Extracellular pectin-RALF phase separation mediates FERONIA global signaling function.

The FERONIA (FER)-LLG1 co-receptor and its peptide ligand RALF regulate myriad processes for plant growth and survival. Focusing on signal-induced cell surface responses, we discovered that intrinsically disordered RALF triggers clustering and endocytosis of its cognate receptors and FER- and LLG1-dependent endocytosis of non-cognate regulators of diverse processes, thus capable of broadly impacting downstream responses. RALF, however, remains extracellular. We demonstrate that RALF binds the cell wall polysaccharide pectin. They phase separate and recruit FER and LLG1 into pectin-RALF-FER-LLG1 condensates to initiate RALF-triggered cell surface responses. We show further that two frequently encountered environmental challenges, elevated salt and temperature, trigger RALF-pectin phase separation, promiscuous receptor clustering and massive endocytosis, and that this process is crucial for recovery from stress-induced growth attenuation. Our results support that RALF-pectin phase separation mediates an exoskeletal mechanism to broadly activate FER-LLG1-dependent cell surface responses to mediate the global role of FER in plant growth and survival.

Developing Immune Profiles of Endangered Australian Sea Lion (Neophoca cinerea) Pups Within the Context of Endemic Hookworm (Uncinaria sanguinis) Infection.

As a top predator, the endangered Australian sea lion (Neophoca cinerea) is a sentinel of ecosystem change, where population trends can reflect broader shifts in the marine environment. The population of this endemic pinniped was historically diminished by commercial sealing, and recovery has been slowed by fishery interactions, disease and, potentially, pollutants. Hookworm infects 100% of neonatal pups and has been identified as a contributor to population decline. Here, a multivariable approach using traditional serological and novel molecular tools such as qPCR and ddPCR was used to examine immune phenotypes of developing Australian sea lion pups infected with the endemic hookworm (Uncinaria sanguinis) from two South Australian colonies. Results show changing immunophenotypes throughout the patent period of infection represented by pro-inflammatory cytokines (IL-6), IgG and acute-phase proteins. Although cytokines may prove useful as markers of resistance, in this study, IL-6 is determined to be an early biomarker of inflammation in Australian sea lion pups, excluding the alternative hypothesis. Additionally, immunological differences between animals from high- and low-intensity hookworm seasons, as well as ivermectin-treated animals, indicate hookworm infection modulation of the host immune response, as evidenced by a lower IL-6 mRNA expression in the non-treated groups. This study of the Australian sea lion is an example of an ecoimmunological approach to disease investigation, which can be applied to evaluate the impact of environmental and anthropogenic factors on susceptibility to infectious diseases in free-ranging species.

Social prediction modulates activity of macaque superior temporal cortex.

The ability to attribute thoughts to others, also called theory of mind (TOM), has been extensively studied in humans; however, its evolutionary origins have been challenged. Computationally, the basis of TOM has been interpreted within the predictive coding framework and associated with activity in the temporoparietal junction (TPJ). Here, we revealed, using a nonlinguistic task and functional magnetic resonance imaging, that activity in a region of the macaque middle superior temporal cortex was specifically modulated by the predictability of social situations. As in human TPJ, this region could be distinguished from other temporal regions involved in face processing. Our result suggests the existence of a precursor for the TOM ability in the last common ancestor of human and Old World monkeys.

Genomic characterisation of Salmonella enterica serovar Wangata isolates obtained from different sources reveals low genomic diversity.

Salmonella enterica serovar Wangata is an important pathogen in New South Wales (NSW), Australia. The incidence of S. Wangata is increasing and transmission is suspected to be via a non-food source. A recent outbreak investigation of sources of S. Wangata recovered isolates from humans, domestic animals, wildlife and the environment. Here, we extend that investigation by characterising and describing the genomic determinates of these isolates. We found that Australian S. Wangata isolates from different sources exhibited similar virulence and antimicrobial resistance gene profiles. There were no major genomic differences between isolates obtained from different geographical regions within Australia or from different host species. In addition, we found evidence (low number of SNPs and identical virulence gene profiles) suggestive of an international transmission event between Australia and the United Kingdom. This study supports the hypothesis that S. Wangata is shared between different hosts in NSW, Australia and provides strong justification for the continued use of genomic surveillance of Salmonella.

