The Well-Being and Resilience of Canadian Christian Clergy.

Clergy play significant leadership, educational, and caregiving roles in society. However, burnout is a concern for the clergy profession, those they serve, and their families. Effects include decreased ministry effectiveness, lower sense of personal accomplishment in their role, and negative impacts on quality of family life and relationships. Given these risks, knowledge of the nature of Christian clergy's current resilience and well-being in Canada may provide valuable intelligence to mitigate these challenges. In summary, the purpose of this research was to describe and analyze the status of clergy resilience and well-being in Canada, together with offering focused insights. Resilience and well-being surveys used by the co-authors with educators and nurses were adapted for use in this study. This instrument was developed to gain insight into baseline patterns of resilience and well-being and included questions across seven sections: (1) demographic information. (2) health status, (3) professional quality of life, (4) Cantril Well-Being Scale, (5) Ego-Resiliency Scale, (6) Grit Scale, and (7) open-ended questions. The findings provided valuable insights into clergy well-being and resilience that can benefit individual clerics, educational institutions, denominations, and congregations. The participants' current resilience and well-being included high levels of resiliency, moderate grit, and satisfaction with health and wellness. Other significant findings included the impact of congregational flourishing and age. This study found that clergy well-being and resilience was doing well despite the increased adversity of the COVID-19 pandemic. Implications of this study are that clerics may need unique supports based on their age and also whether they serve in a congregation they perceive as flourishing.

Economic evaluation of neutral-pH, low-glucose degradation product peritoneal dialysis solutions compared with standard solutions: a secondary analysis of the balANZ Trial.

BACKGROUND: Biocompatible solutions may lower peritonitis rates, but are more costly than conventional solutions. The aim of the present study was to assess the additional costs and health outcomes of biocompatible over conventional solutions in incident peritoneal dialysis patients to guide practice decisions. STUDY DESIGN: Secondary economic evaluation of a randomized controlled trial. SETTING & POPULATION: 185 participants in the balANZ trial. MODEL, PERSPECTIVE, & TIMEFRAME: Cost-effectiveness of biocompatible compared to standard solution over the 2 years using an Australian health care funder perspective. INTERVENTION: Intervention group received biocompatible solutions and control group received standard solutions over 2 years. OUTCOMES: Costs included dialysis charges, costs of treating peritonitis, non-peritonitis-related hospital stays, and medication. Peritonitis was the health outcome of interest; incremental cost-effectiveness ratios were reported in terms of the additional cost per additional patient avoiding peritonitis at 2 years. RESULTS: Mean total per-patient costs were A$57,451 and A$53,930 for the biocompatible and standard-solution groups, respectively. The base-case analysis indicated an incremental cost of A$17,804 per additional patient avoiding peritonitis at 2 years for biocompatible compared to standard solution. In a sensitivity analysis excluding extreme outliers for non-peritonitis-related hospitalizations, mean per-patient costs were A$49,159 and A$52,009 for the biocompatible and standard-solution groups, respectively. Consequently, the incremental cost-effectiveness ratio also was reduced significantly: biocompatible solution became both less costly and more effective than standard solution and, in economic terms, was dominant over standard solution. LIMITATIONS: Peritonitis was a secondary outcome of the balANZ trial. Health outcomes measured only in terms of patients avoiding peritonitis over 2 years may underestimate the longer term benefits (eg, prolonged technique survival). CONCLUSIONS: Biocompatible dialysis solutions may offer a cost-effective alternative to standard solutions for peritoneal dialysis patients. Reductions in peritonitis-related hospital costs may offset the higher costs of biocompatible solution.

Dialysate interleukin-6 predicts increasing peritoneal solute transport rate in incident peritoneal dialysis patients.

