Impact of setup errors on the robustness of linac-based single-isocenter coplanar and non-coplanar VMAT plans for multiple brain metastases.

PURPOSE: Patient setup errors have been a primary concern impacting the dose delivery accuracy in radiation therapy. A robust treatment plan might mitigate the effects of patient setup errors. In this reported study, we aimed to evaluate the impact of translational and rotational errors on the robustness of linac-based, single-isocenter, coplanar, and non-coplanar volumetric modulated arc therapy treatment plans for multiple brain metastases. METHODS: Fifteen patients were retrospectively selected for this study with a combined total of 49 gross tumor volumes (GTVs). Single-isocenter coplanar and non-coplanar plans were generated first with a prescribed dose of 40 Gy in 5 fractions or 42 Gy in 7 fractions to cover 95% of planning target volume (PTV). Next, four setup errors (+1  and +2 mm translation, and +1° and +2° rotation) were applied individually to generate modified plans. Different plan quality evaluation metrics were compared between coplanar and non-coplanar plans. 3D gamma analysis (3%/2 mm) was performed to compare the modified plans (+2 mm and +2° only) and the original plans. Paired t-test was conducted for statistical analysis. RESULTS: After applying setup errors, variations of all plan evaluation metrics were similar (p > 0.05). The worst case for V100% to GTV was 92.07% ± 6.13% in the case of +2 mm translational error. 3D gamma pass rates were > 90% for both coplanar (+2 mm and +2°) and the +2 mm non-coplanar groups but was 87.40% ± 6.89% for the +2° non-coplanar group. CONCLUSION: Translational errors have a greater impact on PTV and GTV dose coverage for both planning methods. Rotational errors have a greater negative impact on gamma pass rates of non-coplanar plans. Plan evaluation metrics after applying setup errors showed that both coplanar and non-coplanar plans were robust and clinically acceptable.

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.

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.

Linac reported steering error insensitive to 6 MV FFF transverse beam position deviations.

Clinically significant beam position deviations were observed for a 6 MV FFF beam during patient specific QA on an Elekta linear accelerator. There was no significant reported transverse steering error from the machine ion chamber, and routine linac QA practices, including cardinal angle Winston-Lutz test, did not identify the deviations. Subsequent investigation using an electronic portal imaging device (EPID) revealed clinically significant beam position deviations for small steering errors. This prompted investigation into further impact and possible solutions. Testing set-points were established by adjusting transverse steering current to achieve introduced 2 T steering errors. Tests at each set-point included scanning water tank profiles and EPID images. A proposed method for adjusting the 2 T error sensitivity was tested via adjusting the 2 T loop parameter such that a reported error corresponds to specific beam position deviations. The testing set-points resulted in positional deviations of greater than 3 mm for reported errors of less than 1. A new method for improving 2 T error sensitivity was implemented. This work has shown that existing vendor protocol for establishing beam steering error for 6 MV FFF beams can lead to beam position deviations without machine interlocks or significant reported steering errors. Thus, an alternative method of establishing steering error sensitivity based on positional deviations is presented.

Intergenerational Commensality: A Critical Discussion on Non-Familial Age Groups Eating Together.

Connecting intergenerational relationships and commensality has been a neglected area in research and conceptual development within both food and life-course studies. This has been especially true of relations beyond the family. Here, public and private settings are explored in order to examine the relationship between eating together and generationally intelligent empathy. This is to help the discovery of spaces where different generations can interact positively around food and mealtimes. Contemporary social and public health challenges include: to adapt to increased longevity and to build solidarity between generations; to repair the relations between generations arising from institutional segregation; and to increase experiences of generational connection and social inclusion. As age-based cohorts are led to see themselves as separate from each other, we must find ways of building and negotiating new complementary roles for different parts of the life-course. Commensality, eating together at the same table provides an important cultural location and opportunity around which complementary understandings between generations may be built. A new framework is proposed to help identify and critically examine the variables underpinning non-familial intergenerational commensal spaces.

