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Psychedelic compounds have displayed antidepressant potential in both humans and rodents. Despite their promise, psychedelics can induce undesired effects that pose safety concerns and limit their clinical scalability. The rational development of optimized psychedelic-related medicines will require a full mechanistic understanding of how these molecules produce therapeutic effects. While the hallucinogenic properties of psychedelics are generally attributed to activation of serotonin 2A receptors (5-HT2ARs), it is currently unclear if these receptors also mediate their antidepressant effects as several nonhallucinogenic analogues of psychedelics with antidepressant-like properties have been developed. Moreover, many psychedelics exhibit promiscuous pharmacology, making it challenging to identify their primary therapeutic target(s). Here, we use a combination of pharmacological and genetic tools to demonstrate that activation of 5-HT2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. Our results suggest that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor.

Photoswitches capable of accessing two geometric states are highly desirable, especially if their design is modular and incorporates a pharmacophore tethering site. We describe a redox isomerization strategy for synthesizing p-formylazobenzenes from p-nitrobenzyl alcohol. The resulting azo-aldehydes can be readily converted to photoswitchable compounds with excellent photophysical properties using simple hydrazide click chemistry. As a proof of principle, we synthesized a photoswitchable surfactant enabling the photocontrol of an emulsion with exceptionally high spatiotemporal precision.

Marla C Dubinsky,1 Louise Newton,2 Laure Delbecque,3 Theresa Hunter,4 Aiste Guobyte,5 April N Naegeli,4 Shehan McFadden,5 Jill Donaldson,6 Tara Symonds,2 James D Lewis7 1Icahn School of Medicine, Mount Sinai, NY, USA; 2Clinical Outcomes Solutions, Folkestone, UK; 3Eli Lilly and Company, Brussels, Belgium; 4Eli Lilly and Company, Indianapolis, IN, USA; 5Clinical Outcomes Solutions, Chicago, IL, USA; 6Crohn’s and Colitis Foundation, New York, NY, USA; 7Perelman School of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Laure Delbecque, Principal Research Scientist, Eli Lilly and Company, Brussels, Belgium, Tel +32 (0)499 72 31 37, Email delbecque_laure@lilly.comPurpose: Achieving and maintaining symptom control is a key treatment goal in ulcerative colitis (UC). Bowel urgency is an important symptom of UC, thus measurement of urgency is critical. This research explored the patient experience of UC and “remission” in UC, with a focus on urgency, and cognitively debriefed the Urgency Numeric Rating Scale (NRS), including score interpretation and examination of meaningful improvement.Patients and Methods: Semi-structured hybrid concept elicitation and cognitive debriefing interviews with adults with moderately-severely active UC were conducted to explore experiences of UC and urgency, as well as examine meaningful improvement and score interpretation of the Urgency NRS. Purposive sampling was used to identify 20 eligible adult participants with UC. Concept elicitation data were analyzed using thematic analysis, and a deductive approach was used to analyze cognitive debriefing data. Thematic analysis was also applied to meaningful change-related data.Results: Twenty participants were interviewed (average age = 42.6 years old, 50% male); 14 with moderately active (70.0%) and 6 with severely active UC (30.0%). Disease remission was not consistently defined by participants and description varied in terms of definition (absence vs not complete absence of symptoms), duration (months vs days) and key symptoms to consider. Urgency was a prominent symptom for all participants, with 8 (40.0%) identifying it as the most bothersome aspect of UC. No issues were identified with the Urgency NRS. Participants were able to define different levels of urgency severity, describe how they relate to daily life impacts, and score them differently on the Urgency NRS. Participants were also able to reflect urgency improvement on the NRS and discuss how small changes in numeric ratings of urgency can reflect meaningful change in the symptom burden of their UC.Conclusion: The Urgency NRS is a content valid and interpretable measure to assess bowel urgency severity.Keywords: ulcerative colitis, qualitative, bowel urgency, content validity