BACKGROUND: Repeated exposure to peritoneal dialysis (PD) solutions contributes to cumulative intraperitoneal inflammation and peritoneal injury. The present study aimed to explore the capacity of dialysate interleukin-6(IL-6) to a) predict peritoneal membrane function and peritonitis in incident PD patients, and b) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on dialysate IL-6 levels. METHODS: The study included 88 incident participants from the balANZ trial who had completed 24-months of follow-up. Change in peritoneal solute transport rate (PSTR) and peritonitis were primary outcome measures, and the utility of IL-6 and IL-6 appearance rate (IL-6 AR) in predicting these outcomes was analyzed using multilevel linear regression and Cox proportional hazards models, respectively. Sensitivity analyses were performed by analyzing outcomes in a peritonitis-free cohort (n = 56). RESULTS: Dialysate IL-6 concentration significantly increased from baseline to 24 months (mean difference 19.07 pg/mL; P < 0.001) but was not affected by the type of PD solution received (P = 0.68). An increase in PSTR from baseline was associated with higher levels of IL-6 (P = 0.004), the use of standard solutions (P = 0.005) and longer PD duration (P < 0.001). Baseline IL-6 level was not associated with a shorter time to first peritonitis (adjusted hazard ratio 1.00, 95% CI 0.99-1.00, P = 0.74). Analysis of IL-6 AR as well as sensitivity analyses in a peritonitis-free cohort yielded comparable results. CONCLUSION: Dialysate IL-6 concentration increased with longer PD duration and was a significant, independent predictor of PSTR. The use of biocompatible PD solutions exerted no significant effect on dialysate IL-6 levels but did abrogate the increase in PSTR associated with standard PD solutions. This is the first study to examine the impact of biocompatible solutions on the utility of IL-6 in predicting PSTR and peritonitis.

Effects of biocompatible versus standard fluid on peritoneal dialysis outcomes.

The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.

Role-Related Stress and Adversity Impacting Christian Clergy Resilience: A Pan-Canadian Study.

Christian clergy are at risk of experiencing the negative impacts of role-related stress and adversity, especially burnout. The findings reported in this article were derived from a Canadian mix-methods study that collected data through an online survey with 519 clerics, 13 one-on-one interviews, and interpretation panels. Adversity themes identified related to workload, expectations, isolation, and personal challenges with various subthemes for each. These findings are relevant to those providing care to clergy by providing insights into the challenges they face.

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial.

BACKGROUND: The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. METHODS: Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. RESULTS: Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference -0.004 per month, 95% confidence interval (95% CI) -0.005 to -0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9-39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. CONCLUSIONS: Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.

Clergy Resilience: Accessing Supportive Resources to Balance the Impact of Role-Related Stress and Adversity.

Resilience is a helpful construct when considering how to support clergy well-being. The purpose of this study was to gain knowledge about clergy resilience, specifically those resources that clergy perceived had supported their professional resilience. The study gave attention to aspects of preservice training and professional development that helped to foster clergy resilience and initiatives that clergy desired to further support their resilience. Clergy reported multiple resources that supported their resilience including supports for spiritual life, relational supports, personal aspects, and organizational practices. Spiritual dimensions of support for resilience were prominent for clergy, especially the centrality of calling to ministry, theological meaning-making, and relationship with God. Participants also revealed helpful aspects of preservice training and professional development. Aspects of preservice training included rigorous discernment and screening of their callings and the inclusion of required practices, such as spiritual direction or mentorship. Aspects of professional development included a variety of skill development opportunities, lifelong learning, conferences, and networking with peers. Participants reported their desire for initiatives that included more wellness opportunities and an increased organizational prioritization of clergy wellness.

Recent insights into host-pathogen interactions from Dictyostelium.

To protect themselves from predation by amoebae and protozoa in the natural environment, some bacteria evolved means of escaping killing. The same mechanisms allow survival in mammalian phagocytes, producing opportunistic human pathogens. The social amoeba Dictyostelium discoideum is a powerful system for analysis of conserved host-pathogen interactions. This report reviews recent insights gained for several bacterial pathogens using Dictyostelium as host.

F-pili dynamics by live-cell imaging.

