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The authors describe a dynamic surface instability between impacting materials, showing that a region of mixing grows between two media. The study implies that this can explain mixed compositions and textures in certain meteorites.

Abstract In situ x-ray diffraction measurements and inverse Monte Carlo simulations of pair distribution functions were used to characterize the local structure of molten AuGa2 up to 16 GPa and 940 K. Our results document systematic changes in liquid structure due to a combination of bond compression and coordination increase. Empirical potential structure refinement shows the first-neighbor coordination of Ga around Au and of Au around Ga to increase from about 8 to 10 and 4 to 5, respectively between 0 and 16 GPa, and the inferred changes in liquid structure can explain the observed melting-point depression of AuGa2 up to 5 GPa. As intermetallic AuGa2 is an analogue for metallic SiO2 at much higher pressures, our results imply that structural changes documented for non-metallic silicate melts below 100 GPa are followed by additional coordination changes in the metallic state at pressures in the 0.2–1 TPa range achieved inside large planets.

OBJECTIVE: to explore the feelings of depression during pregnancy of a local sample of women living in an area of socio-economic deprivation, and to identify the support mechanisms that they report as personally or potentially helpful for antenatal depression. DESIGN: a retrospective study using a qualitative approach, informed by constructivism, to explore the participants' individual experiences of depression during pregnancy. Data were collected via tape-recorded semi-structured interviews. SETTING: a socio-economically deprived area in North London, UK, identified as a Sure Start Local Programme providing local services specifically designed for socially disadvantaged families with children aged 0-4 years. PARTICIPANTS: a self-selected sample of nine women aged 23-40 years, from a variety of ethnic backgrounds, who retrospectively admitted to feeling low or depressed during pregnancy. All the participants had had a baby more than 6 weeks previously and less than 1 year before the start of the study. FINDINGS: despite different cultural and ethnic backgrounds, the participants shared similar feelings of emotional isolation that seemed to contribute largely to their experience of antenatal depression. Partner support (or lack of it) seemed to be crucial to the women's psychological well-being during pregnancy. For some of these women, the research interview was the first opportunity to talk about their needs and feelings during pregnancy. Potentially helpful mechanisms for support were identified by the participants and were judged to be relatively simple to introduce, involving connecting with other women via peer support and having 'somewhere to go' to meet others during pregnancy. IMPLICATIONS FOR PRACTICE: some women do not disclose their feelings of depression during pregnancy, with potentially damaging effects on both the family and the baby. Feelings of loss and emotional isolation may occur, which could be partly alleviated by providing models of midwifery care that offer continuity of carer. Isolated and vulnerable women require increased midwifery resources, and partners may also have particular needs for support and adjustment, which currently remain unmet and need further research. Many 'low tech' interventions aimed at supporting women with antenatal depression could be developed, including peer support, which may offer realistic models of social capital and community empowerment in the new Children's Centres in England and Wales. [ABSTRACT FROM AUTHOR]

Background With over a decade of directed efforts to reduce sex and racial differences in coronary artery bypass grafting (CABG) utilization, and post‐CABG outcomes, we sought to evaluate how the use of CABG and its outcomes have evolved in different sex and racial subgroups. Methods and Results Using data on all fee‐for‐service Medicare beneficiaries undergoing CABG in the United States from 1999 to 2014, we examined differences by sex and race in calendar‐year trends for CABG utilization and post‐CABG outcomes (in‐hospital, 30‐day, and 1‐year mortality and 30‐day readmission). A total of 1 863 719 Medicare fee‐for‐service beneficiaries (33.6% women, 4.6% black) underwent CABG from 1999 to 2014, with a decrease from 611 to 245 CABG procedures per 100 000 person‐years. Men compared with women and whites compared with blacks had higher CABG utilization, with declines in all subgroups. Higher post‐CABG annual declines in mortality (95% confidence interval) were observed in women (in‐hospital, −2.70% [−2.97, −2.44]; 30‐day, −2.29% [−2.54, −2.04]; and 1‐year mortality, −1.67% [−1.88, −1.46]) and blacks (in‐hospital, −3.31% [−4.02, −2.60]; 30‐day, −2.80% [−3.49, −2.12]; and 1‐year mortality, −2.38% [−2.92, −1.84]), compared with men and whites, respectively. Mortality rates remained higher in women and blacks, but differences narrowed over time. Annual adjusted 30‐day readmission rates remained unchanged for all patient groups. Conclusions Women and black patients had persistently higher CABG mortality than men and white patients, respectively, despite greater declines over the time period. These findings indicate progress, but also the need for further progress.

We provide experimental and theoretical evidence for a pressure-induced Mott insulator-metal transition in Fe_{2}O_{3} characterized by site-selective delocalization of the electrons. Density functional plus dynamical mean-field theory (DFT+DMFT) calculations, along with Mössbauer spectroscopy, x-ray diffraction, and electrical transport measurements on Fe_{2}O_{3} up to 100 GPa, reveal this site-selective Mott transition between 50 and 68 GPa, such that the metallization can be described by (^{VI}Fe^{3+HS})_{2}O_{3} [R3[over ¯]c structure][under →]50 GPa(^{VIII}Fe^{3+HS} ^{VI}Fe^{M})O_{3} [P2_{1}/n structure][under →]68 GPa(^{VI}Fe^{M})_{2}O_{3}[Aba2/PPv structure]. Within the P2_{1}/n crystal structure, characterized by two distinct coordination sites (VI and VIII), we observe equal abundances of ferric ions (Fe^{3+}) and ions having delocalized electrons (Fe^{M}), and only at higher pressures is a fully metallic high-pressure structure obtained, all at room temperature. Thereby, the transition is characterized by delocalization/metallization of the 3d electrons on half the Fe sites, with a site-dependent collapse of local moments. Above approximately 50 GPa, Fe_{2}O_{3} is a strongly correlated metal with reduced electron mobility (large band renormalizations) of m^{*}/m∼4 and 6 near the Fermi level. Importantly, upon decompression, we observe a site-selective (metallic) to conventional Mott insulator phase transition (^{VIII}Fe^{3+HS} ^{VI}Fe^{M})O_{3}[under →]50 GPa(^{VIII}Fe^{3+HS} ^{VI}Fe^{3+HS})O_{3} within the same P2_{1}/n structure, indicating a decoupling of the electronic and lattice degrees of freedom. Our results offer a model for understanding insulator-metal transitions in correlated electron materials, showing that the interplay of electronic correlations and crystal structure may result in rather complex behavior of the electronic and magnetic states of such compounds.