Divergent geography of Salmonella Wangata and Salmonella Typhimurium epidemiology in New South Wales, Australia.

Salmonella enterica serovar Wangata is an important cause of salmonellosis in the state of New South Wales, Australia. Standard surveillance has not identified a common food source and cases have been attributed to an unknown environmental or wildlife reservoir. Investigation of the spatial distribution of cases may provide valuable insights into local risk factors for infection and the potential role of the environment and wildlife. Using conditional autoregressive analysis, we explored the association between laboratory-confirmed cases of S. Wangata reported to the New South Wales Department of Health and human socio-demographic, climate, land cover and wildlife features. For comparison, a model was also fitted to investigate the association of cases of Salmonella enterica serovar Typhimurium, an established foodborne serotype, with the same features. To determine if cases of S. Wangata were associated with potential wildlife reservoir species, additional variables were included in the S. Wangata model that indicated areas of high suitability for each species. We found that cases of S. Wangata were associated with warmer temperatures, proximity to wetlands and amphibian species richness. In contrast, cases of S. Typhimurium were associated with human demographic features (proportion of the population comprising children <5 years old), climate (mean annual precipitation and mean annual temperature) and land cover (proportion comprising urban and evergreen broadleaf forest). These findings support the hypothesis that S. Wangata is likely to be associated with an environmental source. Whilst we expected S. Typhimurium to be associated with the human socio-demographic feature, the significance of the land cover features was surprising and might suggest the epidemiology of S. Typhimurium in Australia is more complex than currently understood.

Diversity of Salmonella serotypes from humans, food, domestic animals and wildlife in New South Wales, Australia.

BACKGROUND: Salmonella is an important human pathogen in Australia and annual case rates continue to increase. In addition to foodborne exposures, cases have been associated with animal and contaminated environment contact. However, routine surveillance in Australia has tended to focus on humans and food, with no reported attempts to collate and compare Salmonella data from a wider range of potential sources of exposure. METHODS: Salmonella data from humans, food, animals and environments were collated from a range of surveillance and diagnostic sources in New South Wales (NSW). Data were categorised to reflect one of 29 sample origins. Serotype diversity was described for each category, and the distribution of serotypes commonly isolated from humans was examined for each sample origin. The distribution of serotypes along the livestock-food-human continuum and at the companion animal-wildlife interface was also examined. RESULTS: In total, 49,872 Salmonella isolates were included in this analysis, comprising 325 serotypes. The vast majority of these isolates were from humans (n = 38,106). Overall S. Typhimurium was the most frequently isolated serotype and was isolated from all sample categories except natural environment and game meat. S. Enteriditis was not isolated from any livestock animal, however sporadic cases were documented in food, companion animals and a reptile. Many serotypes that were frequently isolated from livestock animals and associated food products were only rarely isolated from humans. In addition, a number of key human serotypes were only sporadically isolated from livestock and food products, suggesting alternative sources of infection. In particular, S. Paratyphi B Java and S. Wangata were more often isolated from wild animals. Finally, there was some overlap between serotypes in companion animals and wildlife, with cats in particular having a large number of serotypes in common with wild birds. CONCLUSIONS: This is the most comprehensive description of Salmonella data from humans, food, livestock, wildlife, companion animals and various environments in Australia reported to date. Results confirm that livestock and food are important sources of salmonellosis in humans but that alternative sources - such as contact with wildlife and environments - warrant further investigation. Surveillance in NSW is largely human-focussed: major knowledge gaps exist regarding the diversity and frequency of serotypes in animals. More systematic surveillance of domestic animals and wildlife is needed to inform targeted control strategies and quantitative source attribution modelling in this state.

Health system redesign using Collective Impact: implementation of the Behavioural Supports Ontario initiative in Southwest Ontario.

This paper describes how the Collective Impact framework facilitated the design, implementation and development of a quality improvement initiative aimed at changing the way healthcare is provided to older adults living with mental health, addictions, neurocognitive and behavioral issues in southwestern Ontario. By promoting a common agenda, shared measurement systems, mutually reinforcing activities, continuous communication and with leadership from a backbone organization, system-wide change occurred. Outcomes, operational/strategic, clinical, capacity enhancement and community support structures as well as challenges are discussed. Improved coordination with primary care will further support enhanced clinical activities and capacity development strategies. Large-scale, multisectoral change is possible when aligned with a collaborative, problem-solving framework that promotes the commitment of many service providers/agencies to a common agenda.

