bluuebunny/crossref_metadata_2025 huggingface dataset:
Flow boiling in geometrically modified microchannels
Authors: Broughton Justin , Joshi Yogendra K.
Published: October 2021

Microchannels are a promising solution for high-heat-flux thermal management scenarios, including high-performance microelectronics cooling and power electronics cooling. However, thermohydraulic instabilities result from the rapid vapor bubble formation. The prior literature has examined several methods, including constricted inlet microchannels, expanding microchannels, and auxiliary jetting microchannels, to mitigate the effect of these instabilities. Computational fluid dynamics and heat transfer (CFD/HT) modeling of the flow boiling phenomena in these microchannel configurations has seen limited examination, and one-to-one numerical comparisons of the different mitigation strategies have not been performed. In the present investigation, CFD/HT analyses using a three-dimensional (3D) volume of fluid model coupled with a phase-change model for the interfacial heat and mass transfer were performed for multiple microchannel configurations (constricted inlet, expanding, and auxiliary jetting microchannels). A benchmark case of a rectangular microchannel was examined to quantify baseline thermohydraulic performance. Results demonstrated slight to significant thermal performance improvements for all cases, and significant pressure benefits for the expanding and jetting cases, consistent with experimental results in the literature. Bubble dynamics and visualization for the baseline and alternative configurations are provided to give insight into their underlying physics, and the differences in performance were investigated and compared with available literature.
Effect of Coulomb interaction on transport gap in ideal graphene nanoribbons
Authors: Ihnatsenka S.
Published: October 2021

Quantum-mechanical calculations of electron transport in ideal graphene nanoribbons show that the transport gap that is predicted by noninteracting theories vanishes if the long-range Coulomb interaction between electrons is taken into account. This is a result of charge screening with the lowest subband edge being pinned to the chemical potential. However, the transport gap reappears if a ribbon is connected to wider leads, which is typically realized in an experimental setup that is based on lithographically patterned graphene ribbons. The gap is determined by scattering at the lead-to-ribbon interface, which can already be captured by the noninteracting theory.
PCBM/Ag interface dipole management in inverted perovskite solar cells
Authors: Qu Dandan , Guo Tonghui , Zhang Jing , Deng Zhiqiang , Zhang Zequn , Zhao Rui , Liu Xiaohui , Hu Ziyang , Huang Like , Zhu Yuejin
Published: October 2021

In inverted perovskite solar cells, the [6,6]-phenyl-C61-butyric acid methyl ester (PCBM)/Ag back interface is quite important because serious recombination occurs and H2O/O2 directly attacks this interface to induce device instability. Here, bi-functional dipole layers are applied at the interface aiming at improving the charge transport and device stability simultaneously. Silane with -CF3 end group anchored on the PCBM surface induces more effective dipole effect than that with (CH2)7-CH3 end functional silane, bending the interface energy level to promote electron transport and reduce recombination. The hydrophobic nature of -CF3 also enhances the durability of the device. This work highlights the back surface dipole management method to achieve efficient and stable perovskite solar cells.
Effect of urea on the hydration and aggregation of hydrophobic and amphiphilic solute models: Implications to protein aggregation
Authors: Xavier P. , Galamba N.
Published: October 2021

Despite the emergence of a molecular picture of urea’s protein unfolding mechanism in the past few decades, less is known about its action mechanism on protein aggregation. This is especially relevant for understanding the aggregation of amyloid proteins and peptides, implicated in several neurodegenerative diseases. While urea is believed to weaken the hydrophobic effect, a picture consistent with the decrease in the excess chemical potential of sufficiently large alkanes, interactions with protein polar side chains and backbone atoms are also important. Here, we study, through molecular dynamics, the hydration and aggregation of several alkanes and amphiphilic “mutants” of n-dodecane, in an 8M aqueous urea solution, aiming at getting insight into urea’s mode of action. A size-dependent crossover temperature is found, above which the hydration of the alkanes is favored in the aqueous urea solution. The hydration of the alkanes is enhanced via entropy, with the enthalpy opposing hydration, consistent with experiments. The reason is that although solute–solvent interactions are favorable, these are overwhelmed by urea–water and urea–urea interactions. In contrast, water–water interactions and entropy are favored by a water depletion around the solute and a reduced water depletion around methane explains its exceptional solubility decrease. Furthermore, we show that while urea favors the hydration of n-dodecane and the amphiphilic mutants, it slightly enhances and reduces, respectively, the aggregation of the alkanes and the amphiphilic mutants. Thus, opposite to the common view, our results show that urea does not necessarily weaken hydrophobic interactions despite solvation being favored.
Natural hyperbolicity in bulk calcite
Authors: Mukhopadhyay Saikat , Ellis Chase T. , Ratchford Daniel C. , Jackson Eric M. , Tischler Joseph G. , Reinecke Thomas L. , Johannes Michelle D.
Published: October 2021