The management of lakes requires the definition of physico-chemical thresholds to be used for ecosystem preservation or restoration. According to the European Water Framework Directive, the limits between physico-chemical quality classes must be set consistently with biological quality elements. One way to do this consists in analyzing the response of aquatic communities to environmental gradients across monitoring sites and in identifying ecological community thresholds, i.e. zones in the gradients where the species turnover is the highest. In this study, fish data from 196 lakes in France were considered to derive ecological thresholds using the multivariate method of gradient forest. The analysis was performed on 25 species and 36 environmental parameters. The results revealed the highest importance of maximal water temperature in the distribution of fish species. Other important parameters included geographical factors, dissolved organic carbon concentration and water transparency, while nutrients appeared to have low influence. In spite of the diversity of species responses to the gradients, community thresholds were detected in the gradients of the most important physico-chemical parameters and of total phosphorus and nitrate concentrations as well. The thresholds identified in such macroecological study may highlight new patterns of species natural distribution and improve niche characterization. Moreover, when factors that may be influenced by human activities are involved, the thresholds could be used to set environmental standards for lake preservation.

Abstract The trial on endovascular management of unruptured intracranial aneurysms (TEAM), a prospective randomized trial comparing coiling and conservative management, initiated in September 2006, was stopped in June 2009 because of poor recruitment (80 patients). Aspects of the trial design that may have contributed to this failure are reviewed in the hope of identifying better ways to successfully complete this special type of pragmatic trial which seeks to test two strategies that are in routine clinical use. Cultural, conceptual and bureaucratic hurdles and difficulties obstruct all trials. These obstacles are however particularly misplaced when the trial aims to identify what a good medical practice should be. A clean separation between research and practice, with diverging ethical and scientific requirements, has been enforced for decades, but it cannot work when care needs to be provided in the presence of pervasive uncertainty. Hence valid and robust scientific methods need to be legitimately re-integrated into clinical practice when reliable knowledge is in want. A special status should be reserved for what we would call 'clinical care trials', if we are to practice in a transparent and prospective fashion a medicine that leads to demonstrably better patient outcomes.

Abstract The management of patients with unruptured aneurysms remains controversial. Patients with unruptured aneurysms may suffer intracranial haemorrhage, but the incidence of this event is still debated; endovascular treatment may prevent rupture, but involves immediate risks. Hence, the balance of risks and benefits of endovascular treatment is uncertain. Here, we report the design of the TEAM trial, the first international, randomized, controlled trial comparing conservative management with endovascular treatment. Primary endpoint is mortality and morbidity (modified Rankin Score ≥ 3) from intracranial haemorrhage or treatment. Secondary endpoints include incidence of hemorrhagic events, morbidity related to endovascular coiling, morphological results, overall clinical outcome and quality of life. Statistical tests compare between probabilities at 5- and 10-years of 1/mortality from haemorrhage related to the lesion, excluding per-operative complications; 2/mortality from haemorrhage or from complications of treatment; 3/combined disease or treatment related mortality and morbidity in the absence of other causes of death or disability. The study will be conducted in 60 international centres and will enrol 2,002 patients equally divided between the two groups, a size sufficient to achieve 80% power at a 0.0167 significance to detect differences in 1) disease or treatment-related poor outcomes from 7–9% to 3–5%; 2) overall mortality from 16 to 11%. Duration of the study is 14 years, the first three years being for patient recruitment plus a minimum of 10 years of follow-up. The TEAM trial thus offers a means to reconcile the introduction of a new approach with the necessity to acknowledge uncertainties. Trial registration Current Controlled Trials ISRCTN62758344 http://www.controlled-trials.com

Building strong partnerships between academic institutions and community health agencies requires a commitment to time, tactful communications, talented leaders, and trust. The essential elements of partnership building are discussed based on experiences of a mid-Atlantic nursing center, an academic health center established to provide care to underserved and vulnerable populations. [ABSTRACT FROM AUTHOR]

