bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-associated factors are enriched in lymphatic exudate compared to plasma in metastatic melanoma patients
Authors: Broggi Maria A.S. , Maillat Lea , Clement Cristina C. , Bordry Natacha , Corthésy Patricia , Auger Aymeric , Matter Maurice , Hamelin Romain , Potin Lambert , Demurtas Davide , Romano Emanuela , Harari Alexandre , Speiser Daniel E. , Santambrogio Laura , Swartz Melody A.
Published: April 2019

Liquid biopsies allow monitoring of cancer progression and detection of relapse, but reliable biomarkers in melanoma are lacking. Because secreted factors preferentially drain to lymphatic vessels before dilution in the blood, we hypothesized that lymph should be vastly enriched in cancer biomarkers. We characterized postoperative lymphatic exudate and plasma of metastatic melanoma patients after lymphadenectomy and found a dramatic enrichment in lymphatic exudate of tumor-derived factors and especially extracellular vesicles containing melanoma-associated proteins and miRNAs, with unique protein signatures reflecting early versus advanced metastatic spread. Furthermore, lymphatic exudate was enriched in memory T cells, including tumor-reactive CD137+ and stem cell–like types. In mice, lymph vessels were the major route of extracellular vesicle transport from tumors to the systemic circulation. We suggest that lymphatic exudate provides a rich source of tumor-derived factors for enabling the discovery of novel biomarkers that may reflect disease stage and therapeutic response.
The Association of Social Isolation With the Risk of Stroke Among Middle-Aged and Older Adults in China
Authors: Zhou Zi , Lin Cen , Ma Jiaping , Towne Samuel D , Han Yaofeng , Fang Ya
Published: April 2019

Given that there is limited research examining the specific role social isolation plays in stroke risk, we aimed to estimate the controlled direct effect of social isolation on stroke risk in China. A nationally representative sample (n = 12,662) of persons aged 45 years or more at baseline (2011), with corresponding follow-ups in 2013 and 2015, was taken from the China Health and Retirement Longitudinal Study. Stroke was assessed through a self- or proxy-reported physician’s diagnosis. Social isolation was measured by incorporating marital status, frequency of contact with friends, family, and children, and participation in social activities. A marginal structural model with stabilized inverse probability weights was applied to examine the controlled direct effect of social isolation on stroke risk. Overall, 245 persons had a stroke within the 4-year timeline under study. The total effect model indicated that persons experiencing social isolation had a 64% increased risk of stroke (odds ratio (OR) = 1.64, 95% confidence interval (CI): 1.26, 2.13). Results from the marginal structural model also indicated that socially isolated persons had an increased risk of stroke (OR = 2.39, 95% CI: 1.49, 3.82) after adjustment for depression. Interventions to reduce social isolation may be particularly beneficial in preventing the occurrence of stroke among middle-aged and older adults in China.
Characterizing the role of the structural connectome in seizure dynamics
Authors: Shah Preya , Ashourvan Arian , Mikhail Fadi , Pines Adam , Kini Lohith , Oechsel Kelly , Das Sandhitsu R , Stein Joel M , Shinohara Russell T , Bassett Danielle S , Litt Brian , Davis Kathryn A
Published: April 2019

How does the human brain’s structural scaffold give rise to its intricate functional dynamics? This is a central question in translational neuroscience that is particularly relevant to epilepsy, a disorder affecting over 50 million subjects worldwide. Treatment for medication-resistant focal epilepsy is often structural—through surgery or laser ablation—but structural targets, particularly in patients without clear lesions, are largely based on functional mapping via intracranial EEG. Unfortunately, the relationship between structural and functional connectivity in the seizing brain is poorly understood. In this study, we quantify structure-function coupling, specifically between white matter connections and intracranial EEG, across pre-ictal and ictal periods in 45 seizures from nine patients with unilateral drug-resistant focal epilepsy. We use high angular resolution diffusion imaging (HARDI) tractography to construct structural connectivity networks and correlate these networks with time-varying broadband and frequency-specific functional networks derived from coregistered intracranial EEG. Across all frequency bands, we find significant increases in structure-function coupling from pre-ictal to ictal periods. We demonstrate that short-range structural connections are primarily responsible for this increase in coupling. Finally, we find that spatiotemporal patterns of structure-function coupling are highly stereotyped for each patient. These results suggest that seizures harness the underlying structural connectome as they propagate. Mapping the relationship between structural and functional connectivity in epilepsy may inform new therapies to halt seizure spread, and pave the way for targeted patient-specific interventions.
A Hierarchical Watershed Model of Fluid Intelligence in Childhood and Adolescence
Authors: Fuhrmann Delia , Simpson-Kent Ivan L , Bathelt Joe ,   The CALM Team, Kievit Rogier A , Holmes Joni , Gathercole Susan , Astle Duncan , Manly Tom , Kievit Rogier
Published: April 2019

