Impactful co-design: Adult decision-makers' perspectives on actualising children's ideas for health-promoting neighbourhoods in Aotearoa New Zealand.

Our study sought to understand adult decision-makers' views on what was important for actualising children's ideas using co-design, towards creating health-promoting local environments. Ten adult decision-makers, experienced in co-design with children aged 5-13 years in Aotearoa New Zealand, participated in individual interviews. We generated three themes (Empowering children within co-design; Being intentional about children's influence; Curating who is involved) using reflexive thematic analysis. Our themes informed a novel framework of 'impactful co-design' accompanied by a practical checklist for adult decision-makers (practitioners, policy-makers, and researchers). Study findings affirm co-designing local neighbourhoods as an inherently social and technical endeavour, advocate for greater consideration of inclusivity and cultural context, and highlight the need for co-design with children to include safety, empowerment, and evaluation. We position impactful co-design as one useful process to enact children's meaningful participation.

In situ observation of holopelagic Sargassum distribution and aggregation state across the entire North Atlantic from 2011 to 2020.

Between 2011 and 2020, 6,790 visual observations of holopelagic Sargassum were recorded across the North Atlantic Ocean to describe regional distribution, presence, and aggregation state at hourly and 10 km scales. Influences of oceanographic region and wind/sea conditions as well as temporal trends were considered; marine megafauna associates documented the ecological value of aggregations. Holopelagic Sargassum was present in 64% of observations from the western North Atlantic. Dispersed holopelagic Sargassum fragments and clumps were found in 97% of positive observations whereas aggregated windrows (37%) and mats (1%) were less common. Most field observations noted holopelagic Sargassum in quantities below the AFAI algorithm detection limit for the MODIS sensor. Aggregation state patterns were similar across regions; windrow proportion increased with higher wind speeds. In 8 of 10 years in the Sargasso Sea holopelagic Sargassum was found in over 65% of observations. In contrast, the Tropical Atlantic and Caribbean Sea exhibited greater inter-annual variability (1-88% and 11-78% presence, respectively) that did not align with extremes in central Atlantic holopelagic Sargassum areal coverage determined from satellite observations. Megafauna association patterns varied by taxonomic group. While some study regions were impacted by holopelagic Sargassum dynamics in the equatorial Atlantic, the Sargasso Sea had consistently high presence and operated independently. Field observations capture important dynamics occurring at fine spatiotemporal scales, including transient aggregation processes and ecological value for megafauna associates, and therefore remain essential to future studies of holopelagic Sargassum.

A Co-Designed, Culturally-Tailored mHealth Tool to Support Healthy Lifestyles in Maori and Pasifika Communities in New Zealand: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: New Zealand urgently requires scalable, effective, behavior change programs to support healthy lifestyles that are tailored to the needs and lived contexts of Maori and Pasifika communities. OBJECTIVE: The primary objective of this study is to determine the effects of a co-designed, culturally tailored, lifestyle support mHealth tool (the OL@-OR@ mobile phone app and website) on key risk factors and behaviors associated with an increased risk of noncommunicable disease (diet, physical activity, smoking, and alcohol consumption) compared with a control condition. METHODS: A 12-week, community-based, two-arm, cluster-randomized controlled trial will be conducted across New Zealand from January to December 2018. Participants (target N=1280; 64 clusters: 32 Maori, 32 Pasifika; 32 clusters per arm; 20 participants per cluster) will be individuals aged ≥18 years who identify with either Maori or Pasifika ethnicity, live in New Zealand, are interested in improving their health and wellbeing or making lifestyle changes, and have regular access to a mobile phone, tablet, laptop, or computer and to the internet. Clusters will be identified by community coordinators and randomly assigned (1:1 ratio) to either the full OL@-OR@ tool or a control version of the app (data collection only plus a weekly notification), stratified by geographic location (Auckland or Waikato) for Pasifika clusters and by region (rural, urban, or provincial) for Maori clusters. All participants will provide self-reported data at baseline and at 4- and 12-weeks postrandomization. The primary outcome is adherence to healthy lifestyle behaviors measured using a self-reported composite health behavior score at 12 weeks that assesses smoking behavior, fruit and vegetable intake, alcohol intake, and physical activity. Secondary outcomes include self-reported body weight, holistic health and wellbeing status, medication use, and recorded engagement with the OL@-OR@ tool. RESULTS: Trial recruitment opened in January 2018 and will close in July 2018. Trial findings are expected to be available early in 2019. CONCLUSIONS: Currently, there are no scalable, evidence-based tools to support Maori or Pasifika individuals who want to improve their eating habits, lose weight, or be more active. This wait-list controlled, cluster-randomized trial will assess the effectiveness of a co-designed, culturally tailored mHealth tool in supporting healthy lifestyles. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Register ACTRN12617001484336; http://www.ANZCTR.org.au/ACTRN12617001484336.aspx (Archived by WebCite at http://www.webcitation.org/71DX9BsJb). REGISTERED REPORT IDENTIFIER: RR1-10.2196/10789.