Investigating Adsorbing Viscoelastic Fluids Using the Quartz Crystal Microbalance.

There is little research on using the quartz crystal microbalance (QCM) with adsorbing viscoelastic fluids. These fluids are widely encountered but often difficult to study as many are opaque and highly viscous. Since the QCM does not involve any scattering or reflection of input radiation, it has the potential to study these complex fluids to determine the relative viscoelasticity of the bulk fluid and surface adsorption of active species onto different substrates. In the current study, both Newtonian (sucrose) and viscoelastic (sodium polystyrene sulfonate (NaPSS)) fluids were introduced into the QCM, and the sensor responses were compared. QCM responses of Newtonian sucrose solutions matched the Kanazawa and Gordon model (KG model), as expected. The QCM responses with viscoelastic NaPSS solutions were well below those described by the KG model. A viscoelastic model was used to determine the fluid viscosity and shear modulus at a very high frequency. It was found that the viscosity of NaPSS did not change much compared with low-frequency rheometer measurements, but a significant increase in the shear modulus of several orders of magnitude was found at the QCM frequencies. Modifying the KG model frequency shifts by multiplying by the QCM shear wave decay length ratio, X = δV/δN, we were able to match the measured QCM values in viscoelastic NaPSS solutions. The QCM dissipation values for NaPSS were matched in a similar way by multiplying the KG model by X 1/3. By changing the QCM sensor from silica (no NaPSS adsorption) to alumina (NaPSS adsorption), it was shown that the adsorption isotherm of NaPSS on alumina could be recovered and fitted with a Langmuir isotherm despite the frequency response being only a small fraction of the total measured QCM signal.

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.

The Distribution of Regulation in Aged and Dementia Care: A Continuum Approach.

The regulation of care services has become the principal means by which the state influences provision. In this article we examine the regulation of dementia care within organizations to show how some care activities attract more regulation than others. While often perceived to be overwhelming, regulation is in fact unevenly distributed at the system, organization and, in particular, the care practice levels. In practice, some areas of care are heavily regulated, while others are less so. Drawing on research interviews with staff (N = 60) at three levels of care provider organizations-senior managers, facility managers, and direct care workers-a continuum of regulation, with regulations collecting around some care activities and not others, is developed. This is used to plot how different care activities are affected by regulation. Understanding how regulations collect around some activities and not others shows where flexibility and innovation in care are possible. This has implications for the discretion care workers can exercise in daily care, effective organizational strategies for managing care and regulation, and regulatory policy. Current debates around regulation should shift from notions of good/bad and more/less regulation to an analysis of how regulation creates areas that are closely controlled and those that allow practice innovation.

How provider organisations interpret regulation in the context of residential dementia aged care.

OBJECTIVE: To explore how Australian residential dementia aged care providers respond to regulation via organisational culture, level, processes and interpretation. METHODS: Observation took place in three provider organisations. Qualitative, semi-structured in-depth interviews were conducted with aged care staff (n = 60) at three different levels of each organisation: senior management from three head offices (n = 17), facility management (n = 13) and personal care workers (n = 30) from eight residential care facilities. RESULTS: Orientations towards regulation included the following: "above and beyond;" "pushing back;" and "engineering out." Regulation was interpreted differently depending on the level of authority within an organisation where boundaries were managed according to strategic, operational and interactional priorities. DISCUSSION: Examining regulation within an organisational context and at different staff levels suggests ways to balance dementia care with regulatory control. Both generate stress, mitigated by culture and interdependent role differentiation.

Dementia as a source of social disadvantage and exclusion.

OBJECTIVE: To explore perceptions of the impacts of dementia on people living with the condition and those close to them and examine the relationship between dementia, disadvantage and social exclusion. METHODS: Semi-structured in-depth interviews were conducted with 111 participants: people with dementia (n = 19), carers (n = 28), health-care professionals (n = 21), social workers (n = 23) and service professionals (n = 20). NVivo 11 was used to code descriptions and identify impact areas. RESULTS: Participants described social, psychological, carer, material, service-based and disparity impacts associated with the experience of dementia. Some of these impacts correspond to social exclusion associated with age, but some are distinctive to dementia. DISCUSSION: It is argued that dementia generates its own forms of social disadvantage and exclusion. This is in addition to being subject to structural risk factors. The implications of the active effects of dementia as a social phenomenon should give rise to new policy and practice priorities.