Bacteria have evolved numerous mechanisms for cell-cell communication, many of which have important consequences for human health. Among these is conjugation, the direct transfer of DNA from one cell to another. For gram-negative bacteria, conjugation requires thin, flexible filaments (conjugative pili) that are elaborated by DNA donor cells. The structure, function, and especially the dynamics of conjugative pili are poorly understood. Here, we have applied live-cell imaging to characterize the dynamics of F-pili (conjugative pili encoded by the F plasmid of Escherichia coli). We establish that F-pili normally undergo cycles of extension and retraction in the absence of any obvious triggering event, such as contact with a recipient cell. When made, such contacts are able to survive the shear forces felt by bacteria in liquid media. Our data emphasize the role of F-pilus flexibility both in efficiently sampling a large volume surrounding donor cells in liquid culture and in establishing and maintaining cell-cell contact. Additionally and unexpectedly, we infer that extension and retraction are accompanied by rotation about the long axis of the filament.

Curvature recognition and force generation in phagocytosis.

BACKGROUND: The uptake of particles by actin-powered invagination of the plasma membrane is common to protozoa and to phagocytes involved in the immune response of higher organisms. The question addressed here is how a phagocyte may use geometric cues to optimize force generation for the uptake of a particle. We survey mechanisms that enable a phagocyte to remodel actin organization in response to particles of complex shape. RESULTS: Using particles that consist of two lobes separated by a neck, we found that Dictyostelium cells transmit signals concerning the curvature of a surface to the actin system underlying the plasma membrane. Force applied to a concave region can divide a particle in two, allowing engulfment of the portion first encountered. The phagosome membrane that is bent around the concave region is marked by a protein containing an inverse Bin-Amphiphysin-Rvs (I-BAR) domain in combination with an Src homology (SH3) domain, similar to mammalian insulin receptor tyrosine kinase substrate p53. Regulatory proteins enable the phagocyte to switch activities within seconds in response to particle shape. Ras, an inducer of actin polymerization, is activated along the cup surface. Coronin, which limits the lifetime of actin structures, is reversibly recruited to the cup, reflecting a program of actin depolymerization. The various forms of myosin-I are candidate motor proteins for force generation in particle uptake, whereas myosin-II is engaged only in retracting a phagocytic cup after a switch to particle release. Thus, the constriction of a phagocytic cup differs from the contraction of a cleavage furrow in mitosis. CONCLUSIONS: Phagocytes scan a particle surface for convex and concave regions. By modulating the spatiotemporal pattern of actin organization, they are capable of switching between different modes of interaction with a particle, either arresting at a concave region and applying force in an attempt to sever the particle there, or extending the cup along the particle surface to identify the very end of the object to be ingested. Our data illustrate the flexibility of regulatory mechanisms that are at the phagocyte's disposal in exploring an environment of irregular geometry.

Rationale and design of the balANZ trial: a randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function.

BACKGROUND: The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. METHODS/DESIGN: Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance) or conventional dialysis solution (Stay.safe) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. DISCUSSION: This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527.

SigmaS controls multiple pathways associated with intracellular multiplication of Legionella pneumophila.

Legionella pneumophila is the causative agent of the severe and potentially fatal pneumonia Legionnaires' disease. L. pneumophila is able to replicate within macrophages and protozoa by establishing a replicative compartment in a process that requires the Icm/Dot type IVB secretion system. The signals and regulatory pathways required for Legionella infection and intracellular replication are poorly understood. Mutation of the rpoS gene, which encodes sigma(S), does not affect growth in rich medium but severely decreases L. pneumophila intracellular multiplication within protozoan hosts. To gain insight into the intracellular multiplication defect of an rpoS mutant, we examined its pattern of gene expression during exponential and postexponential growth. We found that sigma(S) affects distinct groups of genes that contribute to Legionella intracellular multiplication. We demonstrate that rpoS mutants have a functional Icm/Dot system yet are defective for the expression of many genes encoding Icm/Dot-translocated substrates. We also show that sigma(S) affects the transcription of the cpxR and pmrA genes, which encode two-component response regulators that directly affect the transcription of Icm/Dot substrates. Our characterization of the L. pneumophila small RNA csrB homologs, rsmY and rsmZ, introduces a link between sigma(S) and the posttranscriptional regulator CsrA. We analyzed the network of sigma(S)-controlled genes by mutational analysis of transcriptional regulators affected by sigma(S). One of these, encoding the L. pneumophila arginine repressor homolog gene, argR, is required for maximal intracellular growth in amoebae. These data show that sigma(S) is a key regulator of multiple pathways required for L. pneumophila intracellular multiplication.