Fluid intelligence is the capacity to solve novel problems in the absence of task-specific knowledge and is highly predictive of outcomes like educational attainment and psychopathology. Here, we modeled the neurocognitive architecture of fluid intelligence in two cohorts: the Centre for Attention, Leaning and Memory sample (CALM) (N = 551, aged 5–17 years) and the Enhanced Nathan Kline Institute—Rockland Sample (NKI-RS) (N = 335, aged 6–17 years). We used multivariate structural equation modeling to test a preregistered watershed model of fluid intelligence. This model predicts that white matter contributes to intermediate cognitive phenotypes, like working memory and processing speed, which, in turn, contribute to fluid intelligence. We found that this model performed well for both samples and explained large amounts of variance in fluid intelligence (R2CALM = 51.2%, R2NKI-RS = 78.3%). The relationship between cognitive abilities and white matter differed with age, showing a dip in strength around ages 7–12 years. This age effect may reflect a reorganization of the neurocognitive architecture around pre- and early puberty. Overall, these findings highlight that intelligence is part of a complex hierarchical system of partially independent effects.
Sensory Integration: Cross-Modal Communication Between the Olfactory and Visual Systems in Zebrafish
Authors: Li Lei
Published: April 2019

Cross-modal sensory communication is an innate biological process that refers to the combination and/or interpretation of different types of sensory input in the brain. Often, this process conjugates with neural modulation, by which the neural signals that convey sensory information are adjusted, such as intensity, frequency, complexity, and/or novelty. Although the anatomic pathways involved in cross-modal sensory integration have been previously described, the course of development and the physiological roles of multisensory signaling integration in brain functions remain to be elucidated. In this article, I review some of the recent findings in sensory integration from research using the zebrafish models. In zebrafish, cross-modal sensory integration occurs between the olfactory and visual systems. It is mediated by the olfacto-retinal centrifugal (ORC) pathway, which originates from the terminalis nerve (TN) in the olfactory bulb and terminates in the neural retina. In the retina, the TNs synapse with the inner nuclear layer dopaminergic interplexiform cells (DA-IPCs). Through the ORC pathway, stimulation of the olfactory neurons alters the cellular activity of TNs and DA-IPCs, which in turn modulates retinal neural function and increases behavioral visual sensitivity.
Prevalence of Anxiety or Depression Diagnosis in Deaf Adults
Authors: Kushalnagar Poorna , Reesman Jennifer , Holcomb Tara , Ryan Claire
Published: April 2019

The national prevalence of depression and anxiety disorders among deaf adults who use American Sign Language (ASL) remains largely understudied. Data for self-reported depression and anxiety disorder diagnosis (n = 1,704 deaf adults; n = 3,287 hearing adults) as told by their healthcare providers were drawn from HINTS-ASL and HINTS datasets. Chi-square and Poisson regression analysis compared characteristics and predictors for depression or anxiety disorder diagnosis among deaf adults. Rate of diagnosed depression or anxiety disorder was significantly higher (25%) and occurred at earlier age (45 years; SD = 15) for deaf adults compared to hearing adults (22%; mean age = 56; SD = 14). After adjusting for covariates, deaf individuals who were White, younger, female, educated, or single were significantly more likely to self-report a diagnosis of depression/anxiety disorder as told by their healthcare providers. Deaf adults have higher reported rate of diagnosis of depression or anxiety disorder at an earlier onset compared to the general population. Communication access with healthcare providers is essential for accurate diagnosis, treatment, and follow up care.
Arrhythmic risk stratification in post-myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study
Authors: Gatzoulis Konstantinos A , Tsiachris Dimitrios , Arsenos Petros , Antoniou Christos-Konstantinos , Dilaveris Polychronis , Sideris Skevos , Kanoupakis Emmanuel , Simantirakis Emmanouil , Korantzopoulos Panagiotis , Goudevenos Ioannis , Flevari Panagiota , Iliodromitis Efstathios , Sideris Antonios , Vassilikos Vassilios , Fragakis Nikolaos , Trachanas Konstantinos , Vernardos Michail , Konstantinou Ioannis , Tsimos Konstantinos , Xenogiannis Iosif , Vlachos Konstantinos , Saplaouras Athanasios , Triantafyllou Konstantinos , Kallikazaros Ioannis , Tousoulis Dimitrios
Published: April 2019

Aims

Sudden cardiac death (SCD) annual incidence is 0.6–1% in post-myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)≥40%. No recommendations for implantable cardioverter-defibrillator (ICD) use exist in this population.

Methods and results

We introduced a combined non-invasive/invasive risk stratification approach in post-MI ischaemia-free patients, with LVEF ≥ 40%, in a multicentre, prospective, observational cohort study. Patients with at least one positive electrocardiographic non-invasive risk factor (NIRF): premature ventricular complexes, non-sustained ventricular tachycardia, late potentials, prolonged QTc, increased T-wave alternans, reduced heart rate variability, abnormal deceleration capacity with abnormal turbulence, were referred for programmed ventricular stimulation (PVS), with ICDs offered to those inducible. The primary endpoint was the occurrence of a major arrhythmic event (MAE), namely sustained ventricular tachycardia/fibrillation, appropriate ICD activation or SCD. We screened and included 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive NIRF. Forty-one of 152 patients undergoing PVS (27–7.1% of total sample) were inducible. Thirty-seven (90.2%) of them received an ICD. Mean follow-up was 32 months and no SCDs were observed, while 9 ICDs (1.57% of total screened population) were appropriately activated. None patient without NIRFs or with NIRFs but negative PVS met the primary endpoint. The algorithm yielded the following: sensitivity 100%, specificity 93.8%, positive predictive value 22%, and negative predictive value 100%.

Conclusion

The two-step approach of the PRESERVE EF study detects a subpopulation of post-MI patients with preserved LVEF at risk for MAEs that can be effectively addressed with an ICD.

