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Although teams of negotiators are widely assumed to be better at unlocking integrative solutions compared to individual negotiators, the interteam negotiation context is characterized by unique challenges that can make effective collaboration between teams difficult. We extend our theoretical understanding of interteam negotiations by offering novel insights about when and why teams realize their potential in integrative negotiations. Specifically, we propose a theoretical model that explains how hierarchical team structures reduce information elaboration within teams, which reinforces "fixed-pie" assumptions that prompt the reliance on value-claiming behaviors between teams and lower high-quality outcomes such as the joint gain achieved. Across four studies, each involving interactive team-on-team negotiations, we provide support for the hypothesized effects of formal intrateam hierarchies on joint gain, and test a useful intervention to mitigate the harmful effects of hierarchically structured teams at the negotiation table. Contributions to the literatures on team negotiations, interteam collaboration, and hierarchical differences within teams are discussed. [ABSTRACT FROM AUTHOR]

Immunological adaptions during pregnancy play a crucial role in healthy fetal development. Aberrant immune modifications however contribute to adverse pregnancy outcomes, which may be driven by maternal factors such as previous pregnancies and BMI. This secondary analysis of the MicrobeMom2 RCT investigates the changes to maternal inflammatory biomarkers derived from serum and stimulated peripheral blood mononuclear cells (PBMCs) during pregnancy, and the effects of previous pregnancies (parity) and BMI on maternal immune responses. Changes in immune and metabolic biomarkers from early (11–15 weeks' gestation) to late (28–32 weeks' gestation) pregnancy were compared using paired t-tests. Participants were then split by parity (nulliparous, parous) and BMI (BMI < 25, BMI > = 25), and the relationship between parity and BMI with immune biomarker levels was examined using independent t-tests, paired t-tests, ANCOVA, and linear regression. Equivalent non-parametric tests were used for skewed data. Recruited women (n = 72) were on average 31.17 (SD ± 4.53) years of age and 25.11 (SD ± 3.82) BMI (kg/m2). Of these, 51 (70.8%) had a previous term pregnancy. Throughout gestation, PBMC cytokines displayed contrasting trends to serum, with a dampening of immune responses noted in PBMCs, and enhanced production of cytokines observed in the serum. Significant decreases in PBMC derived TNF-α, IL-10 and IFN-γ were seen from early to late pregnancy. Serum C3, IL-17A, IL-6, TNF-α, CD163, GDF-15 and leptin increased throughout gestation. First pregnancy was associated with higher levels of leptin in late pregnancy, while parous women showed significant decreases in PBMC derived TNF-α, IL10, and IFN-γ with gestation. Differences in levels of C3, IL-17A, TNF-α, GDF-15 and leptin were observed across BMI groups. Overall, serum-derived cytokines exhibit contrasting levels to those derived from stimulated PBMCs. Maternal immune responses undergo significant changes from early to late pregnancy, which are influenced by parity and BMI. These differences aid our understanding as to why first-time mothers are at greater risk of placental disease such as pre-eclampsia and fetal growth restriction. [ABSTRACT FROM AUTHOR]

This article highlights the value in taking a multi‐temporal perspective to the literature on underdogs and favorites in competitive contexts. We contend that an inherent feature of the psychological experience of being an underdog or favorite is the coexistence of thoughts related to the past and future. Building upon this key insight, we adopt a multi‐temporal lens to compare current research on underdogs and favorites to the broader literature studying competition and motivation in intergroup contexts, with the goal of identifying possible areas of coherence and contradiction in relation to other relevant theoretical frameworks. Through this analysis, we put forth a set of what we hope are thought‐provoking research questions that are intended to guide and inspire future work in this domain. [ABSTRACT FROM AUTHOR]

This correction notice addresses errors in a scientific article titled "Caspase-1-dependent inflammasomes mediate photoreceptor cell death in photo-oxidative damage-induced retinal degeneration." The errors involve the use of the same group of wildtype mice as a comparison to multiple knockout models in several figures. The corrected information shows that Caspase1/11−/− mice have better-preserved retinal function and reduced inflammation and cell death following photo-oxidative damage compared to wildtype controls. Similarly, Nlrp3−/− mice show better-preservation of retinal function following photo-oxidative damage compared to wildtype controls. On the other hand, Casp11−/− mice show no preservation of retinal function following photo-oxidative damage. The correction also addresses errors in the legends of Supplementary Figures 1, 2, and 3, clarifying that the wildtype controls used in these figures are the same as in other figures. [Extracted from the article]

Any single competition is rarely a "one-off" event and instead is often part of a larger sequence of related competitions. Thus, we contend that in order to better understand people's competitive experiences, we must take a more holistic view, where their experiences and behaviors in the present are a function of their past and expected future outcomes. This research expands the temporal lens of competition by examining how past outcomes (i.e., winning vs. losing streak) and future expectations (i.e., underdog vs. favorite standing) collectively influence an actor's cognitive and affective reactions to a competition, with implications for their willingness to transgress. Studies 1 (fantasy football managers) and 2 (the English Premiere League teams) show that streaks and underdog vs. favorite standing interact to predict competitive transgressions: winning streaks increase transgressions for underdogs, and losing streaks increase transgressions for favorites. Studies 3 (public defenders) and 4 (Democrats and Republicans) experimentally manipulate streaks and standing and unpack the cognitive (i.e., outcome uncertainty) and affective (i.e., excitement for underdogs, and anxiety for favorites) mechanisms that precipitate these transgressions. Theoretical implications for the competition literature, as well as managerial insights, are discussed. [ABSTRACT FROM AUTHOR]