What you say and what I want: Priorities for public health campaigning and initiatives in relation to dementia.

OBJECTIVE: To examine the overlap between priorities expressed by representatives from national and local campaigning organisations and the views of key voices in relation to dementia. METHODS: Semi-structured, in-depth telephone interviews were conducted with 19 representatives from campaigning organisations, including nine countries and six local community initiatives in Australia. Responses were categorised into nine priorities. Views were compared to the voices of people with dementia (n = 19), carers (n = 28), and health-care (n = 21), social work (n = 23) and service professionals (n = 20). RESULTS: Local groups prioritised user-led decision-making and community normalising agendas. National groups were influenced by service frameworks and increasing public awareness. Professional and carer groups focused on increasing understanding and communication skills while people with dementia valued being a normal part of society. CONCLUSION: Future campaigning should use both national and local approaches to changing social relations, through interpersonal connections, advocacy and social mobilisation, to promote a normalising approach to attitude change.

Ultrasound-triggered release from metal shell microcapsules.

Metal shell microcapsules have been shown to completely retain their core until its release is triggered, making them a promising candidate for use as a controllable drug delivery vehicle due to their superior retention properties as compared to polymer shell microcapsules. Focused ultrasound (FUS) has been successfully utilised to trigger release of lipophilic drugs from polymer microcapsules, and in this work the response of gold shell microcapsules with and without an inner polymeric shell, to FUS and standard ultrasound is explored. The results show that gold shell microcapsules with an inner polymer shell rupture when exposed to standard ultrasound and that there is a linear correlation between the gold shell thickness and the extent of shell rupture. When FUS is applied to these microcapsules, powers as low as 0.16 W delivered in bursts of 10 ms/s over a period of 120 s are sufficient to cause rupture of 53 nm gold shell microcapsules. Additional findings suggest that gold shell microcapsules without the polymer layer dispersed in a hydrogel matrix, as opposed to aqueous media, rupture more efficiently when exposed to FUS, and that thicker gold shells are more responsive to ultrasound-triggered rupture regardless of the external environment. Release of dye from all successfully ruptured capsules was sustained over a period of between 7 and 35 days. These findings suggest that emulsion-templated gold shell microcapsules embedded in a hydrogel matrix would be suitable for use as an implantable drug delivery vehicle with FUS used to externally trigger release.

Encapsulation of Emulsion Droplets with Metal Shells for Subsequent Remote, Triggered Release.

A two-step method to encapsulate an oil core with an impermeable shell has been developed. A thin metallic shell is deposited on the surface of emulsion droplets stabilized by metal nanoparticles. This thin shell is shown to prevent diffusion of the oil from within the core of the metal-shell microcapsules when placed in a continuous phase that fully dissolves the oil. The stabilizing nanoparticles are sterically stabilized by poly(vinyl pyrrolidone) chains and are here used as a catalyst/nucleation site at the oil-water interface to grow a secondary metal shell on the emulsion droplets via an electroless deposition process. This method provides the simplest scalable route yet to synthesize impermeable microcapsules with the added benefit that the final structure allows for drastically improving the overall volume of the encapsulated core to, in this case, >99% of the total volume. This method also allows for very good control over the microcapsule properties, and here we demonstrate our ability to tailor the final microcapsule density, capsule diameter, and secondary metal film thickness. Importantly, we also demonstrate that such impermeable microcapsule metal shells can be remotely fractured using ultrasound-based devices that are commensurate with technologies currently used in medical applications, which demonstrate the possibility to adapt these microcapsules for the delivery of cytotoxic drugs.