The South West Local Health Integration Network Behavioural Supports Ontario Experience.

Creating a seamless system of care with improved system and patient outcomes is imperative to the estimated 35,000 older adults living with mental health problems and addictions in the South West Local Health Integration Network. Building on existing investments and those offered through the Behavioural Supports Ontario program, strategies to improve system coordination were put in place, cross-sectoral partnerships were fostered, interdisciplinary teams from across the care continuum were linked, and educational opportunities were promoted. This evolving, co-created system has resulted in a decrease in alternate level of care cases among those with behavioural specialized needs and improved client/family perceptions of care. Also, in fiscal year 2014/15, it provided more than 7,000 care providers with learning opportunities.

Connecting the learners: improving uptake of a nursing home educational program by focusing on staff interactions.

PURPOSE OF THE STUDY: The CONNECT intervention is designed to improve staff connections, communication, and use of multiple perspectives for problem solving. This analysis compared staff descriptions of the learning climate, use of social constructivist learning processes, and outcomes in nursing facilities receiving CONNECT with facilities receiving a falls education program alone. DESIGN AND METHODS: Qualitative evaluation of a randomized controlled trial was done using a focus group design. Facilities (n = 8) were randomized to a falls education program alone (control) or CONNECT followed by FALLS (intervention). A total of 77 staff participated in 16 focus groups using a structured interview protocol. Transcripts were analyzed using framework analysis, and summaries for each domain were compared between intervention and control facilities. RESULTS: Notable differences in descriptions of the learning climate included greater learner empowerment, appreciation of the role of all disciplines, and seeking diverse viewpoints in the intervention group. Greater use of social constructivist learning processes was evidenced by the intervention group as they described greater identification of communication weaknesses, improvement in communication frequency and quality, and use of sense-making by seeking out multiple perspectives to better understand and act on information. Intervention group participants reported outcomes including more creative fall prevention plans, a more respectful work environment, and improved relationships with coworkers. No substantial difference between groups was identified in safety culture, shared responsibility, and self-reported knowledge about falls. IMPLICATIONS: CONNECT appears to enhance the use of social constructivist learning processes among nursing home staff. The impact of CONNECT on clinical outcomes requires further study.

Tool for evaluating research implementation challenges: a sense-making protocol for addressing implementation challenges in complex research settings.

BACKGROUND: Many challenges arise in complex organizational interventions that threaten research integrity. This article describes a Tool for Evaluating Research Implementation Challenges (TECH), developed using a complexity science framework to assist research teams in assessing and managing these challenges. METHODS: During the implementation of a multi-site, randomized controlled trial (RCT) of organizational interventions to reduce resident falls in eight nursing homes, we inductively developed, and later codified the TECH. The TECH was developed through processes that emerged from interactions among research team members and nursing home staff participants, including a purposive use of complexity science principles. RESULTS: The TECH provided a structure to assess challenges systematically, consider their potential impact on intervention feasibility and fidelity, and determine actions to take. We codified the process into an algorithm that can be adopted or adapted for other research projects. We present selected examples of the use of the TECH that are relevant to many complex interventions. CONCLUSIONS: Complexity theory provides a useful lens through which research procedures can be developed to address implementation challenges that emerge from complex organizations and research designs. Sense-making is a group process in which diverse members interpret challenges when available information is ambiguous; the groups' interpretations provide cues for taking action. Sense-making facilitates the creation of safe environments for generating innovative solutions that balance research integrity and practical issues. The challenges encountered during implementation of complex interventions are often unpredictable; however, adoption of a systematic process will allow investigators to address them in a consistent yet flexible manner, protecting fidelity. Research integrity is also protected by allowing for appropriate adaptations to intervention protocols that preserve the feasibility of 'real world' interventions.

A randomized controlled trial of an integrated care intervention to increase eligibility for chronic hepatitis C treatment.

