Emergency department staff experiences of working with people who self-harm: A qualitative examination of barriers to optimal care.

For people who seek help for self-harm, emergency departments (ED) are often the first point of contact, making them a suitable setting for intervention. In Australia, base rates of self-harm presentations to ED are increasing, while the quality of care these people receive is often considered sub-optimal. This study used qualitative interviews to explore potential barriers ED staff face in delivering best possible self-harm care. Seventeen staff across two EDs in the state of Victoria, Australia, were interviewed regarding their perceptions of barriers to providing optimal self-harm care and suggestions for improvement. Three themes were identified: (1) system-related challenges when managing self-harm in ED, including the shortage of hospital resources, challenges of ED as a physical environment, and insufficient education, training and guidelines about self-harm care for staff; (2) human-related challenges regarding management of self-harm in ED, which encompassed the nature of a person's circumstances and presentation, and staff attitudes towards self-harm; and (3) staff suggestions for improving self-harm care in ED. Specific recommendations that were proposed based on these findings included introducing a separate ED area for mental health-related presentations, provision of specialised education and training about self-harm care to staff, better implementation of guidelines on treating self-harm in ED, and employing mental health educators to provide on-the-floor mentoring to nurses. The relevance of these barriers and recommendations to the wider healthcare sector is also discussed. Together, these findings may inform improvements to the quality of care provided to those who engage in self-harm.

Staff perceptions of barriers to self-harm care in the emergency department: A cross-sectional survey study.

BACKGROUND: Emergency departments (EDs) are often the first point of contact for people with self-harm; however, they do not always receive optimal care. The study objective was to examine the perspectives of ED staff who respond to self-harm presentations, perceived barriers to providing optimal, guideline-concordant care, and staff's familiarity with existing guidelines. METHODS: An online cross-sectional survey comprising purpose-designed questions concerning self-harm in the ED was completed by 131 staff (83.2% nurses) from two hospitals in Victoria, Australia. Survey results were analysed using Stata version 16 and frequencies and percentages were calculated. RESULTS: Respondents reported knowledge of how to appropriately manage a person presenting with self-harm. However, lack of space (62.3%) and time (78.7%) to conduct the appropriate assessments, lack of self-harm training (71.8%), and limited awareness of or access to guidelines and recommendations for self-harm management within the ED (63.6%), were identified as primary barriers to their ability to appropriately manage these presenters. CONCLUSIONS: Improvements to the ED environment and processes, as well as the provision of regular self-harm specific education and training for all ED staff are needed. Implementation of best-practice standards should prioritise guideline-concordant care, with a particular focus on the education needs of nursing staff.

The challenge of unprecedented floods and droughts in risk management.

Risk management has reduced vulnerability to floods and droughts globally1,2, yet their impacts are still increasing3. An improved understanding of the causes of changing impacts is therefore needed, but has been hampered by a lack of empirical data4,5. On the basis of a global dataset of 45 pairs of events that occurred within the same area, we show that risk management generally reduces the impacts of floods and droughts but faces difficulties in reducing the impacts of unprecedented events of a magnitude not previously experienced. If the second event was much more hazardous than the first, its impact was almost always higher. This is because management was not designed to deal with such extreme events: for example, they exceeded the design levels of levees and reservoirs. In two success stories, the impact of the second, more hazardous, event was lower, as a result of improved risk management governance and high investment in integrated management. The observed difficulty of managing unprecedented events is alarming, given that more extreme hydrological events are projected owing to climate change3.

How Do Interpersonal Relationships Affect Children's Weight Management? A Qualitative Analysis of Parents' Long-Term Perceptions after Obesity Treatment.

Background: Childhood obesity interventions are particularly effective during the preschool age, but little is known about parents' long-term perceptions of weight management. This study explores how parents perceive the influence of interpersonal relationships on their children's eating and physical activity 4 years after participating in a randomized controlled trial. Bronfenbrenner's ecological systems theory frames this study, with the child's environment conceptualized as interlocking microsystems that affect weight management. Methods: Interviews were conducted with 33 parents (85% mothers, 48% with university degree) of 33 children [mean age 9.3 (standard deviation 0.7), 46% girls] from Stockholm, Sweden. Interviews were analyzed using thematic analysis, focusing on parents' perceptions of interpersonal relationships: family, relatives, other children, preschool/school staff, and health care practitioners. Results: Two main themes were developed: (1) Discouragement, with the subthemes Conflicting rules and Social comparison, and (2) Support and understanding, with the subthemes Teamwork and Shared responsibility and continuity of care. Parents perceived children's weight management as a continuous orchestration of different influences across social spheres. Years after obesity treatment, parents struggled to maintain the child's healthy routines outside the home. However, when siblings, grandparents, teachers, and friends' parents acted supportively, routines were easier to maintain. Conclusions: The findings suggest that each microsystem in a child's environment has important influence on weight management, such that, as children grow older, children's lifestyles cannot be managed by parents alone. To facilitate weight management, more people in the child's environment should be involved early in the treatment process, and continued professional support should be offered to parents.

