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Chris Ingham and Michael Killilea discuss their roles within The Fountains Independent Hospital. [ABSTRACT FROM AUTHOR]

Objectives: To describe perceptions of providing, and using rapid evidence, to support decision making by two national bodies (one public health policy and one front-line clinical practice) during the COVID-19 pandemic., Design: Descriptive qualitative study (March-August 2020): 25 semistructured interviews were conducted, transcribed verbatim and thematically analysed., Setting: Data were obtained as part of an evaluation of two Irish national projects; the Irish COVID-19 Evidence for General Practitioners project (General Practice (GP) project) which provided relevant evidence to address clinical questions posed by GPs; and the COVID-19 Evidence Synthesis Team (Health Policy project) which produced rapid evidence products at the request of the National Public Health Emergency Team., Participants: Purposive sample of 14 evidence providers (EPs: generated and disseminated rapid evidence) and 11 service ssers (SUs: GPs and policy-makers, who used the evidence)., Main Outcome Measures: Participant perceptions., Results: The Policy Project comprised 27 EPs, producing 30 reports across 1432 person-work-days. The GP project comprised 10 members from 3 organisations, meeting 49 times and posting evidence-based answers to 126 questions. Four unique themes were generated. 'The Work' highlighted that a structured but flexible organisational approach to producing evidence was essential. Ensuring quality of evidence products was challenging, particularly in the context of absent or poor-quality evidence. 'The Use' highlighted that rapid evidence products were considered invaluable to decision making. Trust and credibility of EPs were key, however, communication difficulties were highlighted by SUs (eg, website functionality). 'The Team' emphasised that a highly skilled team, working collaboratively, is essential to meeting the substantial workload demands and tight turnaround time. 'The Future' highlighted that investing in resources, planning and embedding evidence synthesis support, is crucial to national emergency preparedness., Conclusions: Rapid evidence products were considered invaluable to decision making. The credibility of EPs, a close relationship with SUs and having a highly skilled and adaptable team to meet the workload demands were identified as key strengths that optimised the utilisation of rapid evidence., Ethics Approval: Ethical approval was obtained from the National Research Ethics Committee for COVID-19-related Research, Ireland., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute liver injury (ALI) is a highly destructive and potentially life-threatening condition, exacerbated by physical and psychological stress. The endocannabinoid system plays a key role in modulating stress and hepatic function. The aim of this study was to examine the development of acute liver injury in the genetically susceptible stress-sensitive Wistar-Kyoto (WKY) rat compared with normo-stress-sensitive Sprague Dawley (SD) rats, and associated changes in the endocannabinoid system. Administration of the hepatotoxin lipopolysaccharide/D-Galactosamine (LPS/GalN) resulted in marked liver injury in WKY, but not SD rats, with increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) plasma levels, significant histopathological changes, increased hepatic pro-inflammatory cytokine expression and caspase-3 activity and expression and reduced Glutathione (GSH) activity. Furthermore, compared to SD controls, WKY rats display increased anandamide and 2-Arachidonoylglycerol levels concurrent with decreased expression of their metabolic enzymes and a decrease in cannabinoid (CB) 1 receptor expression following LPS/GalN. CB 1 antagonism with AM6545 or CB 2 agonism with JWH133 did not alter LPS/GalN-induced liver injury in SD or WKY rats. These findings demonstrate exacerbation of acute liver injury induced by LPS/GalN in a stress-sensitive rat strain, with effects associated with alterations in the hepatic endocannabinoid system. Further studies are required to determine if the endocannabinoid system mediates or modulates the exacerbation of liver injury in this stress-sensitive rat strain.

Background: The University College Dublin (UCD) Public and Patient Invovlement (PPI) ignite program is focused on embedding PPI in health and social care related research, education and training, professional practice and administration. During a PPI knowledge sharing event challenges were noted during the pre-commencement stage of research projects. This stage includes the time before a research projects/partnership starts or when funding is being applied for. As a response, we agreed there was a need to spend time developing a values-based approach to be used from the pre-commencement of PPI projects and partnerships. Values are deeply held ideals that people consider to be important. They are vital in shaping our attitudes and motivating our choices and behaviours., Methods: Using independent facilitators, we invited a diverse group of participants to a full-day workshop in February. During the workshop, the concept of a values statement and values-based approaches was introduced. The group via a majority consensus, agreed on a core set of values and a shared understanding of them. After the workshop, a draft was shared with participants for further comment and final agreement., Results: The workshop had 22 people representing experts by experience, PPI charity partners, funders, academics and national PPI Ignite partners. The group via consensus identified four values of respect, openness, reciprocity and flexibility for the pre-commencement stage. A frequently reported experience of PPI partners was that some felt that the pre-commencement activities appeared at times like a performance; an act that had to be completed in order to move to the next stage rather than a genuine interest in a mutually beneficial partnership. Being open and transparent with all invovled that the funding application may not be successful was stressed. Another important feature related to 'openness' was the 'spaces' and 'places' in which meetings between partners could occur in an accessible and equitable way. The issue of 'space' is particularly critical for the involvement of seldom heard groups. The benefits of the research are often clear for academics, but for PPI partners, these are often less certain. To achieve reciprocity, academic and PPI partners need to engage in a timely, repeated and transparent dialogue to achieve beneficial outcomes for all stakeholders. Being open to new inputs and differing modes of knowledge and ideas was also stressed. For some, this will require a change in attitudes and behaviours and should result in more collective decision making. Several areas were identified using the four values., Conclusions: This work via majority consensus identified four values of respect, openness, reciprocity, and flexibility for the pre-commencement stage. These values should be used to support inclusive, effective and collective PPI across all stages of involvement. We hope this work will stimulate further action in this area. In particular, we would welcome the evaluation of these values involving diverse PPI groups., Competing Interests: Competing interestsNone declared., (© The Author(s) 2020.)