Organizations benefit from including employees with dissimilar values and perspectives, but their ability to realize these benefits is constrained by the degree to which those holding the dissimilar values (i.e., value minorities) feel comfortable engaging with their colleagues and the work of the collective. We extend theory on value dissimilarity by directly examining the experience of individuals whose values are dissimilar from those of their colleagues, and factors driving their engagement in work. Our examination spanned three studies: a laboratory experiment, a vignette study of employed adults, and a three-wave survey of student project groups. We found that the negative relationship between holding dissimilar values from one's colleagues and engagement was lessened when value minorities disclosed personal information unrelated to their dissimilar values (Studies 1–3). Self-disclosure also moderated the negative relationship between value dissimilarity and feeling respected by one's colleagues (Studies 2 and 3). Furthermore, felt respect mediated the effect of value dissimilarity on engagement, and this indirect effect was moderated by self-disclosure (Studies 2 and 3). Overall, this research is relevant to organizations seeking to capitalize upon the benefits of minority perspectives in the workforce but suggests that a critical first step is to prioritize the experience of value minorities and the decreased sense of social worth that can accompany this experience. By fostering an environment conducive to self-disclosure, organizations can help to alleviate the discomfort associated with value dissimilarity, thereby ensuring that all people, including the value minority, feel respected and are maximally engaged at work. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.15768. [ABSTRACT FROM AUTHOR]

Purpose: Evidence-based guidelines for cancer strongly support nutrition and dietetic services for people with cancer and carers in order to improve patient-centred and health service outcomes. Access to nutrition services and information after completing active cancer treatment is relatively unknown in Australia. This study aimed to determine the availability, accessibility, barriers, and preferences to nutrition services and information after cancer treatment in Australia. Methods: Utilising mixed methods, people with cancer and carers completed a cross-sectional survey, and a sub-group of participants completed a semi-structured interview. The survey evaluated the availability of nutrition services, nutrition information searched, barriers, and preferences for nutrition information. Semi-structured interviews explored participant experience with nutrition services and information. Results: The 149 participants (including 10 carers) were predominately male and with a diagnosis of prostate cancer (63%). Overall, 23% of participants received nutrition information from a dietitian after cancer treatment. Participants (78%) indicated that accessing a nutrition specialist is the main barrier to receiving nutrition care after treatment. Most searched nutrition information on the internet (55%) and found the information easy to understand (89%), but conflicting (52%). Thematic analysis of interviews in fourteen cancer patients revealed three key themes pertaining to (1) preferred referral and timing of nutrition services, (2) lack of confidence in publicly available nutrition information, and (3) streamlining nutrition services for greater access. Conclusion: Access to a dietitian and evidence-based information after cancer treatment is limited for people with cancer and carers in Australia, despite the high interest and need for ongoing nutrition care. Implications for Cancer Survivors: Models of care evaluating the provision of appropriate nutrition care and information provision after cancer treatment are needed to address this unmet survivorship need. [ABSTRACT FROM AUTHOR]

The metallome has been involved in the pathological investigation into ocular tissue for decades; however, as technologies advance, more information can be ascertained from individual tissue sections that were not previously possible. Herein, a demonstration of complementary techniques has been utilized to describe the distribution and concentrations of essential metals in both wildtype (WT) and rhodopsin (Rho−/−) ocular tissues. The multimodal approach described is an example of complementary datasets that can be produced when employing a multifaceted analytical approach. Heterogenous distributions of copper and zinc were observable within both WT and Rho−/− tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and the distributions of further trace elements notoriously problematic for ICP-MS analysis (phosphorous, Sulfur, chlorine, potassium, calcium, iron, and aluminum) were analysed by particle-induced X-ray emission (PIXE). [ABSTRACT FROM AUTHOR]

The current research sheds new light on how and why status hierarchies impact interpersonal helping by examining people's reactions to recently experienced status change. Specifically, we incorporate findings from research on the self-serving attributional bias to theorize about how the direction of status change (i.e., a gain or a loss) can shape the extent to which people accept or deflect personal responsibility for their change in status, which we argue will then impact other-concern and, thus, their willingness to help. Further, we identify status change legitimacy as a key contingency that will strengthen or weaken the psychological and behavioral effects of status change. Among firefighter teams (Study 1), participants in the laboratory (Studies 2 and 3), and student teams (Study 4), we show that (1) status change impacts interpersonal helping through its impact on changes in other-concern and (2) status change legitimacy moderates the effect of status change on both other-concern and interpersonal helping. Additionally, we document an asymmetry with regards to the effects of status change on both other-concern and helping behavior (i.e., with the negative impact of a status loss being stronger than the positive impact of a status gain). Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