Metamaterials are emerging as an unconventional platform to perform computing abstractions in physical systems by processing environmental stimuli into information. While computation functions have been demonstrated in mechanical systems, they rely on compliant mechanisms to achieve predefined states, which impose inherent design restrictions that limit their miniaturization, deployment, reconfigurability, and functionality. Here, a metamaterial system is described based on responsive magnetoactive Janus particle (MAJP) swarms with multiple programmable functions. MAJPs are designed with tunable structure and properties in mind, that is, encoded swarming behavior and fully reversible switching mechanisms, to enable programmable dynamic display, non-volatile and semi-volatile memory, Boolean logic, and information encryption functions in soft, wearable devices. MAJPs and their unique swarming behavior open new functions for the design of multifunctional and reconfigurable display devices, and constitute a promising building block to develop the next generation of soft physical computing devices, with growing applications in security, defense, anti-counterfeiting, camouflage, soft robotics, and human-robot interaction., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Protein nanoparticles are an attractive class of materials for nanomedicine applications due to the intrinsic biocompatibility, biodegradability, and intrinsic functionality of their constituent proteins. Despite the clinical success of select protein nanoparticles, this class of nanocarriers remains understudied and underdeveloped compared to lipid and polymer nanoparticles due to challenges related to formulation optimization, large design space, and their structural complexity. In this work, a modular strategy for protein nanoparticle preparation based on the concept of photoreactive jetting is introduced. The process relies on continuous ultraviolet irradiation during electrohydrodynamic (EHD) jetting of protein solutions that contain a homobifunctional photocrosslinker. Protein nanoparticles exhibit nanogel-like architectures comprised of proteins that are linked via synthetic moieties. Compared to conventional protein nanoparticles, this method reduces nanoparticle processing times to minutes, rather than hours to days. The inclusion of an emissive structural motif as the molecular scaffold of the photocrosslinker is used to study the supramolecular architecture of the stable nanoparticles via time-resolved fluorescence spectroscopy., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

We present a modular strategy to synthesize nanoparticle sensors equipped with dithiomaleimide-based, fluorescent molecular reporters capable of discerning minute changes in interparticle chemical environments based on fluorescence lifetime analysis. Three types of nanoparticles were synthesized with the aid of tailor-made molecular reporters, and it was found that protein nanoparticles exhibited greater sensitivity to changes in the core environment than polymer nanogels and block copolymer micelles. Encapsulation of the hydrophobic small-molecule drug paclitaxel (PTX) in self-reporting protein nanoparticles induced characteristic changes in fluorescence lifetime profiles, detected via time-resolved fluorescence spectroscopy. Depending on the mode of drug encapsulation, self-reporting protein nanoparticles revealed pronounced differences in their fluorescence lifetime signatures, which correlated with burst- vs diffusion-controlled release profiles observed in previous reports. Self-reporting nanoparticles, such as the ones developed here, will be critical for unraveling nanoparticle stability and nanoparticle-drug interactions, informing the future development of rationally engineered nanoparticle-based drug carriers.

Transfer of learning refers to successful application of previously acquired knowledge or skills to novel settings. Although working memory (WM) is thought to play a role in transfer learning, direct evidence of the effect of limitations in WM on transfer learning is lacking. To investigate, we used an acquired equivalence paradigm that included tests of association and transfer learning. The effects of imposing an acute WM limitation on young adults was tested (within-subjects design: N = 27 adults; M age  = 24 years) by conducting learning transfer tests concurrent with a secondary task that required carrying a spatial WM load when performing the learned/transfer trial (Load condition) to acutely limit WM resources or no WM load (No-Load condition; WM was unloaded prior to performing the learned/transfer trial). Analyses showed that although success on the transfer trials was high in the No-Load condition, performance dropped to chance in the Load condition. Performance on tests of learned associations remained high in both conditions. These results indicate that transfer of learning depends on access to WM resources and suggest that even healthy young individuals may be affected in their ability to cross-utilize knowledge when cognitive resources become scarce, such as when engaging in two tasks simultaneously (e.g., using satellite navigation while driving)., (© 2023. The Author(s).)

The potential of therapeutically loaded nanoparticles (NPs) has been successfully demonstrated during the last decade, with NP-mediated nonviral gene delivery gathering significant attention as highlighted by the broad clinical acceptance of mRNA-based COVID-19 vaccines. A significant barrier to progress in this emerging area is the wild variability of approaches reported in published literature regarding nanoparticle characterizations. Here, we provide a brief overview of the current status and outline important concerns regarding the need for standardized protocols to evaluate NP uptake, NP transfection efficacy, drug dose determination, and variability of nonviral gene delivery systems. Based on these concerns, we propose wide adherence to multimodal, multiparameter, and multistudy analysis of NP systems. Adoption of these proposed approaches will ensure improved transparency, provide a better basis for interlaboratory comparisons, and will simplify judging the significance of new findings in a broader context, all critical requirements for advancing the field of nonviral gene delivery., (Copyright © 2023, Yao et al.)

Introduction: Oral squamous cell carcinoma (OSCC), is associated with high morbidity and mortality. Preemptive interventions have been postulated to provide superior therapeutic options, but their implementation has been restricted by the availability of broadly applicable local delivery systems., Methods: We address this challenge by engineering a delivery vehicle, Janus nanoparticles (JNP), that combine the dual mucoadhesive properties of a first cationic chitosan compartment with a second hydrophobic poly(lactide-co-glycolide) release compartment. JNP are designed to avoid rapid mucus clearance while ensuring stable loading and controlled release of the IL-6 receptor antagonist, tocilizumab (TCZ)., Results: The JNP featured defined and monodispersed sizes with an average diameter of 327 nm and a PDI of 0.245, high circularities above 0.90 and supported controlled release of TCZ and effective internalization by oral keratinocytes. TCZ released from JNP retained its biological activity and effectively reduced both, soluble and membrane-bound IL-6Rα (71% and 50%). In full-thickness oral mucosal explants, 76% of the JNP breached the stratum corneum and in 41% were observed in the basal cell layer indicating excellent mucopenetrating properties. When tested in an aggressive OSCC xenograft model, TCZ-loaded JNP showed high levels of xenograft inhibition and outperformed all control groups with respect to inhibition of tumor cell proliferation, reduction in tumor size and reduced expression of the proto-oncogene ERG., Conclusion: By combining critically required, yet orthogonal properties within the same nanoparticle design, the JNP in this study, demonstrate promise as precision delivery platforms for intraoral field-coverage chemoprevention, a vastly under-researched area of high clinical importance., (© 2022. The Author(s).)

Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue-to-bone interfaces. Inspired by the hierarchical structure of native periodontal tissues, tissue engineering technology provides unique opportunities to coordinate multiple cell types into scaffolds that mimic the natural periodontal structure in vitro. In this study, we designed and fabricated highly ordered multicompartmental scaffolds by melt electrowriting, an advanced 3-dimensional (3D) printing technique. This strategy attempted to mimic the characteristic periodontal microenvironment through multicompartmental constructs comprising 3 tissue-specific regions: 1) a bone compartment with dense mesh structure, 2) a ligament compartment mimicking the highly aligned periodontal ligaments (PDLs), and 3) a transition region that bridges the bone and ligament, a critical feature that differentiates this system from mono- or bicompartmental alternatives. The multicompartmental constructs successfully achieved coordinated proliferation and differentiation of multiple cell types in vitro within short time, including both ligamentous- and bone-derived cells. Long-term 3D coculture of primary human osteoblasts and PDL fibroblasts led to a mineral gradient from calcified to uncalcified regions with PDL-like insertions within the transition region, an effect that is challenging to achieve with mono- or bicompartmental platforms. This process effectively recapitulates the key feature of interfacial tissues in periodontium. Collectively, this tissue-engineered approach offers a fundament for engineering periodontal tissue constructs with characteristic 3D microenvironments similar to native tissues. This multicompartmental 3D printing approach is also highly compatible with the design of next-generation scaffolds, with both highly adjustable compartmentalization properties and patient-specific shapes, for multitissue engineering in complex periodontal defects.

Nanoparticle-based delivery of therapeutics to the brain has had limited clinical impact due to challenges crossing the blood-brain barrier (BBB). Certain cells, such as monocytes, possess the ability to migrate across the BBB, making them attractive candidates for cell-based brain delivery strategies. In this work, we explore nanoparticle design parameters that impact both monocyte association and monocyte-mediated BBB transport. We use electrohydrodynamic jetting to prepare nanoparticles of varying sizes, compositions, and elasticity to address their impact on uptake by THP-1 monocytes and permeation across the BBB. An in vitro human BBB model is developed using human cerebral microvascular endothelial cells (hCMEC/D3) for the assessment of migration. We compare monocyte uptake of both polymeric and synthetic protein nanoparticles (SPNPs) of various sizes, as well as their effect on cell migration. SPNPs (human serum albumin/HSA or human transferrin/TF) are shown to promote increased monocyte-mediated transport across the BBB over polymeric nanoparticles. TF SPNPs (200 nm) associate readily, with an average uptake of 138 particles/cell. Nanoparticle loading is shown to influence the migration of THP-1 monocytes. The migration of monocytes loaded with 200 nm TF and 200 nm HSA SPNPs was 2.3-fold and 2.1-fold higher than that of an untreated control. RNA-seq analysis after TF SPNP treatment suggests that the upregulation of several migration genes may be implicated in increased monocyte migration (ex. integrin subunits α M and α L). Integrin β 2 chain combines with either integrin subunit α M chain or integrin subunit α L chain to form macrophage antigen 1 and lymphocyte function-associated antigen 1 integrins. Both products play a pivotal role in the transendothelial migration cascade. Our findings highlight the potential of SPNPs as drug and/or gene delivery platforms for monocyte-mediated BBB transport, especially where conventional polymer nanoparticles are ineffective or otherwise not desirable.

Nanoparticles are frequently pursued as drug delivery carriers due to their potential to alter the pharmacological profiles of drugs, but their broader utility in nanomedicine hinges upon exquisite control of critical nanoparticle properties, such as shape, size, or monodispersity. Electrohydrodynamic (EHD) jetting is a probate method to formulate synthetic protein nanoparticles (SPNPs), but a systematic understanding of the influence of crucial processing parameters, such as protein composition, on nanoparticle morphologies is still missing. Here, we address this knowledge gap by evaluating formulation trends in SPNPs prepared by EHD jetting based on a series of carrier proteins and protein blends (hemoglobin, transferrin, mucin, or insulin). In general, blended SPNPs presented uniform populations with minimum diameters between 43 and 65 nm. Size distributions of as-jetted SPNPs approached monodispersity as indicated by polydispersity indices (PDI SEM ) ranging from 0.11-0.19. Geometric factor analysis revealed high circularities (0.82-0.90), low anisotropy (<1.45) and excellent roundness (0.76-0.89) for all SPNPs prepared via EHD jetting. Tentatively, blended SPNPs displayed higher circularity and lower anisotropy, as compared to single-protein SPNPs. Secondary statistical analysis indicated that blended SPNPs generally present combined features of their constituents, with some properties driven by the dominant protein constituent. Our study suggests SPNPs made from blended proteins can serve as a promising drug delivery carrier owing to the ease of production, the composition versatility, and the control over their size, shape and dispersity., (Copyright © 2022, Habibi et al.)

