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Many species maintain territories, but the degree of overlap between territories and the level of aggression displayed in territorial conflicts can vary widely, even within species. Greater territorial overlap may occur when neighboring territory holders are close relatives. Animals may also differentiate neighbors from strangers, with more familiar neighbors eliciting less‐aggressive responses during territorial conflicts (the “dear enemy” effect). However, research is lacking in how both kinship and overlap affect territorial conflicts, especially in group‐living species. Here, we investigate kinship, territorial overlap, and territorial conflict in a habituated wild population of group‐living cooperatively breeding birds, the southern pied babbler Turdoides bicolor. We find that close kin neighbors are beneficial. Territories overlap more when neighboring groups are close kin, and these larger overlaps with kin confer larger territories (an effect not seen for overlaps with unrelated groups). Overall, territorial conflict is costly, causing significant decreases in body mass, but conflicts with kin are shorter than those conducted with nonkin. Conflicts with more familiar unrelated neighbors are also shorter, indicating these neighbors are “dear enemies.” However, kinship modulates the “dear enemy” effect; even when kin are encountered less frequently, kin elicit less‐aggressive responses, similar to the “dear enemy” effect. Kin selection appears to be a main influence on territorial behavior in this species. Groups derive kin‐selected benefits from decreased conflicts and maintain larger territories when overlapping with kin, though not when overlapping with nonkin. More generally, it is possible that kinship extends the “dear enemy” effect in animal societies. Fights between neighbors are common in many animal species, and often dictate territorial boundaries. We investigate how relatedness affects territorial overlap and size, and how relatedness and territorial overlap affect the intensity and length of territorial conflicts. We find that having kin as neighbors reduces the length of territorial conflicts and results in larger overlaps and larger territories. Overall, having kin as neighbors confers benefits in this cooperatively breeding bird species.

For territorial group-living species, opportunities to reproduce on the natal territory can be limited by a number of factors including the availability of resources within a territory, access to unrelated individuals, and monopolies on reproduction by dominant group members. Individuals looking to reproduce are therefore faced with the options of either waiting for a breeding opportunity to arise in the natal territory, or searching for reproductive opportunities in non-natal groups. In the cooperatively breeding Southern pied babbler, Turdoides bicolor, most individuals who achieve reproductive success do so through taking up dominant breeding positions within non-natal groups. For subordinate pied babblers therefore, searching for breeding opportunities in non-natal groups is of primary importance as this represents the major route to reproductive success. However, prospecting (where individuals leave the group to search for reproductive opportunities within other groups) is costly and individuals rapidly lose weight when not part of a group. Here we demonstrate that subordinate pied babblers adopt an alternative strategy for mate attraction by vocal advertisement from within their natal territories. We show that subordinates focus their calling efforts on the edges of their territory, and specifically near boundaries with neighbouring groups that have potential breeding partners (unrelated individuals of the opposite sex). In contrast to prospecting, calling individuals showed no body mass loss associated with this behaviour, suggesting that calling from within the group may provide a 'cheap' advertisement strategy. Additionally, we show that subordinates use information regarding the composition of neighbouring groups to target the greatest number of potential mating partners.

Neutrophils are the most abundant inflammatory cells at the earliest stages of wound healing and play important roles in wound repair and fibrosis. Formyl peptide receptor 1 (FPR-1) is abundantly expressed on neutrophils and has been shown to regulate their function, yet the importance of FPR-1 in fibrosis remains ill defined. FPR-1–deficient ( fpr1 –/– ) mice were protected from bleomycin-induced pulmonary fibrosis but developed renal and hepatic fibrosis normally. Mechanistically, we observed a failure to effectively recruit neutrophils to the lungs of fpr1 –/– mice, whereas neutrophil recruitment was unaffected in the liver and kidney. Using an adoptive transfer model we demonstrated that the defect in neutrophil recruitment to the lung was intrinsic to the fpr1 –/– neutrophils, as C57BL/6 neutrophils were recruited normally to the damaged lung in fpr1 –/– mice. Finally, C57BL/6 mice in which neutrophils had been depleted were protected from pulmonary fibrosis. In conclusion, FPR-1 and FPR-1 ligands are required for effective neutrophil recruitment to the damaged lung. Failure to recruit neutrophils or depletion of neutrophils protects from pulmonary fibrosis.