Social aspects of dementia and dementia practice.

Social aspects of dementia are becoming increasingly important as part of a wider shift in emphasis from cure to care. This is partly because approaches based on finding a cure have proved far more difficult and complex than originally imagined (WHO, 2016). New evidence on the effectiveness of public health measures, that while incidence is growing as the proportion of older people in society increases its prevalence amongst older adults is actually falling, has also lead to increased interest in social dimensions of prevention, lifestyle change, and practical intervention in community settings (Prince et al., 2016; Kivipelto et al., 2017). This, in turn, has led to a rediscovery of the role of supports to people living with dementia in their daily lives, the needs of informal carers, and professional activities that can maintain the social engagement of each party (Winblad et al., 2016). The expansion of practice around person-centered care, beyond traditional institutional settings, has also contributed to a socialized view of how interactions in dementia care are thought about (Bartlett et al., 2017), as has an increased awareness of the effects of the social construction of dementia in the public mind (Biggs, 2018). Most recently, people living with dementia, and particularly with respect to younger onset dementia, have begun to find a voice and to make connections to the wider disability movement (Dementia Alliance International, 2017). Each of these developments, in their different ways, have led to a re-emphasis on psycho-social elements of dementia, its experience, and how that might translate into clinical practice and service delivery.

Influence of pH-Responsive Monomer Content on the Behavior of Di-Block Copolymers in Solution and as Stabilizers of Pickering Latex Particle Emulsifiers.

In this study, diblock copolymers poly(methyl methacrylate)-block-poly (2-dimethylaminoethyl methacrylate) (pMMA-b-pDMAEMA) are investigated for the steric stabilization of latex particles and the subsequent use of these latex particles as Pickering emulsifiers. Solution properties of the diblock copolymers highlight that the pDMAEMA block length influences the critical micelle concentration (CMC) and micelle hydrodynamic diameter in response to changes in pH and the pKa. The block length can also be used as a way to control the particle size of sterically stabilized polystyrene latex particles prepared via emulsion polymerization. The suspension properties of these latex particles are also presented. Emulsion studies using these latex particles as emulsifiers show that both continuous phase pH and electrolyte concentration affect emulsion stability to coalescence. At high pH, stable emulsions are formed due to the affinity of the particles to the interface. At low pH, protonation of the amine groups reduces the affinity and thus droplet coalescence is observed. Increasing the electrolyte concentration improves emulsion stability, but causes an increase in droplet size due to adsorption of flocculated/aggregated particles. Finally, it is shown that these latex particles can be used in conjunction with membrane emulsification techniques to produce emulsions with low polydispersity.

Differences in priority by age group and perspective: implications for public health education and campaigning in relation to dementia.

ABSTRACTObjectives:A shift toward public health responses to dementia, raises questions about the most appropriate approaches to specific population groups. We examined perspective and age as elements in effective campaigning. Implications from the standpoint of the recipient are drawn for public health education and practice. DESIGN: In-depth semi-structured face-to-face and telephone interview with self-selected participants recruited via adverts, contact with provider organizations and cards placed in retail and service settings. Questions focused on attitudes to dementia and expectations of public campaigning and education. SETTING: Community-dwelling adults were interviewed across five Australian states. PARTICIPANTS: A total of 111 people from 5 target groups: people with dementia (n = 19), carers (n = 28), care work and service professionals from healthcare (n = 21), social work (n = 23) and commercial service professions (n = 20) involving people in younger adulthood (n = 13), early midlife (n = 23), later midlife (n = 54), and older age (n = 21). MEASUREMENTS: All interviews were transcribed and analyzed thematically by three researchers, reaching consensus before coding and further analysis in NVivo. Narrative analysis of transcripts included 330 topics relating to 6 main areas of focus. RESULTS: Attitudes and views on effective future campaigning reflected a desire for greater social inclusion, but did not focus on prevention and health services. Professionals focused on increasing interpersonal skills, people with dementia on normalization, and carers on awareness-raising. CONCLUSIONS: Public health campaigning and education in relation to dementia, could benefit from closer consideration of perspective and age of recipient in intervention design. Interpersonal skills and social inclusion were identified as key issues.