Clinicaltrials.gov identifier

NCT02124018
Empathy and Close Social Ties in Late Life
Authors: Huo Meng , Fuentecilla Jamie L , Birditt Kira S , Fingerman Karen L
Published: April 2019

Objectives

Older adults with stronger social ties often lead longer, healthier, and happier lives, but these ties may differ based on older adults’ ability to share and understand others’ emotions (i.e., empathy). This study asked how empathy was associated with the way that older adults construct and engage in their social worlds.

Method

We drew on the Daily Experiences and Well-being Study to examine how older adults’ empathy was associated with the structure (e.g., network size and contact), function (e.g., support), and quality (e.g., affection and conflict) of their close social ties. Participants (N = 333) self-rated empathy and listed their social partners using three concentric convoy circles.

Results

Empathy was not associated with older adults’ social network structure, but more empathic older adults exchanged support with more social partners and reported greater affection for their social partners. We did not observe a significant link between older adults’ empathy and conflict with social partners.

Discussion

Examining empathy advances our understanding of individual differences in older adults’ close social ties. This study suggests that empathy may play a promising role with regard to promoting older adults’ social experiences and strengthening their close ties.
Engaging Caregivers in Health-Related Housing Decisions for Older Adults With Cognitive Impairment: A Cluster Randomized Trial
Authors: Adekpedjou Rhéda , Stacey Dawn , Brière Nathalie , Freitas Adriana , Garvelink Mirjam M , Dogba Maman Joyce , Durand Pierre J , Desroches Sophie , Croteau Jordie , Rivest Louis-Paul , Légaré France
Published: April 2019

Background and Objectives

Informal caregivers are rarely as involved as they want to be in the housing decisions of cognitively impaired older adults. Lack of awareness of available options and their benefits and risks may lead to decisions that do not reflect older adults’ preferences, and to guilt and regret. We assessed the effect of training home care teams in interprofessional shared decision-making (SDM) on the proportion of caregivers who report being active in this decision.

Research Design and Methods

In a two-arm pragmatic cluster randomized trial with home care teams working in health centers in the Province of Quebec, we randomized health centers to receive training in interprofessional SDM (intervention) or not (control). Eligible caregivers had made a housing decision for a cognitively impaired adult aged 65 years or older who was receiving services from a home care team. The primary outcome was the proportion of caregivers reporting an active role in decision making. We performed intention-to-treat multilevel analysis.

Results

We consecutively enrolled a random group of 16 health centers and recruited 309 caregivers, among whom 296 were included in the analysis. In the intervention arm, the proportion of caregivers reporting an active role in decision making increased by 12% (95% CI −2% to 27%; p = .10). After removal of an influential cluster outlier, the proportion increased to 18% (95% CI: 7%–29%; p < .01).

Discussion and Implications

Training home care teams in interprofessional SDM increased caregiver involvement in health-related housing decisions for cognitively impaired older adults.
Exploring the role of genetic confounding in the association between maternal and offspring body mass index: evidence from three birth cohorts
Authors: Bond Tom A , Karhunen Ville , Wielscher Matthias , Auvinen Juha , Männikkö Minna , Keinänen-Kiukaanniemi Sirkka , Gunter Marc J , Felix Janine F , Prokopenko Inga , Yang Jian , Visscher Peter M , Evans David M , Sebert Sylvain , Lewin Alex , O’Reilly Paul F , Lawlor Debbie A , Jarvelin Marjo-Riitta
Published: April 2019

Background

Maternal pre-pregnancy body mass index (BMI) is positively associated with offspring birth weight (BW) and BMI in childhood and adulthood. Each of these associations could be due to causal intrauterine effects, or confounding (genetic or environmental), or some combination of these. Here we estimate the extent to which the association between maternal BMI and offspring body size is explained by offspring genotype, as a first step towards establishing the importance of genetic confounding.

Methods

We examined the associations of maternal pre-pregnancy BMI with offspring BW and BMI at 1, 5, 10 and 15 years, in three European birth cohorts (n ≤11 498). Bivariate Genomic-relatedness-based Restricted Maximum Likelihood implemented in the GCTA software (GCTA-GREML) was used to estimate the extent to which phenotypic covariance was explained by offspring genotype as captured by common imputed single nucleotide polymorphisms (SNPs). We merged individual participant data from all cohorts, enabling calculation of pooled estimates.

Results

Phenotypic covariance (equivalent here to Pearson’s correlation coefficient) between maternal BMI and offspring phenotype was 0.15 [95% confidence interval (CI): 0.13, 0.17] for offspring BW, increasing to 0.29 (95% CI: 0.26, 0.31) for offspring 15 year BMI. Covariance explained by offspring genotype was negligible for BW [–0.04 (95% CI: –0.09, 0.01)], but increased to 0.12 (95% CI: 0.04, 0.21) at 15 years, which is equivalent to 43% (95% CI: 15%, 72%) of the phenotypic covariance. Sensitivity analyses using weight, BMI and ponderal index as the offspring phenotype at all ages showed similar results.

