Enhancing type 2 diabetes treatment through digital plans of care - a randomized controlled trial: evaluation of change in patient reported outcome measures.

BACKGROUND: We investigated how a personalized care-planning software and linked mobile-app may aid people to self-manage their type 2 diabetes (T2D) more effectively. RESEARCH DESIGN AND METHODS: People with T2D and glycated hemoglobin (HbA1c) greater than 58 mmol/mol (7.5%) were randomized to either an intervention group receiving a personalized care plan, or the control group receiving usual care. Quality of life (QoL) was measured for both groups using validated questionnaires and one-on-one interviews with a subset of 12 participants from each group. RESULTS: QoL for the active treatment group increased, by their EQ -5D-5 L score increasing on average by 0.046, whereas it decreased for the control group on average by 0.009. The EQ Visual Analogue Score (VAS) of the intervention group also increased by 8.2%, whereas the control group had a reduction in EQ VAS score of 2.8% (p = 0.008 for difference). CONCLUSION: In this prospective RCT, the findings point to how the provision of personalized care plans can result in an improvement in individuals' self-rated QoL. This may lead to longer term health benefits.

Bacterial communities of the threatened Western Pond Turtle may be impacted by land use.

As semi-aquatic species that use both terrestrial and aquatic habitats, freshwater turtles and their microbial communities are especially sensitive to the impacts of habitat disturbance. In this study, we use 16S rRNA amplicon sequencing to characterize the shell and cloacal bacterial communities of turtles in the San Francisco Bay Area. We captured western pond turtles (Actinemys/Emys marmorata) across eight sites located in urban and rural environments, along with invasive red-eared sliders (Trachemys scripta elegans). We assessed differences in western pond turtle bacterial communities diversity/composition between shell and cloacal samples and evaluated how alpha/beta diversity metrics were influenced by habitat quality. We found phylum-level bacterial taxonomic turnover in the bacterial communities of western pond turtles relative to the host tissue substrate samples. Our findings indicate that location identity elicits a high degree of lower-level (i.e. species/genus) bacterial taxonomic turnover. Further, we found that samples originating from good quality habitat had poorer shell bacterial communities but more diverse cloacal ones. The shell bacterial communities of red-eared sliders overlapped with those western pond turtles suggesting the existence of microbial dispersal between these two species. Our results add to our current understanding of turtle symbiont microbial ecology by establishing patterns of bacterial symbiont variation in an urban to rural gradient.

Real World Experience of Change in Psycho-Existential Symptoms in Palliative Care.

CONTEXT: Psycho-existential symptoms in palliative care are addressed insufficiently. Routine screening, ongoing monitoring and meaningful treatment of psycho-existential symptoms may contribute to the relief of suffering in palliative care. OBJECTIVES: We sought to explore longitudinal change in psycho-existential symptoms following the routine implementation of the Psycho-existential Symptom Assessment Scale (PeSAS) in Australian palliative care services. METHODS: Using a multisite rolling design, we implemented the PeSAS to longitudinally monitor symptoms in a cohort of 319 patients. We assessed change scores for each symptom in groups with mild (≤3), moderate (4-7) and severe (≥8) symptomatology at baseline. We tested significance between these groups and used regression analyses to identify predictors. RESULTS: While one half of patients denied clinically important psycho-existential symptoms, for the remainder, overall, more patients improved than deteriorated. Between 20% and 60% of patients with moderate and severe symptoms improved, while another 5%-25% developed new symptom distress. Patients with severe baseline scores improved significantly more than those with moderate baseline scores. CONCLUSION: As we better recognize through screening patients carrying psycho-existential distress in palliative care programs, there is considerable room for improvement in ameliorating this suffering. Inadequate clinical skills, poor psychosocial staffing or a biomedical program culture may all contribute to inadequate symptom control. Person-centered care necessitates greater attention to authentic multidisciplinary care that ameliorates psycho-spiritual and existential distress.

Making the transition from student to newly qualified vascular sonographer: An exploration of the domains of professionalism.