Determining the locations of proteins within the eye thought to be involved in ocular pathogenesis is important to determine how best to target them for therapeutic benefits. However, immunohistochemistry is limited by the availability and specificity of antibodies. Additionally, the perceived role of both essential and non-essential metals within ocular tissue has been at the forefront of age-related macular degeneration (AMD) pathology for decades, yet even key metals such as copper and zinc have yet to have their roles deconvoluted. Here, mass spectrometry imaging (MSI) is employed to identify and spatially characterize both proteomic and metallomic species within ocular tissue to advance the application of a multiomic imaging methodology for the investigation of ocular diseases. [ABSTRACT FROM AUTHOR]

Pattern recognition receptors (PRRs) of the innate immune system represent the critical front‐line defense against pathogens, and new vaccine formulations target these PRR pathways to boost vaccine responses, through activation of cellular/Th1 immunity. The majority of pediatric vaccines contain aluminum (ALUM) or monophosphoryl lipid A (MPLA) as adjuvants to encourage immune activation. Evidence suggests that elements of the innate immune system, currently being targeted for vaccine adjuvanticity do not fully develop until puberty and it is likely that effective adjuvants for the neonatal and pediatric populations are being overlooked due to modeling of responses in adult systems. We recently reported that the activity of the cytosolic nucleic acid (CNA) sensing family of PRRs is strong in cord blood and peripheral blood of young children. This study investigates the function of CNA sensors in subsets of neonatal innate immune cells and shows that myeloid cells from cord blood can be activated to express T cell costimulatory markers, and also to produce Th1 promoting cytokines. CD80 and CD86 were consistently up‐regulated in response to cytosolic Poly(I:C) stimulation in all cell types examined and CNA activation also induced robust Type I IFN and low levels of TNFα in monocytes, monocyte‐derived macrophages, and monocyte‐derived dendritic cells. We have compared CNA activation to adjuvants currently in use (MPLA or ALUM), either alone or in combination and found that cytosolic Poly(I:C) in combination with MPLA or ALUM can improve expression of activation marker levels above those observed with either adjuvant alone. This may prove particularly promising in the context of improving the efficacy of existing ALUM‐ or MPLA‐containing vaccines, through activation of T cell‐mediated immunity. [ABSTRACT FROM AUTHOR]

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Staphylococcus aureus persistently colonises the anterior nares of a significant proportion of the healthy population, however the local immune response elicited during S. aureus nasal colonisation remains ill-defined. Local activation of IL-17/IL-22 producing T cells are critical for controlling bacterial clearance from the nasal cavity. However, recurrent and long-term colonisation is commonplace indicating efficient clearance does not invariably occur. Here we identify a central role for the regulatory cytokine IL-10 in facilitating bacterial persistence during S. aureus nasal colonisation in a murine model. IL-10 is produced rapidly within the nasal cavity following S. aureus colonisation, primarily by myeloid cells. Colonised IL-10-/- mice demonstrate enhanced IL-17+ and IL-22+ T cell responses and more rapidly clear bacteria from the nasal tissues as compared with wild-type mice. S. aureus also induces the regulatory cytokine IL-27 within the nasal tissue, which acts upstream of IL-10 promoting its production. IL-27 blockade reduces IL-10 production within the nasal cavity and improves bacterial clearance. TLR2 signalling was confirmed to be central to controlling the IL-10 response. Our findings conclude that during nasal colonisation S. aureus creates an immunosuppressive microenvironment through the local induction of IL-27 and IL-10, to dampen protective T cell responses and facilitate its persistence. Author summary: Nasal colonisation by the bacterium Staphylococcus aureus is a very common occurrence in the human population. However there is a lack of knowledge on the immune response that controls nasal colonisation. It is known that a local pro-inflammatory immune response is important for bacterial clearance, however sustained colonisation is commonplace suggesting efficient clearance may not be occurring. Here we demonstrate for the first time that S. aureus is manipulating the host immune response by promoting immunosuppression in the nasal cavity which enables bacterial survival. We found that the regulatory proteins IL-10 and IL-27 are central to this suppressive response and result in reduced protective T cell responses. We also demonstrate that S. aureus is inducing IL-27 production to enhance IL-10 production in order to prolong bacterial colonisation. Our findings show that the host-pathogen interaction during nasal colonisation is more complex than previously described and that S. aureus is capable of manipulating the regulatory immune response of the host for its' own benefit. [ABSTRACT FROM AUTHOR]