Authenticating valuable objects is widely assumed to involve protracted scrutiny for detection of reproduction flaws. Yet, accurate authentication of banknotes is possible within one second of viewing, suggesting that rapid neural processes may underpin counterfeit detection. To investigate, we measured event-related brain potentials (ERPs) in response to briefly viewed genuine or forensically recovered counterfeit banknotes presented in a visual oddball counterfeit detection task. Three ERP components, P1, P3, and extended P3, were assessed for each combination of banknote type (genuine, counterfeit) and overt response ("real", "fake"). P1 amplitude was greater for oddballs, demonstrating that the initial feedforward sweep of visual processing yields the essential information for differentiating genuine from counterfeit. A similar oddball effect was found for P3. The magnitude of this P3 effect was positively correlated with behavioural counterfeit sensitivity, although the corresponding correlation for P1 was not. For the extended P3, amplitude was greatest for correctly detected counterfeits and similarly small for missed counterfeits, incorrectly and correctly categorised genuine banknotes. These results show that authentication of complex stimuli involves a cascade of neural processes that unfolds in under a second, beginning with a very rapid sensory analysis, followed by a later decision stage requiring higher level processing., (© 2022. The Author(s).)

Experimental studies show that inflammation impairs the ability to interpret the mental state of another person, denoted theory of mind (ToM). The current study attempted a conceptual replication in states associated with elevated low-grade inflammation, i.e., high body weight and advanced age. Ninety young (M = 26.3 years, SD = 4.1) or older (M = 70.7 years, SD = 4.0) participants with either a normal body mass index (BMI) (M = 22.4, SD = 2.2) or high BMI (M = 33.1, SD = 3.8) completed the Reading the Mind in the Eyes Test (RMET) to assess emotion recognition. Plasma interleukin-6 (IL-6) level was measured to index low-grade inflammation. As anticipated, elevated IL-6 levels were found with higher BMI, although not with increased age. IL-6 was associated with poorer task performance, independent of potential demographic and health confounders (e.g., sex, education, smoking status, alcohol intake, presence of medical conditions, and medication intake). Analyses also revealed an interaction whereby young individuals with a high BMI showed worse RMET performance compared to their normal BMI counterparts, whereas the opposite pattern was found in older individuals. The present observational study replicated experimental results showing that elevated low-grade inflammation is correlated with a lower ability to infer the mental states of others. These findings suggest that also naturalistic conditions of (protracted) low-grade inflammation may alter emotion recognition., (Copyright © 2021 Elsevier Inc. All rights reserved.)

How does the brain combine information predictive of the value of a visually guided task (incentive value) with information predictive of where task-relevant stimuli may occur (spatial certainty)? Human behavioural evidence indicates that these two predictions may be combined additively to bias visual selection (Additive Hypothesis), whereas neuroeconomic studies posit that they may be multiplicatively combined (Expected Value Hypothesis). We sought to adjudicate between these two alternatives. Participants viewed two coloured placeholders that specified the potential value of correctly identifying an imminent letter target if it appeared in that placeholder. Then, prior to the target's presentation, an endogenous spatial cue was presented indicating the target's more likely location. Spatial cues were parametrically manipulated with regard to the information gained (in bits). Across two experiments, performance was better for targets appearing in high versus low value placeholders and better when targets appeared in validly cued locations. Interestingly, as shown with a Bayesian model selection approach, these effects did not interact, clearly supporting the Additive Hypothesis. Even when conditions were adjusted to increase the optimality of a multiplicative operation, support for it remained. These findings refute recent theories that expected value computations are the singular mechanism driving the deployment of endogenous spatial attention. Instead, incentive value and spatial certainty seem to act independently to influence visual selection.

Protein nanoparticles are a promising approach for nanotherapeutics, as proteins combine versatile chemical and biological function with controlled biodegradability. In this work, the development of an adaptable synthesis method is presented for synthetic protein nanoparticles (SPNPs) based on reactive electrojetting. In contrast to past work with electrohydrodynamic cojetting using inert polymers, the jetting solutions are comprised of proteins and chemically activated macromers, designed to react with each other during the processing step, to form insoluble nanogel particles. SPNPs made from a variety of different proteins, such as transferrin, insulin, or hemoglobin, are stable and uniform under physiological conditions and maintain monodisperse sizes of around 200 nm. SPNPs comprised of transferrin and a disulfide containing macromer are stimuli-responsive, and serve as markers of oxidative stress within HeLa cells. Beyond isotropic SPNPs, bicompartmental nanoparticles containing human serum albumin and transferrin in two distinct hemispheres are prepared via reactive electrojetting. This novel platform provides access to a novel class of versatile protein particles with nanoscale architectures that i) can be made from a variety of proteins and macromers, ii) have tunable biological responses, and iii) can be multicompartmental, a prerequisite for controlled release of multiple drugs., (© 2020 Wiley-VCH GmbH.)

Ensemble perception refers to awareness of average properties, e.g. size, of "noisy" elements that often comprise visual arrays in natural scenes. Here, we asked how ensemble perception might be influenced when some but not all array elements are associated with monetary reward. Previous studies show that reward associations can speed object processing, facilitate selection, and enhance working-memory maintenance, suggesting they may bias ensemble judgments. To investigate, participants reported the average element size of brief arrays of different-sized circles. In the learning phase, all circles had the same color, but different colors produced high or low performance-contingent rewards. Then, in an unrewarded test phase, arrays comprised three spatially inter-mixed subsets, each with a different color, including the high-reward color. In different trials, the mean size of the subset with the high-reward color was smaller, larger, or the same as the ensemble mean. Ensemble size estimates were significantly biased by the high-reward-associated subset, showing that value associations modulate ensemble perception. In the test phase of a second experiment, a pattern mask appeared immediately after array presentation to limit top-down processing. Not only was value-biasing eliminated, ensemble accuracy improved, suggesting that value associations distort consciously available ensemble representation via late high-level processing.