Analytical Model for Diffusive Evaporation of Sessile Droplets Coupled with Interfacial Cooling Effect.

Current analytical models for sessile droplet evaporation do not consider the nonuniform temperature field within the droplet and can overpredict the evaporation by 20%. This deviation can be attributed to a significant temperature drop due to the release of the latent heat of evaporation along the air-liquid interface. We report, for the first time, an analytical solution of the sessile droplet evaporation coupled with this interfacial cooling effect. The two-way coupling model of the quasi-steady thermal diffusion within the droplet and the quasi-steady diffusion-controlled droplet evaporation is conveniently solved in the toroidal coordinate system by applying the method of separation of variables. Our new analytical model for the coupled vapor concentration and temperature fields is in the closed form and is applicable for a full range of spherical-cap shape droplets of different contact angles and types of fluids. Our analytical results are uniquely quantified by a dimensionless evaporative cooling number Eo whose magnitude is determined only by the thermophysical properties of the liquid and the atmosphere. Accordingly, the larger the magnitude of Eo, the more significant the effect of the evaporative cooling, which results in stronger suppression on the evaporation rate. The classical isothermal model is recovered if the temperature gradient along the air-liquid interface is negligible ( Eo = 0). For substrates with very high thermal conductivities (isothermal substrates), our analytical model predicts a reversal of temperature gradient along the droplet-free surface at a contact angle of 119°. Our findings pose interesting challenges but also guidance for experimental investigations.

The rheology of polyvinylpyrrolidone-coated silica nanoparticles positioned at an air-aqueous interface.

Particle-stabilized emulsions and foams are widely encountered, as such there remains a concerted effort to better understand the relationship between the particle network structure surrounding droplets and bubbles, and the rheology of the particle-stabilized interface. Poly(vinylpyrrolidone)-coated silica nanoparticles were used to stabilize foams. The shear rheology of planar particle-laden interfaces were measured using an interfacial shear rheometer and the rheological properties measured as a function of the sub-phase electrolyte concentration and surface pressure. All particle-laden interfaces exhibited a liquid-like to solid-like transition with increasing surface pressure. The surface pressure-dependent interfacial rheology was then correlated to the formed micron-scale structures of the particle-laden interfaces which were imaged using a Brewster angle microscope. With the baseline knowledge established, foams were prepared using the same composite particles and the particle network structure imaged using cryo-SEM. An attempt has been made to correlate the two structures observed at a planar interface and that surrounding a bubble to elucidate the likely rheology of the bubble stabilizing particle network. Independent of the sub-phase electrolyte concentration, the resulting rheology of the bubble stabilizing particle network was strongly elastic and appeared to be in a compression state at the region of the L-S phase transition.

A two-step synthesis for preparing metal microcapsules with a biodegradable polymer substrate.

Metal microcapsules have recently received attention and are being developed as improved carrier materials when compared to polymer microcapsules. In this work we have developed a novel, simplified method by which polymeric microcapsules can be synthesised using a combination of poly(vinyl pyrrolidone)-stabilised platinum nanoparticles (PVP-Pt) and poly(vinyl pyrrolidone) (PVP) as stabilisers, to allow for a secondary metal shell to be grown. We investigate the relationship between the molar ratio of reducing agent to platinum salt and the size of the resulting NPs and seek to develop further fundamental understanding of the factors governing the secondary metal shell thickness and quality, to allow production of cost-effective metal microcapsules without sacrificing core retention efficiency. We found that the size of the nanoparticles had no significant effect on secondary shell thickness, but did affect the quality of the resulting gold shells. Gold salt concentration was found to be a limiting factor in the electroless deposition of the metal shell. In this work, we have successfully produced PLGA microcapsules with more cost-effective gold shells, as thin as 56 ± 13 nm and capable of complete core retention of volatile actives.