We present deep, sub-arcsecond (⁠|$\sim$| 2000 au) resolution ALMA 0.82-mm observations of the former high-mass prestellar core candidate G11.92–0.61 MM2, recently shown to be an |$\sim$| 500 au-separation protobinary. Our observations show that G11.92–0.61 MM2, located in the G11.92–0.61 protocluster, lies on a filamentary structure traced by 0.82-mm continuum and N |$_2$| H |$^+$| (4-3) emission. The N |$_2$| H |$^+$| (4-3) spectra are multipeaked, indicative of multiple velocity components along the line of sight. To analyse the gas kinematics, we performed pixel-by-pixel Gaussian decomposition of the N |$_2$| H |$^+$| spectra using scousepy and hierarchical clustering of the extracted velocity components using acorns. Seventy velocity- and position-coherent clusters (called 'trees') are identified in the N |$_2$| H |$^+$| -emitting gas, with the eight largest trees accounting for |$\gt $| 60 per cent of the fitted velocity components. The primary tree, with |$\sim$| 20 per cent of the fitted velocity components, displays a roughly north–south velocity gradient along the filamentary structure traced by the 0.82-mm continuum. Analysing an |$\sim$| 0.17 pc-long substructure, we interpret its velocity gradient of |$\sim$| 10.5 km s |$^{-1}$|  pc |$^{-1}$| as tracing filamentary accretion towards MM2 and estimate a mass inflow rate of |$\sim 1.8\times 10^{-4}$| to 1.2 |$\times 10^{-3}$|  M |$_\odot$| yr |$^{-1}$|⁠. Based on the recent detection of a bipolar molecular outflow associated with MM2, accretion on to the protobinary is ongoing, likely fed by the larger scale filamentary accretion flows. If 50 per cent of the filamentary inflow reaches the protostars, each member of the protobinary would attain a mass of 8 M |$_\odot$| within |$\sim 1.6\times 10^5$| yr, comparable to the combined time-scale of the 70- μ m- and mid-infrared-weak phases derived for ATLASGAL-TOP100 massive clumps using chemical clocks. [ABSTRACT FROM AUTHOR]

Abstract Noncompliance is a central challenge for conservation, but in settings with limited access to behavioral data, it can be difficult to evaluate what drives compliance. Conservationists can measure and evaluate resource users' attitudes, and in so doing, leverage a complementary, nonbehavioral measure for evaluating compliance. In Greenland, wild Atlantic salmon (Salmo salar) fishers are under increasing regulatory pressure to report salmon catch because the majority of North Atlantic salmon stocks are classified as suffering. The objective of this study is to measure salmon catch reporting compliance, reporting behavior, and attitudes toward Greenland's salmon management. We surveyed Greenland's licensed salmon fishers, used an unmatched count technique to estimate the incidence of underreporting salmon catch, and linked salmon fishers' actual catch reports to their survey responses. In 2019, more than 84% of salmon fishers reported their catch and demonstrating high levels of compliance. We also found that salmon fishers did not indicate strong instrumental motivations for reporting, but exhibited moral obligations and normative, legitimacy‐based motivations to report catch. Salmon fishers found regulations to be fair, and that regulatory authorities were professional and acted honestly. Catch underreporting was also remarkably low, with 90–94% of respondents stating that they report all their catch. Joining together individuals' attitudinal and behavioral responses to conservation rules illustrates the benefits and limitations of expanding actor‐based theories of compliance. This case of already high levels of compliance offers empirical evidence for further improving fisheries compliance, and it also illustrates the limitations that fishery managers face when conserving a highly migratory species.

BackgroundPublic bicycle-sharing initiatives can act as health enhancement strategies among urban populations. The aim of the study was to determine which attitudes and perceptions of behavioural control toward cycling and a bicycle-sharing system distinguish commuters with a different adherence to bicycle commuting.MethodsThe recruitment process was conducted in 40 random points in Barcelona from 2011 to 2012. Subjects completed a telephone-based questionnaire including 27 attitude and perception statements. Based on their most common one-way commute trip and willingness to commute by bicycle, subjects were classified into Private Bicycle (PB), public bicycle or Bicing Bicycle (BB), Willing Non-bicycle (WN) and Non-willing Non-bicycle (NN) commuters. After reducing the survey statements through principal component analysis, a multinomial logistic regression model was obtained to evaluate associations between attitudinal and commuter sub-groups.ResultsWe included 814 adults in the analysis [51.6% female, mean (SD): age 36.6 (10.3) years]. BB commuters were 2.0 times [95% confidence interval (CI) = 1.1-3.7] less likely to perceive bicycle as a quick, flexible and enjoyable mode compared to PB. BB, WN and NN were 2.5 (95% CI = 1.46-4.24), 2.6 (95% CI = 1.53-4.41) and 2.3 times (95% CI = 1.30-4.10) more likely to perceive benefits of using public bicycles (bicycle maintenance and parking avoidance, low cost and no worries about theft and vandalism) than did PB.ConclusionWilling non-bicycle and public-bicycle commuters had more favourable perception toward public-shared bicycles compared to private cyclists. Hence, public bicycles may be the impetus for those willing to start bicycle commuting, thereby increasing physical activity levels.

