developed in all 4 areas of each experimental rat but not in the sham group. However, areas 3 and 4 had smaller Von Frey g values than areas 1 and 2. When growth hormones were assessed histopathologically and biochemically, nerve growth factor (NGF) levels were found to be higher in areas 3 and 4 than in areas 1 and 2 and the sham group.

Conclusions

Both nonactivated and activated PRP resulted in greater hypersensitivity than saline and sham treatment. Development of hyperalgesia may be associated with an increase in NGF as well as increased inflammatory mediators.
Total artificial heart implantation after right ventricular intimal spindle cell sarcoma
Authors: Smail Hassiba , Monteagudo-Vela Maria , Stock Ulrich , Simon Andre
Published: April 2019

This paper describes the case of a patient with a high-grade spindle sarcoma in the right ventricle. The patient underwent total cardiectomy followed by the implantation of a total artificial heart. The patient had an uneventful postoperative course and remained tumour-free for 12 months; after that time period she underwent a heart transplant.
Alveolar ridge alterations in the maxillary anterior region after tooth extraction through orthodontic forced eruption for implant site development: a clinical CBCT study
Authors: Papadopoulou Alexandra K , Papageorgiou Spyridon N , Hatzopoulos Stavros A , Tsirlis Anastasios , Athanasiou Athanasios E
Published: April 2019

Objective

To investigate the effects of orthodontic forced eruption (OFE) with the straight-wire appliance in the dimensions of the alveolar process when used for extracting compromised maxillary anterior teeth and implant site development.

Material and Methods

Cone-beam computed tomography (CBCT) scans of 7 patients needing extraction of 17 maxillary anterior teeth were obtained before and immediately after OFE. Alveolar plate height and thickness measurements were performed on the buccal and palatal socket walls in CBCT sagittal cross sections. Statistical analysis included sample size calculation, paired t-test, and Wilcoxon test to evaluate alveolar plate dimensional changes and linear regression analysis to assess whether bone changes and the feasibility of implant insertion were associated to tooth type and root length, baseline alveolar plate thickness, and age.

Results

OFE caused statistically significant reduction of the buccal alveolar plate height (1.95 ± 1.83 mm) and significant increase of the palatal alveolar plate height (1.31 ± 2.41 mm) in the central tooth socket areas. Buccal reduction was associated positively to the baseline root length and negatively to the thickness of the corresponding plate in the apical level. A non-significant increase was noted in both buccal (0.23 ± 0.93 mm) and palatal (0.63 ± 1.59 mm) proximal bone. Inadequate buccal bone support hindered immediate implant placement in six sockets; however, all inserted implants showed adequate and gradually increasing stability from insertion to final restoration.

Conclusions

OFE resulted in favourable increase in the heights of the palatal and proximal alveolar bone and significant reduction in the buccal plate height, which inhibited implant placement in 35% of the treated sockets.
Changes in Fathers’ and Mothers’ Time with Children: Spain, 2002–2010
Authors: Cano Tomás
Published: April 2019

Parental time spent with children is a critical determinant for a child’s cognitive, educational, and socio-emotional development. Using two waves of the Spanish Time Use Surveys, this study aims to investigate how mothers and fathers reorganized the time invested in physical and developmental childcare between 2002 and 2010. Results show that, during the period analyzed (marked by the start of the Great Recession in 2007), there had been: (i) a significant increase in the time fathers and mothers invested in childcare (i.e. an intensification of parenting); (ii) a gender convergence in physical care time, primarily driven by couples with very young children; and (iii) the gap in developmental childcare time invested between parents with and without a university degree remained unchanged. The decomposition of the results shows that the increase in father-child time is explained by a combination of changes in behavioural and compositional factors (i.e. increase in unemployment and level of education), whereas for changes in mother-child time, behavioural factors predominantly applied. These findings reinforce ideas of the rapid intensification of parenting, and a slow movement towards gender convergence in parental time spent with children.
Social Participation in the Daily Lives of Frail Older Adults: Types of Participation and Influencing Factors
Authors: Duppen Daan , Lambotte Deborah , Dury Sarah , Smetcoren An-Sofie , Pan Honghui , De Donder Liesbeth ,   D-SCOPE Consortium, Smetcoren A- S , Dury S , De Donder L , De Witte N , Dierckx E , Lambotte D , Fret B , Duppen D , Kardol M , Verté D , Hoeyberghs L , De Witte N , De Roeck E , Engelborghs S , Dedeyn P P , Van der Elst M C J , De Lepeleire J , Schoenmakers B , van der Vorst A , Zijlstra G A R , Kempen G I J M , Schols J M G A , Smetcoren A- S , Dury S , De Donder L , De Witte N , Dierckx E , Lambotte D , Fret B , Duppen D , Kardol M , Verté D , Hoeyberghs L , De Witte N , De Roeck E , Engelborghs S , Dedeyn P P , Van der Elst M C J , De Lepeleire J , Schoenmakers B , van der Vorst A , Zijlstra G A R , Kempen G I J M , Schols J M G A
Published: April 2019

Objectives

The advantages of social participation for older adults are well established and have been adopted in aging policy frameworks. However, little is known about the social participation of frail older adults. This research examined the types of social interaction of very frail older adults and the factors influencing this participation.