The research community is responding with speed to the COVID-19 pandemic, with rapid response mechanisms to fund research, shortened application turnaround times, and expedited research ethics processes. Public and patient involvement (PPI) is under pressure in this rapid response research, where it is easy for researchers and funders to dismiss PPI as non-essential, an added extra, a "nice to have".  In this open letter, we, researchers and PPI contributors, argue that PPI is important, now more than ever. The pandemic is impacting everyone in society, with normal rules of engagement discarded. The solution to overcoming this virus will come from many different sources and many changes will emerge to healthcare delivery and to how we live our lives. It is essential that the research to find solutions is shaped by all who will be impacted: the public and the patient must be central contributors and their voice must be hear., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Murphy E et al.)

A major impediment to understanding human-environment interactions is that data on social systems are not collected in a way that is easily comparable to natural systems data. While many environmental variables are collected with high frequency, gridded in time and space, social data is typically conducted irregularly, in waves that are far apart in time. These efforts typically engage respondents for hours at a time, and suffer from decay in participants' ability to recall their experiences over long periods of time. Systematic use of mobile and smartphones has the potential to transcend these challenges, with a critical first step being an evaluation of where survey respondents experience the greatest recall decay. We present results from, to our knowledge, the first systematic evaluation of recall bias in components of a household survey, using the Open Data Kit (ODK) platform on Android smartphones. We tasked approximately 500 farmers in rural Bangladesh with responding regularly to components of a large household survey, randomizing the frequency of each task to be received weekly, monthly, or seasonally. We find respondents' recall of consumption and experience (such as sick days) to suffer much more greatly than their recall of the use of their households' time for labor and farm activities. Further, we demonstrate a feasible and cost-effective means of engaging respondents in rural areas to create and maintain a true socio-economic "baseline" to mirror similar efforts in the natural sciences., (© The Author(s) 2019.)

Aberrant activation of toll-like receptors (TLRs), key components of the innate immune system, has been proposed to underlie and exacerbate a range of central nervous system disorders. Increasing evidence supports a role for the endocannabinoid system in modulating inflammatory responses including those mediated by TLRs, and thus this system may provide an important treatment target for neuroinflammatory disorders. However, the effect of modulating endocannabinoid tone on TLR-induced neuroinflammation in vivo and associated behavioural changes is largely unknown. The present study examined the effect of inhibiting fatty acid amide hydrolyase (FAAH), the primary enzyme responsible for the metabolism of anandamide (AEA), in vivo on TLR4-induced neuroimmune and behavioural responses, and evaluated sites and mechanisms of action. Systemic administration of the FAAH inhibitor PF3845 increased levels of AEA, and related FAAH substrates N-oleoylethanolamide (OEA) and N-palmitoylethanolamide (PEA), in the frontal cortex and hippocampus of rats, an effect associated with an attenuation in the expression of pro- and anti-inflammatory cytokines and mediators measured 2hrs following systemic administration of the TLR4 agonist, lipopolysaccharide (LPS). These effects were mimicked by central i.c.v. administration of PF3845, but not systemic administration of the peripherally-restricted FAAH inhibitor URB937. Central antagonism of TRPV1 significantly attenuated the PF3845-induced decrease in IL-6 expression, effects not observed following antagonism of CB 1, CB 2 , PPARα, PPARγ or GPR55. LPS-induced a robust sickness-like behavioural response and increased the expression of markers of glial activity and pro-inflammatory cytokines over 24hrs. Systemic administration of PF3845 modulated the TLR4-induced expression of neuroimmune mediators and anhedonia without altering acute sickness behaviour. Overall, these findings support an important role for FAAH substrates directly within the brain in the regulation of TLR4-associated neuroinflammation and highlight a role for TRPV1 in partially mediating these effects., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Anaplasmosis is an emerging infectious disease caused by infection with the bacterium Anaplasma phagocytophilum. In the eastern United States, A. phagocytophilum is transmitted to hosts through the bite of the blacklegged tick, Ixodes scapularis. We determined the realized reservoir competence of 14 species of common vertebrate hosts for ticks by establishing the probability that each species transmits two important strains of A. phagocytophilum (A. phagocytophilum human-active, which causes human cases, and A. phagocytophilum variant 1, which does not) to feeding larval ticks. We also sampled questing nymphal ticks from ∼ 150 sites in a single county over 2 years and sampled over 6 years at one location. White-footed mice (Peromyscus leucopus) and Eastern chipmunks (Tamias striatus) were the most competent reservoirs for infection with the A. phagocytophilum human-active strain. Across the county, prevalence in ticks for both strains together was 8.3%; ticks were more than two times as likely to be infected with A. phagocytophilum human-active as A. phagocytophilum variant 1., (© The American Society of Tropical Medicine and Hygiene.)