Naturally occurring materials with hyperbolic optical properties are attracting considerable interest due to their ability to confine light in small volumes and their resulting potential for applications in photonics. This paper uses a first-principles theoretical approach without adjustable parameters to investigate the hyperbolic optical properties of bulk calcite (CaCO3). This material exhibits natural hyperbolic behavior within its Reststrahlen bands at 1403–1552 and 864–887 cm−1. The calculated results are shown to be in good agreement with our reflectance data obtained from frequency- and polarization-dependent measurements. These results show that calcite is an attractive natural hyperbolic material; in addition, it has the advantage of low losses and is available commercially in a variety of crystal orientations.
Deep learning method for identifying the minimal representations and nonlinear mode decomposition of fluid flows
Authors: Qu Jiagang , Cai Weihua , Zhao Yijun
Published: October 2021

We propose a deep learning method to learn the minimal representations of fluid flows. It uses the deep variational autoencoder (VAE) to decouple the independent representations for fluid flows. We apply this method to several simple flows and show that the network successfully identifies the independent and interpretable representations. It shows that the proposed method can extract the physically suggestive information. We further employ the VAE network to improve the mode decomposing autoencoder framework. It decomposes the cylinder flow fields into two independent ordered states. The cylinder flow at different Reynolds numbers and time can be described as the composition of the two decomposed fields. The present results suggest that the proposed network can be used as an effective nonlinear dimensionality reduction tool for flow fields.
Polymer dependent acoustic mode coupling and Hooke’s law spring constants in stacked gold nanoplates
Authors: Wang Junzhong , Li Mengying , Jiang Yiqi , Yu Kuai , Hartland Gregory V. , Wang Guo Ping
Published: October 2021

Metal nanoparticles are excellent acoustic resonators and their vibrational spectroscopy has been widely investigated. However, the coupling between vibrational modes of different nanoparticles is less explored. For example, how the intervening medium affects the coupling strength is not known. Here, we investigate how different polymers affect coupling in Au nanoplate–polymer–Au nanoplate sandwich structures. The coupling between the breathing modes of the Au nanoplates was measured using single-particle pump–probe spectroscopy, and the polymer dependent coupling strength was determined experimentally. Analysis of the acoustic mode coupling gives the effective spring constant for the polymers. A relative motion mode was also observed for the stacked Au nanoplates. The frequency of this mode is strongly correlated with the coupling constant for the breathing modes. The breathing mode coupling and relative motion mode were analyzed using a coupled oscillator model. This model shows that both these effects can be described using the same spring constant for the polymer. Finally, we present a new type of mass balance using the strongly coupled resonators. We show that the resonators have a mass detection limit of a few femtograms. We envision that further understanding of the vibrational coupling in acoustic resonators will improve the coupling strength and expand their potential applications.
Large rewritable liquid crystal pretilt angle by in situ photoalignment of brilliant yellow films
Authors: McGinty Colin P. , Kołacz Jakub , Spillmann Christopher M.
Published: October 2021

The ability to control the alignment of liquid crystals (LCs) is a challenge that is near-universal in LC research and applications. While several practical solutions exist for controlling the azimuthal (in-plane) alignment of LCs at an interface, control over the polar, or pretilt angle of the LC often requires a combination of materials or expensive and intricate processing. Here, we introduce a method for exerting control over large pretilt angles utilizing a two-step exposure method applied to Brilliant Yellow (BY) photoalignment films. We demonstrate that BY photoalignment films have the unique ability to enforce a large range of pretilt angles spanning homeotropic (90°) and planar (0°) anchoring conditions at the LC-substrate interface. The alignment is stable over time, rewritable, and patternable. Ultimately the control established here provides a powerful and low-cost means to align and take full advantage of the anisotropic and electro-optic properties of LCs for a wide range of applications.
PINK1 drives production of mtDNA-containing extracellular vesicles to promote invasiveness
Authors: Rabas Nicolas , Palmer Sarah , Mitchell Louise , Ismail Shehab , Gohlke Andrea , Riley Joel S. , Tait Stephen W.G. , Gammage Payam , Soares Leandro Lemgruber , Macpherson Iain R. , Norman Jim C.
Published: October 2021

The cystine-glutamate antiporter, xCT, supports a glutathione synthesis program enabling cancer cells to cope with metabolically stressful microenvironments. Up-regulated xCT, in combination with glutaminolysis, leads to increased extracellular glutamate, which promotes invasive behavior by activating metabotropic glutamate receptor 3 (mGluR3). Here we show that activation of mGluR3 in breast cancer cells activates Rab27-dependent release of extracellular vesicles (EVs), which can transfer invasive characteristics to “recipient” tumor cells. These EVs contain mitochondrial DNA (mtDNA), which is packaged via a PINK1-dependent mechanism. We highlight mtDNA as a key EV cargo necessary and sufficient for intercellular transfer of invasive behavior by activating Toll-like receptor 9 in recipient cells, and this involves increased endosomal trafficking of pro-invasive receptors. We propose that an EV-mediated mechanism, through which altered cellular metabolism in one cell influences endosomal trafficking in other cells, is key to generation and dissemination of pro-invasive microenvironments during mammary carcinoma progression.
Single-particle cryo-EM reveals conformational variability of the oligomeric VCC β-barrel pore in a lipid bilayer
Authors: Sengupta Nayanika , Mondal Anish Kumar , Mishra Suman , Chattopadhyay Kausik , Dutta Somnath
Published: October 2021