Illness is often accompanied by perceived cognitive sluggishness, a symptom that may stem from immune system activation. The current study used electroencephalography (EEG) to assess how inflammation affected three different distinct attentional processes: alerting, orienting and executive control. In a double-blinded placebo-controlled within-subjects design (20 healthy males, mean age = 24.5, SD = 3.4), Salmonella typhoid vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur) was used to induce transient mild inflammation, while a saline injection served as a placebo-control. Participants completed the Attention Network Test with concurrent EEG recorded 6 h post-injection. Analyses focused on behavioral task performance and on modulation of oscillatory EEG activity in the alpha band (9-12 Hz) for alerting as well as orienting attention and frontal theta band (4-8 Hz) for executive control. Vaccination induced mild systemic inflammation, as assessed by interleukin-6 (IL-6) levels. While no behavioral task performance differences between the inflammation and placebo condition were evident, inflammation caused significant alterations to task-related brain activity. Specifically, inflammation produced greater cue-induced suppression of alpha power in the alerting aspect of attention and individual variation in the inflammatory response was significantly correlated with the degree of alpha power suppression. Notably, inflammation did not affect orienting (i.e., alpha lateralization) or executive control (i.e., frontal theta activity). These results reveal a unique neurophysiological sensitivity to acute mild inflammation of the neural network that underpins attentional alerting functions. Observed in the absence of performance decrements, these novel findings suggest that acute inflammation requires individuals to exert greater cognitive effort when preparing for a task in order to maintain adequate behavioral performance., (Copyright © 2019. Published by Elsevier Inc.)

The established link between loneliness and poor health outcomes may stem from aberrant inflammatory regulation. The present study tested whether loneliness predicted the inflammatory response to a standardised in vivo immune challenge. Using a within-subjects double blind placebo-controlled design, 40 healthy men (mean age = 25, SD = 5) received a Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK) and placebo (saline) on two separate occasions. Loneliness was assessed using the R-UCLA loneliness scale. Regression analyses showed that those that reported feeling more lonely exhibited an elevated interleukin-6 response (β = 0.564, 95% confidence interval [0.003, 0.042], p < .05). This association withstood adjustment for potentially confounding variables, including age, sleep quality, socio-emotional factors, and health factors. The present findings are in line with evidence that loneliness may shift immune system responsivity, suggesting a potential biobehavioural pathway linking loneliness to impaired health., (Copyright © 2019. Published by Elsevier Inc.)

Stimuli that reliably herald the availability of rewards or punishers can acquire value associations, potentially imbuing them with emotional significance and attentional prioritization. Previous work has shown that an emotional stimulus (prime) presented just prior to an attention-demanding task disrupts performance in a lateralized manner that is independent of the prime's emotional valence. Here, we asked whether neutral stimuli with acquired value associations would similarly disrupt attention. In two experiments, adult participants first learned to associate specific face or chair stimuli with a high or low probability of either winning or losing points. These conditioned stimuli then served as primes in a speeded letter-search task. Primes with high versus low outcome probability, regardless of valence, slowed search for targets appearing in the left but not the right visual hemifield, mirroring previous results using emotional primes, and suggesting that motivational mechanisms that compete for control with non-emotional cognitive processes are right-lateralized in the human brain.

Inflammation (immune system activation) affects neuronal function and may have consequences for the efficiency and speed of functional brain processes. Indeed, unusually slow psychomotor speed, a measure predictive of behavioural performance and health outcomes, is found with obesity and ageing, two conditions also associated with chronic inflammation. Yet whether inflammation is the mediating factor remains unclear. Here, we assessed inflammation by indexing interleukin-6 level in blood and measured psychomotor speed as well as indices of selective visual attention in young (mean = 26 years) or old (mean = 71 years) adults (N = 83) who were either lean or currently significantly overweight (mean body mass index = 22.4 and 33.8, respectively). Inflammation was positively and significantly correlated with psychomotor speed, age, and body mass index but not with attention measures. Using mediation analyses we show for the first time that inflammation fully accounts for the significant psychomotor slowing found in those with high BMI. Moreover, we further show that age-related psychomotor slowing is partially mediated by inflammation. These findings support the proposal that reducing inflammation may mitigate weight- and age-related cognitive decline and thereby improve performance on daily tasks and health outcomes more generally.

Authentication is an important cognitive process used to determine whether one's initial identification of an object is corroborated by additional sensory information. Although authentication is critical for safe interaction with many objects, including food, websites, and valuable documents, the visual orienting strategies used to garner additional sensory data to support authentication remain poorly understood. When reliable visual cues to counterfeit cannot be anticipated, distributing fixations widely across an object's surface might be useful. However, strategic fixation of specific object-defining attributes would be more efficient and should lead to better authentication performance. To investigate, we monitored eye movements during a repetitive banknote authentication task involving genuine and counterfeit banknotes. Although fixations were distributed widely across the note prior to authentication decisions, preference for hard-to mimic areas and avoidance of easily mimicked areas was evident. However, there was a strong tendency to initially fixate the banknote's portrait, and only thereafter did eye movement control appear to be more strategic. Those who directed a greater proportion of fixations at hard-to-mimic areas and resisted more easily mimicked areas performed better on the authenticity task. The tendency to deploy strategic fixation improved with experience, suggesting that authentication benefits from precise visual orienting and refined categorisation criteria.