Background Smoking is a key contributor to health inequalities, particularly impacting oral health. Periodontal (gum) health is significantly affected by smoking. With their extensive reach, regular and frequent patient contact, and potential teachable moments, dental teams are well placed to support patients to stop smoking. This is currently mainly provided through Very Brief Advice (VBA) interventions and so there is scope to enhance the cessation support offered. A large definitive trial is needed to confirm whether this would lead to improved smoking quit rates, improved oral health, and be good value for money. Methods The ENHANCE-D trial is a multi-centre, pragmatic, definitive, 3-arm, parallel group, individually randomised controlled superiority trial, including an internal pilot, conducted in NHS dental settings. In total, 1215 patients who are current regular smokers will be randomly allocated using a 1:2:2 ratio to the following: (i) VBA; (ii) the offer of a standard course of Nicotine Replacement Therapy (NRT); (iii) or the offer of an e-cigarette starter kit. A subgroup of patients with periodontitis (gum disease) will have additional oral examinations and samples collected. The primary outcome is biochemically verified smoking abstinence at 6 months. A key secondary outcome is the percentage of periodontal sites with probing pocket depths (PPDs) ≥ 5 mm at 6 months in the periodontitis subgroup. Participants will be blinded to the purpose of the trial and not be aware of the treatment packages. Periodontal health outcomes will be recorded by trained and aligned assessors, blinded to intervention arm. Participant recruitment started in July 2022 with an internal pilot progressing to the main trial in May 2023. A qualitative process evaluation will explore participants’ experiences of receiving the study interventions, alongside the views of dental teams, NHS commissioners, service managers, and policymakers. An economic evaluation will include a cost-effectiveness analysis and a cost–benefit analysis. Discussion This will be the largest contemporary randomised trial of smoking cessation interventions in dental settings and one of the first to evaluate enhanced interventions. E-cigarettes were included as an intervention due to growing evidence of their effectiveness. They will be compared to VBA and NRT, and oral health outcomes assessed. The multi-centre, pragmatic design of this trial supports the external validity and potential for impacting clinical practice. Trial registration ISRCTN 13158982. Registered on 10 May 2022. https://www.isrctn.com/ISRCTNISRCTN13158982

The COVID-19 pandemic has resulted in unprecedented disruption to society, which indirectly affects infectious disease dynamics. We aimed to assess the effects of COVID-19-related disruption on dengue, a major expanding acute public health threat, in southeast Asia and Latin America. We assembled data on monthly dengue incidence from WHO weekly reports, climatic data from ERA5, and population variables from WorldPop for 23 countries between January, 2014 and December, 2019 and fit a Bayesian regression model to explain and predict seasonal and multi-year dengue cycles. We compared model predictions with reported dengue data January to December, 2020, and assessed if deviations from projected incidence since March, 2020 are associated with specific public health and social measures (from the Oxford Coronavirus Government Response Tracer database) or human movement behaviours (as measured by Google mobility reports). We found a consistent, prolonged decline in dengue incidence across many dengue-endemic regions that began in March, 2020 (2·28 million cases in 2020 vs 4·08 million cases in 2019; a 44·1% decrease). We found a strong association between COVID-19-related disruption (as measured independently by public health and social measures and human movement behaviours) and reduced dengue risk, even after taking into account other drivers of dengue cycles including climatic and host immunity (relative risk 0·01–0·17, p<0·01). Measures related to the closure of schools and reduced time spent in non-residential areas had the strongest evidence of association with reduced dengue risk, but high collinearity between covariates made specific attribution challenging. Overall, we estimate that 0·72 million (95% CI 0·12–1·47) fewer dengue cases occurred in 2020 potentially attributable to COVID-19-related disruption. In most countries, COVID-19-related disruption led to historically low dengue incidence in 2020. Continuous monitoring of dengue incidence as COVID-19-related restrictions are relaxed will be important and could give new insights into transmission processes and intervention options. National Key Research and Development Program of China and the Medical Research Council.