Vibrio cholerae cytolysin (VCC) is a water-soluble, membrane-damaging, pore-forming toxin (PFT) secreted by pathogenic V. cholerae, which causes eukaryotic cell death by altering the plasma membrane permeability. VCC self-assembles on the cell surface and undergoes a dramatic conformational change from prepore to heptameric pore structure. Over the past few years, several high-resolution structures of detergent-solubilized PFTs have been characterized. However, high-resolution structural characterization of small β-PFTs in a lipid environment is still rare. Therefore, we used single-particle cryo-EM to characterize the structure of the VCC oligomer in large unilamellar vesicles, which is the first atomic-resolution cryo-EM structure of VCC. From our study, we were able to provide the first documented visualization of the rim domain amino acid residues of VCC interacting with lipid membrane. Furthermore, cryo-EM characterization of lipid bilayer–embedded VCC suggests interesting conformational variabilities, especially in the transmembrane channel, which could have a potential impact on the pore architecture and assist us in understanding the pore formation mechanism.
Neuronal activity regulates the nuclear proteome to promote activity-dependent transcription
Authors: Herbst Wendy A. , Deng Weixian , Wohlschlegel James A. , Achiro Jennifer M. , Martin Kelsey C.
Published: October 2021

The formation and plasticity of neuronal circuits relies on dynamic activity-dependent gene expression. Although recent work has revealed the identity of important transcriptional regulators and of genes that are transcribed and translated in response to activity, relatively little is known about the cell biological mechanisms by which activity alters the nuclear proteome of neurons to link neuronal stimulation to transcription. Using nucleus-specific proteomic mapping in silenced and stimulated neurons, we uncovered an understudied mechanism of nuclear proteome regulation: activity-dependent proteasome-mediated degradation. We found that the tumor suppressor protein PDCD4 undergoes rapid stimulus-induced degradation in the nucleus of neurons. We demonstrate that degradation of PDCD4 is required for normal activity-dependent transcription and that PDCD4 target genes include those encoding proteins critical for synapse formation, remodeling, and transmission. Our findings highlight the importance of the nuclear proteasome in regulating the activity-dependent nuclear proteome and point to a specific role for PDCD4 as a regulator of activity-dependent transcription in neurons.
Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe
Authors: Zhang Guoxin , Dong Zhen , Gimple Ryan C. , Wolin Arthur , Wu Qiulian , Qiu Zhixin , Wood Lisa M. , Shen Jia Z. , Jiang Li , Zhao Linjie , Lv Deguan , Prager Briana C. , Kim Leo J.Y. , Wang Xiuxing , Zhang Lingdi , Anderson Ryan L. , Moore Jeffrey K. , Bao Shideng , Keller Thomas H. , Lin Grace , Kang Congbao , Hamerlik Petra , Zhao Rui , Ford Heide L. , Rich Jeremy N.
Published: October 2021

Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.
Investigation of Langdon effect on the stimulated backward Raman and Brillouin scattering
Authors: Qiu Jie , Hao Liang , Cao Lihua , Zou Shiyang
Published: October 2021

In a laser-irradiated plasma, the Langdon effect makes the electron energy distribution function tend to a super-Gaussian distribution, which has important influence on laser plasma instabilities. In this work, the influence of a super-Gaussian electron energy distribution function on the convective stimulated backward Raman scattering and stimulated backward Brillouin scattering is studied systematically for a wide range of typical plasma parameters in the inertial confinement fusion. Distinct behaviors are found for stimulated Raman scattering and stimulated Brillouin scattering in the variation trend of the peak spatial growth rate and the corresponding wavelength of the scattered light. Especially, the Langdon effect on the stimulated Brillouin scattering in plasmas with different ion species and isotopes is analyzed in detail, and the parameter boundary for judging the variation trend of the peak spatial growth rate of stimulated Brillouin scattering with the super-Gaussian exponent is presented for the first time. In certain plasma parameter region, it is found that the Langdon effect could enhance stimulated Brillouin scattering in mixed plasma, which may attenuate the improvement in suppressing stimulated Brillouin scattering by mixing low-Z ions into the high-Z plasma. The comprehension of Langdon effect on stimulated Raman scattering and stimulated Brillouin scattering would contribute to a better understanding of laser plasma instabilities in experiments.
Lugsail lag windows for estimating time-average covariance matrices
Authors: Vats D , Flegal J M
Published: October 2021

