Reciprocal transcription factor networks govern tissue-resident ILC3 subset function and identity.

Innate lymphoid cells (ILCs) are guardians of mucosal immunity, yet the transcriptional networks that support their function remain poorly understood. We used inducible combinatorial deletion of key transcription factors (TFs) required for ILC development (RORγt, RORα and T-bet) to determine their necessity in maintaining ILC3 identity and function. Both RORγt and RORα were required to preserve optimum effector functions; however, RORα was sufficient to support robust interleukin-22 production among the lymphoid tissue inducer (LTi)-like ILC3 subset, but not natural cytotoxicity receptor (NCR)+ ILC3s. Lymphoid tissue inducer-like ILC3s persisted with only selective loss of phenotype and effector functions even after the loss of both TFs. In contrast, continued RORγt expression was essential to restrain transcriptional networks associated with type 1 immunity within NCR+ ILC3s, which coexpress T-bet. Full differentiation to an ILC1-like population required the additional loss of RORα. Together, these data demonstrate how TF networks integrate within mature ILCs after development to sustain effector functions, imprint phenotype and restrict alternative differentiation programs.

T-bet and RORα control lymph node formation by regulating embryonic innate lymphoid cell differentiation.

The generation of lymphoid tissues during embryogenesis relies on group 3 innate lymphoid cells (ILC3) displaying lymphoid tissue inducer (LTi) activity and expressing the master transcription factor RORγt. Accordingly, RORγt-deficient mice lack ILC3 and lymphoid structures, including lymph nodes (LN). Whereas T-bet affects differentiation and functions of ILC3 postnatally, the role of T-bet in regulating fetal ILC3 and LN formation remains completely unknown. Using multiple mouse models and single-cell analyses of fetal ILCs and ILC progenitors (ILCP), here we identify a key role for T-bet during embryogenesis and show that its deficiency rescues LN formation in RORγt-deficient mice. Mechanistically, T-bet deletion skews the differentiation fate of fetal ILCs and promotes the accumulation of PLZFhi ILCP expressing central LTi molecules in a RORα-dependent fashion. Our data unveil an unexpected role for T-bet and RORα during embryonic ILC function and highlight that RORγt is crucial in counteracting the suppressive effects of T-bet.

IL-2/IL-7-inducible factors pioneer the path to T cell differentiation in advance of lineage-defining factors.

When dormant naïve T cells first become activated by antigen-presenting cells, they express the autocrine growth factor IL-2 which transforms them into rapidly dividing effector T cells. During this process, hundreds of genes undergo epigenetic reprogramming for efficient activation, and also for potential reactivation after they return to quiescence as memory T cells. However, the relative contributions of IL-2 and T cell receptor signaling to this process are unknown. Here, we show that IL-2 signaling is required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus-dependent alternative pathways of T cell differentiation. We demonstrate that IL-2 activates binding of AP-1 and STAT5 at sites that can subsequently bind lineage-determining transcription factors, depending upon what other external factors exist in the local T cell environment. Once established, priming can also be maintained by the stroma-derived homeostatic cytokine IL-7, and priming diminishes if Il7r is subsequently deleted in vivo. Hence, IL-2 is not just a growth factor; it lays the foundation for T cell differentiation and immunological memory.

Perceptions of a family-based lifestyle intervention for children with overweight and obesity: a qualitative study on sustainability, self-regulation, and program optimization.

BACKGROUND: Family-based lifestyle interventions (FBLIs) are an important method for treating childhood weight problems. Despite being recognized as an effective intervention method, the optimal structure of these interventions for children's overweight and obesity has yet to be determined. Our aim was to better understand participants' (a) implementation of behaviour strategies and long-term outcomes, (b) perceptions regarding the optimal structure of FBLIs, and (c) insights into psychological concepts that may explain the success of these programs. METHODS: Purposive sampling was used to recruit participants. We conducted focus groups as well as one-to-one interviews with parents (n = 53) and children (n = 50; aged 7-13, M = 9.4 yr, SD = 3.1) three months following their involvement in a 10-week, multi-component, FBLI involving education and activities relating to healthy nutrition, physical activity, and behavior modification. Using an interpretivist approach, a qualitative study design was employed to examine participant experiences. RESULTS: We identified three higher-order categories: (a) participants' program experiences and perceptions (b) lifestyle changes post-program, and (c) recommendations for optimizing family-based programs. Themes identified within these categories included (a) support and structure & content, (b) diet and physical activity, and (c) in-program recommendations and post-program recommendations. CONCLUSIONS: We identified several challenges that can impair lasting behavior change (e.g., physical activity participation) following involvement in a FBLI. On optimizing these programs, participants emphasized fun, interactive content, interpersonal support, appropriate educational content, and behavior change techniques. Concepts rooted in motivational theory could help address calls for greater theoretical and mechanistic insight in FBLIs. Findings may support research advancement and assist health professionals to more consistently realize the potential of these interventions.