Method

Interviews with 38 very frail older adults were analyzed using Levasseur and colleagues’ (Levasseur, Richard, Gauvin, & Raymond (2010). Inventory and analysis of definitions of social participation found in the aging literature: Proposed taxonomy of social activities. Social Science and Medicine (1982), 71, 2141–2149) taxonomy activity levels of involvement with others. A qualitative hybrid approach with inductive and deductive thematic analyses was used.

Results

Participants often disengaged from activities with high involvement with others, preferring activities with less involvement. Low-key participation emerged as an important type of social participation enabling frail older adults to remain engaged in society. Key factors that influenced social participation were functional decline, and the physical (e.g., traffic, the disappearance of local stores) and social environment (e.g., social networks and the presence of meeting places such as community centers).

Discussion

Findings advance our knowledge and recognition of the different ways frail older adults participate in society. Despite their frailty, older adults wish to stay socially active. Focusing on the social environment in the frameworks and policies of Age-Friendly Cities and Communities will benefit these individuals.
Risk of suicide attempt associated with isotretinoin: a nationwide cohort and nested case-time-control study
Authors: Droitcourt Catherine , Nowak Emmanuel , Rault Caroline , Happe André , Le Nautout Béranger , Kerbrat Sandrine , Balusson Frédéric , Poizeau Florence , Travers David , Sapori Jean-Marc , Lagarde Emmanuel , Rey Grégoire , Guillot Bernard , Oger Emmanuel , Dupuy Alain
Published: April 2019

Background

Isotretinoin is the only effective treatment for severe acne. An isotretinoin-related suicide risk is still debated and under scrutiny by regulatory agencies. Our objectives were: to assess the risk of suicide attempt before, during and after isotretinoin treatment; to detect any potential triggering effect of isotretinoin initiation on suicide attempt.

Methods

We implemented a cohort and nested case-time-control study of subjects treated with oral isotretinoin (course or initiation) aged 10–50 years, using the Nationwide French Health Insurance data (2009–2016). The main outcome was hospitalized suicide attempt. Standardized incidence ratios for hospitalized suicide attempts were calculated before, during and after isotretinoin treatment. The number of isotretinoin initiations was compared in risk and control periods of 2 months using a case-time-control analysis.

Results

In all, 443 814 patients (median age 20.0 years; interquartile range 17.0–27.0 years) were exposed to isotretinoin, amounting to 244 154 person-years, with a marked seasonality for treatment initiation. Compared with the French general population, the occurrence of suicide attempts under isotretinoin treatment was markedly lower, with a standardized incidence ratio of 0.6 [95% confidence interval (CI) = 0.53–0.67]; the same applied, to a lesser extent, before and after isotretinoin treatment. In the case-time-control analysis, among cases of suicide attempt, 108 and 127 isotretinoin initiations were observed in the risk and control periods respectively (i.e. 0–2 months and 2–4 months before the date of suicide attempt). The comparison with the 1199 and 1253 initiations observed among matched controls in the same two periods yielded a case-time-control odds ratio of 0.89 (95% CI = 0.68–1.16). A sensitivity analysis using three-month periods and a complementary analysis adding completed suicides for case definition showed consistent results.

Conclusion

Compared with the general population, a lower risk of suicide attempt was observed among patients exposed to isotretinoin and there was no evidence for a triggering effect of isotretinoin initiation on suicide attempt. A selection of patients at lower risk for suicidal behaviour and appropriate treatment management could explain these findings. Risk management plans should therefore be maintained.
Ceftazidime-Avibactam in Combination With Fosfomycin: A Novel Therapeutic Strategy Against Multidrug-Resistant Pseudomonas aeruginosa
Authors: Papp-Wallace Krisztina M , Zeiser Elise T , Becka Scott A , Park Steven , Wilson Brigid M , Winkler Marisa L , D’Souza Roshan , Singh Indresh , Sutton Granger , Fouts Derrick E , Chen Liang , Kreiswirth Barry N , Ellis-Grosse Evelyn J , Drusano George L , Perlin David S , Bonomo Robert A
Published: April 2019

Previously, by targeting penicillin-binding protein 3, Pseudomonas-derived cephalosporinase (PDC), and MurA with ceftazidime-avibactam-fosfomycin, antimicrobial susceptibility was restored among multidrug-resistant (MDR) Pseudomonas aeruginosa. Herein, ceftazidime-avibactam-fosfomycin combination therapy against MDR P. aeruginosa clinical isolate CL232 was further evaluated. Checkerboard susceptibility analysis revealed synergy between ceftazidime-avibactam and fosfomycin. Accordingly, the resistance elements present and expressed in P. aeruginosa were analyzed using whole-genome sequencing and transcriptome profiling. Mutations in genes that are known to contribute to β-lactam resistance were identified. Moreover, expression of blaPDC, the mexAB-oprM efflux pump, and murA were upregulated. When fosfomycin was administered alone, the frequency of mutations conferring resistance was high; however, coadministration of fosfomycin with ceftazidime-avibactam yielded a lower frequency of resistance mutations. In a murine infection model using a high bacterial burden, ceftazidime-avibactam-fosfomycin significantly reduced the P. aeruginosa colony-forming units (CFUs), by approximately 2 and 5 logs, compared with stasis and in the vehicle-treated control, respectively. Administration of ceftazidime-avibactam and fosfomycin separately significantly increased CFUs, by approximately 3 logs and 1 log, respectively, compared with the number at stasis, and only reduced CFUs by approximately 1 log and 2 logs, respectively, compared with the number in the vehicle-treated control. Thus, the combination of ceftazidime-avibactam-fosfomycin was superior to either drug alone. By employing a "mechanism-based approach" to combination chemotherapy, we show that ceftazidime-avibactam-fosfomycin has the potential to offer infected patients with high bacterial burdens a therapeutic hope against infection with MDR P. aeruginosa that lack metallo-β-lactamases.
The Contribution of Kaposi’s Sarcoma–Associated Herpesvirus to Mortality in Hospitalized Human Immunodeficiency Virus–Infected Patients Being Investigated for Tuberculosis in South Africa
Authors: Blumenthal Melissa J , Schutz Charlotte , Barr David , Locketz Michael , Marshall Vickie , Whitby Denise , Katz Arieh A , Uldrick Thomas , Meintjes Graeme , Schäfer Georgia
Published: April 2019