Lag windows are commonly used in time series analysis, econometrics, steady-state simulation and Markov chain Monte Carlo to estimate time-average covariance matrices. In the presence of positive correlation in the underlying process, estimators of this matrix almost always exhibit significant negative bias, leading to undesirable finite-sample properties. We propose a new family of lag windows specifically designed to improve finite-sample performance by offsetting this negative bias. Any existing lag window can be adapted into a lugsail equivalent with no additional assumptions. We use these lag windows in spectral variance estimators and demonstrate their advantages in a linear regression model with autocorrelated and heteroskedastic residuals. We further employ the lugsail lag windows in weighted batch means estimators because of their computational efficiency on large simulation output. We obtain bias and variance results for these multivariate estimators and significantly weaken the mixing condition on the process. Superior finite-sample properties are demonstrated in a vector autoregressive process and a Bayesian logistic regression model.
Anger or emotional upset and heavy physical exertion as triggers of stroke: the INTERSTROKE study
Authors: Smyth Andrew , O’Donnell Martin , Hankey Graeme J , Rangarajan Sumathy , Lopez-Jaramillo Patricio , Xavier Denis , Zhang Hongye , Canavan Michelle , Damasceno Albertino , Langhorne Peter , Avezum Alvaro , Pogosova Nana , Oguz Aytekin , Yusuf Salim ,   INTERSTROKE investigators
Published: October 2021

Aims

In INTERSTROKE, we explored the association of anger or emotional upset and heavy physical exertion with acute stroke, to determine the importance of triggers in a large, international population.

Methods and results

INTERSTROKE was a case–control study of first stroke in 32 countries. Using 13 462 cases of acute stroke we adopted a case-crossover approach to determine whether a trigger within 1 hour of symptom onset (case period), vs. the same time on the previous day (control period), was associated with acute stroke. A total of 9.2% (n = 1233) were angry or emotional upset and 5.3% (n = 708) engaged in heavy physical exertion during the case period. Anger or emotional upset in the case period was associated with increased odds of all stroke [odds ratio (OR) 1.37, 99% confidence interval (CI), 1.15–1.64], ischaemic stroke (OR 1.22, 99% CI, 1.00–1.49), and intracerebral haemorrhage (ICH) (OR 2.05, 99% CI 1.40–2.99). Heavy physical exertion in the case period was associated with increased odds of ICH (OR 1.62, 99% CI 1.03–2.55) but not with all stroke or ischaemic stroke. There was no modifying effect by region, prior cardiovascular disease, risk factors, cardiovascular medications, time, or day of symptom onset. Compared with exposure to neither trigger during the control period, the odds of stroke associated with exposure to both triggers were not additive.

Conclusion

Acute anger or emotional upset was associated with the onset of all stroke, ischaemic stroke, and ICH, while acute heavy physical exertion was associated with ICH only.
A Mediterranean Lifestyle and Frailty Incidence in Older Adults: The Seniors-ENRICA-1 Cohort
Authors: Maroto-Rodriguez Javier , Delgado-Velandia Mario , Ortolá Rosario , García-Esquinas Esther , Martinez-Gomez David , Struijk Ellen A , Lopez-Garcia Esther , Rodríguez-Artalejo Fernando , Sotos-Prieto Mercedes
Published: October 2021

Background

Frailty is a geriatric syndrome that entails high risk of hospitalization, disability, and death. While adherence to Mediterranean diet has been associated with lower risk of frailty, the joint effect of diet and lifestyle is uncertain. This study examined the association between a Mediterranean lifestyle (diet, customs, and traditions) and frailty incidence in older adults.

Methods

We analyzed data from 1 880 individuals aged ≥ 60 from the prospective Seniors-ENRICA-1 cohort. Adherence to the Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (higher scores representing better adherence), divided into 3 blocks: (1) “Mediterranean food consumption,” (2) “Mediterranean dietary habits” (practices around meals),” and (3) “Physical activity, rest, social habits and conviviality.” Frailty was ascertained as the presence of ≥ 3 of the 5 Fried criteria: (a) Exhaustion; (b) Muscle weakness; (c) Low physical activity; (d) Slow walking speed; and (e) Unintentional weight loss. Main statistical analyses were performed using logistic regression models, adjusting for the main confounders.

Results

After a 3.3-year follow-up, 136 incident frailty cases were ascertained. Compared with participants in the lowest tertile of the MEDLIFE score, the OR (95% CI) for frailty was 0.88 (0.58–1.34) for the second tertile, and 0.38 (0.21–0.69) for the third tertile (p-trend = .003). Blocks 1 and 3 of the MEDLIFE score were independently associated with lower frailty risk. Most items within these blocks showed a tendency to reduced frailty.

Conclusions

Higher adherence to a Mediterranean lifestyle was associated with lower risk of frailty.
Low Serum Klotho Associated With All-cause Mortality Among a Nationally Representative Sample of American Adults
Authors: Kresovich Jacob K , Bulka Catherine M
Published: October 2021

α-Klotho (klotho) is a protein involved in suppressing oxidative stress and inflammation. In animal models, it is reported to underlie numerous aging phenotypes and longevity. Among a nationally representative sample of adults aged 40–79 years in the United States, we investigated whether circulating concentrations of klotho is a marker of mortality risk. Serum klotho was measured by ELISA on 10 069 individuals enrolled in the National Health and Nutrition Examination Survey between 2007 and 2014. Mortality follow-up data based on the National Death Index were available through December 31, 2015. After a mean follow-up of 58 months (range: 1–108), 616 incident deaths occurred. Using survey-weighted Cox regression models adjusted for age, sex, and survey cycle, low serum klotho concentration (<666 pg/mL) was associated with a 31% higher risk of death (compared to klotho concentration > 985 pg/mL, hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.00, 1.71, p = .05). Associations were consistent for mortality caused by heart disease or cancer. Associations of klotho with all-cause mortality did not appear to differ by most participant characteristics. However, we observed effect modification by physical activity, such that low levels of serum klotho were more strongly associated with mortality among individuals who did not meet recommendation-based physical activity guidelines. Our findings suggest that, among the general population of American adults, circulating levels of klotho may serve as a marker of mortality risk.
Embodied Cognition and Media Engagement: When the Loneliness of the Protagonist Makes the Reader Sense Coldness (and Vice Versa)
Authors: Tal-Or Nurit , Razpurker-Apfeld Irene
Published: October 2021