Associations of preschoolers' dietary patterns with eating behaviors and parental feeding practices at a 12-month follow-up of obesity treatment.

Although dietary patterns are key to the management of childhood obesity, they are rarely assessed and thus poorly understood. This study examines preschoolers' dietary patterns and correlates 12 months after the start of obesity treatment (n = 99, mean age 5.2 years, 52% girls). A food frequency questionnaire (FFQ), the Child Eating Behavior Questionnaire (CEBQ), Child Feeding Questionnaire (CFQ) and Lifestyle Behavior Checklist (LBC) were answered by parents to assess children's food intake, eating behaviors, parental feeding practices, and obesity-related behaviors, respectively. Principal component analysis identified dietary patterns based on FFQ data. Through multiple linear regressions we examined correlations between a healthy (HD) and a less healthy (LHD) dietary pattern and mean scores of the CEBQ, CFQ, LBC scales as well as BMI z-scores. The reported intake of items in the LHD decreased after treatment while no differences were found for the HD. Children's eating behaviors, in particular food fussiness, showed consistent associations with diet (b = -0.39, 95% CI -0.63, -0.14 for HD and b = 0.41, 95% CI 0.15, 0.66 for LHD). Feeding practices and obesity-related behaviours were weakly associated with the dietary patterns (HD and Monitoring: b = 0.36, 95% CI 0.09, 0.62; LHD and Screen time b = 0.08, 95% CI 0.01, 0.15). Among the measured variables, eating behaviors had the largest impact on children's dietary patterns. The LHD was associated with a higher BMI z-score but no associations were found between changes in LHD intake and changes in BMI z-scores. Our findings suggest that decreasing food fussiness in children with obesity is key to positive dietary changes. Assessment of children's eating behaviors can help tailor dietary advice and provide support for families of children with obesity.

Natural Biomaterials and Their Use as Bioinks for Printing Tissues.

The most prevalent form of bioprinting-extrusion bioprinting-can generate structures from a diverse range of materials and viscosities. It can create personalized tissues that aid in drug testing and cancer research when used in combination with natural bioinks. This paper reviews natural bioinks and their properties and functions in hard and soft tissue engineering applications. It discusses agarose, alginate, cellulose, chitosan, collagen, decellularized extracellular matrix, dextran, fibrin, gelatin, gellan gum, hyaluronic acid, Matrigel, and silk. Multi-component bioinks are considered as a way to address the shortfalls of individual biomaterials. The mechanical, rheological, and cross-linking properties along with the cytocompatibility, cell viability, and printability of the bioinks are detailed as well. Future avenues for research into natural bioinks are then presented.

Expression of Siglec-E Alters the Proteome of Lipopolysaccharide (LPS)-Activated Macrophages but Does Not Affect LPS-Driven Cytokine Production or Toll-Like Receptor 4 Endocytosis.