Introduction: Rapid increases in the utility of vascular ultrasound combined with increasing expectations from reporting physicians have required a shift to a more defined professional role for the vascular sonographer in Australia. This has created increasing pressure on newly qualified sonographers to be more job-ready and better able to navigate the challenges of the clinical workplace early in their career. Topic Description: There is a distinct lack of structured strategies that newly qualified sonographers can utilise to assist their transition from student to employee. In our paper, we aimed to answer the question of 'What makes a sonographer a Professional?' with the view to extending understanding of how a structured framework can assist the development of a professional identity and can encourage participating in Continuing Professional Development by the newly qualified sonographer. Discussion: The authors reviewed their own clinical experiences and the current literature to source tangible and practical strategies that can be easily enacted by newly qualified sonographers to motivate their continuing growth. Through this review, the 'Domains of Professionalism in the role of the sonographer' framework was developed. In this framework, we describe the various domains of professionalism and their associated dimensions, making it specific to the discipline of sonography and to the point of view of a newly qualified sonographer. Conclusion: Our paper contributes to the discussion on Continuing Professional Development using a purposeful and targeted approach to support newly qualified sonographers across all discipline areas of ultrasound specialisation to navigate the often challenging pathway to becoming a professional.

A Randomised Control Trial to Explore the Impact and Efficacy of the Healum Collaborative Care Planning Software and App on Condition Management in the Type 2 Diabetes Mellitus Population in NHS Primary Care.

INTRODUCTION: Effective and scalable solutions to support management of Type 2 Diabetes (T2D) at a distance are a priority for health systems worldwide. The use of personalised care planning has been shown to be effective at improving the health outcomes and the experience of care amongst people with T2D and other long-term health conditions. Here we describe a specific example of such an intervention. METHODS: The sample comprised 197 participants with T2D randomised to either the active intervention group with digital health planning (App + usual care), with 115 participants, or the control group (usual care), with 82 participants. We analysed data in relation to changes in body mass index (BMI) and glycated haemoglobin (HbA1c) over a 6-month follow-up period. We also analysed responses to questionnaires sent out and held interviews with participants that were in the active treatment group and therefore had a care plan created and access to an app. RESULTS: The active treatment group had significant reductions in HbA1c (p < 0.01) and BMI (p < 0.037) vs the control group (no significant change). The average percentage change in HbA1c for the treatment group over 6 months was - 7.4% (± SE 1.4%), compared with 1.8% (± SE 2.1%) for the control group. The average percentage change in BMI for the treatment group was - 0.7% (± SE 0.4%) and it was - 0.2% (± SE 0.5%) for the control group. A higher percentage of the active treatment group reduced their HbA1c and BMI than the control group. For HbA1c, 72.4% of the active treatment group reduced their HbA1c, compared to 41.5% of the control group. For BMI, 52.7% of the active treatment group experienced a reduction, compared to 42.9% for the control group. Self-measured quality of life (QoL) improved for patients in the active treatment group, shown by an increase in their pre-trial to post-trial EQ-5D-5L rating by an average of 0.0464 (± SE 0.0625), compared to a decrease of 0.0086 (± SE 0.0530) for the control group. The average EQ VAS score also increased pre- to post-trial for the active treatment group, on average by 8.2%, whereas it decreased by an  average of - 2.8% for the control group. CONCLUSION: These findings point to how the provision of personalised plans of care, support and education linked to a mobile app, can result in HbA1c and BMI reduction for many individuals with T2D. The use of a patient management app as well as a personalised care plan also led to an improvement in patient self-rated QoL and engagement.

Controlling adsorption density of polymer-stabilised metal nanoparticles at the oil-water interface.