Embodied cognition research documents the interplay between physical sensations and corresponding psychological experiences within the individual. Accordingly, physical warmth leads to a sense of social inclusion, and being socially rejected leads to physical coldness. In the current research, we demonstrate that these embodied cognition relationships also apply to a media consumer and a media character with whom the consumer identifies. In Study 1, participants (N  =  120) read one of four narratives in which we manipulated identification with the protagonist and her social exclusion/inclusion situation. In Study 2 (N  =  120), the narrative described the protagonist experiencing coldness/warmth in high/low identification conditions. The findings suggest that when the character experiences either the physical or the psychological state, the identifying consumer consequently experiences either psychological feelings or physical sensations, respectively. We discuss potential limitations of the study and also its contribution to media psychology and to embodied cognition research.
Why NATO survived Trump: the neglected role of Secretary-General Stoltenberg
Authors: Schuette Leonard August
Published: October 2021

The election of Donald Trump posed an existential challenge to NATO. At the end of his tenure, however, the US president had neither withdrawn membership nor substantially undermined the alliance from within. This article helps explain the puzzle of why NATO survived Trump's presidency. Extant explanations emphasize domestic factors such as the US foreign policy machinery and entrenched liberal ideology, structural reasons and Trump's idiosyncratic personality. While these accounts possess some explanatory value, they remain incomplete as they omit one central factor: NATO's leadership. Drawing on more than twenty original interviews with senior officials, the article demonstrates that particularly Secretary-General Stoltenberg's strategic responses were a necessary factor in changing Trump's stance on burden-sharing and helped maintain a robust deterrence policy toward Russia. These findings carry important implications both for theoretical debates on international organizations' agency in fending off contestation and policy debates on which actors shape NATO by emphasising the hitherto understated role of the secretary-general.
Probability of Stoma in Incident Patients With Crohn’s Disease in Sweden 2003-2019: A Population-based Study
Authors: Everhov Åsa H , Kalman Thordis Disa , Söderling Jonas , Nordenvall Caroline , Halfvarson Jonas , Ekbom Anders , Ludvigsson Jonas F , Olén Ola , Myrelid Pär
Published: October 2021

Background

Surgery rates in patients with Crohn’s disease have decreased during the last few decades, and use of antitumor necrosis agents (anti-TNF) has increased. Whether these changes correlate with a decreased probability of stoma is unknown. The objective of this study was to investigate the incidence of stoma in patients with Crohn’s disease over time.

Methods

Through linkage of national registers, we identified patients who were diagnosed with Crohn’s disease in 2003–2014 and were followed through 2019. We compared formation and closure of stomas over the calendar periods of diagnosis (2003–2006, 2007–2010, and 2011–2014).

Results

In a nationwide cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. This was mostly performed in conjunction with ileocolic resection (39%). The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods (P = .61). Less than half of the patients (44%) had their stoma reversed. Stomas were more common in elderly-onset compared with pediatric-onset disease: 5-year cumulative incidence 3.6% vs 1.3%. Ileostomies were most common (64%), and 24.5% of the patients who underwent stoma surgery had perianal disease at end of follow-up. Within 5 years of diagnosis, 0.8% of the incident patients had a permanent stoma, and 0.05% had undergone proctectomy. The time from diagnosis to start of anti-TNF treatment decreased over calendar periods (P < .001).

Conclusions

Despite increasing use of anti-TNF and a low rate of proctectomy, the cumulative incidence of stoma formation within 5 years of Crohn’s disease diagnosis has not decreased from 2003 to 2019.
Editorial to Homoclinic snaking at 21: in memory of Patrick Woods
Authors: Champneys Alan
Published: October 2021

This editorial serves as an extended introduction to the Special Issue. It gives the context to homoclinic snaking, especially the contribution of Patrick Woods. A very brief summary of more recent developments serves as a motivation to each paper that follows.
Policy Signaling and Foreign Electoral Uncertainty: Implications for Currency Markets
Authors: Slaski Alexander
Published: October 2021