The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean age = 25, SD = 5 years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6 h 30 m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (p < .001), without fever, sickness symptoms (e.g., nausea, light-headedness), or mood changes (all p's > .21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (p < .05). RMET stimuli selected on valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Shape memory polymers (SMPs) are promising for non-invasive medical devices and tissue scaffolds, but are limited by a lack of visibility under clinical imaging. Fluorescent dyes are an alternative to radiocontrast agents in medical applications, they can be utilized in chemical sensors and monitors and may be anti-microbial agents. Thus, a fluorescent SMP could be a highly valuable biomaterial system. Here, we show that four fluorescent dyes (phloxine B (PhB), eosin Y (Eos), indocyanine green(IcG), and calcein (Cal)) can be crosslinked into the polymer backbone to enhance material optical properties without alteration of shape memory and thermomechanical properties. Examinations of the emission wavelengths of the materials compared with the dye solutions showed a slight red shift in the peak emissions, indicative of crosslinking of the material. Quantitative analysis revealed that PhB enabled visibility through 1 cm of blood and through soft tissue. We also demonstrate the utility of these methods in combination with radio-opaque microparticle additives and the use of laser-induced shape recovery to allow for rapid shape recovery below the glass transition temperature. The crosslinking of fluorescent dyes into the SMP enables tuning of physical properties and shape memory and independently of the fluorescence functionality. This fluorescent SMP biomaterial system allows for use of multiple imaging modalities with potential application in minimally invasive medical devices.

Unlabelled: In contrast to modification with conventional PEO-silanes (i.e. no siloxane tether), silicones with dramatically enhanced protein resistance have been previously achieved via bulk-modification with poly(ethylene oxide) (PEO)-silane amphiphiles α-(EtO)3Si(CH2)2-oligodimethylsiloxane13-block-PEOn-OCH3 when n=8 and 16 but not when n=3. In this work, their efficacy was evaluated in terms of optimal PEO-segment length and minimum concentration required in silicone. For each PEO-silane amphiphile (n=3, 8, and 16), five concentrations (5, 10, 25, 50, and 100μmol per 1g silicone) were evaluated. Efficacy was quantified in terms of the modified silicones' abilities to undergo rapid, water-driven surface restructuring to form hydrophilic surfaces as well as resistance to fibrinogen adsorption. Only n=8 and 16 were effective, with a lower minimum concentration in silicone required for n=8 (10μmol per 1g silicone) versus n=16 (25μmol per 1g silicone)., Statement of Significance: Silicone is commonly used for implantable medical devices, but its hydrophobic surface promotes protein adsorption which leads to thrombosis and infection. Typical methods to incorporate poly(ethylene oxide) (PEO) into silicones have not been effective due to the poor migration of PEO to the surface-biological interface. In this work, PEO-silane amphiphiles - comprised of a siloxane tether (m=13) and variable PEO segment lengths (n=3, 8, 16) - were blended into silicone to improve its protein resistance. The efficacy of the amphiphiles was determined to be dependent on PEO length. With the intermediate PEO length (n=8), water-driven surface restructuring and resulting protein resistance was achieved with a concentration of only 1.7wt%., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Nanoparticles (NPs) play expanding roles in biomedical applications including imaging and therapy, however, their long-term fate and clearance profiles have yet to be fully characterized in vivo. NP delivery via the airway is particularly challenging, as the clearance may be inefficient and lung immune responses complex. Thus, specific material design is required for cargo delivery and quantitative, noninvasive methods are needed to characterize NP pharmacokinetics. Here, biocompatible poly(acrylamidoethylamine)-b-poly(dl-lactide) block copolymer-based degradable, cationic, shell-cross-linked knedel-like NPs (Dg-cSCKs) were employed to transfect plasmid DNA. Radioactive and optical beacons were attached to monitor biodistribution and imaging. The preferential release of cargo in acidic conditions provided enhanced transfection efficiency compared to non-degradable counterparts. In vivo gene transfer to the lung was correlated with NP pharmacokinetics by radiolabeling Dg-cSCKs and performing quantitative biodistribution with parallel positron emission tomography and Čerenkov imaging. Quantitation of imaging over 14 days corresponded with the pharmacokinetics of NP movement from the lung to gastrointestinal and renal routes, consistent with predicted degradation and excretion. This ability to noninvasively and accurately track NP fate highlights the advantage of incorporating multifunctionality into particle design., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Linearly arranged metal atoms that are embedded in discrete molecules have fascinated scientists across various disciplines for decades; this is attributed to their potential use in microelectronic devices on a submicroscopic scale. Luminescent oligonuclear Group 11 metal complexes are of particular interest for applications in molecular light-emitting devices. Herein, we describe the synthesis and characterization of a rare, homoleptic, and neutral linearly arranged tetranuclear Cu(I) complex that is helically bent, thus representing a molecular coil in the solid state. This tetracuprous arrangement dimerizes into a unique octanuclear assembly bearing a linear array of six Cu(I) centers with two additional bridging cuprous ions that constitute a central pseudo-rhombic Cu(I) 4 cluster. The crystal structure determinations of both complexes reveal close d(10) ⋅⋅⋅d(10) contacts between all cuprous ions that are adjacent to each other. The dynamic behavior in solution, DFT calculations, and the luminescence properties of these remarkable complexes are also discussed., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Shape memory polymer (SMP) foams have been developed for use in neurovascular occlusion applications. These materials are predominantly polyurethanes that are known for their biocompatibility and tunable properties. However, these polymers inherently lack X-ray visibility, which is a significant challenge for their use as implantable materials. Herein, low density, highly porous shape memory polyurethane foams were developed with tungsten nanoparticles dispersed into the foam matrix, at increasing concentrations, to serve as a radiopaque agent. Utilizing X-ray fluoroscopy sufficient visibility of the foams at small geometries was observed. Thermal characterization of the foams indicated altered thermal response and delayed foam actuation with increasing nanoparticle loading (because of restricted network mobility). Mechanical testing indicated decreased toughness and strength for higher loading because of disruption of the SMP matrix. Overall, filler addition imparted x-ray visibility to the SMP foams and allowed for tuned control of the transition temperature and actuation kinetics for the material.