Background: Cycling for transportation has become an increasingly important component of strategies to address public health, climate change, and air quality concerns in urban centers. Within this context, planners and policy makers would benefit from an improved understanding of available interventions and their relative effectiveness for cycling promotion. We examined predictors of bicycle commuting that are relevant to planning and policy intervention, particularly those amenable to short- and medium-term action. Methods: We estimated a travel mode choice model using data from a survey of 765 commuters who live and work within the municipality of Barcelona. We considered how the decision to commute by bicycle was associated with cycling infrastructure, bike share availability, travel demand incentives, and other environmental attributes (e.g., public transport availability). Self-reported and objective (GIS-based) measures were compared. Point elasticities and marginal effects were calculated to assess the relative explanatory power of the independent variables considered. Results: While both self-reported and objective measures of access to cycling infrastructure were associated with bicycle commuting, self-reported measures had stronger associations. Bicycle commuting had positive associations with access to bike share stations but inverse associations with access to public transport stops. Point elasticities suggested that bicycle commuting has a mild negative correlation with public transport availability (-0.136), bike share availability is more important at the work location (0.077) than at home (0.034), and bicycle lane presence has a relatively small association with bicycle commuting (0.039). Marginal effects suggested that provision of an employer-based incentive not to commute by private vehicle would be associated with an 11.3% decrease in the probability of commuting by bicycle, likely reflecting the typical emphasis of such incentives on public transport. Conclusions: The results provide evidence of modal competition between cycling and public transport, through the presence of public transport stops and the provision of public transport-oriented travel demand incentives. Education and awareness campaigns that influence perceptions of cycling infrastructure availability, travel demand incentives that encourage cycling, and policies that integrate public transport and cycling may be promising and cost-effective strategies to promote cycling in the short to medium term.

This paper proposes a novel origami-inspired adult diaper design that improves discretion by reducing sag and increasing wicking across the entire diaper pad. While other diapers rely on supporting elastics to reduce the sag of the diaper as a whole, this paper proposes an absorbent core that uses liquid activated shaping to take a specified shape. Origami-based folds are also incorporated into the diaper design to increase wicking performance. The paper introduces a disposable compliant mechanism waistband used to deploy the diaper, making it easier to put onto one’s body.

Abstract The formation of neutrophil extracellular traps (NETs), known as NETosis, was first observed as a novel immune response to bacterial infection, but has since been found to occur abnormally in a variety of other inflammatory disease states including cancer. Breast cancer is the most commonly diagnosed malignancy in women. In breast cancer, NETosis has been linked to increased disease progression, metastasis, and complications such as venous thromboembolism. NET-targeted therapies have shown success in preclinical cancer models and may prove valuable clinical targets in slowing or halting tumor progression in breast cancer patients. We will briefly outline the mechanisms by which NETs may form in the tumor microenvironment and circulation, including the crosstalk between neutrophils, tumor cells, endothelial cells, and platelets as well as the role of cancer-associated extracellular vesicles in modulating neutrophil behavior and NET extrusion. The prognostic implications of cancer-associated NETosis will be explored in addition to development of novel therapeutics aimed at targeting NET interactions to improve outcomes in patients with breast cancer.

Waste PCBs the core of e‐waste is rich in copper, tin, zinc, iron, and nickel. Leaching base metals from PCB used to be done in toxic, corrosive acidic/alkali mediums. In this work, an environmentally friendly method for leaching metals from thermally treated PCBs (TPCBs) of mobile phones was proposed using choline chloride based deep eutectic solvents (DES). DES selectivity and solubility of metals from metal oxides were the main screening criteria. FA−ChCl had the maximum solubility of Cu, Fe, and Ni, while Urea−ChCl had high Zn selectivity and solubility. Oxalic acid has high selectivity for Sn. FA−ChCl extracted Cu and Fe best at 16 h, 100 °C, and 1/30 g/mL. Urea−ChCl extracted Zn (90.4±2.9 %) from TPCBs at 100 °C, 21 h, 1/20 g/mL, and 400 rpm. Oxalic acid (1 M) removed 92.3±2.1 % Sn from TPCBs in 1 h at 80 °C and 1/20 g/mL. The shrinking core model‐based kinetic investigation of FA−ChCl for Cu extraction showed a diffusion‐controlled process. The proposed method is greener than mineral acids utilized for metal extraction. [ABSTRACT FROM AUTHOR]

Data-driven models are rising as an auspicious method for the geometrical design of materials and structural systems. Nevertheless, existing data-driven models customarily address the optimization of structural designs rather than metamaterial designs. Metamaterials are emerging as promising materials exhibiting tailorable and unprecedented properties for a wide spectrum of applications. In this paper, we develop a deep learning (DL) model based on a convolutional neural network (CNN) that predicts optimal metamaterial designs. The developed DL model non-iteratively optimizes metamaterials for either maximizing the bulk modulus, maximizing the shear modulus, or minimizing the Poisson's ratio (including negative values). The data are generated by solving a large set of inverse homogenization boundary values problems, with randomly generated geometrical features from a specific distribution. Such s data-driven model can play a vital role in accelerating more computationally expensive design problems, such as multiscale metamaterial systems.