SARM1 (sterile alpha and armadillo motif-containing protein) is a highly conserved Toll/IL-1 Receptor (TIR) adaptor with important roles in mediating immune responses. Studies in the brain have shown that SARM1 plays a role in induction of neuronal axon degeneration in response to a variety of injuries. We recently demonstrated that SARM1 is pro-degenerative in a genetic model of inherited retinopathy. This current study aimed to characterise the effect of SARM1 deletion in an alternative model of retinal degeneration (RD) in which the retinal pigment epithelium (RPE) fragments following administration of oxidising agent, sodium iodate (NaIO3), leading to subsequent photoreceptor cell death. Following administration of NaIO3, we observed no apparent difference in rate of loss of RPE integrity in SARM1 deficient mice compared to WT counterparts. However, despite no differences in RPE degeneration, photoreceptor cell number and retinal thickness were increased in Sarm1–/– mice compared to WT counterparts. This apparent protection of the photoreceptors in SARM1 deficient mice is supported by an observed decrease in pro-apoptotic caspase-3 in the photoreceptor layer of Sarm1–/– mice compared to WT. Together these data indicate a pro-degenerative role for SARM1 in the photoreceptors, but not in the RPE, in an oxidative stress induced model of retinal degeneration consistent with its known degenerative role in neurons in a range of neurodegenerative settings. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory infection (ARI) in childhood is common, but more knowledge on the burden and natural history of ARI in the community is required. A better understanding of ARI risk factors, treatment, and outcomes will help support parents to manage their sick child at home. Digital health tools are becoming more widely adopted in clinical care and research and may assist in understanding and managing common pediatric diseases, including ARI, in hospitals and in the community. We integrated 2 digital tools--a web-based discharge communication system and the REDCap (Research Electronic Data Capture) platform--into the Pragmatic Adaptive Trial for Acute Respiratory Infection in Children to enhance parent and physician engagement around ARI discharge communication and our patient registry. Objective: The objective of this study is to determine the efficacy and usability of digital tools integrated into a pediatric patient registry for ARI. Methods: Semistructured interviews and software interface usability testing were conducted with 11 parents and 8 emergency department physicians working at a tertiary pediatric hospital and research center in Perth, Western Australia, in 2019. Questions focused on experiences of discharge communication and clinical trial engagement. Responses were analyzed using the qualitative Framework Method. Participants were directly observed using digital interfaces as they attempted predetermined tasks that were then classified as success, failure, software failure, or not observed. Participants rated the interfaces using the System Usability Scale (SUS). Results: Most parents (9/11, 82%) indicated that they usually received verbal discharge advice, with some (5/11, 45%) recalling receiving preprinted resources from their physician. Most (8/11, 73%) would also like to receive discharge advice electronically. Most of the physicians (7/8, 88%) described their usual practice as verbal discharge instructions, with some (3/8, 38%) reporting time pressures associated with providing discharge instructions. The digital technology option was preferred for engaging in research by most parents (8/11, 73%). For the discharge communication digital tool, parents gave a mean SUS score of 94/100 (SD 4.3; A grade) for the mobile interface and physicians gave a mean usability score of 93/100 (SD 4.7; A grade) for the desktop interface. For the research data management tool (REDCap), parents gave a mean usability score of 78/100 (SD 11.0; C grade) for the mobile interface. Conclusions: Semistructured interviews allowed us to better understand parent and physician experiences of discharge communication and clinical research engagement. Software interface usability testing methods and use of the SUS helped us gauge the efficacy of our digital tools with both parent and physician users. This study demonstrates the feasibility of combining qualitative research methods with software industry interface usability testing methods to help determine the efficacy of digital tools in a pediatric clinical research setting. [ABSTRACT FROM AUTHOR]

Hepatitis A virus (HAV) infection is a notifiable disease in Ireland, with national coverage of clinical and laboratory surveillance. In December 2020, a cluster of 11 HAV cases among the Irish Traveller community was detected. The outbreak investigation identified 61 total HAV cases from September 2020 to November 2021. Sequenced isolates were sub-genotype IA with identical genome sequence. Case-patients were predominantly aged under 18 (77%), hospitalised (46%) and lived on communal residential sites. Mass onsite HAV vaccination was employed following failure of initial ring vaccination to contain the outbreak. This is the largest outbreak of HAV described in Ireland, involving spillover to the UK and Netherlands. We recommend mass HAV vaccination and tailored communication for outbreak control in migratory subpopulations. [ABSTRACT FROM AUTHOR]

Background: Contact tracing is conducted with the primary purpose of interrupting transmission from individuals who are likely to be infectious to others. Secondary analyses of data on the numbers of close contacts of confirmed cases could also: provide an early signal of increases in contact patterns that might precede larger than expected case numbers; evaluate the impact of government interventions on the number of contacts of confirmed cases; or provide data information on contact rates between age cohorts for the purpose of epidemiological modelling. We analysed data from 140,204 close contacts of 39,861 cases in Ireland from 1st May to 1st December 2020.Results: Negative binomial regression models highlighted greater numbers of contacts within specific population demographics, after correcting for temporal associations. Separate segmented regression models of the number of cases over time and the average number of contacts per case indicated that a breakpoint indicating a rapid decrease in the number of contacts per case in October 2020 preceded a breakpoint indicating a reduction in the number of cases by 11 days.Conclusions: We found that the number of contacts per infected case was overdispersed, the mean varied considerable over time and was temporally associated with government interventions. Analysis of the reported number of contacts per individual in contact tracing data may be a useful early indicator of changes in behaviour in response to, or indeed despite, government restrictions. This study provides useful information for triangulating assumptions regarding the contact mixing rates between different age cohorts for epidemiological modelling. [ABSTRACT FROM AUTHOR]