Mechanically induced actin-mediated rocketing of phagosomes.

Actin polymerization can be induced in Dictyostelium by compressing the cells to bring phagosomes filled with large particles into contact with the plasma membrane. Asymmetric actin assembly results in rocketing movement of the phagosomes. We show that the compression-induced assembly of actin at the cytoplasmic face of the plasma membrane involves the Arp2/3 complex. We also identify two other proteins associated with the mechanically induced actin assembly. The class I myosin MyoB accumulates at the plasma membrane-phagosome interface early during the initiation of the response, and coronin is recruited as the actin filaments are disassembling. The forces generated by rocketing phagosomes are sufficient to push the entire microtubule apparatus forward and to dislocate the nucleus.

Heterogeneous modes of uptake for latex beads revealed through live cell imaging of phagocytes expressing a probe for phosphatidylinositol-(3,4,5)-trisphosphate and phosphatidylinositol-(3,4)-bisphosphate.

Latex beads are the preferred phagocytic substrate in biochemical studies of phagosome composition and maturation. Using living Dictyostelium cells and fluorescent probes, we compared the properties of phagosomes formed to ingest latex beads or digestible prey. Significant differences were found during the initial steps of phagocytosis. During uptake of bacteria or yeast, PHcrac-GFP, a probe that binds to membranes enriched in PI(3,4,5)P(3) and PI(3,4)P(2), always labeled the nascent phagosome and faded shortly after it sealed. However, labeling of bead-containing phagosomes was highly variable. Beads were engulfed by phagosomes either lacking or displaying the PHcrac-GFP label, and that label, if present, often persisted for many minutes, revealing that early trafficking steps for bead-containing phagosomes are quite heterogeneous. Later stages of the endocytic pathway appeared more similar for phagosomes containing prey and latex beads. Both types of phagosomes fused with acidic endosomes while undergoing transport along microtubules, both acquired the V-ATPase and lost it prior to exocytosis, and both bound the late endosome marker vacuolin B, which was transferred to the plasma membrane upon exocytosis. We conclude that caution is needed in extrapolating results from latex bead phagosomes to phagosomes containing physiological substances, especially in early stages of the endocytic pathway.

Differences in sleep patterns, sleepiness, and physical activity levels between young adults with autism spectrum disorder and typically developing controls.

OBJECTIVE: To investigate the differences in sleep, sleepiness, and physical activity (PA) between young adults with autism spectrum disorder (ASD) and typically developing controls (TDC). METHOD: Actigraphic data and questionnaires on sleep, sleepiness, and PA were compared between fifteen adults with ASD (ADOS range 7-19; ages 22.8 ± 4.5 years) and TDC. RESULTS: In comparison to the TDC group, the ASD group slept longer on average per night but took longer to fall asleep. In relationship to PA levels, the objective PA levels were lower in the ASD group than the TDC group. Fewer wake minutes during the sleep period in the ASD sample were associated with more PA the following day. CONCLUSION: The findings support previous research that demonstrates differences in sleep parameters and PA between ASD and TDC. Interventions aimed at increasing PA in an ASD population may be beneficial for improved sleep.

Rural-urban differences in provider practice related to preconception counselling and fetal alcohol spectrum disorders.