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4.

IRAK4 is responsible for initiating signaling from Toll-like receptors (TLRs) and members of the IL-1/18 receptor family. Kinase-inactive knock-ins and targeted deletions of IRAK4 in mice cause reductions in TLR induced pro-inflammatory cytokines and these mice are resistant to various models of arthritis. Herein we report the identification and optimization of a series of potent IRAK4 inhibitors. Representative examples from this series showed excellent selectivity over a panel of kinases, including the kinases known to play a role in TLR-mediated signaling. The compounds exhibited low nM potency in LPS- and R848-induced cytokine assays indicating that they are blocking the TLR signaling pathway. A key compound (26) from this series was profiled in more detail and found to have an excellent pharmaceutical profile as measured by predictive assays such as microsomal stability, TPSA, solubility, and clogP. However, this compound was found to afford poor exposure in mouse upon IP or IV administration. We found that removal of the ionizable solubilizing group (32) led to increased exposure, presumably due to increased permeability. Compounds 26 and 32, when dosed to plasma levels corresponding to ex vivo whole blood potency, were shown to inhibit LPS-induced TNFα in an in vivo murine model. To our knowledge, this is the first published in vivo demonstration that inhibition of the IRAK4 pathway by a small molecule can recapitulate the phenotype of IRAK4 knockout mice.

Distribution of surface plastic debris in the eastern Pacific Ocean from an 11-year data set.

We present an extensive survey of floating plastic debris in the eastern North and South Pacific Oceans from more than 2500 plankton net tows conducted between 2001 and 2012. From these data we defined an accumulation zone (25 to 41 °N, 130 to 180 °W) in the North Pacific subtropical gyre that closely corresponds to centers of accumulation resulting from the convergence of ocean surface currents predicted by several oceanographic numerical models. Maximum plastic concentrations from individual surface net tows exceeded 10(6) pieces km(-2), with concentrations decreasing with increasing distance from the predicted center of accumulation. Outside the North Pacific subtropical gyre the median plastic concentration was 0 pieces km(-2). We were unable to detect a robust temporal trend in the data set, perhaps because of confounded spatial and temporal variability. Large spatiotemporal variability in plastic concentration causes order of magnitude differences in summary statistics calculated over short time periods or in limited geographic areas. Utilizing all available plankton net data collected in the eastern Pacific Ocean (17.4 °S to 61.0 °N; 85.0 to 180.0 °W) since 1999, we estimated a minimum of 21,290 t of floating microplastic.

Gooseneck barnacles (Lepas spp.) ingest microplastic debris in the North Pacific Subtropical Gyre.

Substantial quantities of small plastic particles, termed "microplastic," have been found in many areas of the world ocean, and have accumulated in particularly high densities on the surface of the subtropical gyres. While plastic debris has been documented on the surface of the North Pacific Subtropical Gyre (NPSG) since the early 1970s, the ecological implications remain poorly understood. Organisms associated with floating objects, termed the "rafting assemblage," are an important component of the NPSG ecosystem. These objects are often dominated by abundant and fast-growing gooseneck barnacles (Lepas spp.), which predate on plankton and larval fishes at the sea surface. To assess the potential effects of microplastic on the rafting community, we examined the gastrointestinal tracts of 385 barnacles collected from the NPSG for evidence of plastic ingestion. We found that 33.5% of the barnacles had plastic particles present in their gastrointestinal tract, ranging from one plastic particle to a maximum of 30 particles. Particle ingestion was positively correlated to capitulum length, and no blockage of the stomach or intestines was observed. The majority of ingested plastic was polyethylene, with polypropylene and polystyrene also present. Our results suggest that barnacle ingestion of microplastic is relatively common, with unknown trophic impacts on the rafting community and the NPSG ecosystem.

How equitation science can elucidate and refine horsemanship techniques.