Mixed hardwood forests of the northeast United States support a guild of granivorous/omnivorous rodents including gray squirrels (Sciurus carolinensis), eastern chipmunks (Tamias striatus), and white-footed mice (Peromyscus leucopus). These species coincide geographically, co-occur locally, and consume similar food resources. Despite their idiosyncratic responses to landscape and patch variables, patch occupancy models suggest that competition may influence their respective distributions and abundances, and accordingly their influence on the rest of the forest community. Experimental studies, however, are wanting. We present the result of a large-scale experiment in which we removed white-footed mice or gray squirrels from small, isolated forest fragments in Dutchess County, New York, and added these mammals to other fragments in order to alter the abundance of these two species. We then used mark-recapture analyses to quantify the population-level and individual-level effects on resident mice, squirrels, and chipmunks. Overall, we found little evidence of competition. There were essentially no within-season numerical responses to changes in the abundance of putative competitors. Moreover, while individual-level responses (apparent survival and capture probability) did vary with competitor densities in some models, these effects were often better explained by site-specific parameters and were restricted to few of the 19 sites we studied. With only weak or nonexistent competition among these three common rodent species, we expect their patterns of habitat occupancy and population dynamics to be largely independent of one another.

Fourteen vertebrate species (10 mammals and 4 birds) were assessed for their ability to transmit Anaplasma phagocytophilum, the bacterium that causes human granulocytic anaplasmosis, to uninfected feeding ixodid ticks. Small mammals were most likely to infect ticks but all species assessed were capable of transmitting the bacterium, in contrast to previous findings.

Blacklegged ticks (Ixodes scapularis Say) are exquisitely sensitive to very cold and dry conditions. For this reason it has long been assumed that climatic differences among locations and within microhabitats have a strong influence on variation in their survival over winter. This assumption, however, rests largely on laboratory exposures and on broad-scale associations between climatic variables and the observed distributions of ticks. We present the results of a study of the overwintering survival of I. scapularis nymphs in their natural environment from October through May in two locations in New York State using a repeated sampling strategy to determine when mortality occurred, and whether those events coincide with extreme conditions. We then fit these data to a simple, flexible statistical model in which the hazard of mortality varies with measurable conditions, here minimum daily temperature and mean daily relative humidity. Regardless of winter conditions, > 80% of ticks survived at both sites. A model with constant hazard (i.e., independent of temperature and humidity) was best supported by the data. Although models with hazard increasing at temperatures below 0 deg C and at > 90% relative humidity provided slightly better fits to the data, these models were less parsimonious. These results weaken the expectation that cold-related overwintering mortality necessarily plays a major role in restricting populations of these ticks and thus, risk of tick-borne zoonoses.

The blacklegged tick (Ixodes scapularis) is an important vector of emerging human pathogens. It has three blood-feeding stages, as follows: larva, nymph, and adult. Owing to inefficient transovarial transmission, at least for the Lyme disease agent (Borrelia burgdorferi), larval ticks rarely hatch infected, but they can acquire infection during their larval blood meal. Nymphal ticks are primarily responsible for transmitting pathogens to hosts, including humans. The transition from uninfected host-seeking larva to infectious host-seeking nymph is therefore a key aspect of human risk of infection. It can be divided into a series of steps, as follows: finding a host, taking a blood meal, becoming infected, molting, and overwintering. The chance of succeeding in each of these steps may depend on the species identity of the blood meal host. We used a Bayesian method to estimate the molting success of larval I. scapularis collected from four commonly parasitized species of birds and eight commonly parasitized small and mid-sized mammals found in the forests of Dutchess County, New York. We show that molting success varies substantially among host species; white-footed mice, veeries, and gray catbirds support particularly high molting success, whereas ticks feeding on short-tailed shrews, robins, and wood thrushes were less successful. We also show that larval molting success varies substantially between individual blood meal hosts, and that this intraspecific variability is much higher in some species than in others. The causes of both inter- and intraspecific variation in molting success remain to be determined.