Novel metal oxide nanoparticle (NP) contrast agents may offer safety and functionality advantages over conventional gadolinium-based contrast agents (GBCAs) for cancer diagnosis by magnetic resonance imaging. However, little is known about the behavior of metal oxide NPs, or of their effect, upon coming into contact with the innate immune system. As neutrophils are the body’s first line of defense, we sought to understand how manganese oxide and iron oxide NPs impact leukocyte functionality. Specifically, we evaluated whether contrast agents caused neutrophils to release web-like fibers of DNA known as neutrophil extracellular traps (NETs), which are known to enhance metastasis and thrombosis in cancer patients. Murine neutrophils were treated with GBCA, bare manganese oxide or iron oxide NPs, or poly(lactic-co-glycolic acid) (PLGA)-coated metal oxide NPs with different incorporated levels of poly(ethylene glycol) (PEG). Manganese oxide NPs elicited the highest NETosis rates and had enhanced neutrophil uptake properties compared to iron oxide NPs. Interestingly, NPs with low levels of PEGylation produced more NETs than those with higher PEGylation. Despite generating a low rate of NETosis, GBCA altered neutrophil cytokine expression more than NP treatments. This study is the first to investigate whether manganese oxide NPs and GBCAs modulate NETosis and reveals that contrast agents may have unintended off-target effects which warrant further investigation.

Fishery observers are prevalent actors in the global effort to reduce discards in fisheries, but there remains considerable uncertainty about how effective they are. We analyzed high-resolution logbook records of individual hauls ( n = 127 415) across five-and-a-half-years (2012–2018) for all of Greenland’s large-scale fisheries to determine if onboard fishery observers influence the mandatory reporting of discards. To do so, we used exact matching to compare reported discards for observed and unobserved hauls (each time a catch is recorded), thus controlling for systematic differences between monitored and unmonitored practices. After adjusting for variables that represent species caught, gear, vessel, owner, year, license, and location, we found that skippers systematically underreport discards when no observers are on board. Systematic underreporting was most pronounced in less valuable fisheries, in contrast to theoretical arguments in previous studies. The differences between reported discards from observed and unobserved fishing leads us to assume that onboard observers encourage more faithful logbook records. Thus, onboard observers play a vital role in improving information on the environmental impact of fishing and in turn, make a key contribution to sustainable fisheries management.

Electronic cigarettes are frequently viewed as a safer alternative to conventional cigarettes; however, evidence to support this perspective has not materialized. Indeed, the current literature reports that electronic cigarette use is associated with both acute lung injury and subclinical dysfunction to the lung and vasculature that may result in pathology following chronic use. E-cigarettes can alter vascular dynamics, polarize innate immune populations towards a proinflammatory state, compromise barrier function in the pulmonary endothelium and epithelium, and promote pre-oncogenic phenomena. This review will summarize the variety of e-cigarette products available to users, discuss current challenges in e-cigarette study design, outline the range of pathologies occurring in cases of e-cigarette associated acute lung injury, highlight disease supporting tissue- and cellular-level changes resulting from e-cigarette exposure, and briefly examine how these changes may promote tumorigenesis. Continued research of the mechanisms by which e-cigarettes induce pathology benefit users and clinicians by resulting in increased regulation of vaping devices, informing treatments for emerging diseases e-cigarettes produce, and increasing public awareness to reduce e-cigarette use and the onset of preventable disease.

