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Abstract The fungal genus Phytophthora includes an array of destructive plant pathogens that have had severe impacts on native, agricultural, and horticultural systems worldwide. Preventing the spread of Phytophthora species is critical for protecting vulnerable plants and ecosystems; yet detection remains a challenge due to their microscopic size, broad host range, and latent and cryptic expression in host plants. We tested the effectiveness of trained detection dogs to discriminate the odor of a target Phytophthora species, from among other non‐target odors, by conducting a multi‐choice experiment. We tasked two dogs with discriminating the scent of P. agathidicida—the causal agent of the lethal root rot disease “kauri dieback”—from two non‐target Phytophthora scents (P. cinnamomi and P. multivora), and four non‐target control treatments. We assessed the dogs' scent detection abilities by measuring the sensitivity and precision of their indications toward the target scent over 120 randomized trials. The dogs had a combined sensitivity of 68.6% (CI: 64.1–72.9) and precision of 52.2% (CI: 48.1–56.4), meaning they often identified P. agathidicida when it was present but also signaled on the other non‐target Phytophthora species. Moreover, we characterized the nature of false positive indications made for non‐target scents, which has important implications for how future multi‐choice experiments should be conducted. Our study shows that detection dogs are likely to be an adequate first‐pass detection tool for Phytophthora within a wider biosecurity framework. However, further research is warranted before dogs can be deployed for this purpose in the field.

Artificial light at night (ALAN) is a growing conservation concern for seabirds, which can become disoriented and grounded by lights from buildings, bridges and boats. Many fledgling seabirds, especially Procellariiformes such as petrels and shearwaters, are susceptible to light pollution. The Hauraki Gulf, a seabird hotspot located near Tāmaki Makaurau/Auckland, Aotearoa—New Zealand’s largest urban city, with a considerable amount of light pollution and regularly documented events of seabird groundings. We aim to identify the characteristics of locations especially prone to seabird groundings. We used an online database of seabirds taken to a wildlife rescue facility by the public to map 3 years of seabird groundings and test for correlations between seabird groundings and the natural night sky brightness. We found that areas with lower amounts of natural night sky brightness and greater light pollution often had a higher number of seabirds grounded. Further, we identified important seasonal patterns and species differences in groundings. Such differences may be a by-product of species ecology, visual ecology and breeding locations, all of which may influence attraction to lights. In general, seabird groundings correlate with the brightness of the area and are species-specific. Groundings may not be indicative of human or seabird population abundance considering some areas have a lower human population with high light levels and had high amounts of seabird groundings. These findings can be applied worldwide to mitigate groundings by searching and targeting specific brightly lit anthropogenic structures. Those targeted structures and areas can then be the focus of light mitigation efforts to reduce seabird groundings. Finally, this study illustrates how a combination of community science, and a concern for seabirds grounded from light attraction, in addition to detailed animal welfare data and natural night sky brightness data can be a powerful, collaborative tool to aid global conservation efforts for highly-at-risk animals such as seabirds.

OBJECTIVE: To identify factors related to health promotion professionals' decisions to use computer-mediated instruction for continuing education (CMI-CE). METHODS: Employing a cross-sectional survey design, data were collected from 500 respondents using an online survey. RESULTS: Among respondents having positive intentions toward CMI-CE, characteristics distinguishing between individuals with positive and negative CMI-CE behavior included perceived behavioral control, license/ certification, lack of programs and relevant program topics, and availability of technical support. CONCLUSIONS: Health promotion professionals have positive intentions toward CMI-CE, and introducing relevant programs accompanied by strong technical support teams will help move them beyond intention and into action. [ABSTRACT FROM AUTHOR]

The Internet plays an important role in health education today. This study attempts to fill a void in the literature regarding Internet use, including motivators and barriers for health educators. Using a modified version of the Total Design Method, a survey concerning Internet use was mailed to a stratified random sample of 1559 health educators in the United States. Seven-hundred thirty-eight surveys were usable for a 55% response rate. Descriptive statistics were calculated for all variables, and exploratory factor analyses were performed on three domains of questions from the survey. Adequate access, relative advantage and problems with Web sites are factors that influence Internet use among health educators. The majority of respondents had access to the Internet at home and work, and over two-thirds used e-mail daily. Implications for the health education profession are provided. [ABSTRACT FROM AUTHOR]