Conclusions

Offspring genotype explains a substantial fraction of the covariance between maternal BMI and offspring adolescent BMI. This is consistent with a potentially important role for genetic confounding as a driver of the maternal BMI–offspring BMI association.
A cell-centred pressure-correction scheme for the compressible Euler equations
Authors: Herbin Raphaèle , Latché Jean-Claude , Zaza Chady
Published: April 2019

We propose a robust pressure-correction scheme for the numerical solution of the compressible Euler equations discretized by a collocated finite volume method. The scheme is based on an internal energy formulation, which ensures that the internal energy is positive. More generally, the scheme enjoys fundamental stability properties: without restriction on the time step, both the density and the internal energy are positive, the integral of the total energy over the computational domain is preserved thanks to an estimate on the discrete kinetic energy and a discrete entropy inequality is satisfied. These stability properties ensure the existence of a solution to the scheme. The internal energy balance features a corrective source term, which is needed for the scheme to compute the correct shock solutions; we are indeed able to prove a Lax-consistency-type convergence result, in the sense that, under some compactness assumptions, the limit of a converging sequence of approximate solutions obtained with space and time discretization steps tending to zero is an entropy weak solution of the Euler equations. Moreover, constant pressure and velocity are preserved through contact discontinuities. The obtained theoretical results and the scheme accuracy are verified by numerical experiments; a numerical stabilization is introduced in order to reduce the oscillations that appear for some tests. The qualitative behaviour of the scheme is assessed on one-dimensional and two-dimensional Riemann problems and compared with other schemes.
In vitro activity and in vivo efficacy of fexinidazole against New World Leishmania species
Authors: de Morais-Teixeira Eliane , Rabello Ana , Aguiar Marta Marques Gontijo
Published: April 2019

Objectives

To evaluate the in vitro activity and in vivo efficacy of fexinidazole against the main species that cause visceral and cutaneous New World leishmaniasis.

Methods

The inhibitory concentrations of fexinidazole against Leishmania (Leishmania) infantum chagasi, Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis in amastigotes were determined by in vitro activity assays. For the in vivo evaluation, animals were infected with L. (L.) infantum chagasi, L. (L.) amazonensis, L. (V.) braziliensis or Leishmania (Viannia) guyanensis and divided into groups: (i) control; and (ii) treated with oral fexinidazole, from 50 to 300 mg/kg/day. For cutaneous leishmaniasis, the size of the lesion was determined weekly after the beginning of the treatment. Upon completion, parasites were recovered from the spleen and liver, or skin lesion and spleen, and evaluated by a limiting dilution assay.

Results

All Leishmania isolates were susceptible to fexinidazole in the in vitro assays. The viable parasites in the liver and spleen were reduced with 100 and 300 mg/kg/day, respectively, for L. (L.) infantum chagasi. For the species causing cutaneous leishmaniasis, the viable parasites in lesions and the size of the lesions were reduced, starting from 200 mg/kg/day. The viable parasites in the spleen were also reduced with 200 and 300 mg/kg/day for L. (V.) braziliensis and L. (L.) amazonensis.

Conclusions

Considering the defined parameters, fexinidazole showed in vitro and in vivo activity against all tested species. This drug may represent an alternative treatment for the New World species.
Inhalation Injury: Unmet Clinical Needs and Future Research
Authors: Dyamenahalli Kiran , Garg Gaurav , Shupp Jeffrey W , Kuprys Paulius V , Choudhry Mashkoor A , Kovacs Elizabeth J
Published: April 2019

Pulmonary and systemic insults from inhalation injury can complicate the care of burn patients and contribute to significant morbidity and mortality. However, recent progress in diagnosis and treatment of inhalation injury has not kept pace with the care of cutaneous thermal injury. There are many challenges unique to inhalation injury that have slowed advancement, including deficiencies in our understanding of its pathophysiology, the relative difficulty and subjectivity of bronchoscopic diagnosis, the lack of diagnostic biomarkers, the necessarily urgent manner in which decisions are made about intubation, and the lack of universal recommendations for the application of mucolytics, anticoagulants, bronchodilators, modified ventilator strategies, and other measures. This review represents a summary of critical shortcomings in our understanding and management of inhalation injury identified by the American Burn Association’s working group on Cutaneous Thermal Injury and Inhalation Injury in 2018. It addresses our current understanding of the diagnosis, pathophysiology, and treatment of inhalation injury and highlights topics in need of additional research, including 1) airway repair mechanisms; 2) the airway microbiome in health and after injury; and 3) candidate biomarkers of inhalation injury.
Predictive Biomarkers for Acute Kidney Injury in Burn Patients
Authors: Emami Amir , Javanmardi Fatemeh , Rajaee Mahrokh , Pirbonyeh Neda , Keshavarzi Abdolkhalegh , Fotouhi Maryam , Hosseini Seyed Mohammad
Published: April 2019

Acute kidney injury (AKI) is an independent and complicated risk factor in burn patients, which cause high mortality and morbidity rate. Diagnosing the biomarkers and early detection of AKI may be helpful in treatment and control the stability of these patients. In this study, we aim to identify predictive biomarkers in order to prevent AKI incidence and sudden death in burn victims. In this retrospective study, 258 burn patients who were admitted to burn center in Shiraz, Iran were evaluated during January 2016 to February 2018. Demographic characteristics, biochemical biomarkers, length of hospital stay, and mortality information were obtained from patient registries program and evaluated the biomarkers in identifying AKI patients into early and late groups. Receiver operating characteristic curve, area under the curve (AUC), univariate, and multivariate logistic regression analysis were used to diagnose the performance of biomarkers in order to predict the AKI. Of 258 patients, 40 (15.50%) were detected as AKI, with estimated mortality rate of 76.9%. Among all the variables, total BSA (P = .01), blood urea nitrogen (BUN; P = .001), potassium (P = .02), and mortality (P = .03) were significantly different in AKI developing. Moreover, AUC of serum creatinin, albumin, and BUN as predictive biomarkers were 0.73, 0.44, and 0.707, respectively. Among all variables, BUN marker was independently associated with AKI developing. Following burn shock, AKI is a common complication that causes increasing mortality and morbidity. Early diagnosis and identifying the biomarkers is preventing sudden death in burn patients and develop appropriate treatments in these victims.
The Securitization Dilemma
Authors: Van Rythoven Eric
Published: April 2019