Background

Despite increasing numbers of human immunodeficiency virus (HIV)–infected South Africans receiving antiretroviral therapy (ART), tuberculosis (TB) remains the leading cause of mortality. Approximately 25% of patients treated for TB have microbiologically unconfirmed diagnoses. We assessed whether elevated Kaposi’s sarcoma–associated herpesvirus (KSHV) viral load (VL) contributes to mortality in hospitalized HIV-infected patients investigated for TB.

Methods

Six hundred eighty-two HIV-infected patients admitted to Khayelitsha Hospital, South Africa, were recruited, investigated for TB, and followed for 12 weeks. KSHV serostatus, peripheral blood KSHV-VL, and KSHV-associated clinical correlates were evaluated.

Results

Median CD4 count was 62 (range, 0–526) cells/μL; KSHV seropositivity was 30.7% (95% confidence interval [CI], 27%–34%); 5.8% had detectable KSHV-VL (median, 199.1 [range, 13.4–2.2 × 106] copies/106 cells); 22% died. Elevated KSHV-VL was associated with mortality (adjusted odds ratio, 6.5 [95% CI, 1.3–32.4]) in patients without TB or other microbiologically confirmed coinfections (n = 159). Six patients had “possible KSHV-inflammatory cytokine syndrome” (KICS): 5 died, representing significantly worse survival (P < .0001), and 1 patient was diagnosed with KSHV-associated multicentric Castleman disease at autopsy.

Conclusions

Given the association of mortality with elevated KSHV-VL in critically ill HIV-infected patients with suspected but not microbiologically confirmed TB, KSHV-VL and KICS criteria may guide diagnostic and therapeutic evaluation.
The Complexity of Multilateral Negotiations: Problem or Opportunity? A Qualitative Study of Five Simulations with Mexican Students
Authors: Meschoulam Mauricio , Muhech Andrea , Naanous Tania , Quintanilla Sofía , Aguilar Renata , Ochoa Jorge , Rodas Cristobal
Published: April 2019

Education in International Relations requires continual evolution. One approach is the use of negotiation simulations for complex issues. Despite the extensive literature on the subject, there is a lack of qualitative research on this approach, particularly in Latin America and Mexico. This paper presents the findings of a qualitative research on five simulations with Mexican students. The five exercises were characterized by the application of elements that are not usually included in traditional simulations, such as a multiweek phase of prior negotiations, the use of Twitter, the introduction of nonstate actors, a gala dinner, and a continuous feed of real world news. We investigated 118 participants through 30 in depth interviews analyzed with NVivo, a systematized analysis of 118 reports, documents and tweets, and a pre-post questionnaire applied to the fifth group. The results in the five simulations were highly positive. The students reported a greater awareness of the complexity of international negotiations. Such awareness can present both a risk and an opportunity: a risk because those circumstances caused discouragement and frustration in many participants, and an opportunity because those same circumstances, properly channeled, triggered parallel skills, and creative thinking. Therefore, the role of the facilitation team was fundamental.
Heparin-Induced Fever: A Case Report and Literature Review
Authors: Laun Jake , Laun Katie , Farooqi Adeel , Smith David J
Published: April 2019

Burn patients are often plagued by fever due to the inflammatory nature of their injuries as well as the normal postoperative systemic inflammatory response syndrome. One etiology for fever, often not initially considered, is drug-induced fever. A rare cause of drug-induced fever is heparin with only one documented case reported in the literature. We present a case of heparin-induced fever in a patient who experienced a 32% total BSA friction burn after a motorcycle crash.
Spatial and Temporal Dynamics of the Native Banana-Spotting Bug, Amblypelta lutescens lutescens (Hemiptera: Coreidae), in Avocado Crops in North Queensland, Australia
Authors: Lindsay Karel R , Zalucki Myron P , Newton Ian R , Furlong Michael J
Published: April 2019