While the health-enhancing benefits of exercise and good nutrition have been well documented, the ability of health professionals to encourage healthier lifestyle behaviors among those they serve continues to prove challenging. Creating the conditions where healthier living can both occur and be sustained requires thinking beyond the traditional provision of services and prescriptions that occur in healthcare settings. Healthy Lifestyle Centers are emerging as a way of deploying lifestyle medicine practices. Turning these centers into cooperative businesses has the potential to make them more effective. Cooperative business principles are well established, and they enable individuals to become makers and producers of their own healthy lifestyles, providing a greater opportunity for sustained lifestyles changes. The purpose of this article is to further examine the role of engagement practices and coproduction as they relate to cooperative business models and to propose a framework for a Cooperative Healthy Lifestyle Center., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 The Author(s).)

Whereas effector CD4 + and CD8 + T cells promote immune activation and can drive clearance of infections and cancer, CD4 + regulatory T (T reg ) cells suppress their function, contributing to both immune homeostasis and cancer immunosuppression. The transcription factor BACH2 functions as a pervasive regulator of T cell differentiation, promoting development of CD4 + T reg cells and suppressing the effector functions of multiple effector T cell (T eff ) lineages. Here, we report the development of a stable cell-based bioluminescence assay of the transcription factor activity of BACH2. Tetracycline-inducible BACH2 expression resulted in suppression of phorbol 12-myristate 13-acetate (PMA)/ionomycin-driven activation of a luciferase reporter containing BACH2/AP-1 target sequences from the mouse Ifng + 18k enhancer. BACH2 expression repressed the luciferase signal in a dose-dependent manner but this activity was abolished at high levels of AP-1 signalling, suggesting contextual regulation of AP-1 driven gene expression by BACH2. Finally, using the reporter assay developed, we find that the histone deacetylase 3 (HDAC3)-selective inhibitor, RGFP966, inhibits BACH2-mediated repression of signal-driven luciferase expression. In addition to enabling mechanistic studies, this cell-based reporter may enable identification of small molecule agonists or antagonists of BACH2 function for drug development.

Aims: In-hospital cardiac arrests are often preceded by a period of physiological deterioration that has often gone unnoticed. We proposed that the same might be true for out-of-hospital cardiac arrests (OHCAs) where ambulance crews leave patients at home who then subsequently go on to suffer a cardiac arrest., Methods and Results: We identified all OHCA over a 12-month period that had been seen and assessed by an ambulance crew within the 48 h preceding their cardiac arrest. We retrospectively calculated the patient's NEWS2 score at the time of their initial assessment as a marker of their physiological status and need for hospital admission. Of 1960 OHCA patients, 184 (9.4%) had been assessed by ambulance crews within the preceding 48 h. Excluding those who had been taken to hospital (and then discharged), declined hospital conveyance or were on end-of-life care pathways, 79 (56% of total) were left at home through crew discretion. Thirty-four out of 79 (43%) patients not conveyed had either a NEWS score of 3 in a single parameter or a score of ≥5, which in hospital would mandate an urgent medical review. The most overlooked observation was respiratory rate., Conclusions: In total, 1.7% of all OHCA had been assessed in the previous 48 h and inappropriately left at home by ambulance crews. This represents a missed opportunity to avert cardiac arrest. NEWS scoring has the potential to improve pre-hospital triage of these patients and avoid missing the deteriorating patient., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