Barriers and facilitators of physical activity participation for young people and adults with childhood-onset physical disability: a mixed methods systematic review.

AIM: To understand the attitudes, barriers, and facilitators to physical activity participation for young people and adults with childhood-onset physical disability. METHOD: Seven electronic databases (Embase, MEDLINE, PsychINFO, AMED, CINAHL, SPORTDiscus, and ERIC) were searched to November 2019. English language studies were included if they investigated attitudes, barriers, or facilitators to physical activity for young people (≥15y) or adults with childhood-onset physical disabilities. Two reviewers applied eligibility criteria and assessed methodological quality. Data were synthesized in three stages: (1) thematic analysis into descriptive themes, (2) thematic synthesis via conceptual framework, and (3) an interpretive synthesis of the thematic results. RESULTS: Nineteen studies were included. Methodological quality varied, with only four qualitative studies and one quantitative study meeting all quality items. An overarching theme of 'finding the right balance' emerged. Six subthemes relating to capability, opportunity, and motivation contributed to physical activity participation being seen as 'the right fit' or 'all too hard'. The interpretive synthesis found social connections, social environment support, and an appropriate physical environment were essential to 'finding the right balance' to be physically active. INTERPRETATION: Physical activity participation for young people and adults with childhood-onset physical disabilities is primarily influenced by the social and physical environment. What this paper adds Physical activity participation for young people and adults with childhood-onset physical disabilities is primarily influenced by environmental factors. 'Finding the right balance' between enabling and inhibitory factors was important to physical activity participation being perceived as 'the right fit'. The opportunity for social connection is an important motivator for physical activity participation for young people and adults. The physical environment continues to act as a barrier to physical activity participation for those with physical disabilities.

Dynamic changes in intrathymic ILC populations during murine neonatal development.

Members of the innate lymphoid cell (ILC) family have been implicated in the development of thymic microenvironments and the recovery of this architecture after damage. However, a detailed characterization of this family in the thymus is lacking. To better understand the thymic ILC compartment, we have utilized multiple in vivo models including the fate mapping of inhibitor of DNA binding-2 (Id2) expression and the use of Id2 reporter mice. Our data demonstrate that ILCs are more prominent immediately after birth, but were rapidly diluted as the T-cell development program increased. As observed in the embryonic thymus, CCR6+ NKp46- lymphoid tissue inducer (LTi) cells were the main ILC3 population present, but numbers of these cells swiftly declined in the neonate and ILC3 were barely detectable in adult thymus. This loss of ILC3 means ILC2 are the dominant ILC population in the thymus. Thymic ILC2 were able to produce IL-5 and IL-13, were located within the medulla, and did not result from ILC3 plasticity. Furthermore, in WT mice, thymic ILC2 express little RANKL (receptor activator of nuclear factor kappa-B ligand) arguing that functionally, these cells provide different signals to LTi cells in the thymus. Collectively, these data reveal a dynamic switch in the ILC populations of the thymus during neonatal development.

Safety performance testing of climbing helmet-mounted cameras.

BACKGROUND: No research establishing the effects of climbing helmet-mounted cameras on head injury biomechanics. OBJECTIVE: Establish the potential effects of climbing helmet-mounted cameras on the injury risks associated with falling object strikes and falls onto flat and angled surfaces. METHODS: Three experimental studies were developed via the adaptation of European helmet testing standards and regulations. Study 1 performed falling striker tests to the helmet, Study 2 performed linear headform drop tests onto a flat anvil and Study 3 performed oblique headform drop tests onto an anvil angled 15° from vertical. Three helmet categories (hard-shell, foam and hybrid) were impacted at three locations (vertex, front and side), using five camera mounting combinations and three control helmets. Data was collected for the forces, linear accelerations, rotational velocities and rotational accelerations experienced by the headform. RESULTS: All helmet and camera combinations investigated by this project complied with current legislative performance criteria, while no combination exceeded published injury thresholds. No increase in head injury risk was observed for the forces transferred to the head during falling object strikes or with the linear accelerations experienced during falls onto flat and angled surfaces. Finally, although greater rotational head velocities and accelerations were observed with falls onto flat and angled surfaces, no injury threshold was exceeded by any investigated helmet and camera combination. CONCLUSIONS: All helmet and camera combinations investigated by this project complied with current legislative performance criteria, while no combination exceeded published injury thresholds. Further research may be required to establish the effects of additional impact mechanism, helmet or camera mounting configurations.