Background We describe the epidemiological trends and report and review the public health restrictions implemented during the first wave of the COVID-19 pandemic in Ireland. Methods The study reviewed confirmed cases of COVID-19 notified from 1 March to 18 July 2020. Data were obtained from the national COVID-19 Data Hub, the National Health Protection Surveillance Centre, the National Contact Management Programme and the European Centre for Disease Prevention and Control. Results A total of 25 617 cases were notified during the study period. Weekly cases and deaths peaked in mid-April 2020 at 5701 and 316, respectively. Mean number of close contacts per case was lowest at 0.7 in April, rising to 6.6 by July. Outbreak settings shifted from travel and workplace in March, to healthcare in April. Restrictions implemented on 12 March extended to full lockdown on 27 March. Phased relaxation of restrictions commenced 18 May. Effective suppression of community transmission of COVID-19 was achieved by June 2020. Conclusion Lockdown is a crude population-level restriction effective in controlling COVID-19. Phased relaxation of restrictions in Ireland, however, led to an immediate increase in mean number of contacts per case, which facilitates viral transmission unless individual-level restrictions are adhered to. This demonstrates a limitation of lockdown as a long-term mechanism of pandemic control. [ABSTRACT FROM AUTHOR]

Background: The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms.Results: After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector.Conclusions: Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population. [ABSTRACT FROM AUTHOR]

This essay offers a critical appreciation of the occurrence and function of meteorological language and imagery in selected Romantic poetry. Focusing on individual poems by Wordsworth, Coleridge, Clare, Keats and Shelley, I examine the ways in which weather writing in these examples may transcend the observational and become experiential, with weather conditions being a vehicle by which personal concerns can be articulated in a conflation of the external and the internal. [ABSTRACT FROM AUTHOR]

Cerebrovascular pathologies occur in up to 80% of cases of Alzheimer's disease; however, the underlying mechanisms that lead to perivascular pathology and accompanying blood–brain barrier (BBB) disruption are still not fully understood. We have identified previously unreported mutations in colony stimulating factor‐1 receptor (CSF‐1R) in an ultra‐rare autosomal dominant condition termed adult‐onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP). Cerebrovascular pathologies such as cerebral amyloid angiopathy (CAA) and perivascular p‐Tau were some of the primary neuropathological features of this condition. We have identified two families with different dominant acting alleles with variants located in the kinase region of the CSF‐1R gene, which confer a lack of kinase activity and signalling. The protein product of this gene acts as the receptor for 2 cognate ligands, namely colony stimulating factor‐1 (CSF‐1) and interleukin‐34 (IL‐34). Here, we show that depletion in CSF‐1R signalling induces BBB disruption and decreases the phagocytic capacity of peripheral macrophages but not microglia. CSF‐1R signalling appears to be critical for macrophage and microglial activation, and macrophage localisation to amyloid appears reduced following the induction of Csf‐1r heterozygosity in macrophages. Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF‐1R signalling causes re‐modelling of BBB‐associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer's‐like dementias. Synopsis: Two familial cohorts of ALSP, with novel pathological CSF1R variants were examined and an associating cerebrovascular amyloid‐β pathology identified. Deficits in peripheral macrophage function and blood‐brain barrier maintenance identified and suggested to contribute to ALSP. Two novel pathological CSF1R mutations were identified and characterised, indicating the observed pathology to be driven by CSF1R haploinsufficiency.Cerebral amyloid angiopathy (CAA) was identified as a novel accompanying pathology in ALSP, providing a potential single‐gene mutation capable of driving CAA itself.CSF1R heterozygosity was shown to negatively impact macrophage differentiation, phagocytosis and chemotaxis to the brain in response to amyloid‐β.Microglia heterozygous for Csf1r were shown to be uniquely capable of downregulating tight junction expression in brain endothelial cells. [ABSTRACT FROM AUTHOR]

The Girlhood Project (TGP) is a community based, service-learning/ research program that is part of the undergraduate course at Lesley University called "Girlhood, Identity and Girl Culture." TGP works with community partners to bring middle and high school girls to Lesley's campus for nine weeks as part of intergenerational girls' groups that are co-facilitated by Lesley students (also referred to as TGP students). TGP fosters the development of feminist leadership, critical consciousness, voice, and community action, and activism in all participants. In this article, we describe how we adapted TGP's model to a virtual and synchronous platform for students during COVID-19 and supported their learning competencies. We reflect critically on this experience by centering the voices and perspectives of girls, students, and professors. [ABSTRACT FROM AUTHOR]

Objective: This pilot study assessed the efficacy of personalised, printed and mobile‐accessible discharge instructions for pain relief for patients discharged from the ED. Methods: Patients presenting with pain caused by acute musculoskeletal or visceral complaints not requiring admission were eligible. Both groups received usual pain relief discharge advice, the intervention group received additional personalised printed and mobile‐accessible discharge instructions. Numerical Rating Scale pain scores were measured at ED visit. Pain scores, Patient Global Impression of Change scale improvement scores, satisfaction with instructions, recall of pain relief advice, receipt of side effects advice and unscheduled visits were measured at 5 days. Results: A total of 80 patients, recruited over 14 days, were randomly allocated to the intervention or control group. Two patients were excluded and 81% (n = 65) were followed up at 5 days. There was no significant difference in change of pain scores or improvement scores between groups from visit to 5 day follow up. The intervention group showed significantly higher odds of being 'very satisfied' compared to the control group (odds ratio [OR] 7.14, 95% confidence interval [CI] 1.18–50.00), significantly higher odds of full recall of pain relief medication advice (OR 20.00, 95% CI 1.56–100.00) and significantly higher odds of receiving information on medication side effects (OR 6.25, 95% CI 1.67–20.00). Conclusions: Patients who received personalised printed and mobile‐accessible ED discharge instructions for pain relief reported higher levels of satisfaction with their instructions, had better recall of their pain relief medications advice and received more information on medication side‐effects. [ABSTRACT FROM AUTHOR]