The Lysophosphatidic Acid 1 Receptor (LPA 1 receptor) has been linked to the initiation and progression of a variety of poorly treated fibrotic conditions. Several compounds that have been described as LPA 1 receptor antagonists have progressed into clinical trials: 1-(4-{4-[3-methyl-4-({[(1R)-1-phenylethoxy]carbonyl}amino)-1,2-oxazol-5-yl]phenyl}phenyl)cyclopropane-1-carboxylic acid (BMS-986202) and 2-{4-methoxy-3-[2-(3-methylphenyl)ethoxy]benzamido}-2,3-dihydro-1H-indene-2-carboxylic acid (SAR-100842). We considered that as LPA 1 receptor function is involved in many normal physiological processes, inhibition of specific signalling pathways associated with fibrosis may be therapeutically advantageous. We compared the binding and functional effects of a novel compound; 4-({(Cyclopropylmethyl)[4-(2-fluorophenoxy)benzoyl]amino}methyl}benzoic acid (TAK-615) with BMS-986202 and SAR-100842. Back-scattering interferometry (BSI) was used to show that the apparent affinity of TAK-615 was enhanced in the presence of LPA. The binding signal for BMS-986202 was not detected in the presence of LPA suggesting competition but interestingly the apparent affinity of SAR-100842 was also enhanced in the presence of LPA. Only BMS-986202 was able to fully inhibit the response to LPA in calcium mobilisation, β-arrestin, cAMP, GTPγS and RhoA functional assays. TAK-615 and SAR-100842 showed different inhibitory profiles in the same functional assays. Further binding studies indicated that TAK-615 is not competitive with either SAR-100842 or BMS-986202, suggesting a different site of binding. The results generated with this set of experiments demonstrate that TAK-615 acts as a negative allosteric modulator (NAM) of the LPA 1 receptor. Surprisingly we find that SAR-100842 also behaves like a NAM. BMS-986202 on the other hand behaves like an orthosteric antagonist., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Irregular N-methyl-D-aspartate receptor (NMDAR) function is one of the main hypotheses employed to facilitate understanding of the underlying disease state of schizophrenia. Although direct agonism of the NMDAR has not yielded promising therapeutics, advances have been made by modulating the NMDAR co-agonist site which is activated by glycine and D-serine. One approach to activate the co-agonist site is to increase synaptic D-serine levels through inhibition of D-amino acid oxidase (DAO), the major catabolic clearance pathway for this and other D-amino acids. A number of DAO inhibitors have been developed but most have not entered clinical trials. One exception to this is sodium benzoate which has demonstrated efficacy in small trials of schizophrenia and Alzheimer's disease. Herein we provide data on the effect of sodium benzoate and an optimised Takeda compound, PGM030756 on ex vivo DAO enzyme occupancy and cerebellar D-serine levels in mice. Both compounds achieve high levels of enzyme occupancy; although lower doses of PGM030756 (1, 3 and 10 mg/kg) were required to achieve this compared to sodium benzoate (300, 1000 mg/kg). Cerebellar D-serine levels were increased by both agents with a delay of approximately 6 h after dosing before the peak effect was achieved. Our data and methods may be useful in understanding the effects of sodium benzoate that have been seen in clinical trials of schizophrenia and Alzheimer's disease and to support the potential clinical assessment of other DAO inhibitors, such as PGM030756, which demonstrate good enzyme occupancy and D-serine increases following administration of low oral doses.

Catechol O-methyl transferase belongs to the diverse family of S-adenosyl-l-methionine transferases. It is a target involved in the treatment of Parkinson's disease. Here we present a fragment-based screening approach to discover noncatechol derived COMT inhibitors which bind at the SAM binding pocket. We describe the identification and characterization of a series of highly ligand efficient SAM competitive bisaryl fragments (LE = 0.33-0.58). We also present the first SAM-competitive small-molecule COMT co-complex crystal structure.

The term social marketing has been used to describe a multitude of interventions that incorporate the use of traditional marketing techniques to promote a behavior that will improve the health or well-being of a target audience or of society as a whole. However, there is wide variation in the way social marketing is defined and used. This systematic review article examines how social marketing has been defined and applied to social problems within the public health literature from 2001-2006, by adapting a grading-system borrowed from evidence-based medicine and utilizing Kotler and Zaltman's definition of social marketing. Additionally, definitions of social marketing were identified in the reviewed articles. Identifying a common language in the description and design of social marketing interventions will benefit researchers and practitioners interested in social marketing as a behavior change approach.