Motivated by the neglect of uncertainty and perverse consequences in constructivist studies of security, this article pursues a reconceptualization of the security dilemma. Approaching the dilemma as a “logic of self-limitation” constituted by choice, uncertainty, and tragedy, the article explores how this logic can be transposed to the constructivist context of securitization theory. The resulting “securitization dilemma” draws renewed attention to the unintended character of social life, highlights how the choice to engage in practices of threat construction are shaped by uncertainty, and shows how the failure to recognize these limitations can have tragic consequences. While the argument aims to broaden the empirical focus of securitization studies to include perverse and unintended consequences, it also looks to engage with the literature's distinctive ethical claim over how speaking security is never a neutral act. Political actors may well be responsible for the security claims they make, but we need to recognize that this responsibility includes the effects of security claims that actors anticipate, as well as those they do not.
Involvement of phosphatidylinositol metabolism in aluminum-induced malate secretion in Arabidopsis
Authors: Wu Liujie , Sadhukhan Ayan , Kobayashi Yuriko , Ogo Naohisa , Tokizawa Mutsutomo , Agrahari Raj Kishan , Ito Hiroki , Iuchi Satoshi , Kobayashi Masatomo , Asai Akira , Koyama Hiroyuki
Published: April 2019

To identify the upstream signaling of aluminum-induced malate secretion through aluminum-activated malate transporter 1 (AtALMT1), a pharmacological assay using inhibitors of human signal transduction pathways was performed. Early aluminum-induced transcription of AtALMT1 and other aluminum-responsive genes was significantly suppressed by phosphatidylinositol 4-kinase (PI4K) and phospholipase C (PLC) inhibitors, indicating that the PI4K–PLC metabolic pathway activates early aluminum signaling. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and PI4K reduced aluminum-activated malate transport by AtALMT1, suggesting that both the PI3K and PI4K metabolic pathways regulate this process. These results were validated using T-DNA insertion mutants of PI4K and PI3K-RNAi lines. A human protein kinase inhibitor, putatively inhibiting homologous calcineurin B-like protein-interacting protein kinase and/or Ca-dependent protein kinase in Arabidopsis, suppressed late-phase aluminum-induced expression of AtALMT1, which was concomitant with the induction of an AtALMT1 repressor, WRKY46, and suppression of an AtALMT1 activator, Calmodulin-binding transcription activator 2 (CAMTA2). In addition, a human deubiquitinase inhibitor suppressed aluminum-activated malate transport, suggesting that deubiquitinases can regulate this process. We also found a reduction of aluminum-induced citrate secretion in tobacco by applying inhibitors of PI3K and PI4K. Taken together, our results indicated that phosphatidylinositol metabolism regulates organic acid secretion in plants under aluminum stress.
High-speed photometry of faint cataclysmic variables – IX. Targets from multiple transient surveys
Authors: Paterson K , Woudt P A , Warner B , Breytenbach H , Gilligan C K , Motsoaledi M , Thorstensen J R , Worters H L
Published: April 2019

We present high-speed photometric observations of 25 cataclysmic variables detected by the All Sky Automated Search for Super-Novae, the Mobile Astronomical System of the TElescope-Robot, and the Catalina Real-Time Transient Survey. From these observations we determine 16 new orbital periods and 1 new superhump period. Two systems (ASASSN-14ik and ASASSN-14ka) have outburst periods of approximately 1 month, with a third (ASASSN-14hv) having outbursts approximately every 2 months. Included in the sample are 11 eclipsing systems, one probable intermediate polar (ASASSN-15fm), 1 SW Sex-type star (MLS 0720+17), 1 WZ Sge-type star (ASASSN-17fz), and one system showing different photometric and spectroscopic periods (ASASSN-15kw).
ALMA reveals a pseudo-disc in a proto-brown dwarf
Authors: Riaz B , Machida M N , Stamatellos D
Published: April 2019