This paper examines the effects of foreign electoral shocks on currency markets. I develop a theory of signaling and uncertainty to explain why elections in countries with close economic ties should affect exchange rates. Methodologically, this paper focuses on several case studies, with the 2016 US election as a central case. I utilize an event analysis framework to measure the impact of the election on the Mexican peso by exploiting the plausible exogeneity of Donald Trump's tweets. I also measure changes in the peso using Trump's predicted chance of winning the election and show that the peso is weakest when Trump has the highest chance of winning the election. In addition, I include a series of robustness checks and analyses of other notable recent cases when electoral uncertainty affected currencies in other countries, including the 2018 Brazilian election. The results quantify the effect of foreign elections on exchange rates, building on the existing literature that focuses on how domestic elections shape currency markets. I conclude with a discussion of the external validity of the phenomenon demonstrated by the cases in the paper, charting future research on the topic and outlining ways to extend the findings.
Coup Agency and Prospects for Democracy
Authors: Albrecht Holger , Koehler Kevin , Schutz Austin
Published: October 2021

This research note introduces new global data on military coups. Conventional aggregate data so far have conflated two distinct types of coups. Military interventions by leading officers are coups “from above,” characterized by political power struggles within authoritarian elite coalitions where officers move against civilian elites, executive incumbents, and their loyal security personnel. By contrast, power grabs by officers from the lower and middle ranks are coups “from below,” where military personnel outside of the political elite challenge sitting incumbents, their loyalists, and the regime itself. Disaggregating coup types offers leverage to revise important questions about the causes and consequences of military intervention in politics. This research note illustrates that coup attempts from the top of the military hierarchy are much more likely to be successful than coups from the lower and middle ranks of the military hierarchy. Moreover, coups from the top recalibrate authoritarian elite coalitions and serve to sustain autocratic rule; they rarely produce an opening for a democratic transition. Successful coups from below, by contrast, can result in the breakdown of authoritarian regimes and generate an opening for democratic transitions.
First Report of Adult Aedes aegypti (Diptera: Culicidae) Resistance to Pyrethroids in Argentina
Authors: Harburguer Laura , Gonzalez Paula V , Zerba Eduardo
Published: October 2021

Severe human arboviral diseases can be transmitted by the mosquito Aedes aegypti (Linnaeus), including dengue, chikungunya, Zika, and yellow fever. Adult control using spatial sprays with adulticides is recommended only when dengue outbreaks occur. In Argentina, mainly pyrethroids, like cis-permethrin, have been used as an adulticide, especially since 2008. The evolution and spread of resistance to insecticides is a major concern for vector control. This study reports for the first time pyrethroid resistance in Ae. aegypti adults from Argentina, in the city of Salvador Mazza (Salta). WHO discriminating doses of 0.75% were used for permethrin, 0.05% for deltamethrin, and 5% for malathion. Also the discriminating dose for cis-permethrin (0.6%) was calculated and evaluated for the first time. We found a resistance ratio 50 (RR50) of 10.3 (9.7–10.4) for cis-permethrin, which is considered as high resistance. Our results also indicated resistance to deltamethrin (22.6% mortality) and permethrin (53.6% mortality), and a total susceptibility to malathion (100% mortality). Results from this study highlight the importance of the correct use of insecticides within an Integrated Vector Management (IVM) approach and of early detection of resistance to enable Ae. aegypti control in Argentina. More studies are needed to determine the spread of mosquito resistance to pyrethroids.
Predictions of TeV emission for a set of hard BL Lac objects
Authors: Paiano Simona , Treves Aldo , Franceschini Alberto , Falomo Renato
Published: October 2021

We focus our analysis on 55 BL Lac objects with a hard Fermi gamma-ray spectrum, and for which a redshift or a lower limit to it has been determined by a previous study of ours. We extrapolate the spectral fits given by the 4FGL catalogue to the VHE band (>0.1 TeV), which can be explored by imaging atmospheric Cherenkov telescopes. Furthermore, we take into account the absorption due to the extragalactic background light, strongly depending on the redshift. Finally, we compare our results with publicly available sensitivity curves for a selection of imaging atmospheric Cherenkov telescope arrays currently operating or under construction. From our extrapolations and simulations we find a large number of promising candidates for observation with the forthcoming Cherenkov Telescope Array observatory.
Controls for Phylogeny and Robust Analysis in Pareto Task Inference
Authors: Adler Miri , Tendler Avichai , Hausser Jean , Korem Yael , Szekely Pablo , Bossel Noa , Hart Yuval , Karin Omer , Mayo Avi , Alon Uri
Published: October 2021

Understanding the tradeoffs faced by organisms is a major goal of evolutionary biology. One of the main approaches for identifying these tradeoffs is Pareto task inference (ParTI). Two recent papers claim that results obtained in ParTI studies are spurious due to phylogenetic dependence (Mikami T, Iwasaki W. 2021. The flipping t-ratio test: phylogenetically informed assessment of the Pareto theory for phenotypic evolution. Methods Ecol Evol. 12(4):696–706) or hypothetical p-hacking and population-structure concerns (Sun M, Zhang J. 2021. Rampant false detection of adaptive phenotypic optimization by ParTI-based Pareto front inference. Mol Biol Evol. 38(4):1653–1664). Here, we show that these claims are baseless. We present a new method to control for phylogenetic dependence, called SibSwap, and show that published ParTI inference is robust to phylogenetic dependence. We show how researchers avoided p-hacking by testing for the robustness of preprocessing choices. We also provide new methods to control for population structure and detail the experimental tests of ParTI in systems ranging from ammonites to cancer gene expression. The methods presented here may help to improve future ParTI studies.
Complex Portal 2022: new curation frontiers
Authors: Meldal Birgit H M , Perfetto Livia , Combe Colin , Lubiana Tiago , Ferreira Cavalcante João Vitor , Bye-A-Jee Hema , Waagmeester Andra , del-Toro Noemi , Shrivastava Anjali , Barrera Elisabeth , Wong Edith , Mlecnik Bernhard , Bindea Gabriela , Panneerselvam Kalpana , Willighagen Egon , Rappsilber Juri , Porras Pablo , Hermjakob Henning , Orchard Sandra
Published: October 2021

The Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated, encyclopaedic database of macromolecular complexes with known function from a range of model organisms. It summarizes complex composition, topology and function along with links to a large range of domain-specific resources (i.e. wwPDB, EMDB and Reactome). Since the last update in 2019, we have produced a first draft complexome for Escherichia coli, maintained and updated that of Saccharomyces cerevisiae, added over 40 coronavirus complexes and increased the human complexome to over 1100 complexes that include approximately 200 complexes that act as targets for viral proteins or are part of the immune system. The display of protein features in ComplexViewer has been improved and the participant table is now colour-coordinated with the nodes in ComplexViewer. Community collaboration has expanded, for example by contributing to an analysis of putative transcription cofactors and providing data accessible to semantic web tools through Wikidata which is now populated with manually curated Complex Portal content through a new bot. Our data license is now CC0 to encourage data reuse. Users are encouraged to get in touch, provide us with feedback and send curation requests through the ‘Support’ link.
OnTheFly2.0: a text-mining web application for automated biomedical entity recognition, document annotation, network and functional enrichment analysis
Authors: Baltoumas Fotis A , Zafeiropoulou Sofia , Karatzas Evangelos , Paragkamian Savvas , Thanati Foteini , Iliopoulos Ioannis , Eliopoulos Aristides G , Schneider Reinhard , Jensen Lars Juhl , Pafilis Evangelos , Pavlopoulos Georgios A
Published: October 2021

Extracting and processing information from documents is of great importance as lots of experimental results and findings are stored in local files. Therefore, extracting and analyzing biomedical terms from such files in an automated way is absolutely necessary. In this article, we present OnTheFly2.0, a web application for extracting biomedical entities from individual files such as plain texts, office documents, PDF files or images. OnTheFly2.0 can generate informative summaries in popup windows containing knowledge related to the identified terms along with links to various databases. It uses the EXTRACT tagging service to perform named entity recognition (NER) for genes/proteins, chemical compounds, organisms, tissues, environments, diseases, phenotypes and gene ontology terms. Multiple files can be analyzed, whereas identified terms such as proteins or genes can be explored through functional enrichment analysis or be associated with diseases and PubMed entries. Finally, protein–protein and protein–chemical networks can be generated with the use of STRING and STITCH services. To demonstrate its capacity for knowledge discovery, we interrogated published meta-analyses of clinical biomarkers of severe COVID-19 and uncovered inflammatory and senescence pathways that impact disease pathogenesis. OnTheFly2.0 currently supports 197 species and is available at http://bib.fleming.gr:3838/OnTheFly/ and http://onthefly.pavlopouloslab.info.
Implicit–explicit gradient of nondual awareness or consciousness as such
Authors: Josipovic Zoran
Published: October 2021

Consciousness is multi-dimensional but is most often portrayed with a two-dimensional (2D) map that has global levels or states on one axis and phenomenal contents on the other. On this map, awareness is conflated either with general alertness or with phenomenal content. This contributes to ongoing difficulties in the scientific understanding of consciousness. Previously, I have proposed that consciousness as such or nondual awareness—a basic non-conceptual, non-propositional awareness in itself free of subject-object fragmentation—is a unique kind that cannot be adequately specified by this 2D map of states and contents. Here, I propose an implicit–explicit gradient of nondual awareness to be added as the z-axis to the existing 2D map of consciousness. This gradient informs about the degree to which nondual awareness is manifest in any experience, independent of the specifics of global state or local content. Alternatively, within the multi-dimensional state space model of consciousness, nondual awareness can be specified by several vectors, each representing one of its properties. In the first part, I outline nondual awareness or consciousness as such in terms of its phenomenal description, its function and its neural correlates. In the second part, I explore the implicit–explicit gradient of nondual awareness and how including it as an additional axis clarifies certain features of everyday dualistic experiences and is especially relevant for understanding the unitary and nondual experiences accessed via different contemplative methods, mind-altering substances or spontaneously.
O022 Long-term cardiovascular risk in obstructive sleep apnoea: a sleep clinic cohort study
Authors: Shenoy B , Singh B , Cadby G , McQuillan B , Hung J , Rea S , Walsh J , Eastwood P , Hillman D , Mukherjee S , Palmer L , McArdle N
Published: October 2021

The relationship between obstructive sleep apnoea (OSA) and the development of long-term cardiovascular disease (CVD) is incompletely understood. We therefore investigated the impact of OSA severity, assessed by polysomnographic (PSG) metrics, on the development of long-term CVD in a sleep clinic cohort.