Explosive volcanism on the ultraslow-spreading Gakkel ridge, Arctic Ocean.

Roughly 60% of the Earth's outer surface is composed of oceanic crust formed by volcanic processes at mid-ocean ridges. Although only a small fraction of this vast volcanic terrain has been visually surveyed or sampled, the available evidence suggests that explosive eruptions are rare on mid-ocean ridges, particularly at depths below the critical point for seawater (3,000 m). A pyroclastic deposit has never been observed on the sea floor below 3,000 m, presumably because the volatile content of mid-ocean-ridge basalts is generally too low to produce the gas fractions required for fragmenting a magma at such high hydrostatic pressure. We employed new deep submergence technologies during an International Polar Year expedition to the Gakkel ridge in the Arctic Basin at 85 degrees E, to acquire photographic and video images of 'zero-age' volcanic terrain on this remote, ice-covered ridge. Here we present images revealing that the axial valley at 4,000 m water depth is blanketed with unconsolidated pyroclastic deposits, including bubble wall fragments (limu o Pele), covering a large (>10 km(2)) area. At least 13.5 wt% CO(2) is necessary to fragment magma at these depths, which is about tenfold the highest values previously measured in a mid-ocean-ridge basalt. These observations raise important questions about the accumulation and discharge of magmatic volatiles at ultraslow spreading rates on the Gakkel ridge and demonstrate that large-scale pyroclastic activity is possible along even the deepest portions of the global mid-ocean ridge volcanic system.

Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes.

BACKGROUND: Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group. OBJECTIVE: To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease. DESIGN: DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued. RESULTS: Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and HLA-class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of <5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within NOD2: the previously described R702W variant was the sole NOD2 variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the GSDMB, ERAP2 and SEC16A genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the BACH2 and IL10 genes not seen in other patients. CONCLUSION: For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.

Identifying and prioritising strategies to optimise community gym participation for young adults with cerebral palsy: an e-Delphi study.

PURPOSE: Identify and prioritise strategies to optimise physical activity participation in the community gym setting for young adults with cerebral palsy. METHODS: An e-Delphi method was implemented over three rounds with four stakeholder groups (young adults with cerebral palsy, their families, gym staff or exercise professionals, and health professionals). Strategies for change were identified by the stakeholders in round 1. In rounds 2 and 3, strategies for change were rated on the importance for implementation using a 7-point Likert scale (1 being lowest importance, 7 being highest). The consensus was achieved if ≥70% of participants identified a strategy as high importance. RESULTS: Seventy participants (20 young adults 10 family members, 21 health professionals, and 19 exercise professionals) identified 83 strategies for improving gym participation. Of these, 44 strategies met the consensus criteria. The highest priority strategies related to changing the physical environment, addressing cost barriers, gym staff training, and developing partnerships between sectors. CONCLUSIONS: Addressing physical accessibility, cost of attendance and the skills of gym staff were agreed upon by the stakeholder groups as priority areas for future resource allocation and research translation. Clinicians and community leisure facilities must work with consumers to implement strategies in their local contexts.

The physical environment, gym staff training, and the cost of attendance are the priority areas for future interventions agreed on by key stakeholder groupsHealth professionals can facilitate community participation by partnering with the recreation and research sectors to create pathways to gym exerciseHealth professionals can play a role in developing the knowledge, skills and confidence of gym staff to support young people with cerebral palsy in the gymWhen implementing 1:1 social support in community gym settings, consider the preferences of young adults and the resources available.

Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity.

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.

Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity.

Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived.

'Finding what works for me' - a qualitative study of factors influencing community gym participation for young adults with cerebral palsy.