Rationale: Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene form the basis of cystic fibrosis (CF). There remains an important knowledge gap in CF as to how diminished CFTR activity leads to the dominant inflammatory response within CF airways.Objectives: To investigate if extracellular vesicles (EVs) contribute to inflammatory signalling in CF.Methods: EVs released from CFBE41o-, CuFi-5, 16HBE14o- and NuLi-1 cells were characterised by nanoparticle tracking analysis (NTA). EVs isolated from bronchoalveolar lavage fluid (BALF) from 30 people with CF (PWCF) were analysed by NTA and mass spectrometry and compared with controls. Neutrophils were isolated from the blood of 8 PWCF to examine neutrophil migration in the presence of CFBE41o- EVs.Results: A significantly higher level of EVs were released from CFBE41o- (p<0.0001) and CuFi-5 (p=0.0209) relative to control cell lines. A significantly higher level of EVs were detected in BALF of PWCF, in three different age groups relative to controls (p=0.01, 0.001, 0.002). A significantly lower level of EVs were released from CFBE41o- (p<0.001) and CuFi-5 (p=0.0002) cell lines treated with CFTR modulators. Significant changes in the protein expression of 126 unique proteins was determined in EVs obtained from the BALF of PWCF of different age groups (p<0.001-0.05). A significant increase in chemotaxis of neutrophils derived from PWCF was observed in the presence of CFBE41o EVs (p=0.0024) compared with controls.Conclusion: This study demonstrates that EVs are produced in CF airway cells, have differential protein expression at different ages and drive neutrophil recruitment in CF. [ABSTRACT FROM AUTHOR]

Activation of the inflammasome is involved in the progression of retinal degenerative diseases, in particular, in the pathogenesis of Age-Related Macular Degeneration (AMD), with NLRP3 activation the focus of many investigations. In this study, we used genetic and pharmacological approaches to explore the role of the inflammasome in a mouse model of retinal degeneration. We identify that Casp1/11−/− mice have better-preserved retinal function, reduced inflammation and increased photoreceptor survivability. While Nlrp3−/− mice display some level of preservation of retinal function compared to controls, pharmacological inhibition of NLRP3 did not protect against photoreceptor cell death. Further, Aim2−/−, Nlrc4−/−, Asc−/−, and Casp11−/− mice show no substantial retinal protection. We propose that CASP-1-associated photoreceptor cell death occurs largely independently of NLRP3 and other established inflammasome sensor proteins, or that inhibition of a single sensor is not sufficient to repress the inflammatory cascade. Therapeutic targeting of CASP-1 may offer a more promising avenue to delay the progression of retinal degenerations. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare the incidence of airway haemorrhage between participants who received manual cardiopulmonary resuscitation (CPR) and those who had received mechanical CPR using the LUCAS device.Methods: A retrospective cohort study was conducted by means of a medical chart review. All non-traumatic cardiac arrest patients that presented to the ED, from May 2014 to February 2018, were recruited. The groups were stratified according to those who had the majority of CPR performed using the LUCAS and those who had the majority of CPR performed manually. The primary outcome was the proportion of participants with airway haemorrhage, defined as blood observed in the endotracheal tube, pharynx, trachea or mouth, and documented in the doctor or nursing notes. Logistic regression analysis was performed to adjust for confounders.Results: 12 of 54 (22%) participants in the majority LUCAS CPR group had airway haemorrhage, compared with 20 of 215 (9%) participants in the majority manual CPR group, a difference of 13% (95% CI 3% to 26%, p=0.02). The unadjusted odds for developing airway haemorrhage in the majority LUCAS CPR group was 2.8 (95% CI 1.3 to 6.1). After adjusting for confounders, the odds for developing airway haemorrhage in the majority LUCAS CPR group was 2.5 (95% CI 1.1 to 5.7).Conclusions: The LUCAS mechanical CPR device is associated with a higher incidence of airway haemorrhage compared with manual CPR. Limitations in the study design mean this conclusion is not robust. [ABSTRACT FROM AUTHOR]

Low Density Granulocytes (LDGs), which appear in the peripheral blood mononuclear cell layer of density-separated blood, are seen in cancer, sepsis, autoimmunity, and pregnancy. Their significance in ANCA vasculitis (AAV) is little understood. As these cells bear the autoantigens associated with this condition and have been found to undergo spontaneous NETosis in other diseases, we hypothesized that they were key drivers of vascular inflammation. We found that LDGs comprise a 3-fold higher fraction of total granulocytes in active vs. remission AAV and disease controls. They are heterogeneous, split between cells displaying mature (75%), and immature (25%) phenotypes. Surprisingly, LDGs (unlike normal density granulocytes) are hyporesponsive to anti-myeloperoxidase antibody stimulation, despite expressing myeloperoxidase on their surface. They are characterized by reduced CD16, CD88, and CD10 expression, higher LOX-1 expression and immature nuclear morphology. Reduced CD16 expression is like that observed in the LDG population in umbilical cord blood and in granulocytes of humanized mice treated with G-CSF. LDGs in AAV are thus a mixed population of mature and immature neutrophils. Their poor response to anti-MPO stimulation suggests that, rather than being a primary driver of AAV pathogenesis, LDGs display characteristics consistent with generic emergency granulopoiesis responders in the context of acute inflammation. [ABSTRACT FROM AUTHOR]