Siglec-E is a murine CD33-related siglec that functions as an inhibitory receptor and is expressed mainly on neutrophils and macrophage populations. Recent studies have suggested that siglec-E is an important negative regulator of lipopolysaccharide (LPS)-toll-like receptor 4 (TLR4) signaling and one report (1) claimed that siglec-E is required for TLR4 endocytosis following uptake of Escherichia coli by macrophages and dendritic cells (DCs). Our attempts to reproduce these observations using cells from wild-type (WT) and siglec-E-deficient mice were unsuccessful. We used a variety of assays to determine if siglec-E expressed by different macrophage populations can regulate TLR4 signaling in response to LPS, but found no consistent differences in cytokine secretion in vitro and in vivo, comparing three different strains of siglec-E-deficient mice with matched WT controls. No evidence was found that the siglec-E deficiency was compensated by expression of siglecs-F and -G, the other murine inhibitory CD33-related siglecs. Quantitative proteomics was used as an unbiased approach and provided additional evidence that siglec-E does not suppress inflammatory TLR4 signaling. Interestingly, proteomics revealed a siglec-E-dependent alteration in macrophage protein composition that could be relevant to functional responses in host defense. In support of this, siglec-E-deficient mice exhibited enhanced growth of Salmonella enterica serovar Typhimurium in the liver following intravenous infection, but macrophages lacking siglec-E did not show altered uptake or killing of bacteria in vitro. Using various cell types including bone marrow-derived DCs (BMDCs), splenic DCs, and macrophages from WT and siglec-E-deficient mice, we showed that siglec-E is not required for TLR4 endocytosis following E. coli uptake or LPS challenge. We failed to see expression of siglec-E by BMDC even after LPS-induced maturation, but confirmed previous studies that splenic DCs express low levels of siglec-E. Taken together, our findings do not support a major role of siglec-E in regulation of TLR4 signaling functions or TLR4 endocytosis in macrophages or DCs. Instead, they reveal that induction of siglec-E by LPS can modulate the phenotype of macrophages, the functional significance of which is currently unclear.

Siglec-E promotes ß2-integrin-dependent NADPH oxidase activation to suppress neutrophil recruitment to the lung.

Siglec-E is a sialic acid-binding Ig-like lectin expressed on murine myeloid cells. It has recently been shown to function as a negative regulator of ß2-integrin-dependent neutrophil recruitment to the lung following exposure to lipopolysaccharide (LPS). Here, we demonstrate that siglec-E promoted neutrophil production of reactive oxygen species (ROS) following CD11b ß2-integrin ligation with fibrinogen in a sialic acid-dependent manner, but it had no effect on ROS triggered by a variety of other stimulants. Siglec-E promotion of ROS was likely mediated via Akt activation, because siglec-E-deficient neutrophils plated on fibrinogen exhibited reduced phosphorylation of Akt, and the Akt inhibitor, MK2206, blocked fibrinogen-induced ROS. In vivo imaging showed that siglec-E also promoted ROS in acutely inflamed lungs following exposure of mice to LPS. Importantly, siglec-E-promoted ROS were required for its inhibitory function, as the NADPH oxidase inhibitor, apocynin, reversed the siglec-E-mediated suppression of neutrophil recruitment and blocked neutrophil ROS production in vitro. Taken together, these results demonstrate that siglec-E functions as an inhibitory receptor of neutrophils via positive regulation of NADPH oxidase activation and ROS production. Our findings have implications for the inhibitory role of siglec-9 on human neutrophils in sepsis and acute lung injury.

Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model.

Siglec-8 and siglec-F are paralogous membrane proteins expressed on human and murine eosinophils respectively. They bind similar sialylated and sulphated glycans and mediate eosinophil apoptosis when cross-linked with antibodies or glycan ligands. In models of allergic eosinophilic airway inflammation, siglec-F was shown previously to be important for negatively regulating eosinophilia. It was proposed that this was due to siglec-F-dependent apoptosis, triggered via engagement with ligands that are upregulated on bronchial epithelium. Our aim was to further investigate the functions of siglec-F by comparing two commonly used models of ovalbumin-induced airway inflammation that differ in the dose and route of administration of ovalbumin. In confirmation of published results, siglec-F-deficient mice had enhanced lung tissue eosinophilia in response to intranasal ovalbumin delivered every other day. However, following aerosolised ovalbumin delivered daily, there was no influence of siglec-F deficiency on lung eosinophilia. Expression of siglec-F ligands in lung tissues was similar in both models of allergen induced inflammation. These data demonstrate that siglec-F-dependent regulation of eosinophilia is subtle and depends critically on the model used. The findings also indicate that mechanisms other than ligand-induced apoptosis may be important in siglec-F-dependent suppression of eosinophilia.