The native banana-spotting bug, Amblypelta lutescens lutescens Distant, is a major polyphagous insect pest of many tropical and subtropical horticultural crops in Australia, including high-valued commodities such as avocado (Persea americana Mill. (Laurales: lauraceae)). The cryptic nature of A. l. lutescens makes it difficult to sample, and much about its ecology and behavior remains poorly understood. A lure based on the main components of the semiochemicals emitted by male A. l. lutescens, which is attractive to adult males, adult females, and nymphs, has been developed and incorporated into a trap, facilitating sampling of A. l. lutescens in the field. A 2-yr study investigated the spatial and temporal dynamics of the pest in two conventionally managed avocado (cv. Shepard) orchards using a grid (36 m × 36 m) of traps across each. In each year of the study, higher numbers of A. l. lutescens were recorded from October to June. In one field, spatial clustering of adults was detected in close proximity to an adjacent lime [Citrus aurantiifolia (Christm.) (Rutales: rutaceae) Swingle] crop that was not managed with insecticides during the study. Spatial clustering of nymphs was detected adjacent to native riparian vegetation in the other field. The results suggest that source populations of A. l. lutescens could originate from neighboring crops that host A. l. lutescens and from riparian vegetation. Focused sampling of trees at the interface with these vegetation types could lead to early pest detection, timely suppression, and therefore improved pest management.
US Bias in the Study of Asian Security: Using Europe to Study Asia
Authors: Kang David C , Lin Alex Yu-Ting
Published: April 2019

Scholars have been particularly hampered in their explanations and understanding of Asian security because they often learn little about Asia in their graduate training. The international relations (IR) literature draws an overwhelming proportion of its empirical source material from the European historical experience. We show that the curricula and training that graduate students of international relations receive in the United States are overwhelmingly focused on European examples. In short, the median American scholar of IR is deeply comfortable with European examples and analogies and has almost no exposure to Asian examples and history. Thus, when faced with Asian examples, they are considered within the context they are taught: through the European lens. We conclude with a call for greater attention to the empirical reality that is Asia.
Destruction and multiple ionization of PAHs by X-rays in circumnuclear regions of AGNs
Authors: Monfredini Thiago , Quitián-Lara Heidy M , Fantuzzi Felipe , Wolff Wania , Mendoza Edgar , Lago Alexsandre F , Sales Dinalva A , Pastoriza Miriani G , Boechat-Roberty Heloisa M
Published: April 2019

The infrared signatures of polycyclic aromatic hydrocarbons (PAHs) are observed in a variety of astrophysical objects, including the circumnuclear medium of active galactic nuclei (AGNs). These are sources of highly energetic photons (0.2–10 keV), exposing the PAHs to a harsh environment. In this work, we examined experimentally the photoionization and photostability of naphthalene (C10H8), anthracene (C14H10), 2-methyl-anthracene (C14H9CH3), and pyrene (C16H10) upon interaction with photons of 275, 310, and 2500 eV. The measurements were performed at the Brazilian Synchrotron Light Laboratory using time-of-flight mass-spectrometry. We determined the absolute photoionization and photodissociation cross-sections as a function of the incident photon energy; the production rates of singly, doubly, and triply charged ions; and the molecular half-lives in regions surrounding AGNs. Even considering moderate X-ray optical depth values (τ = 4.45) due to attenuation by the dusty torus, the half-lives are not long enough to account for PAH detection. Our results suggest that a more sophisticated interplay between PAHs and dust grains should be present in order to circumvent molecular destruction. We could not see any significant difference in the half-life values by increasing the size of the PAH carbon backbone, NC, from 10 to 16. However, we show that the multiple photoionization rates are significantly greater than the single ones, irrespective of the AGN source. We suggest that an enrichment of multiply charged ions caused by X-rays can occur in AGNs.
Can we quickly flag ultra-long gamma-ray bursts?
Authors: Gendre B , Joyce Q T , Orange N B , Stratta G , Atteia J L , Boër M
Published: April 2019

Ultra-long gamma-ray bursts are a class of high-energy transients lasting several hours. Their exact nature is still elusive, and several models have been proposed to explain them. Because of the limited coverage of wide-field gamma-ray detectors, the study of their prompt phase with sensitive narrow-field X-ray instruments could help in understanding the origin of ultra-long GRBs. However, the observers face a true problem in rapidly activating follow-up observations, due to the challenging identification of an ultra-long GRB before the end of the prompt phase. We present here a comparison of the prompt properties available after a few tens of minutes of a sample of ultra-long GRBs and normal long GRBs, looking for prior indicators of the long duration. We find that there is no such clear prior indicator of the duration of the burst. We also found that statistically, a burst lasting at least 10 and 20 minutes has respectively $28{{\ \rm per\ cent}}$ and $50{{\ \rm per\ cent}}$ probability to be an ultralong event. These findings point towards a common central engine for normal long and ultra-long GRBs, with the collapsar model privileged.
On the dynamics and survival of fractal clouds in galactic winds
Authors: Banda-Barragán W E , Zertuche F J , Federrath C , García Del Valle J , Brüggen M , Wagner A Y
Published: April 2019