We present the observational evidence of a pseudo-disc around the proto-brown dwarf Mayrit 1701117, the driving source of the large-scale HH 1165 jet. Our analysis is based on Atacama Large Millimeter/submillimeter Array 12CO (2–1) line and 1.37 mm continuum observations at an angular resolution of ∼0.4 arcsec. The pseudo-disc is a bright feature in the CO position–velocity diagram, elongated in a direction perpendicular to the jet axis, with a total (gas+dust) mass of ∼0.02 M$\odot$, size of 165–192 au, and a velocity spread of ±2 km s−1. The large velocity gradient is a combination of infalling and rotational motions, indicating a contribution from a pseudo-disc and an unresolved inner Keplerian disc. There is weak emission detected in the H2CO (3–2) and N2D+ (3–2) lines. H2CO emission likely probes the inner Keplerian disc where CO is expected to be frozen, while N2D+ possibly originates from an enhanced clump at the outer edge of the pseudo-disc. We have considered various models (core collapse, disc fragmentation, circumbinary disc) that can fit both the observed CO spectrum and the position–velocity offsets. The observed morphology, velocity structure, and the physical dimensions of the pseudo-disc are consistent with the predictions from the core collapse simulations for brown dwarf formation. From the best model fit, we can constrain the age of the proto-brown dwarf system to be ∼30 000–40 000 yr. A comparison of the H2 column density derived from the CO line and 1.37 mm continuum emission indicates that only about 2 per cent of the CO is depleted from the gas phase.
The unbiased frequency of planetary signatures around single and binary white dwarfs using Spitzer and Hubble
Authors: Wilson Thomas G , Farihi Jay , Gänsicke Boris T , Swan Andrew
Published: April 2019

This paper presents combined Spitzer IRAC and Hubble COS results for a double-blind survey of 195 single and 22 wide binary white dwarfs for infrared excesses and atmospheric metals. The selection criteria include cooling ages in the range 9 to 300 Myr, and hydrogen-rich atmospheres so that the presence of atmospheric metals can be confidently linked to ongoing accretion from a circumstellar disc. The entire sample has infrared photometry, whereas 168 targets have corresponding ultraviolet spectra. Three stars with infrared excesses due to debris discs are recovered, yielding a nominal frequency of $1.5_{-0.5}^{+1.5}$ per cent, while in stark contrast, the fraction of stars with atmospheric metals is 45 ± 4 per cent. Thus, only one out of 30 polluted white dwarfs exhibits an infrared excess at 3–4 $\mu$m in IRAC photometry, which reinforces the fact that atmospheric metal pollution is the most sensitive tracer of white dwarf planetary systems. The corresponding fraction of infrared excesses around white dwarfs with wide binary companions is consistent with zero, using both the infrared survey data and an independent assessment of potential binarity for well-established dusty and polluted stars. In contrast, the frequency of atmospheric pollution among the targets in wide binaries is indistinct from apparently single stars, and moreover the multiplicity of polluted white dwarfs in a complete and volume-limited sample is the same as for field stars. Therefore, it appears that the delivery of planetesimal material on to white dwarfs is ultimately not driven by stellar companions, but by the dynamics of planetary bodies.
Reducing activity-induced variations in a radial-velocity time series of the Sun as a star
Authors: Lanza A F , Collier Cameron A , Haywood R D
Published: April 2019

The radial velocity (RV) of the Sun as a star is affected by its surface convection and magnetic activity. The moments of the cross-correlation function between the solar spectrum and a binary line mask contain information about the stellar RV and line-profile distortions caused by stellar activity. As additional indicators, we consider the disc-averaged magnetic flux and the filling factor of the magnetic regions. Here we show that the activity-induced radial-velocity fluctuations are reduced when we apply a kernel regression to these activity indicators. The disc-averaged magnetic flux proves to be the best activity proxy over a time-scale of one month and gives a standard deviation of the regression residuals of 1.04 m s−1, more than a factor of 2.8 smaller than the standard deviation of the original RV fluctuations. This result has been achieved thanks to the high-cadence and time continuity of the observations that simultaneously sample both the RV and the activity proxies.
Orbital relaxation and excitation of planets tidally interacting with white dwarfs
Authors: Veras Dimitri , Efroimsky Michael , Makarov Valeri V , Boué Gwenaël , Wolthoff Vera , Reffert Sabine , Quirrenbach Andreas , Tremblay Pier-Emmanuel , Gänsicke Boris T
Published: April 2019

Observational evidence of white dwarf planetary systems is dominated by the remains of exo-asteroids through accreted metals, debris discs, and orbiting planetesimals. However, exo-planets in these systems play crucial roles as perturbing agents, and can themselves be perturbed close to the white dwarf Roche radius. Here, we illustrate a procedure for computing the tidal interaction between a white dwarf and a near-spherical solid planet. This method determines the planet’s inward and/or outward drift, and whether the planet will reach the Roche radius and be destroyed. We avoid constant tidal lag formulations and instead employ the self-consistent secular Darwin–Kaula expansions from Boué & Efroimsky (2019), which feature an arbitrary frequency dependence on the quality functions. We adopt wide ranges of dynamic viscosities and spin rates for the planet in order to straddle many possible outcomes, and provide a foundation for the future study of individual systems with known or assumed rheologies. We find that (i) massive Super-Earths are destroyed more readily than minor planets (such as the ones orbiting WD 1145+017 and SDSS J1228+1040), (ii) low-viscosity planets are destroyed more easily than high-viscosity planets, and (iii) the boundary between survival and destruction is likely to be fractal and chaotic.
EpiAlign: an alignment-based bioinformatic tool for comparing chromatin state sequences
Authors: Ge Xinzhou , Zhang Haowen , Xie Lingjue , Li Wei Vivian , Kwon Soo Bin , Li Jingyi Jessica
Published: April 2019