Using an experiential qualitative design, this study explored 11 female prisoners' perspectives of problems living in prison. The findings reflected the immediate impact of the physical, social, and institutional environment. Problems with drug detoxification and bullying were prevalent. Prisoners were outward-looking and future-focused. Some feared substance-abuse relapse on release while mothers persistently worried about family outside prison. Many used maladaptive strategies to cope with their problems and most used activities to remain occupied. The study recommended creating supportive prison environments and interventions that enable women to manage the everyday problems they experience living in prison. [ABSTRACT FROM AUTHOR]

This research examines how an individual's place in the status hierarchy affects their willingness to expend effort on group tasks, why this occurs, and a contingency governing this relationship. Among firefighter teams (Study 1), MBA student workgroups (Study 2), and undergraduates in the laboratory (Study 3), we find that the relationship between status and effort, through performance expectations, is contingent on the perceived visibility of one's efforts (i.e., task visibility). When task visibility is high, greater status leads to higher performance expectations. When task visibility is low or absent, this relationship was not present. Overall, our findings help paint a more complete picture of the relationship between status, performance expectations, and effort in workgroups while also furthering our understanding of the psychological experience of status. Data are available at https://doi.org/10.1287/mnsc.2018.3103. [ABSTRACT FROM AUTHOR]

The IL-1 family of cytokines are well-known for their primary role in initiating inflammatory responses both in response to and acting as danger signals. It has long been established that IL-1 is capable of simultaneously regulating inflammation and angiogenesis, indeed one of IL-1's earliest names was haemopoeitn-1 due to its pro-angiogenic effects. Other IL-1 family cytokines are also known to have roles in mediating angiogenesis, either directly or indirectly via induction of proangiogenic factors such as VEGF. Of note, some of these family members appear to have directly opposing effects in different tissues and pathologies. Here we will review what is known about how the various IL-1 family members regulate vascular permeability and angiogenic function in a range of different tissues, and describe some of the mechanisms employed to achieve these effects. [ABSTRACT FROM AUTHOR]

There has been an ongoing debate in the research literature on violations of trustworthiness and the effectiveness of various forms of repair. In this article, three studies compare the effectiveness of several variables hypothesized to repair perceived trustworthiness in a negotiation context: (a) the use of words (accounts or apologies) versus deeds (compensation for the costs of violation), separately and in combination; (b) whether words or deeds pointed to the past or to the future; (c) the effect of an active or passive third‐party monitor of the negotiation, and (d) the type of trustworthiness (competence versus integrity) that was violated. Results show support for the repair effects for deeds over words, and that a focus on the past violation (through either words or deeds) is more effective than looking toward the future. Deeds, rather than words, also accounts for the strong impact of the combination of the two courses of action. In addition, results show that an active third‐party intervention has a stronger impact on repair than a passive intervention. Implications for theory and practice are discussed along with suggestions for future research. [ABSTRACT FROM AUTHOR]

Background: A measles outbreak occurred in age-appropriately vaccinated children in a school in a town in the South East of Ireland in September-November 2013.Aims: The purpose of this study was to investigate the risk factors associated with catching measles during the outbreak.Methods: Ninety-five children (4-5 years) in three classes, in the first year of primary school, were included in the study. Immunisation records on the South East Child Health Information System for first Measles Mumps and Rubella (MMR) vaccine for the 95 children were reviewed. Data collected included age at MMR, date of administration of MMR, MMR brand and batch number, and the General Practice at which MMR was administered. The risk factors analysed included age at vaccination, time of vaccination, class and the GP practice where MMR was administered. Statistical analysis was performed using Epi info 7 and SPSS v24.Results: Thirteen children in the cohort developed measles during the outbreak. All children in the cohort were age-appropriately vaccinated, with one dose of MMR vaccine. Analysis demonstrated statistically significant differences in the relative risk of developing measles according to the class a child was in, and the General Practice at which they were vaccinated.Conclusions: The reason for intense measles activity in one class was not established. Although a concurrent investigation into cold chain and vaccine stock management did not identify a cause for the high relative risk of measles in children vaccinated, recommendations were made for improving cold chain and vaccine stock management in General Practices. [ABSTRACT FROM AUTHOR]