Emulsion droplets offer an alternative to solid supports as templates for the deposition of metallic nanoparticles. An emulsion interface provides the opportunity to exploit both sides of the nanoparticles and to utilise the liquid core as a microreactor in addition to forming a scaffold for encapsulation. However, despite the extensive literature studying a very broad range of factors influencing the characteristics of particle-stabilised (Pickering) emulsions, most reports focus on particles of diameters >100 nm and a very small proportions consider particles of diameters <10 nm. For catalytic purposes of course, the latter species are of utmost interest. Here, we report the synthesis of poly(vinyl pyrrolidone) (PVP) stabilised platinum nanoparticles, where the platinum core ranges between 3 and 5 nm in diameter and their subsequent use as emulsifiers for the oil-water interface where they form a densely packed layer. The nanoparticle density at the interface is quantified by both measuring the remaining concentration of nanoparticles in the aqueous phase after adsorption and also directly at the oil-water interface via cryo-TEM. The effect of electrolyte concentration and of addition of excess PVP in the bulk aqueous nanoparticle dispersion prior to emulsification on the resulting nanoparticle density at the oil-water interface is also determined.

Enhancing type 2 diabetes treatment through digital plans of care. First results from the East Cheshire Study of an App to support people in the management of type 2 diabetes.

Introduction: The use of personalised care planning has been effective at improving health outcomes for people with long-term health conditions. Methods: We analysed data in relation to changes in BMI/HbA1c. The sample was made up of (n = 36) participants randomised to either the active intervention group (App+usual care) or the control group (usual care). Results: The average HbA1c percentage change for the treatment group was 9.5%, but just -2% for the control (usual care) group (P = 0.015 for the difference). The average percentage change in BMI for the treatment group was -0.4%, but 0.1% for the control group (P = 0.03 for the difference). Conclusion: These preliminary findings point to how the provision of personalised plans of care, support and education linked to a mobile app, can result in HbA1c and BMI reduction over a 6-month period. While the results are preliminary, they portend the potential for digital plans of care to enhance T2DM management.

Ancient surgeons: A characterization of Mesopotamian surgical practices.

BACKGROUND: The Ancient Mesopotamian civilization, the earliest known, emerged in the fourth millennium BCE.1 While the advent of medicine is established, there is little understanding of surgery's origins. We sought to describe the characteristics and medical acumen of the surgeons of the first civilization. METHODS: Source documents and commentary on Mesopotamian medicine were systematically analyzed for evidence of surgery and physician descriptions. RESULTS: Early tablets reveal evidence of the incisional drainage of a scalp abscess and empyema, advanced wound care, fracture alignment, and possible caesarians without evidence of wound suturing, emergency procedures, trephination, or circumcision.2 While the asû and asipu understood disease processes, strong evidence of an inextricable connection between spiritual and diagnostic/curative roles exists. CONCLUSIONS: Mesopotamian physicians were diagnosticians and healers, approaching surgery as part of their holistic practice rather than a separate entity. Surgery was utilized as an endpoint to a careful process aided by objective evaluation and spiritual incantation.

Applying the Digital Health Social Justice Guide.

Introduction: Digital health, the use of apps, text-messaging, and online interventions, can revolutionize healthcare and make care more equitable. Currently, digital health interventions are often not designed for those who could benefit most and may have unintended consequences. In this paper, we explain how privacy vulnerabilities and power imbalances, including racism and sexism, continue to influence health app design and research. We provide guidelines for researchers to design, report and evaluate digital health studies to maximize social justice in health. Methods: From September 2020 to April 2021, we held five discussion and brainstorming sessions with researchers, students, and community partners to develop the guide and the key questions. We additionally conducted an informal literature review, invited experts to review our guide, and identified examples from our own digital health study and other studies. Results: We identified five overarching topics with key questions and subquestions to guide researchers in designing or evaluating a digital health research study. The overarching topics are: 1. Equitable distribution; 2. Equitable design; 3. Privacy and data return; 4. Stereotype and bias; 5. Structural racism. Conclusion: We provide a guide with five key topics and questions for social justice digital health research. Encouraging researchers and practitioners to ask these questions will help to spark a transformation in digital health toward more equitable and ethical research. Future work needs to determine if the quality of studies can improve when researchers use this guide.