OBJECTIVES: Mental health and substance abuse (MH/SA) comorbidities are the most oft-cited reasons for deferral from peginterferon (PegIFN) therapy for chronic hepatitis C virus (HCV). We sought to determine whether an integrated care intervention (INT) for patients deferred from PegIFN owing to MH/SA could improve subsequent treatment eligibility rates. METHODS: In this randomized controlled trial, 101 HCV patients who were evaluated at two hepatology centers and deferred from antiviral therapy owing to MH/SA were enrolled. Participants were randomized to an INT (N=50) or standard of care (SC; N=51). The INT group received counseling and case management for up to 9 months. All participants underwent 3-, 6-, and 9-month clinical follow-up visits, where hepatologists, masked to group, re-evaluated patients for treatment eligibility. Standardized mood and alcohol use instruments were administered to all participants to aid clinicians in treatment decisions. RESULTS: Of 101 participants, the mean age was 48 years and 50% were men, 61% Caucasian, and 77% genotype 1. Patients were initially deferred owing to psychiatric issues (35%), alcohol abuse (31%), drug abuse (9%), or more than one of these reasons (26%). In an intent-to-treat analysis, 42% (21/50) of INT participants became eligible for therapy compared to 18% (9/51) of SC participants (P=0.009, relative risk (RR)=2.38, 95% confidence interval (CI) (1.21, 4.68)). When baseline predictors significant at P<0.10 in univariate models were entered into multivariate models adjusted for treatment group, only baseline depression remained significant (P=0.05, RR=0.98, 95% CI (0.96, 1.00)). With the exception of a model adjusted for genotype, treatment group remained significant in all models. CONCLUSIONS: This trial suggests that INTs can increase eligibility for HCV treatment and expand treatment to the underserved population with MH/SA comorbidities.

Ara h 1-reactive T cells in individuals with peanut allergy.

BACKGROUND: Effective immunotherapy for peanut allergy is hampered by a lack of understanding of peanut-reactive CD4(+) T cells. OBJECTIVE: To identify, characterize, and track Ara h 1-reactive cells in subjects with peanut allergy by using Ara h 1-specific class II tetramers. METHODS: Tetramer-guided epitope mapping was used to identify the antigenic peptides within the peanut allergen Ara h 1. Subsequently, HLA class II/Ara h 1-specific tetramers were used to determine the frequency and phenotype of Ara h 1-reactive T cells in subjects with peanut allergy. Cytokine profiles of Ara h 1-reactive T cells were also determined. RESULTS: Multiple Ara h 1 epitopes with defined HLA restriction were identified. Ara h 1-specific CD4(+) T cells were detected in all of the subjects with peanut allergy tested. Ara h 1-reactive T cells in subjects with allergy expressed CCR4 but did not express CRTH2. The percentage of Ara h1-reactive cells that expressed the ß7 integrin was low compared with total CD4(+) T cells. Ara h 1- reactive cells that secreted IFN-γ, IL-4, IL-5, IL-10, and IL-17 were detected. CONCLUSION: In individuals with peanut allergy, Ara h 1-reactive T cells occurred at moderate frequencies, were predominantly CCR4(+) memory cells, and produced IL-4. Class II tetramers can be readily used to detect Ara h 1-reactive T cells in the peripheral blood of subjects with peanut allergy without in vitro expansion and would be effective for tracking peanut-reactive CD4(+) T cells during immunotherapy.

Structural forces and the production of TB-related stigma among Haitians in two contexts.

In recent years renewed interest in health-related stigma has underscored the importance of better understanding the structural underpinnings of stigma processes. This study investigated the influence of sociocultural context on perceived components of tuberculosis-related stigma in non-affected persons by comparing Haitians living in South Florida, USA, with Haitians residing in Léogane Commune, Haiti. Using the methods of cultural epidemiology, a two-phase study based on fieldwork between 2004 and 2007 collected ethnographic data on the cultural context and components of tuberculosis (TB) stigma, and administered a stigma scale developed specifically for these populations. Thematic analysis of stigma components expressed in interviews, focus groups and observation revealed commonalities as well as distinctive emphases of TB stigma in the two comparison groups. Factor analyses of stigma scale scores confirmed the thematic differences revealed in ethnographic findings and highlight the influence of political and economic factors in shaping the meaning and experience of illness. Perceived components of TB stigma among Haitians in South Florida incorporated aspects of Haitian identity as a negatively stereotyped minority community within the larger society, while in Haiti, stigma was associated primarily with poverty, malnutrition, and HIV co-infection. Discussion of findings focuses on the social production of perceived and anticipated stigma as it is influenced by structural forces including the influences of politics, economics, institutional policies, and health service delivery structures. The findings also demonstrate the value of a transnational framework encompassing both sending and receiving countries for understanding TB-related stigma in immigrant communities.