Participants in the Western Australian Sleep Health Study, who attended a sleep clinic at a tertiary hospital between 2006 and 2010, were linked to state health administrative data from 1969 to 2016. Cox regression was used to investigate associations between standard PSG metrics of OSA severity (including the apnoea-hypopnoea index [AHI], time with oxygen saturation <90% [T90], and arousal index) and a CVD composite outcome (hospitalisation due to coronary heart disease, heart failure, stroke, or atrial fibrillation), controlling for baseline CVD risk factors such as age, sex, and body mass index (BMI).

A total of 4067 participants were included: mean (SD) age of 50.6 (14.0) years, with 60.8% men. The mean BMI was 32.7 (7.7) kg/m². Over a median follow-up of 7.3 years, 584 (14.4%) participants developed the composite CVD outcome. Following adjustment for risk factors, independent predictors of incident CVD were an AHI ≥30 events/hour (hazard ratio [HR], 1.21; 95% CI, 1.02–1.45), log (T90 + 1) (HR, 1.16; 95% CI, 1.03–1.31), and the periodic limb movements of sleep index (PLMSI) (HR, 1.01; 95% CI, 1.00–1.01).

We demonstrated independent effects of AHI, hypoxaemia, and PLMSI on incident CVD in this large sleep clinic cohort, suggesting multi-faceted aspects of disrupted sleep influence cardiovascular risk in OSA.
O030 Changes in sleep-wake patterns, circadian timing, and mood in Australian teens during the COVID-19 pandemic
Authors: Stone J , Phillips A , Wiley J , Chachos E , Hand A , Lu S , Carskadon M , Klerman E , Lockley S , Bei B , Rajaratnam S
Published: October 2021

During the COVID-19 pandemic, schools rapidly transitioned from in-person to remote learning. We examined sleep- and mood-related changes in early adolescents, before and after this transition to assess the impact of in-person vs. remote learning. Sleep-wake timing was measured using wrist-actigraphy and sleep diaries over 1–2 weeks in Year 7 students (age M±SD =12.79±0.42 years) during in-person learning (n=28) and remote learning (n=58; n=27 were studied in both conditions). Circadian timing was measured under a single condition in each individual using salivary melatonin (Dim Light Melatonin Onset; DLMO). Online surveys assessed mood (PROMIS Pediatric Anxiety and Depressive Symptoms) and sleepiness (Epworth Sleepiness Scale – Child and Adolescent) in each condition. During remote vs. in-person learning: (i) on school days, students went to sleep 26 min later and woke 49 min later, resulting in 22 min longer sleep duration (all p<0.0001); (ii) DLMO time did not differ significantly between conditions, although participants woke at a later relative circadian phase (43 minutes, p=0.03) during remote learning; (iii) participants reported significantly lower sleepiness (p=0.048) and lower anxiety symptoms (p=0.006). Depressive symptoms did not differ between conditions. Changes in mood symptoms were not mediated by changes in sleep timing. Although remote learning had the same school start times as in-person learning, removing morning commutes likely enabled adolescents to sleep longer, wake later, and to wake at a later circadian phase. These results indicate that remote learning, or later school start times, may extend sleep duration and improve some subjective symptoms in adolescents.
P044 Primary care management of chronic insomnia by general practitioners: an Australian perspective
Authors: Grivell N , Haycock J , Redman A , Saini B , Vakulin A , Lack L , Lovato N , Sweetman A , Zwar N , Stocks N , Franks O , Mukherjee S , Adams R , McEvoy R , Hoon E
Published: October 2021

Introduction

Chronic insomnia is a common sleep disorder, with an estimated 15% of Australian adults reporting symptoms of insomnia. Australian general practitioner (GP) guidelines recommend cognitive behavioural therapy for insomnia (CBTi) as first-line treatment for insomnia however research suggests that GPs instead rely heavily on sleep hygiene and pharmacotherapy. GPs commonly provide treatment for insomnia; however, little is known about the experiences of Australian GPs and their interest when managing patients with insomnia. This study was conducted to explore the perspectives of GPs towards insomnia management and to identify factors that could influence the implementation of new models of insomnia care within general practice.

Methods

A pragmatic, inductive qualitative study. Purposive sampling was used to recruit 28 Australian GPs varying in age, experience, and distance from specialist sleep services. Semi-structured interviews were conducted, and data were analysed using thematic analysis.

Results

Three themes were identified: 1) Responsibility for insomnia care; 2) Complexities in managing insomnia; and 3) Navigating treatment pathways. Whilst GPs accepted insomnia care as part of their role, they often found it difficult to provide evidence-based care within the time and funding limitations of general practice. Co-morbidity of mental health conditions and insomnia, and long-term use of benzodiazepines presented challenges for GPs. GPs’ knowledge and experience of CBTi and access to specialised referral pathways for insomnia was limited.

Discussion

Insomnia presents complexities for GPs. Education about insomnia treatments, funding that enables recommended treatment, and pathways to specialist services would support insomnia management within general practice.