Deposition of non-porous calcium phosphate shells onto liquid filled microcapsules.

The efficient encapsulation of small molecule active ingredients has been a challenge for many decades across many commercial applications. Recently, successful attempts to address this issue have included deposition of thin metal shells onto liquid filled polymer microcapsules or emulsion droplets to provide an impermeable barrier to diffusion. In this work we have developed a novel method to protect small molecule active ingredients by deposition of thin mineral shells. Platinum nanoparticles are used to catalyse and direct growth of a calcium phosphate shell onto liquid filled polymer microcapsules under various reaction conditions. Findings indicate that a non-porous protective shell is formed on the majority of the microcapsule population, with small concentrations of the core material being released only from those microcapsules with defects, over a 7 days period, when conducting forced release studies into a solvent for the core oil. The resulting microcapsules show no significant cell toxicity when exposed to HEK 293 cells for 72 h.

Facilitating Systems Thinking Through Arts-Based STEM Integration.

Engaging with socio-scientific issues often involves making sense of how - and for whom - actions, choices, and policies might affect aspects of daily life. Understanding the complexity of socio-scientific issues also requires recognizing the interconnectedness of - and working across - multiple communities and professions. We suggest that art, whether musical composition, illustrations, or sculpture / collage across materials would promote the synthesis of different types of knowledge across different scales and systems. The present investigation seeks to understand how arts integration into STEM curriculum could support systems thinking around socio-scientific issues, specifically around the issue of pathogen transmission in rural-agricultural communities. Our after-school program, which works with 3rd - 5th grade students in rural-agricultural communities, leverages the arts to promote systems-level understanding of zoonotic diseases and ecosystem dynamics. A total of 23 students across two sites located in rural communities in the Western United States participated in our afterschool program. We found that after completing the program students expanded their understanding of both the connections between concepts and an understanding of careers related to ecosystem dynamics. We suggest that educators can integrate both arts and sciences together to enhance systems thinking and expand student perception of the interconnectedness of STEM disciplines and their everyday lives.

Virus-encoded histone doublets are essential and form nucleosome-like structures.

The organization of genomic DNA into defined nucleosomes has long been viewed as a hallmark of eukaryotes. This paradigm has been challenged by the identification of "minimalist" histones in archaea and more recently by the discovery of genes that encode fused remote homologs of the four eukaryotic histones in Marseilleviridae, a subfamily of giant viruses that infect amoebae. We demonstrate that viral doublet histones are essential for viral infectivity, localize to cytoplasmic viral factories after virus infection, and ultimately are found in the mature virions. Cryogenic electron microscopy (cryo-EM) structures of viral nucleosome-like particles show strong similarities to eukaryotic nucleosomes despite the limited sequence identify. The unique connectors that link the histone chains contribute to the observed instability of viral nucleosomes, and some histone tails assume structural roles. Our results further expand the range of "organisms" that require nucleosomes and suggest a specialized function of histones in the biology of these unusual viruses.

Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer.