Stages of development and injury patterns in the early years: a population-based analysis.

BACKGROUND: In Canada, there are many formal public health programs under development that aim to prevent injuries in the early years (e.g. 0-6). There are paradoxically no population-based studies that have examined patterns of injury by developmental stage among these young children. This represents a gap in the Canadian biomedical literature. The current population-based analysis explores external causes and consequences of injuries experienced by young children who present to the emergency department for assessment and treatment. This provides objective evidence about prevention priorities to be considered in anticipatory counseling and public health planning. METHODS: Four complete years of data (1999-2002; n = 5876 cases) were reviewed from the Kingston sites of the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP), an ongoing injury surveillance initiative. Epidemiological analyses were used to characterize injury patterns within and across age groups (0-6 years) that corresponded to normative developmental stages. RESULTS: The average annual rate of emergency department-attended childhood injury was 107 per 1000 (95% CI 91-123), with boys experiencing higher annual rates of injury than girls (122 vs. 91 per 1000; p < 0.05). External causes of injury changed substantially by developmental stage. This lead to the identification of four prevention priorities surrounding 1) the optimization of supervision; 2) limiting access to hazards; 3) protection from heights; and 4) anticipation of risks. CONCLUSION: This population-based injury surveillance analysis provides a strong evidence-base to inform and enhance anticipatory counseling and other public health efforts aimed at the prevention of childhood injury during the early years.

Risk taking and recurrent health symptoms in Canadian adolescents.

OBJECTIVE: Psychosomatic health symptoms are commonly experienced by young people and are associated with chronic health problems. This study examines reports of psychosomatic health symptoms during adolescence, and associations between adolescent risk-taking and the occurrence of these symptoms. METHOD: A cross-sectional national health survey was performed in 2001/02 and involved 1746 young Canadians. Principal components analyses were used to derive a multiple risk-taking score. Multi-level regression models with individual participants (1st level) nested in schools (2nd level) were used to examine associations between individual then multiple risk-taking behaviors and psychosomatic symptoms. RESULTS: 37% of males and 48% of female students reported psychological health symptoms > once per week, while 30% of males and 41% of females reported somatic health symptoms. Strong associations were observed between individual risk-taking behaviors (cannabis use, other illicit drug use, drunkenness, smoking, unprotected sex) and psychosomatic health symptoms. A risk gradient was observed between multiple risk behaviors and these health symptoms. Youth who engaged in high levels of risk-taking behavior were two to four times more likely to report health symptoms. CONCLUSION: Adolescent lifestyles that include risk-taking behavior are strongly associated with the occurrence of psychosomatic health symptoms. Collectively, these measures are useful clinical indicators of adolescent health status.

Influence of individual- and area-level measures of socioeconomic status on obesity, unhealthy eating, and physical inactivity in Canadian adolescents.

BACKGROUND: Low socioeconomic status (SES) is a risk factor for obesity. However, few studies have used a multilevel analysis to determine the influence of both individual- and area-level determinants of SES on obesity, and these studies have been limited to adults. OBJECTIVE: The primary objective was to examine associations between individual- and area-level measures of SES and obesity among adolescents by using a multilevel analytic approach. A secondary objective was to examine associations between individual- and area-level measures of SES with unhealthy eating and physical inactivity. DESIGN: The study sample consisted of 6684 youth in grades 6-10 from 169 schools across Canada. Individual-level SES exposures included material wealth and perceived family wealth. Area-level SES exposures included unemployment rate, percentage of adult residents with less than a high school education, and average employment income from head of household. Associations between SES and the outcome measures were examined by using multilevel logistic regression procedures that modeled students (individual level) nested within schools (area level). RESULTS: Both individual-level and all 3 area-level SES measures were inversely associated with obesity. The odds for unhealthy eating were increased for those living in an area with a low percentage of residents with a high school education. The odds of being physically inactive increased with decreasing levels of material wealth and perception of family wealth. CONCLUSIONS: Individual- and area-level SES measures were independently related to obesity, which suggests that both individual and environmental approaches may be required to curtail adolescent obesity.