Recent observations suggest that dense gas clouds can survive even in hot galactic winds. Here we show that the inclusion of turbulent densities with different statistical properties has significant effects on the evolution of wind-swept clouds. We investigate how the initial standard deviation of the lognormal density field influences the dynamics of quasi-isothermal clouds embedded in supersonic winds. We compare uniform, fractal solenoidal, and fractal compressive cloud models in both 3D and 2D hydrodynamical simulations. We find that the processes of cloud disruption and dense gas entrainment are functions of the initial density distribution in the cloud. Fractal clouds accelerate, mix, and are disrupted earlier than uniform clouds. Within the fractal cloud sample, compressive clouds retain high-density nuclei, so they are more confined, less accelerated, and have lower velocity dispersions than their solenoidal counterparts. Compressive clouds are also less prone to Kelvin–Helmholtz and Rayleigh–Taylor instabilities, so they survive longer than solenoidal clouds. By comparing the cloud properties at the destruction time, we find that dense gas entrainment is more effective in uniform clouds than in either of the fractal clouds, and it is more effective in solenoidal than in compressive models. In contrast, mass loading into the wind is more efficient in compressive cloud models than in uniform or solenoidal models. Overall, wide density distributions lead to inefficient entrainment, but they facilitate mass loading and favour the survival of very dense gas in hot galactic winds.
Horizon-AGN virtual observatory – 1. SED-fitting performance and forecasts for future imaging surveys
Authors: Laigle C , Davidzon I , Ilbert O , Devriendt J , Kashino D , Pichon C , Capak P , Arnouts S , de la Torre S , Dubois Y , Gozaliasl G , Le Borgne D , Lilly S , McCracken H J , Salvato M , Slyz A
Published: April 2019

Using the light-cone from the cosmological hydrodynamical simulation horizon-AGN, we produced a photometric catalogue over 0 < z < 4 with apparent magnitudes in COSMOS, Dark Energy Survey, Large Synoptic Survey Telescope (LSST)-like, and Euclid-like filters at depths comparable to these surveys. The virtual photometry accounts for the complex star formation history (SFH) and metal enrichment of horizon-AGN galaxies, and consistently includes magnitude errors, dust attenuation, and absorption by intergalactic medium. The COSMOS-like photometry is fitted in the same configuration as the COSMOS2015 catalogue. We then quantify random and systematic errors of photometric redshifts, stellar masses, and star formation rates (SFR). Photometric redshifts and redshift errors capture the same dependencies on magnitude and redshift as found in COSMOS2015, excluding the impact of source extraction. COSMOS-like stellar masses are well recovered with a dispersion typically lower than 0.1 dex. The simple SFHs and metallicities of the templates induce a systematic underestimation of stellar masses at z < 1.5 by at most 0.12 dex. SFR estimates exhibit a dust-induced bimodality combined with a larger scatter (typically between 0.2 and 0.6 dex). We also use our mock catalogue to predict photometric redshifts and stellar masses in future imaging surveys. We stress that adding Euclid near-infrared photometry to the LSST-like baseline improves redshift accuracy especially at the faint end and decreases the outlier fraction by a factor ∼2. It also considerably improves stellar masses, reducing the scatter up to a factor 3. It would therefore be mutually beneficial for LSST and Euclid to work in synergy.
Automated distant galaxy merger classifications from Space Telescope images using the Illustris simulation
Authors: Snyder Gregory F , Rodriguez-Gomez Vicente , Lotz Jennifer M , Torrey Paul , Quirk Amanda C N , Hernquist Lars , Vogelsberger Mark , Freeman Peter E
Published: April 2019

We present image-based evolution of galaxy mergers from the Illustris cosmological simulation at 12 time-steps over 0.5 < z < 5. To do so, we created approximately one million synthetic deep Hubble Space Telescope and James Webb Space Telescope images and measured common morphological indicators. Using the merger tree, we assess methods to observationally select mergers with stellar mass ratios as low as 10:1 completing within ±250 Myr of the mock observation. We confirm that common one- or two-dimensional statistics select mergers so defined with low purity and completeness, leading to high statistical errors. As an alternative, we train redshift-dependent random forests (RFs) based on 5–10 inputs. Cross-validation shows the RFs yield superior, yet still imperfect, measurements of the late-stage merger fraction, and they select more mergers in bulge-dominated galaxies. When applied to CANDELS morphology catalogues, the RFs estimate a merger rate increasing to at least z = 3, albeit two times higher than expected by theory. This suggests possible mismatches in the feedback-determined morphologies, but affirms the basic understanding of galaxy merger evolution. The RFs achieve completeness of roughly $70{{\ \rm per\ cent}}$ at 0.5 < z < 3, and purity increasing from $10{{\ \rm per\ cent}}$ at z = 0.5–60 per cent at z = 3. At earlier times, the training sets are insufficient, motivating larger simulations and smaller time sampling. By blending large surveys and large simulations, such machine learning techniques offer a promising opportunity to teach us the strengths and weaknesses of inferences about galaxy evolution.
The minimum metallicity of globular clusters and its physical origin – implications for the galaxy mass–metallicity relation and observations of proto-globular clusters at high redshift
Authors: Kruijssen J M Diederik
Published: April 2019