Sialoadhesin deficiency does not influence the severity of lupus nephritis in New Zealand black x New Zealand white F1 mice.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic inflammatory condition with multisystem involvement. One of the key features of the disease is the upregulation of type I interferons, resulting in the so-called "interferon signature". Recent flow cytometric and transcriptomic studies identified Sialoadhesin (Sn, CD169) as an important interferon-induced blood monocyte biomarker in diseased patients. To investigate a potential causative role of Sn in SLE, we generated NZBWF1 (New Zealand Black x New Zealand White F1) mice lacking Sn and compared onset and progression of disease with NZBWF1 expressing normal levels of Sn. METHODS: Sn expression in renal tissues of pre-diseased and diseased NZBWF1 mice was evaluated by Quantitative real time PCR (QPCR) and immunohistochemistry. Sn-/- NZBWF1 mice were generated by speed congenics. Disease severity of Sn+/+ and Sn-/- NZBWF1 mice was assessed by serum immunoassays, flow cytometry, light microscopy and immunohistochemistry. RESULTS: Renal tissues from proteinuric NZBWF1 mice exhibited a significant upregulation of Sn mRNA and protein expression following disease onset. Further immunohistochemical analysis showed that Sn+ macrophages assumed a distinct periglomerular distribution and, unlike CD68+ macrophages, were not present within the glomeruli. Analysis of disease severity in Sn-/- and Sn+/+ NZBWF1 mice revealed no significant differences in the disease progression between the two groups although Sn-deficient mice showed a more rapid onset of proteinuria. CONCLUSIONS: These data confirm a positive correlation of Sn with disease activity. However, Sn deficiency does not have a significant effect on the severity and progression of lupus nephritis in the NZBWF1 mouse model.

Sialoadhesin ligand expression identifies a subset of CD4+Foxp3- T cells with a distinct activation and glycosylation profile.

Sialoadhesin (Sn) is a sialic acid-binding Ig-like lectin expressed selectively on macrophage subsets. In a model of experimental autoimmune encephalomyelitis, Sn interacted with sialylated ligands expressed selectively on CD4(+)Foxp3(+) regulatory T cells (Tregs) and inhibited their proliferation. In this study, we examined the induction of Sn ligands (SnL) on all splenic CD4(+) T cells following in vitro activation. Most CD4(+) Tregs strongly upregulated SnL, whereas only a small subset of ~20% CD4(+)Foxp3(-) T cells (effector T cells [Teffs]) upregulated SnL. SnL(+) Teffs displayed higher levels of activation markers CD25 and CD69, exhibited increased proliferation, and produced higher amounts of IL-2 and IFN-γ than corresponding SnL(-) Teffs. Coculture of activated Teffs with Sn(+) macrophages or Sn(+) Chinese hamster ovary cells resulted in increased cell death, suggesting a regulatory role for Sn-SnL interactions. The key importance of α2,3-sialylation in SnL expression was demonstrated by increased binding of α2,3-linkage-specific Maackia amurensis lectin, increased expression of α2,3-sialyltransferase ST3GalVI, and loss of SnL following treatment with an α2,3-linkage-specific sialidase. The induction of SnL on activated CD4(+) T cells was dependent on N-glycan rather than O-glycan biosynthesis and independent of the mucin-like molecules CD43 and P-selectin glycoprotein ligand-1, previously implicated in Sn interactions. Induction of ligands on CD4(+)Foxp3(-) Teffs was also observed in vivo using the New Zealand Black × New Zealand White F1 murine model of spontaneous lupus and SnL levels on Teffs correlated strongly with the degree of proteinuria. Collectively, these data indicate that SnL is a novel marker of activated CD4(+) Teffs that are implicated in the pathogenesis of autoimmune diseases.

Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b ß2-integrin-dependent signaling.

Neutrophil entry into the lung tissues is a key step in host defense to bacterial and yeast infections, but if uncontrolled can lead to severe tissue damage. Here, we demonstrate for the first time that sialic acid binding Ig-like lectin E (siglec-E) functions to selectively regulate early neutrophil recruitment into the lung. In a model of acute lung inflammation induced by aerosolized lipopolysaccharide, siglec-E-deficient mice exhibited exaggerated neutrophil recruitment that was reversed by blockade of the ß2 integrin, CD11b. Siglec-E suppressed CD11b "outside-in" signaling, because siglec-E-deficient neutrophils plated on the CD11b ligand fibrinogen showed exaggerated phosphorylation of Syk and p38 mitogen-activated protein kinase. Sialidase treatment of fibrinogen reversed the suppressive effect of siglec-E on CD11b signaling, suggesting that sialic acid recognition by siglec-E is required for its inhibitory function. Siglec-E in neutrophils was constitutively associated with the tyrosine phosphatase SHP-1 and may therefore function to constitutively dampen inflammatory responses of neutrophils. These data reveal that siglec-E is an important negative regulator of neutrophil recruitment to the lung and ß2 integrin-dependent signaling. Our findings have implications for the human functional ortholog, siglec-9, and its potential role in regulating inflammatory lung disease.

CD33-related siglecs as potential modulators of inflammatory responses.