OBJECTIVE: Fetal alcohol spectrum disorders (FASDs) are the most common form of nongenetic birth defect in North America with devastating, long-term consequences. Physicians are the primary providers of medical care for pregnant women and they play an important role in the prevention and diagnosis of FASD. We sought to determine whether differences exist between rural and urban health care providers in knowledge of, attitudes about and awareness of FASD and preconception counselling. METHODS: Surveys were mailed to a national, random sample of Canadian health care providers (n = 5361) between October 2001 and May 2002. Bivariate data analysis was completed using SPSS 14.0. RESULTS: Compared with their urban counterparts, rural providers were more likely to report being prepared to access resources related to alcohol use and dependency, yet they were less likely to agree that it was the physician's role to manage these issues (78.4% v. 82.8%, p < 0.05). Rural providers were more likely than urban providers to use a standardized tool to screen patients for alcohol use, to ask all pregnant women if they were drinking, to have cared for a patient with an FASD (56.7% v. 48.8%), to agree that providers do not make a diagnosis because of lack of time and training, and to recognize legal issues and inappropriate behaviour as secondary outcomes of FASD. Rural and urban providers were similar in their diagnostic knowledge of FASD. CONCLUSION: Few differences between rural and urban providers exist with regard to knowledge and diagnosis of FASD; however, rural providers are more prepared to access resources for women with addiction issues and are more likely to care for patients with an FASD.

An Ecosystem Approach to Employment and Autism Spectrum Disorder.

Relatively little is yet known about employment readiness and elements that promote access to, and the retention of, employment for adults with autism spectrum disorder (ASD). This paper posits elements within the ecosystem of employment and ASD. The ecosystem approach locates employment among persons with ASD as inextricably linked with broader community resources, family support, workplace capacity building (e.g., employer, co-workers) and policy. Application of the approach is offered through process evaluation data yielded from an ecosystem-informed job readiness program entitled, 'EmploymentWorks Canada'. Findings illustrate job readiness in the context of the broader ecosystem that envelopes salient components in the aim of community engagement and quality of life. Recommendations are offered for community-based applications and for program and research development.

Evaluation of employment-support services for adults with autism spectrum disorder.

The employment rate among persons with autism spectrum disorder has been noted as unacceptably low. Employment-support services are increasingly linked to the potential for favorable job outcomes, yet little is known about employment-support practices and the outcome of these interventions. This mixed-methods study examined employment-support resources for persons with autism spectrum disorder. An online survey was completed by 137 senior clinicians or administrators in employment-support programs in Canada. Additionally, 122 follow-up interviews were conducted with individuals with autism spectrum disorder (n = 71) and their parents/caregivers (n = 51). Findings indicate that the quality and beneficial impact of employment-support services for adults with autism spectrum disorder may be more favorably perceived by employment-support personnel than by individuals with autism spectrum disorder and their families. Furthermore, employment-support personnel were more disparaging about autism spectrum disorder vocational support capacity within their community, compared to their own programs. Individuals with autism spectrum disorder and their families seek services that support both accessing and retaining employment. Capacity-building in employment support for youth and adults with autism spectrum disorder is recommended, based on a reported insufficiency of, and a lack of evidence guiding, existing services. Program recommendations and an emerging model for integrated vocational support in autism spectrum disorder are offered.

Dynamic actin patterns and Arp2/3 assembly at the substrate-attached surface of motile cells.

BACKGROUND: In the cortical region of motile cells, the actin network rapidly reorganizes as required for movement in various directions and for cell-to-substrate adhesion. The analysis of actin network dynamics requires the combination of high-resolution imaging with a specific fluorescent probe that highlights the filamentous actin structures in live cells. RESULTS: Combining total internal reflection fluorescence (TIRF) microscopy with a method for labeling actin filaments, we analyze the dynamics of actin patterns in the highly motile cells of Dictyostelium. A rapidly restructured network of single or bundled actin filaments provides a scaffold for the assembly of differentiated actin complexes. Recruitment of the Arp2/3 complex characterizes stationary foci with a lifetime of 7-10 s and traveling waves. These structures are also formed in the absence of myosin-II. Arp2/3-actin assemblies similar to those driving the protrusion of a leading edge form freely at the inner face of the plasma membrane. CONCLUSIONS: The actin system of highly motile cells runs far from equilibrium and generates a multitude of patterns within a dynamic filamentous network. Traveling waves are the most complicated patterns based on recruitment of the Arp2/3 complex. They are governed by the propagated induction of actin polymerization. We hypothesize that the actin system autonomously generates primordia of specialized structures such as phagocytic cups or lamellipodia. These primordia would represent an activated state of the actin system and enable cells to respond within seconds to local stimuli by chemotaxis or phagocytic-cup formation.