Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (vRGD) of integrin ligand RGD-motifs. vRGD was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243 μm−2 (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels

Promoting mental health in small-medium enterprises: An evaluation of the "Business in Mind" program

<p>Abstract</p> <p>Background</p> <p>Workplace mental health promotion (WMHP) aims to prevent and effectively manage the social and economic costs of common mental illnesses such as depression. The mental health of managers and employees within small-medium enterprises (SMEs) is a neglected sector in occupational health research and practice, despite the fact that this sector is the most common work setting in most economies. The availability and propensity of SME staff to attend face-to-face training/therapy or workshop style interventions often seen in corporate or public sector work settings is a widely recognised problem. The 'Business in Mind' program employs a DVD mode of delivery that is convenient for SME managers, particularly those operating in regional and remote areas where internet delivery may not be optimal. The objective of the intervention program is to improve the mental health of SME managers, and examine whether employees of managers' whose mental health improves, report positive change in their psychosocial work environment. The mechanisms via which we aim to improve managers' mental health are through the development of their psychological capital (a higher order construct comprised of hope, self efficacy, resilience and optimism) and their skills and capacities for coping with work stress.</p> <p>Methods/Design</p> <p>The effectiveness of two versions of the program (self administered and telephone facilitated) will be assessed using a randomised trial with an active control condition (psychoeducation only). We aim to recruit a minimum of 249 managers and a sample of their employees. This design allows for 83 managers per group, as power analyses showed that this number would allow for attrition of 20% and still enable detection of an effect size of 0.5. The intervention will be implemented over a three month period and postal surveys will assess managers and employees in each group at baseline, intervention completion, and at 6 month follow up. The intervention groups (managers only) will also be assessed at 12 and 24 month follow-up to examine maintenance of effects. Primary outcomes are managers' levels of psychological capital (hope, resilience, self-efficacy and optimism), coping strategies, anxiety and depression symptoms, self-reported health, job satisfaction and job tension. Secondary outcomes are participating managers subordinates' perceptions of manager support, relational justice, emotional climate and job tension. In order to provide an economic evaluation of the intervention, both employees and manager rates of absenteeism and presenteeism will also be assessed.</p> <p>Discussion</p> <p>The intervention being trialled is expected to improve both primary and secondary outcomes. If proven efficacious, the intervention could be disseminated to reach a much larger proportion of the business community.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN 62853520</p

Outcome measures in chronic obstructive pulmonary disease (COPD): strengths and limitations

Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires. The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality. Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology. Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD

The Australian Reproductive Genetic Carrier Screening Project (Mackenzie's Mission): Design and Implementation

Reproductive genetic carrier screening (RGCS) provides people with information about their chance of having children with autosomal recessive or X-linked genetic conditions, enabling informed reproductive decision-making. RGCS is recommended to be offered to all couples during preconception or in early pregnancy. However, cost and a lack of awareness may prevent access. To address this, the Australian Government funded Mackenzie’s Mission—the Australian Reproductive Genetic Carrier Screening Project. Mackenzie’s Mission aims to assess the acceptability and feasibility of an easily accessible RGCS program, provided free of charge to the participant. In study Phase 1, implementation needs were mapped, and key study elements were developed. In Phase 2, RGCS is being offered by healthcare providers educated by the study team. Reproductive couples who provide consent are screened for over 1200 genes associated with &gt;750 serious, childhood-onset genetic conditions. Those with an increased chance result are provided comprehensive genetic counseling support. Reproductive couples, recruiting healthcare providers, and study team members are also invited to complete surveys and/or interviews. In Phase 3, a mixed-methods analysis will be undertaken to assess the program outcomes, psychosocial implications and implementation considerations alongside an ongoing bioethical analysis and a health economic evaluation. Findings will inform the implementation of an ethically robust RGCS program.</jats:p

Direct measurement of large-scale quantum states via expectation values of non-Hermitian matrices

In quantum mechanics, predictions are made by way of calculating expectation values of observables, which take the form of Hermitian operators. Non-Hermitian operators, however, are not necessarily devoid of physical significance, and they can play a crucial role in the characterization of quantum states. Here we show that the expectation values of a particular set of non-Hermitian matrices, which we call column operators, directly yield the complex coefficients of a quantum state vector. We provide a definition of the state vector in terms of measurable quantities by decomposing these column operators into observables. The technique we propose renders very-large-scale quantum states significantly more accessible in the laboratory, as we demonstrate by experimentally characterizing a 100,000-dimensional entangled state. This represents an improvement of two orders of magnitude with respect to previous phase-and-amplitude characterizations of discrete entangled states