In the local Universe, globular clusters (GCs) with metallicities [Fe/H] < −2.5 are extremely rare. In this Letter, the close connection between GC formation and galaxy evolution is used to show that this GC metallicity ‘floor’ results from the galaxy mass–metallicity relation of ultra low-luminosity galaxies (ULLGs) at high redshift, where the most metal-poor GCs must have formed. Galaxies with metallicities [Fe/H] ≲ −2.5 have too low masses to form GCs with initial masses Mi ≳ 105 M⊙ needed to survive for a Hubble time. This translates the galaxy mass–metallicity relation into a maximum initial cluster mass–metallicity relation for [Fe/H] ≲ −1.8, which naturally leads to the observed colour–magnitude relation of metal-poor GCs at z = 0 (the ‘blue tilt’). Its strength traces the slope of the gas phase mass–metallicity relation of ULLGs. Based on the observed blue tilt of GCs in the Virgo and Fornax Clusters, the galaxy mass–metallicity relation is predicted to have a slope of α = 0.4 ± 0.1 for 105 ≲ M⋆/M⊙ ≲ 107 at z ≳ 2. The GC metallicity floor implies a minimum host galaxy mass and a maximum redshift for GC formation. Any proto-GCs that may be detected at z > 9 are most likely to end up in galaxies presently more massive than the Milky Way, whereas GCs in low-mass galaxies such as the Fornax dSph (M⋆ ≈ 4 × 107 M⊙) formed at z ≲ 3.
Explaining the enhanced star formation rate of Jellyfish galaxies in galaxy clusters
Authors: Safarzadeh Mohammadtaher , Loeb Abraham
Published: April 2019

We study the recently observed JellyFish galaxies (JFGs), which are found to have their gas content ram pressure stripped away in galaxy clusters. These galaxies are observed to have an enhanced star formation rate of about 0.2 dex compared with a control sample of the same stellar mass in their discs. We model the increase in the star formation efficiency as a function of intracluster medium pressure and parametrize the cold gas content of the galaxies as a function of cluster-centric distance. We show that regarding the external pressure as a positive feedback results in agreement with the observed distribution of enhanced star formation in the JFGs if clouds are shielded from evaporation by magnetic fields. Our results predict that satellites with halo mass $\lt 10^{11}{\rm \, M_\odot }$ moving with Mach numbers $\mathcal {M}\approx 2$, and inclination angles below 60 deg, are more likely to be detected as JFGs.
Colloid Cysts: Evolution of Surgical Approach Preference and Management of Recurrent Cysts
Authors: Heller Robert S , Heilman Carl B
Published: April 2019

BACKGROUND

Optimal management of third ventricular colloid cysts remains debated. While microsurgery offers greater resection rates and lower recurrences, endoscopy offers a perceived less invasive option.

OBJECTIVE

To describe the evolution of our practice to favor microsurgery and determine the optimal management of recurrent colloid cysts

METHODS

Any patient having undergone surgery for a colloid cyst by the senior author was identified and included in the study cohort. Clinical, radiographic, and operative records were reviewed, with attention paid to those patients requiring recurrent surgery.

RESULTS

Thirty-three patients were treated for intracranial colloid cysts between 1995 and 2017. Two patients had initial surgical treatment at an outside institution prior to presentation at our institution. Microsurgery was used in 15/31 initial cases, endoscopy in 13 cases, and ventriculoperitoneal shunting in 3 cases. Between 1995 and 2005, 89% of colloid cysts (8/9 cases) were resected endoscopically, whereas 74% of colloid cysts (14/19 cases) were resected by microsurgery after 2005. Of the 13 patients treated endoscopically, 6 (46%) required surgery for recurrent cysts. Incomplete cyst wall resection at the initial operation increased the recurrence rate to 55%. There were no recurrences in the microsurgery cohort.

CONCLUSION

Surgical resection of recurrent colloid cysts should focus on complete removal of the cyst wall to minimize the chance of recurrence. Microsurgery has been shown to provide the highest success rates for cyst wall resection and lowest rates of recurrence and is therefore recommended for patients undergoing surgery for primary and recurrent colloid cysts.
Sounds of Loss: Church Bells, Place, and Time in the Habsburg Empire During the First World War*
Authors: Morelon Claire
Published: April 2019

This article examines the rupture created by the First World War in towns and villages of the Habsburg Empire by focusing on the requisition of church bells, which were melted for the production of munitions. Bells performed an important social function for both rural and urban populations in the early twentieth century. They gathered communities at important times, stood as symbols of local identity, and gave a structure to the days and lives of rural inhabitants. Their removal generated an intense emotional response among parishioners, which is documented in newspapers, parish newsletters or chronicles, and petitions to the Ministry of Religion. These various reactions shed light on the difficult conciliation between local identity, religiosity, and imperial patriotism during the war. The requisitions contributed to the de-legitimization process experienced by the Habsburg Empire at the end of the war, as well as in the disruption of soundscapes in the region. The sense of time was also disturbed as daily rhythms, religious celebrations, and death rituals changed. This exploration of material culture draws on insights from the history of emotions and sensory history to study the changes in the sense of place that the war provoked in local communities.
Enhanced formation of transparent exopolymer particles (TEP) under turbulence during phytoplankton growth
Authors: Burns Wilton G , Marchetti Adrian , Ziervogel Kai
Published: April 2019