The availability of genome-wide epigenomic datasets enables in-depth studies of epigenetic modifications and their relationships with chromatin structures and gene expression. Various alignment tools have been developed to align nucleotide or protein sequences in order to identify structurally similar regions. However, there are currently no alignment methods specifically designed for comparing multi-track epigenomic signals and detecting common patterns that may explain functional or evolutionary similarities. We propose a new local alignment algorithm, EpiAlign, designed to compare chromatin state sequences learned from multi-track epigenomic signals and to identify locally aligned chromatin regions. EpiAlign is a dynamic programming algorithm that novelly incorporates varying lengths and frequencies of chromatin states. We demonstrate the efficacy of EpiAlign through extensive simulations and studies on the real data from the NIH Roadmap Epigenomics project. EpiAlign is able to extract recurrent chromatin state patterns along a single epigenome, and many of these patterns carry cell-type-specific characteristics. EpiAlign can also detect common chromatin state patterns across multiple epigenomes, and it will serve as a useful tool to group and distinguish epigenomic samples based on genome-wide or local chromatin state patterns.
BDNF, COMT, and DRD2 polymorphisms and ability to return to work in adult patients with low- and high-grade glioma
Authors: Altshuler David B , Wang Lin , Zhao Lili , Miklja Zachary , Linzey Joey , Brezzell Amanda , Kakaizada Sofia , Krishna Saritha , Orringer Daniel A , Briceño Emily M , Gabel Nicolette , Hervey-Jumper Shawn L
Published: April 2019

Background

Cognitive and language dysfunction is common among patients with glioma and has a significant impact on survival and health-related quality of life (HRQOL). Little is known about the factors that make individual patients more or less susceptible to the cognitive sequelae of the disease. A better understanding of the individual and population characteristics related to cognitive function in glioma patients is required to appropriately stratify patients, prognosticate, and develop more efficacious treatment regimens. There is evidence that allelic variation among genes involved in neurotransmission and synaptic plasticity are related to neurocognitive performance in states of health and neurologic disease.

Methods

We studied the association of single-nucleotide polymorphism variations in brain-derived neurotrophic factor (BDNF, rs6265), dopamine receptor 2 (DRD2, rs1076560), and catechol-O-methyltransferase (COMT, rs4680) with neurocognitive function and ability to return to work in glioma patients at diagnosis and at 3 months. We developed a functional score based on the number of high-performance alleles that correlates with the capacity for patients to return to work.

Results

Patients with higher-performing alleles have better scores on neurocognitive testing with the Repeatable Battery for the Assessment of Neuropsychological Status and Stroop test, but not the Trail Making Test.

Conclusions

A better understanding of the genetic contributors to neurocognitive performance in glioma patients and capacity for functional recovery is necessary to develop improved treatment strategies based on patient-specific factors.
Nicotine Self-Administration With Tobacco Flavor Additives in Male Rats
Authors: Palmatier Matthew I , Smith Amanda L , Odineal Ethan M , Williams Emily A , Sheppard Ashley B , Bradley Curtis A
Published: April 2019

Introduction

Nicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. Menthol and licorice are tobacco flavoring agents also found in sweet foods (eg, candy and ice cream), making them putative CRs before they are consumed in tobacco. We sought to determine if intravenous self-administration (IVSA) of nicotine was enhanced by the inclusion of oral tobacco flavor CRs.

Methods

Menthol (160 or 320 µM) or licorice root extract (0.1% or 1%) were established as CRs (paired with 20% sucrose) or “neutral” stimuli (paired with water) in separate groups. During subsequent IVSA tests, nicotine was delivered in conjunction with oral presentations of the CR.

Results

In experiment 1, a menthol CR significantly shifted the peak nicotine dose from 15 µg/kg/infusion (Neutral group) to 3.25 µg/kg/infusion (CR group). In experiment 2, a menthol CR significantly increased operant licks for nicotine (3 µg/kg/infusion) relative to control groups. In experiment 3, both licorice and menthol CRs significantly increased operant licks for nicotine (7.5 µg/kg/infusion) relative to an “inactive” sipper. The licorice CR increased nicotine IVSA in proportion to the strength of the flavor, but both menthol concentrations increased nicotine IVSA to a similar extent.

Conclusion

Tobacco flavor additives with conditioned reinforcing properties promote acquisition of nicotine self-administration at low unit doses and may have robust impact on tobacco consumption when nicotine yield is low.

Implications

Tobacco flavor additives are found in rewarding foods (eg, ice cream) and gain palatability based on associations with primary rewards (eg, sugar) making them “conditioned reinforcers.” Nicotine increases the motivation for flavor conditioned reinforcers and the present studies show that tobacco flavor additives can interact with nicotine to promote more nicotine self-administration. The interaction between flavors additives and nicotine may promote nicotine exposure and subsequently dependence.
Modulation of “Protective” Nicotine Perception and Use Profile by Flavorants: Preliminary Findings in E-cigarettes
Authors: DeVito Elise E , Jensen Kevin P , O’Malley Stephanie S , Gueorguieva Ralitza , Krishnan-Sarin Suchitra , Valentine Gerald , Jatlow Peter I , Sofuoglu Mehmet
Published: April 2019

Introduction

Characterizing flavors are widely available in e-cigarettes and motivate initiation and continued use. Flavors may enhance appeal and facilitate development of addiction to tobacco products through modulation of tobacco products’ reinforcing or aversive actions. Palatable flavors (eg, fruit) may increase appeal through primary reinforcing properties. Menthol’s cooling and anesthetic effects may increase appeal by counteracting nicotine’s aversive effects. Genetics provide a method for modeling individual differences in sensitivity to nicotine’s effects. A common polymorphism, rs16969968, encoded in the α5 nicotinic acetylcholine receptor subunit gene (CHRNA5), is a well-recognized marker for smoking risk and reduces sensitivity to nicotine aversiveness.