Cross-national study of fighting and weapon carrying as determinants of adolescent injury.

OBJECTIVES: We sought to (1) compare estimates of the prevalence of fighting and weapon carrying among adolescent boys and girls in North American and European countries and (2) assess in adolescents from a subgroup of these countries comparative rates of weapon carrying and characteristics of fighting and injury outcomes, with a determination of the association between these indicators of violence and the occurrence of medically treated injury. DESIGN AND SETTING: Cross-sectional self-report surveys using 120 questions were obtained from nationally representative samples of 161082 students in 35 countries. In addition, optional factors were assessed within individual countries: characteristics of fighting (9 countries); characteristics of weapon carrying (7 countries); and medically treated injury (8 countries). PARTICIPANTS: Participants included all consenting students in sampled classrooms (average age: 11-15 years). MEASURES: The primary measures assessed included involvement in physical fights and the types of people involved; frequency and types of weapon carrying; and frequency and types of medically treated injury. RESULTS: Involvement in fighting varied across countries, ranging from 37% to 69% of the boys and 13% to 32% of the girls. Adolescents most often reported fighting with friends or relatives. Among adolescents reporting fights, fighting with total strangers varied from 16% to 53% of the boys and 5% to 16% of the girls. Involvement in weapon carrying ranged from 10% to 21% of the boys and 2% to 5% of the girls. Among youth reporting weapon carrying, those carrying handguns or other firearms ranged from 7% to 22% of the boys and 3% to 11% of the girls. In nearly all reporting countries, both physical fighting and weapon carrying were significantly associated with elevated risks for medically treated, multiple, and hospitalized injury events. CONCLUSIONS: Fighting and weapon carrying are 2 common indicators of physical violence that are experienced by young people. Associations of fighting and weapon carrying with injury-related health outcomes are remarkably similar across countries. Violence is an important issue affecting the health of adolescents internationally.

Multilevel analysis of associations between socioeconomic status and injury among Canadian adolescents.

STUDY OBJECTIVE: To determine the contribution of individual and area level measures of socioeconomic status (SES) to the occurrence of various injury types among Canadian adolescents. DESIGN AND SETTING: Cross sectional Canadian data were used from two sources: (1) the 2001/02 health behaviour in school aged children survey (individual level SES measures, injury measures), and (2) the 2001 Canada census of population (area level SES measures). Injury outcomes included: medically treated injury, injury hospitalisation, sport/recreational injury, and fighting injury. Multilevel logistic regression models were used to examine individual and area level SES measures as potential determinants of adolescent injury. PARTICIPANTS: 7235 students in grades 6-10 from 170 schools across Canada. MAIN RESULTS: Associations between SES and injury were identified for each injury outcome examined, although a clear direction of association was not present for the overall measure of medically treated injury. In general, lower SES was associated with increased risk for hospitalised and fighting injury. Higher SES was associated with increased risks for sport/recreational injury. Independent contributions of individual and area level measures of SES were seen for hospitalised and fighting injury. CONCLUSIONS: Associations between SES and adolescent injury exist; however, the direction of these relations becomes more apparent with particular indicators of SES and when homogenous injury outcomes are evaluated.

Rates and external causes of blunt head trauma in Ontario: analysis and review of Ontario Trauma Registry datasets.

Contemporary studies of blunt head trauma and its determinants are important for prevention. It is also important to understand the strengths and limitations of the common sources of data used for the ongoing study of these injuries. Using the Ontario Trauma Registry, we described frequent patterns of blunt head trauma and identified priorities for prevention and research. A review of methodological issues that arose during the analysis of these trauma registry data is also provided. Blunt head trauma cases were identified within two data sets of the Ontario Trauma Registry. The Minimal Data Set is population-based and contains acute care injury hospitalizations, and the Comprehensive Data Set contains "major injuries" treated at a lead trauma hospital. Injury control priorities varied by age group, sex and data set and these are profiled in the manuscript. The results indicate the importance of examining multiple sources of surveillance data in establishing injury control priorities. The methodological review demonstrated the need to critically examine the completeness and accuracy of trauma registry data in arriving at decisions about priorities.