Background While it is recommended that childcare services implement policies and practices to support obesity prevention, there remains limited evidence to inform policy and practice. The aim of this study is to examine the effectiveness of performance review and facilitated feedback in increasing the implementation of healthy eating and physical activity-promoting policies and practices in childcare services. Methods The study was conducted with childcare services in the Hunter New England region of New South Wales, Australia. Eligible services were randomised to a wait-list control group or to receive the implementation strategy. The strategy targeted the implementation of written nutrition, physical activity, and small screen recreation policies; providing information to families regarding healthy eating, physical activity, and small screen time; providing twice weekly healthy eating learning experiences to children; providing water and plain milk only to children; providing fundamental movement skills activities for children every day; and limiting the use of electronic screen time for educational purposes and learning experiences. Intervention services received a performance review and facilitated feedback process five times over the 10 months that included an assessment of current practices, goal setting, identification of barriers to implementation, problem-solving, and resource provision. The primary outcome was the proportion of services implementing all six policies and practices, assessed by nominated supervisor completion of a computer-assisted telephone interview at baseline and 12-month follow-up. Results One hundred and eight services took part. There were no significant differences in the proportion of services implementing all six practices at 12 months (mean difference 0.51; 95% CI 0.16 to 1.58; p  = 0.24). There were also no differences between groups in the mean number of policies and practices implemented (mean difference 0.1; 95% CI − 0.4 to 0.6; p  = 0.71), or the proportion implementing each of the six individual policies and practices at 12 months (OR range 0.57 to 1.85; p  > 0.05). Conclusions Further support may be required to assist childcare services to make recommended changes to their policies and practices. Trial registration The trial was registered retrospectively on 10 September 2014 with the Australian New Zealand Clinical Trials Registry ACTRN12614000972628 .

Background Despite the known benefits of healthy eating in childhood, few Australian childcare services provide food that is consistent with dietary guidelines. The effectiveness of a web-based menu planning intervention to increase childcare service provision of healthy foods and decrease provision of discretionary foods in long day-care services in Australia was assessed in a randomised controlled trial. Here we consider the costs, consequences, cost-effectiveness and budget impact of the intervention using data collected within the trial. Methods The prospective trial-based economic evaluation involved 54 childcare services across New South Wales (NSW), Australia. Services were randomised to a 12-month intervention or usual care. The intervention involved access to a web-based menu planning and decision support tool and online resources. Effectiveness measures included mean number of food groups, overall menu and individual food group compliance with dietary guidelines, and mean servings of food groups at 12 months. Costs (reported in $AUD, 2017/18) were evaluated from both health sector and societal perspectives. The direct cost to support uptake of the intervention was calculated, as were costs to each childcare service. The incremental cost of the intervention was calculated as the net difference in the cost to undertake menu planning and review plus the direct cost of the intervention. Incremental cost-effectiveness ratios (ICERs) including uncertainty intervals were estimated for differences in costs and effects between intervention and control groups. A relative value index was calculated to determine overall value for money. Results Over the 12 months of the trial, we calculated a difference in cost between usual practice and intervention groups of − $482 (95% UI − $859, − $56). While the measured increase in menu and food group compliance within the trial did not reach statistical significance, there were significant improvements in mean servings of fruit and discretionary food, represented in the cost-consequence analysis. The calculated relative value index of 1.1 suggests that the intervention returns acceptable value for money for the outcomes generated. Conclusion Compared to usual practice, web-based programmes may offer an efficient and sustainable alternative for childcare services to improve the provision of healthy foods to children in their care. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12616000974404

Limiting dysfunctional neutrophilic inflammation while preserving effective immunity requires a better understanding of the processes that dictate neutrophil function in the tissues. Quantitative mass-spectrometry identified how inflammatory murine neutrophils regulated expression of cell surface receptors, signal transduction networks, and metabolic machinery to shape neutrophil phenotypes in response to hypoxia. Through the tracing of labeled amino acids into metabolic enzymes, proinflammatory mediators, and granule proteins, we demonstrated that ongoing protein synthesis shapes the neutrophil proteome. To maintain energy supplies in the tissues, neutrophils consumed extracellular proteins to fuel central carbon metabolism. The physiological stresses of hypoxia and hypoglycemia, characteristic of inflamed tissues, promoted this extracellular protein scavenging with activation of the lysosomal compartment, further driving exploitation of the protein-rich inflammatory milieu. This study provides a comprehensive map of neutrophil proteomes, analysis of which has led to the identification of active catabolic and anabolic pathways that enable neutrophils to sustain synthetic and effector functions in the tissues.