Block copolymer micelles have been prepared with a dithiomaleimide (DTM) fluorophore located in either the core or shell. Poly(triethylene glycol acrylate)- b -poly( tert -butyl acrylate) (P(TEGA)- b -P( t BA)) was synthesized by RAFT polymerization, with a DTM-functional acrylate monomer copolymerized into either the core forming P( t BA) block or the shell forming P(TEGA) block. Self-assembly by direct dissolution afforded spherical micelles with R h of ca . 35 nm. Core-labeled micelles (CLMs) displayed bright emission (Φ f = 17%) due to good protection of the fluorophore, whereas shell-labeled micelles (SLMs) had lower efficiency emission due to collisional quenching in the solvated corona. The transition from micelles to polymer unimers upon dilution could be detected by measuring the emission intensity of the solutions. For the core-labeled micelles, the fluorescence lifetime was also responsive to the supramolecular state, the lifetime being significantly longer for the micelles (τ Av,I = 19 ns) than for the polymer unimers (τ Av,I = 9 ns). The core-labeled micelles could also self-report on the presence of a fluorescent hydrophobic guest molecule (Nile Red) as a result of Förster resonance energy transfer (FRET) between the DTM fluorophore and the guest. The sensitivity of the DTM fluorophore to its environment therefore provides a simple handle to obtain detailed structural information for the labeled polymer micelles. A case will also be made for the application superiority of core-labeled micelles over shell-labeled micelles for the DTM fluorophore.

Learning allows the value of motivationally salient events to become associated with stimuli that predict those events. Here, we asked whether value associations could facilitate visual working memory (WM), and whether such effects would be valence dependent. Our experiment was specifically designed to isolate value-based effects on WM from value-based effects on selective attention that might be expected to bias encoding. In a simple associative learning task, participants learned to associate the color of tinted faces with gaining or losing money or neither. Tinted faces then served as memoranda in a face identity WM task for which previously learned color associations were irrelevant and no monetary outcomes were forthcoming. Memory was best for faces with gain-associated tints, poorest for faces with loss-associated tints, and average for faces with no-outcome-associated tints. Value associated with 1 item in the WM array did not modulate memory for other items in the array. Eye movements when studying faces did not depend on the valence of previously learned color associations, arguing against value-based biases being due to differential encoding. This valence-sensitive value-conditioning effect on WM appears to result from modulation of WM maintenance processes., ((c) 2015 APA, all rights reserved).)

Although the performance of simple cognitive tasks can be enhanced if an incentive is provided, the mechanisms enabling such motivational control are not known. This study sought to uncover how mechanisms of attention and readiness are altered by reward-associated incentive stimuli. We measured EEG/ERP activity as human adults viewed a high- or low-incentive cue, experienced a short preparation interval, and then performed a simple visual search task to gain the predicted reward. Search performance was faster with high versus low incentives, and this was accompanied by distinct incentive-related EEG/ERP patterns at each phase of the task (incentive, preparation, and search). First, and most surprisingly, attention to high but not low incentive cues was actively suppressed, as indexed by a PD component in response to the incentive display. During the subsequent preparation interval, neural oscillations in the alpha frequency range were reduced after high-incentive cues, indicating heightened visual readiness. Finally, attentional orienting to the target in the search array was deployed with relatively little effort on high-incentive trials, as indexed by a reduced N2pc component. These results reveal the chain of events by which the brain's executive control mechanisms respond to incentives by altering the operation of multiple processing systems to produce optimal performance.

Three microparticle additives, tungsten (W), zirconium oxide (ZrO 2 ), and barium sulfate (BaSO 4 ) were selected to enhance the radio-opacity in shape memory polymer (SMP) foam biomaterials. The addition of filler causes no significant alterations of glass transition temperatures, density of the materials increases, pore diameter decreases, and total volume recovery decreases from approximately 70 times in unfilled foams to 20 times (4% W and 10% ZrO 2 ). The addition of W increases time to recovery; ZrO 2 causes little variation in time to shape recovery; BaSO 4 increases the time to recovery. On a 2.00 mean X-ray density (mean X.D.) scale, a GDC coil standard has a mean X.D. of 0.62; 4% W enhances the mean X.D. to 1.89, 10% ZrO 2 to 1.39 and 4% BaSO 4 to 0.74. Radio-opacity enhancing additives could be used to produce SMP foams with controlled shape memory kinetics, low density, and enhanced X -ray opacity for medical materials.

An antibiofouling polymer coating, combined with both zwitterionic and amphiphilic features, is engineered by a two-step modification of a commodity polymer. The surface properties of the resultant polymer coating can be easily tuned by varying the extent of cross-linking in the network. Higher antibiofouling efficiency was observed for these surfaces vs. an elastomeric polydimethylsiloxane standard (Sylgard 184) against the adsorption of biomacromolecules and a marine fouling organism ( Ulva zoospores) has been demonstrated. This design establishes a platform for the achievement of functionalized amphiphilic zwitterionic copolymers from relatively inexpensive starting materials via simple chemical manipulations.