Selective flow-induced vesicle rupture to sort by membrane mechanical properties

International audienceVesicle and cell rupture caused by large viscous stresses in ultrasonication is central to biomedical and bioprocessing applications. The flow-induced opening of lipid membranes can be exploited to deliver drugs into cells, or to recover products from cells, provided that it can be obtained in a controlled fashion. Here we demonstrate that differences in lipid membrane and vesicle properties can enable selective flow-induced vesicle break-up. We obtained vesicle populations with different membrane properties by using different lipids (SOPC, DOPC, or POPC) and lipid:cholesterol mixtures (SOPC:chol and DOPC:chol). We subjected vesicles to large deformations in the acoustic microstreaming flow generated by ultrasound-driven microbubbles. By simultaneously deforming vesicles with different properties in the same flow, we determined the conditions in which rupture is selective with respect to the membrane stretching elasticity. We also investigated the effect of vesicle radius and excess area on the threshold for rupture, and identified conditions for robust selectivity based solely on the mechanical properties of the membrane. Our work should enable new sorting mechanisms based on the difference in membrane composition and mechanical properties between different vesicles, capsules, or cells

Instrumental variable methods to assess quality of care the marginal effects of process-of-care on blood pressure change and treatment costs

Background: Hypertension is poorly controlled. Team-based care and changes in the process of care have been proposed to address these quality problems. However, assessing care processes is difficult because they are often confounded even in randomized behavioral studies by unmeasured confounders based on discretion of health care providers. Objective: To evaluate the effects of process measures including number of counseling sessions about lifestyle modification and number of antihypertensive medications on blood pressure change and payer-perspective treatment costs. Methods: Data were obtained from two prospective, cluster randomized controlled clinical trials (Trial A and B) implementing physician-pharmacist collaborative interventions compared with usual care over six months in community-based medical offices in the Midwest. Multivariate linear regression models with both instrumental variable methods and as-treated methods were utilized. Instruments were indicators for trial and study arms. Models of blood pressure change and costs included both process measures, demographic variables, and clinical variables. Results: The analysis included 496 subjects. As-treated methods showed no significant associations between process and outcomes. The instruments used in the study were insufficient to simultaneously identify distinct process effects. However, the post-hoc instrumental variable models including one process measure at a time while controlling for the other process demonstrated significant associations between the processes and outcomes with estimates considerably larger than as-treated estimates. Conclusions: Instrumental variable methods with combined randomized behavioral studies may be useful to evaluate the effects of different care processes. However, substantial distinct process variation across studies is needed to fully capitalize on this approach. Instrumental variable methods focusing on individual processes provided larger and stronger outcome relationships than those found using as-treated methods which are subject to confounding

A proposal for a comprehensive grading of Parkinson's disease severity combining motor and non-motor assessments: meeting an unmet need.

Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification

The transient voltage response of ReBCO coated conductors exhibiting dynamic resistance

Abstract: Dynamic resistance can be observed in a superconducting tape carrying a DC current which is exposed to an oscillating magnetic field. This effect is attributed to the interaction between the transport current and moving fluxons, and can occur in various superconducting components including high temperature superconducting (HTS) flux pumps, fast-ramping magnets and HTS rotating machines. Although conventionally expressed in terms of a DC ‘resistance,’ the phenomenon is inherently transient in nature, and the voltage drop across the superconductor follows a time-dependent periodic waveform. Here we present experimental measurements of the dynamic resistance of different REBCO tapes carrying a DC current and exposed to an oscillating perpendicular field. Measurements of both the transient voltage waveforms and the time-averaged DC resistances are compared with numerical finite element simulations obtained using the H-formulation. We observe clear variations between the voltage response from different tapes, which can be understood in terms of their differing Jc(B, θ) dependence. In particular, a key feature of the experimentally measured waveforms is the emergence of a split ‘double peak’ at higher applied fields. Graphical visualisations of the finite element data show that this coincides with a periodic increase in Jc(B, θ) throughout the tape. This occurs during each cycle at those times when the applied field falls below the shielding threshold of the tape (as the penetrating field within the tape then approaches zero). Our findings show that models which assume a constant Jc irrespective of local field strength cannot capture the full range of behaviour observed by experiment. This emphasises the importance of employing experimentally measured Jc(B, θ) data when simulating transient effects in HTS materials