PURPOSE: To understand the factors influencing participation in community-based gym exercise for young adults with cerebral palsy (CP). METHODS: A qualitative study using semi-structured interviews was conducted. Interviews were completed with 39 young adults with CP (15-30 years, GMFCS I-IV) following a peer-supported, gym-based exercise program called FitSkills. RESULTS: "Finding what works for me" was the overarching theme. Through their gym experiences, young adults with CP identified four interrelated main themes that influenced whether gym participation "worked" for them, or not: (i) psychological factors, (ii) a "social" participation context, (iii) organisational and logistical support, and (iv) cost. The social context of FitSkills was perceived to positively influence psychological health outcomes and attenuate perceived barriers to participation. Organisational support facilitated their initial attendance, while logistical effort and cost affected ongoing or future gym participation. CONCLUSIONS: Social involvement plays a critical role in positive participation experiences in community exercise settings for young adults with CP. Clinicians supporting exercise participation for this group should prioritise intervention strategies that promote social engagement and mental wellbeing. Collaboration between clinicians, community leisure organisations, and funding bodies may be essential to overcome logistical and financial barriers during the transition to adulthood. Implications for rehabilitationThe main factor influencing the attendance, involvement, and ongoing exercise preferences of young adults with cerebral palsy (CP) was the social context of the participation experience.Altering the social environment through peer-mentoring can facilitate participation in the gym.Young adults with CP consider mental wellbeing to be an important motivator and outcome of gym-based exercise participation.Mental wellbeing should be prioritised for health promotion for this group.Collaboration between recreation organisations, health services, clinicians, and consumers to address logistical and financial factors can facilitate positive physical activity participation experiences in community settings.

"Capturing the magic": identifying the active ingredients of a physical activity participation intervention for children and youth with disabilities.

PURPOSE: This study aimed to define the active ingredients of a participation-focused physical activity intervention for children and youth with disabilities. MATERIALS AND METHODS: An ethnographic approach was employed, triangulating participant observation, interviews and focus groups. Participant recruitment occurred through purposive sampling of staff employed at Beitostolen Healthsports Centre (BHC), and paediatric service providers visiting the centre. Interviews were transcribed verbatim and coded together with observation data. Secondary coding linked data to corresponding categories of the International Classification of Functioning, Disability and Health: Child and Youth version. RESULTS: Thirteen staff from BHC and 7 paediatric service providers participated in the study. Fourteen active ingredients were identified and were characterised at the level of the intervention (k = 8), the organisation (k = 4), and the individual (k = 2). Within the ingredients, 53 unique ICF-CY categories were identified. Twenty-six categories belonged to the ICF-CY component of "environment," and 26 categories to "activities and participation." No categories related to "body functions" or "body structures." CONCLUSIONS: The role of the environment, and specifically support and relationships, may be an essential consideration for enabling physical activity participation. Outcomes may guide program design and implementation to promote and sustain physical activity behaviours for children and youth with disabilities.Implications for rehabilitationThe active ingredients identified in this study may guide the design and implementation of programs to promote and sustain physical activity behaviours of children and youth with disabilities.Leadership qualities and strength-based attitudes may be key characteristics of organisational practice that optimise outcomes for children and families.A "relationship-centred" approach, i.e., a network of children, families, health professionals, peers, mentors, and services in the community, may support children and young people with disabilities to achieve their physical activity participation goals.

Cardiac cycle: an observational/interventional study protocol to characterise cardiopulmonary function and evaluate a home-based cycling program in children and adolescents born extremely preterm.

INTRODUCTION: Extremely preterm (EP)/extremely low birthweight (ELBW) individuals may have an increased risk for adverse cardiovascular outcomes. Compared with term-born controls, these individuals have poorer lung function and reduced exercise capacity. Exercise interventions play an important role in reducing cardiopulmonary risk, however their use in EP/ELBW cohorts is unknown. This study, cardiac cycle, aims to characterise the cardiopulmonary system of children and adolescents who were born EP compared with those born at term, following acute and chronic exercise bouts. METHODS AND ANALYSIS: The single-centre study comprises a home-based exercise intervention, with physiological characterisation at baseline and after completion of the intervention. Fifty-eight children and adolescents aged 10-18 years who were born EP and/or with ELBW will be recruited. Cardiopulmonary function assessed via measures of blood pressure, arterial stiffness, capillary density, peak oxygen consumption, lung clearance indexes and ventricular structure/function, will be compared with 58 age-matched and sex-matched term-born controls at baseline and post intervention. The intervention will consist of a 10-week stationary cycling programme, utilising Zwift technology. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of the Royal Children's Hospital Melbourne under HREC2019.053. Results will be disseminated via peer-reviewed journal regardless of outcome. TRIAL REGISTRATION NUMBER: 12619000539134, ANZCTR.

Feasibility of scaling-up a community-based exercise program for young people with disability.