The immune system must be tightly regulated to prevent unwanted tissue damage caused by exaggerated immune and inflammatory reactions. Inhibitory and activating immune receptors play a crucial role in this function via phosphotyrosine-dependent signaling pathways. A significant body of evidence has accumulated suggesting that the siglec family of sialic acid binding Ig-like lectins makes an important contribution to this immunoregulation. The CD33-related siglecs are a distinct subset of inhibitory and activating receptors, expressed primarily on leukocytes in a cell type-specific manner. Here, we critically assess the in vitro and in vivo evidence on the functional role for CD33-related siglecs in modulation of inflammatory and immune responses.

Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes.

Genome-wide association studies have identified many genetic variants associated with complex traits. However, at only a minority of loci have the molecular mechanisms mediating these associations been characterized. In parallel, whereas cis regulatory patterns of gene expression have been extensively explored, the identification of trans regulatory effects in humans has attracted less attention. Here we show that the type 2 diabetes and high-density lipoprotein cholesterol-associated cis-acting expression quantitative trait locus (eQTL) of the maternally expressed transcription factor KLF14 acts as a master trans regulator of adipose gene expression. Expression levels of genes regulated by this trans-eQTL are highly correlated with concurrently measured metabolic traits, and a subset of the trans-regulated genes harbor variants directly associated with metabolic phenotypes. This trans-eQTL network provides a mechanistic understanding of the effect of the KLF14 locus on metabolic disease risk and offers a potential model for other complex traits.

Delineating immune-mediated mechanisms underlying hair follicle destruction in the mouse mutant defolliculated.

Defolliculated (Gsdma3(Dfl)/+) mice have a hair loss phenotype that involves an aberrant hair cycle, altered sebaceous gland differentiation with reduced sebum production, chronic inflammation, and ultimately the loss of the hair follicle. Hair loss in these mice is similar to that seen in primary cicatricial, or scarring alopecias in which immune targeting of hair follicle stem cells has been proposed as a key factor resulting in permanent hair follicle destruction. In this study we examine the mechanism of hair loss in GsdmA3(Dfl)/+ mice. Aberrant expression patterns of stem cell markers during the hair cycle, in addition to aberrant behavior of the melanocytes leading to ectopic pigmentation of the hair follicle and epidermis, indicated the stem cell niche was not maintained. An autoimmune mechanism was excluded by crossing the mice with rag1-/- mice. However, large numbers of macrophages and increased expression of ICAM-1 were still present and may be involved either directly or indirectly in the hair loss. Reverse transcriptase-PCR (RT-PCR) and immunohistochemistry of sebaceous gland differentiation markers revealed reduced peroxisome proliferator-activated receptor-γ (PPARγ), a potential cause of reduced sebum production, as well as the potential involvement of the innate immune system in the hair loss. As reduced PPARγ expression has recently been implicated as a cause for lichen planopilaris, these mice may be useful for testing therapies.

Novel role of regulatory T cells in limiting early neutrophil responses in skin.

It is clear that CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells inhibit chronic inflammatory responses as well as adaptive immune responses. Among the CD4(+) T-cell population in the skin, at least one-fifth express Foxp3. As the skin is constantly exposed to antigenic challenge and is a common site of vaccination, understanding the role of these skin-resident Treg cells is important. Although the suppressive effect of Treg cells on T cells is well documented, less is known about the types of innate immune cells influenced by Treg cells and whether the Treg cells suppress acute innate immune responses in vivo. To address this we used a mouse melanoma cell line expressing Fas ligand (B16FasL), which induces an inflammatory response following subcutaneous injection of mice. We demonstrate that Treg cells limit this response by inhibiting neutrophil accumulation and survival within hours of tumour cell inoculation. This effect, which was associated with decreased expression of the neutrophil chemoattractants CXCL1 and CXCL2, promoted survival of the inoculated tumour cells. Overall, these data imply that Treg cells in the skin are rapidly mobilized and that this activity serves to limit the amplification of inflammatory responses at this site.

Characterization of the specific interaction between sialoadhesin and sialylated Campylobacter jejuni lipooligosaccharides.