We present a study of the physical and chemical properties of the Extended Green Object (EGO) G19.01−0.03 using sub-arcsecond angular resolution Atacama Large Millimetre/submillimetre Array (ALMA) 1.05 mm and Karl G. Jansky Very Large Array (VLA) 1.21 cm data. G19.01−0.03 MM1, the millimetre source associated with the central massive young stellar object (MYSO), appeared isolated and potentially chemically young in previous Submillimetre Array observations. In our ∼0.4 arcsec-resolution ALMA data, MM1 has four low-mass millimetre companions within 0.12 pc, all lacking maser or outflow emission, indicating they may be pre-stellar cores. With a rich ALMA spectrum full of complex organic molecules, MM1 does not appear chemically young, but has molecular abundances typical of high-mass hot cores in the literature. At the 1.05 mm continuum peak of MM1, N(CH3OH) = (2.22 ± 0.01) × 1018 cm−2 and |$T_{\mathrm{ex}} = 162.7\substack{+0.3 \\ -0.5}$|  K based on pixel-by-pixel Bayesian analysis of LTE synthetic methanol spectra across MM1. Intriguingly, the peak CH3OH T ex = 165.5 ± 0.6 K is offset from MM1's millimetre continuum peak by 0.22 arcsec ∼ 880 au, and a region of elevated CH3OH T ex coincides with free–free VLA 5.01 cm continuum, adding to the tentative evidence for a possible unresolved high-mass binary in MM1. In our VLA 1.21 cm data, we report the first NH3(3,3) maser detections towards G19.01−0.03, along with candidate 25 GHz CH3OH 5(2, 3) − 5(1, 4) maser emission; both are spatially and kinematically coincident with 44 GHz Class I CH3OH masers in the MM1 outflow. We also report the ALMA detection of candidate 278.3 GHz Class I CH3OH maser emission towards this outflow, strengthening the connection of these three maser types to MYSO outflows. [ABSTRACT FROM AUTHOR]

Background: The amount of time it takes for bone allograft particles to be replaced with new vital bone during ridge preservation is unclear. The purpose of this article was to compare the wound healing and vital bone formation following ridge preservation using a combination allograft of 70% mineralized and 30% demineralized freeze-dried bone allograft at 4 months (short-term, ST) versus 12 months (long-term, LT). Methods: Fifty-seven patients were enrolled in the study who required extraction of a single tooth (excluding second and third molars) and were planned for replacement with a dental implant. After tooth extraction, all sites were grafted with a combination allograft procured from a single donor, and patients were randomized into the ST or LT healing groups. Patients returned for implant placement and an 8-mm bone core biopsy was harvested using a trephine drill during initial implant osteotomy preparation. The cores were then analyzed histologically to determine the percentages of vital bone formation, residual graft particles, and connective tissue/other. Results: There was significantly greater vital bone formation in the LT group (51.38%) compared with the ST group (31.39%) (p = 0.0025) and significantly fewer residual graft particles in the LT group (18.04%) compared with the ST group (40.38%). Conclusions:Alonger healing time following ridge preservation results in more vital bone formation and less residual graft particles at the time of implant placement. However, residual allograft material still remains at 12 months after ridge preservation. [ABSTRACT FROM AUTHOR]

In March of 1860 the eminent Harvard Botanist and orthodox Christian Asa Gray began promoting the Origin of Species in hopes of securing a fair examination of Darwin's evolutionary theory among theistic naturalists. To this end, Gray sought to demonstrate that Darwin had not written atheistically and that his theory of evolution by natural selection had not presented any new scientific or theological difficulties for traditional Christian belief. From his personal correspondence with the author of the Origin, Gray well knew that Darwin did not affirm God's "particular" design of nature but conceded to the possibility that evolution proceeded according to "designed laws." From this concession, Gray attempted to develop a post-Darwinian natural theology which encouraged theistic naturalists to view God's design of nature through the evolutionary process in a manner similar to the way in which they viewed God's Providential interaction with human history. Indeed, securing a fair reading of the Origin was not Gray's sole aim as a promoter of Darwinian ideas. In Darwin's theory of natural selection, Gray believed he had discovered the means by which a more robust natural theological conception of the living and evolving natural world could be developed. In this paper I outline Gray's efforts to produce and popularize a theistic interpretation of Darwinian theory in order to correct various misconceptions concerning Gray's natural theological views and their role in the Darwinian Revolution.

A new tool to identify possible Zeeman pairs is presented here: the right circularly polarized (RCP) and left circularly polarized (LCP) components of a pair with velocity drift at the same rate. Long-term monitoring of hydroxyl transitions towards NGC 6334I-MM3 has resulted in the identification of three possible Zeeman pairs, one each at the 1.667, 6.030, and 6.035 GHz transitions, where the rate of drift of the RCP feature equals that of the LCP component. Historical observations suggest that their drift has been occurring over 40 yr. A fourth pair in the 1.720 GHz OH transition may indicate magnetic field variation over 50 yr. [ABSTRACT FROM AUTHOR]