PURPOSE: To evaluate feasibility of scaling up a 12-week community-based exercise program (FitSkills) in which young people with disability exercise with a student mentor. METHOD: Within a stepped wedge cluster randomised trial, seven domains of feasibility were assessed: demand, implementation, acceptability, practicality, adaptation, integration, and expansion. RESULTS: Of the 163 participants with disability (61 females; 20.8 ± 5 y) and 226 mentors who enrolled, 123 participants and mentors completed FitSkills. Population demand was estimated at 9% of members of participating organisations. Most participants (76%) completed the twice-weekly program within 12 weeks, attending 79% of sessions (mean 18.9 ± 4.7). Key program elements valued by participants were the mentor, tailored exercise, and regular program schedule. Majority (87%) of mentors were recruited from physiotherapy, occupational therapy, and exercise science courses. Positives for participants were perceived benefits and organisational support, and for mentors, understanding disability. Communication and scheduling were burdens. Three serious and 28 non-serious adverse events occurred. Adaptations (additional screening, risk analysis, extra mentor support, or in-person consultation) enabled 29 young people with complexity to participate. The number of trial sites was expanded to 11 to accommodate participants. CONCLUSIONS: Scaling-up FitSkills is feasible, but with caveats related to communication, scheduling, and efficiency of recruitment.IMPLICATIONS FOR REHABILITATIONKey elements valued by participants as part of the successful scale-up of a community-based exercise program (FitSkills) across a large metropolitan city included a peer-mentor, tailored exercise, and organisational support structure.FitSkills can be adapted to include young people with complex disability with additional supports including screening, risk analysis, and professional support for the peer-mentor.The benefits of FitSkills, including social connectedness for young people with a disability and normalisation of disability for mentors, outweigh the burdens of participation.Communication with program organisers and scheduling logistics between the young person, their family/carers and peer mentors are important factors to manage for the successful implementation of FitSkills.

In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.

Improving the efficacy of immune checkpoint therapies will require a better understanding of how immune cells are recruited and sustained in tumors. Here, we used the photoconversion of the tumor immune cell compartment to identify newly entering lymphocytes, determine how they change over time, and investigate their egress from the tumor. Combining single-cell transcriptomics and flow cytometry, we found that while a diverse mix of CD8 T cell subsets enter the tumor, all CD8 T cells retained within this environment for more than 72 h developed an exhausted phenotype, revealing the rapid establishment of this program. Rather than forming tumor-resident populations, non-effector subsets, which express TCF-1 and include memory and stem-like cells, were continuously recruited into the tumor, but this recruitment was balanced by concurrent egress to the tumor-draining lymph node. Thus, the TCF-1+ CD8 T cell niche in tumors is highly dynamic, with the circulation of cells between the tumor and peripheral lymphoid tissue to bridge systemic and intratumoral responses.

Gel formulation containing mixed surfactant and lipids associating with carboplatin.

The interaction of amphiphilic molecules such as lipids and surfactants with the hydrophilic drug carboplatin was investigated to identify suitable self-assembling components for a potential gel-based delivery formulation. (1) H-NMR Studies in sodium bis(2-ethylhexyl) sulfosuccinate (aerosol-OT, AOT)-based reverse micelles show that carboplatin associates and at least partially penetrates the surfactant interface. Langmuir monolayers formed by dipalmitoyl(phosphatidyl)choline are penetrated by carboplatin. Carboplatin was found to also penetrate the more rigid monolayers containing cholesterol. A combined mixed surfactant gel formulation containing carboplatin and cholesterol for lymphatic tissue targeting was investigated for the intracavitary treatment of cancer. This formulation consists of a blend of the surfactants lecithin and AOT (1 : 3 ratio), an oil phase of isopropyl myristate, and an aqueous component. The phases of the system were defined within a pseudo-ternary phase diagram. At low oil content, this formulation produces a gel-like system over a wide range of H(2) O content. The carboplatin release from the formulation displays a prolonged discharge with a rate three to five times slower than that of the control. Rheological properties of the formulation exhibit pseudoplastic behavior. Microemulsion and Langmuir monolayer studies support the interactions between carboplatin and amphiphilic components used in this formulation. To target delivery of carboplatin, two formulations containing cholesterol were characterized. These two formulations with cholesterol showed that, although cholesterol does little to alter the phases in the pseudo-ternary system or to increase the initial release of the drug, it contributes significantly to the structure of the formulation under physiological temperature, as well as increases the rate of steady-state discharge of carboplatin.