BACKGROUND: Retrospective analyses suggest that capecitabine may carry superior activity in hormone receptor-positive relative to hormone receptor-negative metastatic breast cancer. This review examined the veracity of that finding and explored whether this differential activity extends to early breast cancer. OBJECTIVES: To assess effects of chemotherapy regimens containing capecitabine compared with regimens not containing capecitabine for women with hormone receptor-positive versus hormone receptor-negative breast cancer across the three major treatment scenarios: neoadjuvant, adjuvant, metastatic. SEARCH METHODS: On 4 June 2019, we searched the Cochrane Breast Cancer Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5) in the Cochrane Library; MEDLINE; Embase; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials looking at chemotherapy regimens containing capecitabine alone or in combination with other agents versus a control or similar regimen without capecitabine for treatment of breast cancer at any stage. The primary outcome measure for metastatic and adjuvant trials was overall survival (OS), and for neoadjuvant studies pathological complete response (pCR). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and odds ratios (ORs) for dichotomous outcomes, and meta-analysis was performed using a fixed-effect model. MAIN RESULTS: We included 26 studies with outcome data by hormone receptor: 12 metastatic studies (n = 4325), 6 neoadjuvant trials (n = 3152), and 8 adjuvant studies (n = 13,457). Capecitabine treatment was added in several different ways across studies. These could be classified as capecitabine alone compared to another treatment, capecitabine substituted for part of the control chemotherapy, and capecitabine added to control chemotherapy. In the metastatic setting, the effect of capecitabine was heterogenous between hormone receptor-positive and -negative tumours. For OS, no difference between capecitabine-containing and non-capecitabine-containing regimens was observed for all participants taken together (HR 1.01, 95% confidence interval (CI) 0.98 to 1.05; 12 studies, 4325 participants; high-certainty evidence), for those with hormone receptor-positive disease (HR 0.93, 95% CI 0.84 to 1.04; 7 studies, 1834 participants; high-certainty evidence), and for those with hormone receptor-negative disease (HR 1.00, 95% CI 0.88 to 1.13; 8 studies, 1577 participants; high-certainty evidence). For progression-free survival (PFS), a small improvement was seen for all people (HR 0.89, 95% CI 0.82 to 0.96; 12 studies, 4325 participants; moderate-certainty evidence). This was largely accounted for by a moderate improvement in PFS for inclusion of capecitabine in hormone receptor-positive cancers (HR 0.82, 95% CI 0.73 to 0.91; 7 studies, 1594 participants; moderate-certainty evidence) compared to no difference in PFS for hormone receptor-negative cancers (HR 0.96, 95% CI 0.83 to 1.10; 7 studies, 1122 participants; moderate-certainty evidence). Quality of life was assessed in five studies; in general there did not seem to be differences in global health scores between the two treatment groups at around two years' follow-up. Neoadjuvant studies were highly variable in design, having been undertaken to test various experimental regimens using pathological complete response (pCR) as a surrogate for disease-free survival (DFS) and OS. Across all patients, capecitabine-containing regimens resulted in little difference in pCR in comparison to non-capecitabine-containing regimens (odds ratio (OR) 1.12, 95% CI 0.94 to 1.33; 6 studies, 3152 participants; high-certainty evidence). By subtype, no difference in pCR was observed for either hormone receptor-positive (OR 1.22, 95% CI 0.76 to 1.95; 4 studies, 964 participants; moderate-certainty evidence) or hormone receptor-negative tumours (OR 1.28, 95% CI 0.61 to 2.66; 4 studies, 646 participants; moderate-certainty evidence). Four studies with 2460 people reported longer-term outcomes: these investigators detected no difference in either DFS (HR 1.02, 95% CI 0.86 to 1.21; high-certainty evidence) or OS (HR 0.97, 95% CI 0.77 to 1.23; high-certainty evidence). In the adjuvant setting, a modest improvement in OS was observed across all participants (HR 0.89, 95% CI 0.81 to 0.98; 8 studies, 13,547 participants; moderate-certainty evidence), and no difference in OS was seen in hormone receptor-positive cancers (HR 0.86, 95% CI 0.68 to 1.09; 3 studies, 3683 participants), whereas OS improved in hormone receptor-negative cancers (HR 0.72, 95% CI 0.59 to 0.89; 5 studies, 3432 participants). No difference in DFS or relapse-free survival (RFS) was observed across all participants (HR 0.93, 95% CI 0.86 to 1.01; 8 studies, 13,457 participants; moderate-certainty evidence). As was observed for OS, no difference in DFS/RFS was seen in hormone receptor-positive cancers (HR 1.03, 95% CI 0.91 to 1.17; 5 studies, 5604 participants; moderate-certainty evidence), and improvements in DFS/RFS with inclusion of capecitabine were observed for hormone receptor-negative cancers (HR 0.74, 95% CI 0.64 to 0.86; 7 studies, 3307 participants; moderate-certainty evidence). Adverse effects were reported across all three scenarios. When grade 3 or 4 febrile neutropenia was considered, no difference was seen for capecitabine compared to non-capecitabine regimens in neoadjuvant studies (OR 1.31, 95% CI 0.97 to 1.77; 4 studies, 2890 participants; moderate-certainty evidence), and a marked reduction was seen for capecitabine in adjuvant studies (OR 0.55, 95% CI 0.47 to 0.64; 5 studies, 8086 participants; moderate-certainty evidence). There was an increase in diarrhoea and hand-foot syndrome in neoadjuvant (diarrhoea: OR 1.95, 95% CI 1.32 to 2.89; 3 studies, 2686 participants; hand-foot syndrome: OR 6.77, 95% CI 4.89 to 9.38; 5 studies, 3021 participants; both moderate-certainty evidence) and adjuvant trials (diarrhoea: OR 2.46, 95% CI 2.01 to 3.01; hand-foot syndrome: OR 13.60, 95% CI 10.65 to 17.37; 8 studies, 11,207 participants; moderate-certainty evidence for both outcomes). AUTHORS' CONCLUSIONS: In summary, a moderate PFS benefit by including capecitabine was seen only in hormone receptor-positive cancers in metastatic studies. No benefit of capecitabine for pCR was noted overall or in hormone receptor subgroups when included in neoadjuvant therapy. In contrast, the addition of capecitabine in the adjuvant setting led to improved outcomes for OS and DFS in hormone receptor-negative cancer. Future studies should stratify by hormone receptor and triple-negative breast cancer (TNBC) status to clarify the differential effects of capecitabine in these subgroups across all treatment scenarios, to optimally guide capecitabine inclusion.