Fas (CD95) signalling is best known for its role in apoptosis, however, recent reports have shown it to be involved in other cellular responses as well, including inflammation. Fas and its adaptor protein FADD are known to negatively regulate LPS‐induced proinflammatory responses, but their role in LPS‐induced type I interferon production is unknown. Here, we demonstrate that Fas engagement on macrophages, using an agonistic Fas antibody CH11, augments LPS‐induced NF‐κB responses, causing increased production of TNFα, IL‐8, IL‐6 and IL‐12. Conversely, costimulation with both LPS and CH11 causes a significant reduction in the level of interferon‐beta (IFNβ) production. This differential effect involves the Fas adaptor FADD because while LPS‐induced IL‐6 production increased in FADD−/− murine embryonic fibroblasts, LPS‐induced IFNβ production was significantly reduced in these cells. Overexpression of a dominant negative form of FADD (FADD‐DD) inhibits LPS‐induced IFNβ luciferase but not LPS‐induced NF‐κB luciferase. In contrast, overexpression of full‐length FADD inhibited LPS‐induced NF‐κB luciferase activation but was seen to augment LPS‐induced IFNβ luciferase. Moreover, FADD‐DD inhibits TRIF‐, TRAM‐, IKKε‐, TBK‐1‐ and TRAF3‐induced IFNβ luciferase production, with coimmunoprecipitation experiments demonstrating an interaction between FADD and TRIF. These data identify FADD as a novel component of the noncanonical Toll‐like receptor 4/IFNβ signalling pathway and demonstrate that both Fas and its adaptor FADD can differentially regulate the production of LPS‐induced proinflammatory cytokines and type I interferons. We have identified that the death receptor Fas and its adaptor protein FADD are able to differentially regulate the MYD88‐dependent and ‐independent arms of the TLR4 signalling pathway. FADD is a negative regulator of the MyD88‐dependent arm (A) but is an essential component of the MyD88‐independent pathway (B), facilitating induction of LPS‐induced IFN‐beta through an interaction with TRIF. [ABSTRACT FROM AUTHOR]

Background/aims Age-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland. Methods Prevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression. Results Older age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline. Conclusions The prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features. [ABSTRACT FROM AUTHOR]

Recent critiques of both the uses of and discourse surrounding big data have raised important questions as to the extent to which big data and big data techniques should be embraced. However, while the contextdependence of data has been recognized, there remains a tendency among social theorists and other commentators to treat certain aspects of the big data phenomenon, including not only the data but also the methods and tools used to move from data as database to data that can be interpreted and assigned meaning, in a homogenizing way. In this paper, we seek to challenge this tendency, and to explore the ways in which explicit consideration of the plurality of big data might inform particular instances of its exploitation. We compare one currently popular big data-inspired innovation — learning analytics — with three other big data contexts — the physical sciences, business intelligence and public health. Through these comparisons, we highlight some dangers of learning analytics implemented without substantial theoretical, ethical and design effort. In so doing, we also highlight just how plural data, analytical approaches and intentions are, and suggest that each new big data context needs to be recognized in its own singularity. [ABSTRACT FROM AUTHOR]

Learning analytic implementations are increasingly being included in learning management systems in higher education. We lay out some concerns with the way learning analytics – both data and algorithms – are often presented within an unproblematized Big Data discourse. We describe some potential problems with the often implicit assumptions about learning and learners – and indeed the tendency not to theorize learning explicitly – that underpin such implementations. Finally, we describe an attempt to devise our own analytics, grounded in a sociomaterial conception of learning. We use the data obtained to suggest that the relationships between learning and the digital traces left by participants in online learning are far from trivial, and that any analytics that relies on these as proxies for learning tends towards a behaviorist evaluation of learning processes. [ABSTRACT FROM PUBLISHER]

High prevalence rates of aggression during adolescence and associated adjustment difficulties for perpetrators and victims highlight the need for effective violence prevention programs. School-based prevention programs are advantageous as they occur in a key setting for youths' social and emotional development. The current study compared the efficacy of a combined universal violence prevention approach that included individual-level skill-building (i.e., lessons from Second Step) and school environment (i.e., Olweus Bullying Prevention Program; OBPP) interventions to OBPP alone. Participants were 231 sixth, seventh, and eighth graders (ages 11-15; M = 12.6, SD = 1.0) in middle school (48 % male, 67 % African American). A total of 14 classrooms were randomly assigned to the combined intervention (seven) or OBPP only comparison (seven) condition, split evenly across grades. Intervention effects were moderated by disability status and gender. Among students without disabilities those who received the combined intervention reported greater increases in anger regulation coping skills than those in the comparison condition. In contrast, among youth with disabilities greater increases in teacher-rated social skills were found for students in the combined intervention than students in the comparison condition at posttest. Gender-moderated effects included greater decreases in teacher ratings of externalizing problems and bullying behaviors for boys in the combined intervention versus the comparison condition at posttest. Study results inform school-based violence prevention programs and are discussed along with implications. [ABSTRACT FROM AUTHOR]

The current study examined longitudinal relations between overt and relational victimization, sadness and anger dysregulation, and depressive and anxiety symptoms across 6 months among an ethnically diverse sample of sixth graders (N = 485; 48% male; 65% African American). No direct longitudinal relations were found between peer victimization and internalizing symptoms or between internalizing symptoms and peer victimization, and these findings were consistent across gender and disability status. The relation between overt victimization and subsequent increases in relational victimization was stronger for youth with versus without high incidence disabilities. Significant indirect effects were found for overt victimization on both depressive and anxiety symptoms via sadness dysregulation. The strength of the indirect effects did not differ by gender. Findings highlight the merits of school-based violence prevention programs that address emotional management and are embedded within multi-tiered school environment interventions. [ABSTRACT FROM AUTHOR]