Small-scale turbulence in the surface ocean is ubiquitous, influencing phytoplankton dynamics with consequences for energy flow. The underlying mechanisms that drive changes in phytoplankton dynamics under turbulence are not well constrained. We investigated growth of four phytoplankton species at different turbulence levels in oscillating grid tanks. We also measured transparent exopolymer particles (TEP) from phytoplankton exudates, which play a major role in biogeochemical fluxes in the ocean. Turbulence levels in the tanks reflected in situ conditions in surface waters from the open ocean to higher turbulent environments such as estuaries. Growth rates were unaffected by turbulence while TEP concentrations as xanthan gum (XG) equivalents normalized to algal cells showed generally higher levels in the high turbulence compared to the low turbulence treatments particularly during initial algal growth. Results from a mixing experiment without algal cells and XG also revealed enhanced formation of TEP-like particles under high mixing conditions, indicating that TEP formation in the phytoplankton turbulence treatments was mainly driven by physical processes, such as enhanced encounter rates of TEP-precursors under high mixing. Our results underline the importance of small-scale turbulence on TEP formation with possible consequences for particle aggregation and vertical carbon fluxes in the ocean.
Cancer Chemoprevention: Preclinical In Vivo Alternate Dosing Strategies to Reduce Drug Toxicities
Authors: Mohammed Altaf , Fox Jennifer T , Miller Mark Steven
Published: April 2019

Cancer chemopreventive agents inhibit the formation of precursor lesions and/or the progression of these lesions to late stage disease. This approach to disease control has the potential to reduce the physical and financial costs of cancer in society. Several drugs that have been approved by the FDA for other diseases and have been extensively evaluated for their safety and pharmacokinetic/pharmacodynamic characteristics have the potential to be repurposed for use as cancer chemopreventive agents. These agents often mechanistically inhibit signaling molecules that play key roles in the carcinogenic process. The safety profile of agents is a primary concern when considering the administration of drugs for chemoprevention, as the drugs will be given chronically to high-risk, asymptomatic individuals. To decrease drug toxicity while retaining efficacy, several approaches are currently being explored. In this short review, we describe studies that use preclinical in vivo models to assess efficacy of alternative drug dosing strategies and routes of drug administration on chemopreventive drug efficacy. In vivo drug dosing strategies that reduce toxicity while retaining efficacy will pave the way for future cancer prevention clinical trials.
Detection and Quantification of Potato virus Y Genomes in Single Aphid Stylets
Authors: Khelifa M.
Published: April 2019

Typically, the detection of a plant virus within its vector is carried out on the entire insect body. This process can be a possible source of confusion in the quantification of transmissible virus particles for styletborne viruses such as Potato virus Y (PVY), since the transmissible virus fraction is the one only retained in the aphid vector’s mouthparts. The objective of this study was to develop and validate the quantitative PCR method for the detection and quantification of PVY in the vector’s stylet. Using a specific method based on TaqMan chemistry with higher sensitivity than conventional reverse transcription PCR, this study reveals that a significant amount of the virus is enclosed within the dissected stylets of Myzus persicae. Because this quantification only concerns the portion of the virus attached to the stylets, uniformity was observed in the recorded numbers of virus targets. This novel assay is applicable to several PVY strains as a rapid and sensitive detection method for use in PVY research and offers a convenient tool for deciphering the mechanism of Potyvirus acquisition.
Investigation of the pathogenic RFC1 repeat expansion in a Canadian and a Brazilian ataxia cohort: identification of novel conformations
Authors: Akçimen Fulya , Ross Jay P. , Bourassa Cynthia V. , Liao Calwing , Rochefort Daniel , Gama Maria Thereza Drumond , Dicarie Marie-Josée , Barsottini Orlando G. , Brais Bernard , Pedroso José Luiz , Dion Patrick A. , Rouleau Guy A.
Published: April 2019

A homozygous pentanucleotide expansion in the RFC1 gene has been shown to be a common cause of late-onset ataxia. In the general population a total of four different repeat conformations have been observed: a wild type sequence AAAAG (11 repeats), and longer expansions of AAAAG, AAAGG and AAGGG sequences. However, in ataxia cases only the AAGGG expansion has been shown to be pathogenic. In this study, we assessed the prevalence and nature of RFC1 repeat expansions in three adult-onset ataxia cohorts: Brazilian (n = 23) and Canadian (n = 26) cases that tested negative for other known ataxia mutations, as well as a cohort of randomly selected Canadian cases (n = 128) without regard to a genetic diagnosis. We identified the homozygous AAGGG pathogenic expansion in only one Brazilian family with two affected siblings, and in one Canadian case. The RFC1 expansion may therefore not be a common cause of adult-onset ataxia in these populations. Interestingly we observed two new repeat motifs, AAGAG and AGAGG, which indicates the dynamic nature of the pentanucleotide expansion sequence. To assess the frequency of these two new repeat conformations in the general population we screened 163 healthy individuals. These novel motifs were more frequent in patients versus controls. While we cannot be certain that the homozygous genotypes of the novel expanded conformations are pathogenic, their occurrence should nonetheless be taken into consideration in future studies.
Arbovirus emergence in temperate climates: the case of Córdoba, Argentina, 2009-2018
Authors: Robert Michael A. , Tinunin Daniela Tatiana , Benitez Elisabet Marina , Ludueña-Almeida Francisco , Romero Moory , Stewart-Ibarra Anna M. , Estallo Elizabet Lilia
Published: April 2019