Integrating Arts with STEM to Foster Systems Thinking.

Interest is growing among out-of-school time (OST) educators in integrating the arts into STEM (science, technology, engineering, and mathematics) programming (e.g., Kelton & Saraniero, 2018). Arts-integrated STEM-or STEAM-programming now takes place in a wide variety of OST environments, from relatively institutional learning settings, such as a library, to emergent or fluid settings, such as a pop-up program in a housing development community room.

Treating Women with Recurrent Stress Urinary Incontinence: A Hornet's Nest Still Needing Proper Clinical Evidence.

Evidence is lacking on the best treatment for women presenting with recurrent stress urinary incontinence. PURSUIT is a randomised trial of urethral bulking agent injection versus surgical intervention. It will provide high-quality evidence to aid counselling and inform choice.

Case of ventricular septal rupture following acute myocardial infarction.

Ventricular septal rupture is a rare and potentially fatal complication of transmural myocardial infarction. Early identification utilising transthoracic echocardiography significantly improves long term outcomes in these patients. We report on a case of a 77-year-old male who presented with signs and symptoms of cardiac failure and a loud systolic murmur. The patient underwent an initial point-of-care ultrasound which revealed evidence of a transmural myocardial infarction and a high suspicion of an apical ventricular septal rupture. A complete transthoracic echocardiogram confirmed the septal rupture diagnosis and the patient subsequently underwent surgical repair of the ventricular rupture. This case highlights the role of echocardiography in decreasing adverse outcomes in patients with ventricular septal rupture.

MR-guided focused ultrasound increases antibody delivery to nonenhancing high-grade glioma.