Methods

This pilot study tested how flavors impacted e-cigarette appeal and self-administration. In a single testing day, cigarette smokers (N = 32; 94% menthol-smokers) self-administered e-cigarettes containing e-liquids differing in nicotine level (0 mg/mL, 24 mg/mL) and flavor (unflavored, menthol, fruit-flavored) within directed and ad libitum e-cigarette paradigms. Subjective drug effects, number of puffs, rs16969968 genotype, plasma nicotine, and menthol glucuronide levels were collected.

Results

Menthol partially ameliorated nicotine aversiveness; fruit did not. In nicotine’s absence, fruit flavor increased self-reported preference and ad libitum use relative to menthol-containing or unflavored e-liquids. Individuals with high-smoking-risk rs16969968 genotype (N = 7) reported greater craving alleviation following directed administration of nicotine-containing e-liquids, showed a trend rating nicotine-containing e-liquids as less harsh, and self-administered more nicotine during ad libitum compared to individuals with low-smoking-risk genotype (N = 23).

Conclusions

While menthol countered aversiveness of nicotine-containing e-liquids, fruit flavor increased appeal of nicotine-free e-liquids. These preliminary findings suggest menthol and fruit flavor increase e-cigarettes’ appeal through distinct mechanisms.

Implications

This study provides a detailed characterization of the effects of flavors (unflavored, menthol, fruit), nicotine (0 mg/mL, 24 mg/mL) and their interactions on the subjective drug effects and ad libitum self-administration of e-cigarettes. Genetics were used to assess these effects in higher-smoking-risk (diminished sensitivity to nicotine aversiveness) and lower-risk groups. Findings could inform impact of regulation of flavors or nicotine in e-cigarettes, and their impacts on vulnerable sub-populations.
The lung in a cohort of rheumatoid arthritis patients—an overview of different types of involvement and treatment
Authors: Duarte Ana C , Porter Joanna C , Leandro Maria J
Published: April 2019

Objectives

Lung involvement in RA has several manifestations and is a major cause of morbidity and mortality. The aim of this study was to characterize the different types of lung disease and response to treatment in a UK cohort of RA patients.

Methods

RA patients who had undergone high resolution CT scans of the lung were identified and scans reviewed. Demographic data, RA features, complementary exams and treatments were recorded for those with radiological evidence of lung involvement. Descriptive analysis was performed, and Mann–Whitney U and χ2 tests were used for comparison between different radiological subtypes.

Results

Lung disease was reported in 87 (7.7%) of 1129 RA patients, usually (97.7%) post-dating articular symptoms. Most patients had positive RF (74/84; 88.1%) and ACPA (72/82; 87.7%). Interstitial lung disease (ILD) was the most common pattern, reported in 45 (51.7%) patients. Drug-induced lung disease was reported in 2 of 64 (3.1%) patients treated with MTX. Rituximab was used in 26 (57.8%) patients with ILD, with evidence of disease improvement or stabilization in patients with non-specific interstitial pneumonia and organizing pneumonia. During lung disease follow-up (6.7 ± 4.1 years), 22 (25.3%) patients were admitted to hospital with respiratory infections, with 14 (63.6%) of them having underlying bronchiectasis. Lung disease-related mortality was estimated at 8%.

Conclusion

ILD was the most prevalent manifestation of lung involvement in RA and was associated with higher mortality. Immunosuppressive drugs used in RA were rarely associated with lung toxicity, and rituximab demonstrated promising results for the treatment of RA-ILD.
DEVELOPMENT OF CALCULATION TOOL FOR RESPIRATORY TRACT DEPOSITION DEPENDING ON AEROSOLS PARTICLE DISTRIBUTION
Authors: Iwaoka Kazuki , Hosoda Masahiro , Tokonami Shinji , Enriquez Eliza B , Palad Lorna Jean H , Kanda Reiko
Published: April 2019

Inhalation exposures occur by inhaled radioactive nuclides depositing in the various locations in the respiratory tract (International Commission on Radiological Protection Publication 66). Respiratory tract deposition depends on particle size. The sensitivity to ionising radiation is different among respiratory regions. Under actual atmospheric environments, the radionuclides attach to aerosols of various size in the atmosphere, so the particle size of radionuclides changes differently. Therefore, it is important for the estimation of health impact to calculate the respiratory tract deposition under atmospheric environment wherein the various sizes of radioactive nuclides (i.e. polydisperse particles) exists. In this study, a tool which can calculate the respiratory tract deposition on the basis of polydisperse particle size distribution was developed to estimate dose depending on variable aerosol particle sizes.
The “Power of Presence”: Professional Women Leaders and Family Law Reform in Morocco
Authors: Charrad Mounira M , Stephan Rita
Published: April 2019

The 2004 reforms of Islamic family law in Morocco brought about a long-awaited expansion of women’s rights. The Moroccan women’s movement was a key player in the promulgation of the reforms. We highlight the role of professional women leaders in the movement and show how they developed political capital and the “power of presence” by combining (i) professional attainment, (ii) leadership in women’s organizations, and (iii) active participation or positions in politics and civil society. We suggest that more needs to be understood about the implications of women’s education and professional attainment for legal change, especially in the Middle East.