The distribution of arbovirus disease transmission is expanding from the tropics and subtropics into temperate regions worldwide. The aim of this study was to characterize the emergence of arboviruses in the temperate city of Córdoba, Argentina (2009-2018), including dengue virus (DENV) serotypes and origins of imported cases. The first cases of dengue fever were reported in 2009, followed by outbreaks in 2013, 2015, and 2016, each outbreak having greater incidence than the previous. DENV1 was the predominant serotype. Cases were imported from Venezuela, Brazil, Bolivia, Mexico, Costa Rica, and northern Argentina. The first imported cases of chikungunya were reported in 2014 and the first imported and autochthonous of Zika fever in 2016. Regional efforts are needed to strengthen surveillance, due to the key role of human movement in arbovirus introductions.
Loss of adipocyte identity through synergistic repression of PPARγ by TGF-β and mechanical stress
Authors: Bielczyk-Maczyńska Ewa , Taylor Brooks , Miller Cayla M , Zhao Michael L , Shah Arnav , Bahrami-Nejad Zahra , Dunn Alexander R , Teruel Mary N
Published: April 2019

Adipocytes convert into myofibroblasts in a TGF-β-dependent mouse model of fibrosis. The molecular steps and timing underlying this conversion are poorly understood, hindering development of antifibrotic therapies. Here we used two single-cell approaches, lineage tracing and live-cell imaging of an adipocyte marker PPARγ, to track the fate of adipocytes induced to convert by TGF-β. We found that TGF-β alone was not sufficient to activate the TGF-β pathway and to induce myofibroblast conversion in cells with high PPARγ expression. However, robust conversion was observed when an additional PPARγ-inhibiting stimulus, mechanical stress applied by increasing adhesion area on a stiff matrix, was applied simultaneously with TGF-β. We show that the PPARγ downregulation in response to increased adhesion area required both fibronectin and a sufficiently stiff extracellular matrix (ECM) and was partially mediated by Rho. Our results show for the first time the order of the molecular processes driving fat tissue fibrosis and the requirement for signal convergence for the loss of adipocyte identity.
Shifting from fear to safety through deconditioning-update: a novel approach to attenuate fear memories
Authors: Popik Bruno , Amorim Felippe E. , Amaral Olavo B. , de Oliveira Alvares Lucas
Published: April 2019

Aversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of “deconditioning” animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval. Our results indicate that deconditioning-update is more effective than traditional extinction in reducing fear responses; moreover, such effects are long lasting and resistant to renewal and spontaneous recovery. Remarkably, this strategy overcame important boundary conditions for memory updating, such as remote or very strong traumatic memories. The same beneficial effect was found in other types of fear-related memories. Deconditioning was mediated by L-type voltage-gated calcium channels and is consistent with computational accounts of mismatch-induced memory updating. Our results suggest that shifting from fear to safety through deconditioning-update is a promising approach to attenuate traumatic memories.
Acquired FGFR and FGF alterations confer resistance to estrogen receptor (ER) targeted therapy in ER+ metastatic breast cancer
Authors: Mao Pingping , Cohen Ofir , Kowalski Kailey J. , Kusiel Justin G. , Buendia-Buendia Jorge E. , Cuoco Michael S. , Exman Pedro , Wander Seth A. , Waks Adrienne G. , Nayar Utthara , Chung Jon , Freeman Samuel , Rozenblatt-Rosen Orit , Miller Vincent A. , Piccioni Federica , Root David E. , Regev Aviv , Winer Eric P. , Lin Nancy U. , Wagle Nikhil
Published: April 2019

Beyond acquired mutations in the estrogen receptor (ER), mechanisms of resistance to ER-directed therapies in ER+ breast cancer have not been clearly defined. We conducted a genome-scale functional screen spanning 10,135 genes to investigate genes whose overexpression confer resistance to selective estrogen receptor degraders. Pathway analysis of candidate resistance genes demonstrated that the FGFR, ERBB, insulin receptor, and MAPK pathways represented key modalities of resistance. In parallel, we performed whole exome sequencing in paired pre-treatment and post-resistance biopsies from 60 patients with ER+ metastatic breast cancer who had developed resistance to ER-targeted therapy. The FGFR pathway was altered via FGFR1, FGFR2, or FGF3 amplifications or FGFR2 mutations in 24 (40%) of the post-resistance biopsies. In 12 of the 24 post-resistance tumors exhibiting FGFR/FGF alterations, these alterations were not detected in the corresponding pre-treatment tumors, suggesting that they were acquired or enriched under the selective pressure of ER-directed therapy. In vitro experiments in ER+ breast cancer cells confirmed that FGFR/FGF alterations led to fulvestrant resistance as well as cross-resistance to the CDK4/6 inhibitor palbociclib. RNA sequencing of resistant cell lines treated with different drug combinations demonstrated that FGFR/FGF induced resistance through ER reprogramming and activation of the MAPK pathway. The resistance phenotypes were reversed by FGFR inhibitors, a MEK inhibitor, and/or a SHP2 inhibitor, suggesting potential treatment strategies. The detection of targetable, clonally acquired genetic alterations in the FGFR pathway in metastatic tumor biopsies highlights the value of serial tumor testing to dissect mechanisms of resistance in human breast cancer and its potential application in directing clinical management.