ObjectivesAn interferon (IFN) gene signature (IGS) is present in approximately 50% of early, treatment naive rheumatoid arthritis (eRA) patients where it has been shown to negatively impact initial response to treatment. We wished to validate this effect and explore potential mechanisms of action.MethodsIn a multicentre inception cohort of eRA patients (n=191), we examined the whole blood IGS (MxA, IFI44L, OAS1, IFI6, ISG15) with reference to circulating IFN proteins, clinical outcomes and epigenetic influences on circulating CD19+ B and CD4+ T lymphocytes.ResultsWe reproduced our previous findings demonstrating a raised baseline IGS. We additionally showed, for the first time, that the IGS in eRA reflects circulating IFN-α protein. Paired longitudinal analysis demonstrated a significant reduction between baseline and 6-month IGS and IFN-α levels (p<0.0001 for both). Despite this fall, a raised baseline IGS predicted worse 6-month clinical outcomes such as increased disease activity score (DAS-28, p=0.025) and lower likelihood of a good EULAR clinical response (p=0.034), which was independent of other conventional predictors of disease activity and clinical response. Molecular analysis of CD4+ T cells and CD19+ B cells demonstrated differentially methylated CPG sites and dysregulated expression of disease relevant genes, including PARP9, STAT1, and EPSTI1, associated with baseline IGS/IFNα levels. Differentially methylated CPG sites implicated altered transcription factor binding in B cells (GATA3, ETSI, NFATC2, EZH2) and T cells (p300, HIF1α).ConclusionsOur data suggest that, in eRA, IFN-α can cause a sustained, epigenetically mediated, pathogenic increase in lymphocyte activation and proliferation, and that the IGS is, therefore, a robust prognostic biomarker. Its persistent harmful effects provide a rationale for the initial therapeutic targeting of IFN-α in selected patients with eRA.

Foods provided in childcare services are not consistent with dietary guideline recommendations. Web-based systems offer unique opportunities to support the implementation of such guidelines. This study aimed to assess the effectiveness of a Web-based menu planning intervention in increasing the mean number of food groups on childcare service menus that comply with dietary guidelines. Secondary aims were to assess the impact of the intervention on the proportion of service menus compliant with recommendations for (1) all food groups; (2) individual food groups; and (3) mean servings of individual food groups. Childcare service use and acceptability of the Web-based program were also assessed. A single-blind, parallel-group randomized controlled trial was undertaken with 54 childcare services in New South Wales, Australia. Services were randomized to a 12-month intervention or usual care control. Intervention services received access to a Web-based menu planning program linked to their usual childcare management software system. Childcare service compliance with dietary guidelines and servings of food groups were assessed at baseline, 3-month follow-up, and 12-month follow-up. No significant differences in the mean number of food groups compliant with dietary guidelines and the proportion of service menus compliant with recommendations for all food groups, or for individual food groups, were found at 3- or 12-month follow-up between the intervention and control groups. Intervention service menus provided significantly more servings of fruit (P<.001), vegetables (P=.03), dairy (P=.03), and meat (P=.003), and reduced their servings of discretionary foods (P=.02) compared with control group at 3 months. This difference was maintained for fruit (P=.03) and discretionary foods (P=.003) at 12 months. Intervention childcare service staff logged into the Web-based program an average of 40.4 (SD 31.8) times and rated the program as highly acceptable. Although improvements in childcare service overall menu and individual food group compliance with dietary guidelines were not statistically significant, findings indicate that a Web-based menu planning intervention can improve the servings for some healthy food groups and reduce the provision of discretionary foods. Future research exploring the effectiveness of differing strategies in improving the implementation of dietary guidelines in childcare services is warranted. Australian New Zealand Clinical Trial Registry (ANZCTR): 16000974404; http://www.anzctr.org.au/ACTRN12616000974404.aspx.