In Campylobacter jejuni-induced Guillain-Barré syndrome (GBS), molecular mimicry between C. jejuni lipooligosaccharide (LOS) and host gangliosides leads to the production of cross-reactive antibodies directed against the peripheral nerves of the host. Currently, the presence of surface exposed sialylated LOS in C. jejuni is the single known bacterial pathogenesis factor associated with the development of GBS. Using a unique, well-characterized strain collection, we demonstrate that GBS-associated C. jejuni strains bind preferentially to sialoadhesin (Sn, Siglec-1, or CD169), a sialic acid receptor found on a subset of macrophages. In addition, using a whole-cell enzyme-linked immunosorbent assay (ELISA), C. jejuni strains with sialylated LOS bound exclusively to soluble Sn. Mass spectrometry revealed that binding was sialic acid-linkage specific with a preference for alpha(2,3)-linked sialic acid attached to the terminal galactose of the LOS chain as seen in the gangliosides GD1a, GM1b, and GM3. This molecular interaction was also related to functional consequences as a GBS-associated C. jejuni strain that bound Sn in a whole-cell ELISA adhered to surface-expressed Sn of Sn-transfected CHO cells but was unable to adhere to wild-type CHO cells. Moreover, a sialic acid-negative mutant of the same C. jejuni strain was unable to bind Sn-transfected CHO cells. This is the first report of the preferential binding of GBS-associated C. jejuni strains to the Sn immune receptor (P = 0.014). Moreover, because this binding is dependent on sialylated LOS, the main pathogenic factor in GBS progression, the present findings bring us closer to unraveling the mechanisms that lead to formation of cross-reactive antibodies in GBS disease.

CD62L (L-selectin) down-regulation does not affect memory T cell distribution but failure to shed compromises anti-viral immunity.

The down-regulation of CD62L that accompanies T lymphocyte activation is thought to redirect cells away from lymph nodes to sites of infection. In this study, CD62L was maintained on Ag-activated T cells and their distribution, and ability to clear pathogen from peripheral sites determined. CD62L was down-regulated on Ag-specific CD8 T cells in lungs of C57BL/6 mice but maintained in CD62L transgenic mice at day 8 after influenza infection. However, the numbers of influenza-specific CD8 T cells recruited were similar in CD62L transgenic and C57BL/6 mice. Memory CD8 T cell numbers in the lungs and noninvolved organs 100 days after primary infection were similar in CD62L transgenic and C57BL/6 mice, despite differing CD62L expression. Transgenic mice expressing wild-type CD62L cleared a recombinant vaccinia virus expressing an influenza-derived CD8 T cell epitope as efficiently as C57BL/6 mice. However, transgenic mice expressing a protease resistant mutant of CD62L showed significantly delayed viral clearance, despite normal CTL generation and the presence of CD107a and IFN-gamma expressing influenza-specific CD8 T cells. These results demonstrate that CD62L down-regulation is not required for CD8 memory cells to home to sites of infection. However, their ability to clear virus is significantly compromised if CD62L shedding is abrogated.

Regulatory T cells inhibit Fas ligand-induced innate and adaptive tumour immunity.

CD4+CD25+ regulatory T cells (Treg) are known to influence T cell responses to tumours. Here we have explored the role of Treg in inhibiting not only adaptive, but also innate immune responses to tumours. To this end we used a Fas ligand (FasL)-expressing melanoma cell line in a mouse model. In this system, innate immunity is sufficient to reject the tumour. All mice depleted of Treg and challenged with FasL-expressing melanoma remained tumour-free. Investigation of the underlying cellular effector mechanisms revealed that depletion of Treg enhanced an NK cell response capable of tumour lysis. Furthermore, this initial innate immune response primed mice to make an effective adaptive immune response leading to complete rejection of challenge with the parental melanoma. Both antigen-specific antibody and CD4+ T cells were implicated in protection via adaptive immunity. We conclude that removal of Treg and vaccination with whole tumour cells expressing FasL activates multiple arms of the immune system, leading to efficient tumour rejection. These findings highlight a novel role for FasL in inducing innate immune responses that are normally inhibited by Treg and uncover an adjuvant effect of FasL that can be used to stimulate tumour immunity after depletion of Treg.

Evaluation of commercial rubella immunoglobulin G avidity assays.

We compared the performances of five commercial rubella virus immunoglobulin G (IgG) avidity assays. The Adaltis (kappa = 0.28) and Diesse (kappa = 0.33) assays showed poor correlation, the Behring assay (kappa = 0.68) showed good correlation, and the Euroimmun (kappa = 0.95) and Radim (kappa = 0.94) assays showed excellent correlation with a well-established in-house rubella virus IgG avidity assay. The Euroimmun and Radim assays were statistically significantly better than the other commercial assays (P < 0.01).