BACKGROUND: High-grade glioma (HGG) remains a recalcitrant clinical problem despite many decades of research. A major challenge in improving prognosis is the inability of current therapeutic strategies to address a clinically significant burden of infiltrating tumor cells that extend beyond the margins of the primary tumor mass. Such cells cannot be surgically excised nor efficiently targeted by radiation therapy. Therapeutic targeting of this tumor cell population is significantly hampered by the presence of an intact blood-brain barrier (BBB). In this study, we performed a preclinical investigation of the efficiency of MR-guided Focused Ultrasound (FUS) to temporarily disrupt the BBB to allow selective delivery of a tumor-targeting antibody to infiltrating tumor. METHODS: Structural MRI, dynamic-contrast enhancement MRI, and histology were used to fully characterize the MR-enhancing properties of a patient-derived xenograft (PDX) orthotopic mouse model of HGG and to develop a reproducible, robust model of nonenhancing HGG. PET-CT imaging techniques were then used to evaluate the efficacy of FUS to increase 89Zr-radiolabeled antibody concentration in nonenhancing HGG regions and adjacent non-targeted tumor tissue. RESULTS: The PDX mouse model of HGG has a significant tumor burden lying behind an intact BBB. Increased antibody uptake in nonenhancing tumor regions is directly proportional to the FUS-targeted volume. FUS locally increased antibody uptake in FUS-targeted regions of the tumor with an intact BBB, while leaving untargeted regions unaffected. CONCLUSIONS: FUS exposure successfully allowed temporary BBB disruption, localized to specifically targeted, nonenhancing, infiltrating tumor regions and delivery of a systemically administered antibody was significantly increased.

Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: the importance of reproducing blood-brain barrier heterogeneity.

The clinical translation of new nanoparticle-based therapies for high-grade glioma (HGG) remains extremely poor. This has partly been due to the lack of suitable preclinical mouse models capable of replicating the complex characteristics of recurrent HGG (rHGG), namely the heterogeneous structural and functional characteristics of the blood-brain barrier (BBB). The goal of this study is to compare the characteristics of the tumor BBB of rHGG with two different mouse models of HGG, the ubiquitously used U87 cell line xenograft model and a patient-derived cell line WK1 xenograft model, in order to assess their suitability for nanomedicine research. Method: Structural MRI was used to assess the extent of BBB opening in mouse models with a fully developed tumor, and dynamic contrast enhanced MRI was used to obtain values of BBB permeability in contrast enhancing tumor. H&E and immunofluorescence staining were used to validate results obtained from the in vivo imaging studies. Results: The extent of BBB disruption and permeability in the contrast enhancing tumor was significantly higher in the U87 model than in rHGG. These values in the WK1 model are similar to those of rHGG. The U87 model is not infiltrative, has an entirely abnormal and leaky vasculature and it is not of glial origin. The WK1 model infiltrates into the non-neoplastic brain parenchyma, it has both regions with intact BBB and regions with leaky BBB and remains of glial origin. Conclusion: The WK1 mouse model more accurately reproduces the extent of BBB disruption, the level of BBB permeability and the histopathological characteristics found in rHGG patients than the U87 mouse model, and is therefore a more clinically relevant model for preclinical evaluations of emerging nanoparticle-based therapies for HGG.

Metal-shell nanocapsules for the delivery of cancer drugs.

Cytotoxic drugs tend to have substantial side effects on healthy tissues leading to systemic toxicity, limited tolerated doses and reduced drug efficacy. A prominent research area focuses on encapsulating cytotoxic drugs for targeted delivery to cancer tissues. However, existing carriers suffer from low drug loading levels and high drug leaching both when circulating systemically and when accumulating in non-target organs. These challenges mean that only few encapsulation technologies for delivery of cytotoxic drugs have been adopted for clinical use. Recently, we have demonstrated efficient manufacture of impermeable metal-shell/liquid core microcapsules that permit localised delivery by triggering release with ultrasound. This method has the potential to improve on existing methods for localised drug delivery because it:We demonstrate here the further miniaturization of both the emulsion droplet template and the thickness of the surrounding metal shell to the nanoscale in an attempt to take advantage of the EPR effect and the excretion of nanoparticles by the hepatobiliary system.

Assessing Science Learning and Systems Thinking Through Arts.

We present two interventions aimed at promoting science learning. We utilize arts-based assessments alongside traditional measures to examine systems thinking. Taking place in rural communities in Washington State and focusing on students in third through fifth grades, our results indicate that arts-based assessment in STEM can support demonstration of systems thinking about socio-scientific issues. We conclude by illustrating the viability of arts-based approaches for assessment and how these methods can complement and extend more traditional measures of learning in and out of the classroom.