The long-held belief that human dominance and equine submission are key to successful training and that the horse must be taught to 'respect' the trainer infers that force is often used during training. Many horses respond by trialling unwelcome evasions, resistances and flight responses, which readily become established. When unable to cope with problem behaviours, some handlers in the past might have been encouraged to use harsh methods or devices while others may have called in a so-called 'good horseman' or 'horse whisperer' to remediate the horse. Frequently, the approaches such practitioners offer could not be applied by the horse's owner or trainer because of their lack of understanding or inability to apply the techniques. Often it seemed that these 'horse-people' had magical ways with horses (e.g., they only had to whisper to them) that achieved impressive results although they had little motivation to divulge their techniques. As we begin to appreciate how to communicate with horses sensitively and consistently, misunderstandings and misinterpretations by horse and trainer should become less common. Recent studies have begun to reveal what comprises the simplest, most humane and most effective mechanisms in horse training and these advances are being matched by greater sharing of knowledge among practitioners. Indeed, various practitioners of what is referred to here as 'natural horsemanship' now use techniques similar to the 'whisperers' of old, but they are more open about their methods. Reputable horse trainers using natural horsemanship approaches are talented observers of horse behaviour and respond consistently and swiftly to the horse's subtle cues during training. For example, in the roundpen these trainers apply an aversive stimulus to prompt a flight response and then, when the horse slows down, moves toward them, or offers space-reducing affiliative signals, the trainer immediately modifies his/her agonistic signals, thus negatively reinforcing the desired response. Learning theory and equine ethology, the fundamentals of the emerging discipline of equitation science, can be used to explain almost all the behaviour modification that goes on in these contexts and in conventional horsemanship. By measuring and evaluating what works and what does not, equitation science has the potential to have a unifying effect on traditional practices and developing branches of equitation.

Differential place and response learning in horses displaying an oral stereotypy.

Significant similarities exist between the neural and behavioural features of environmentally and drug-induced stereotypy. For example, exposure to dopamine agonists, such as amphetamine, induces stereotypy and causes alterations in midbrain neurophysiology similar to those observed following chronic stress. An additional behavioural feature of these neural changes in the drug-induced phenotype is an enhanced rate of switching from response-outcome (R-O) to stimulus-response (S-R) learning. The aim of the current experiment was to examine R-O and S-R learning in horses displaying environmentally induced oral stereotypies. This was achieved by employing variations of the place/response paradigm. In Experiment 1, we found that crib-biting horses displayed 'response' learning after 20 learning trials, whereas non-crib-biting controls tended to display 'place' learning throughout the experiment. In Experiment 2, we used a modified version of the procedure, in which the subjects were introduced to the maze from different start points and forced always to turn the same way. We found that the crib-biters acquired the task at a faster rate suggesting again that this group was displaying 'response' learning. Finally, in Experiment 3, we carried out an arena test to ensure that crib-biters were capable of 'place' learning. These results are the first to show that horses displaying an oral stereotypy, a behavioural phenotype previously associated with stress-induced perturbations of the basal ganglia, preferentially use 'response' learning. The findings are discussed in relation to the search for an aetiological model of stereotypy.

Preliminary investigation of morphological differences between ten breeds of horses suggests selection for paedomorphosis.

Paedomorphosis is the retention of juvenile morphology at maturity and is important in generating evolutionary change in domestic species and species in the wild. When comparing dogs with the wolf, this preliminary study saw paedomorphosis in their physical and behavioral traits (Goodwin, Bradshaw, & Wickens, 1997). This preliminary study compared morphological characteristics of 10 breeds from northern regions (Shetland ponies) and southern regions (Arabians) with the Exmoor pony. Twenty-three respondents from the United Kingdom and Australia rated the breeds for 7 physical traits. As evidenced by low standard deviations, the respondents demonstrated a high degree of agreement. The study ranked breeds from the most similar (Highland pony) to the least similar (Arabian) to the Exmoor pony. The least similar breeds had physical traits suggestive of paedomorphosis: small heads, long legs, and a low head-to-body ratio. This preliminary study suggests that morphological, behavioral, and physiological differences between the breeds-plus morphometric comparisons of extant breeds and faunal remains of predomestication horses-warrant further study.

Is there evidence of learned helplessness in horses?

Learned helplessness is a psychological condition whereby individuals learn that they have no control over unpleasant or harmful conditions, that their actions are futile, and that they are helpless. In a series of experiments in which dogs were exposed to inescapable shocks, this lack of control subsequently interfered with the ability to learn an avoidance task. There is evidence that both neural adaptations and behavioral despair occur in response to uncontrollable aversive experiences in rodents, although this has yet to be demonstrated in other species such as horses. However, certain traditional methods of horse training and some behavioral modification techniques--it has been suggested--may involve aversive conditions over which the horse has little or no control. When training and management procedures are repeatedly unpleasant for the horse and there is no clear association between behavior and outcome, this is likely to interfere with learning and performance-in addition to compromising welfare. This article reviews published literature and anecdotal evidence to explore the possibility that the phenomenon, learned helplessness, occurs in the horse.

Impaired instrumental choice in crib-biting horses (Equus caballus).

Horses displaying an oral stereotypy were tested on an instrumental choice paradigm to examine differences in learning from non-stereotypic counterparts. Stereotypic horses are known to have dysfunction of the dorsomedial striatum, and lesion studies have shown that this region may mediate response-outcome learning. The paradigm was specifically applied in order to examine learning that requires maintenance of response-outcome judgements. The non-stereotypic horses learned, over three sessions, to choose a more immediate reinforcer, whereas the stereotypic horses failed to do so. This suggests an initial behavioural correlate for dorsomedial striatum dysregulation in the stereotypy phenotype.