Empathic reflections by themselves are not effective: Meta-analysis and qualitative synthesis.

Objective: We present a mixed methods systematic review of the effectiveness of therapist empathic reflections, which have been adopted by a range of approaches to communicate an understanding of client communications and experiences. Methods: We begin with definitions and subtypes of empathic reflection, drawing on relevant research and theory, including conversation analysis. We distinguish between empathic reflections, reviewed here, and the relational quality of empathy (reviewed in previous meta-analyses). We look at how empathic reflections are assessed and present examples of successful and unsuccessful empathic reflections, also providing a framework of the different criteria used to assess their effectiveness (e.g., association with session or treatment outcome, or client next-turn good process). Results: In our meta-analysis of 43 samples, we found virtually no relation between presence/absence of empathic reflection and effectiveness, both overall and separately within-session, post-session and post-treatment. Although not statistically significant, we did find weak support for reflections of change talk and summary reflections. Conclusions: We argue for research looking more carefully at the quality of empathy sequences in which empathic reflections are ideally calibrated in response to empathic opportunities offered by clients and sensitively adjusted in response to client confirmation/disconfirmation. We conclude with training implications and recommended therapeutic practices.

A continuous flow microfluidic calorimeter: 3-D numerical modeling with aqueous reactants.

A computational analysis of the reacting flow field, species diffusion and heat transfer processes with thermal boundary layer effects in a microchannel reactor with a coflow configuration was performed. Two parallel adjacent streams of aqueous reactants flow along a wide, shallow, enclosed channel in contact with a substrate, which is affixed to a temperature controlled plate. The Fluent computational fluid dynamics package solved the Navier-Stokes, mass transport and energy equations. The energy model, including the enthalpy of reaction as a nonuniform heat source, was validated by calculating the energy balance at several control volumes in the microchannel. Analysis reveals that the temperature is nearly uniform across the channel thickness, in the direction normal to the substrate surface; hence, measurements made by sensors at or near the surface are representative of the average temperature. Additionally, modeling the channel with a glass substrate and a silicone cover shows that heat transfer is predominantly due to the glass substrate. Finally, using the numerical results, we suggest that a microcalorimeter could be based on this configuration, and that temperature sensors such as optical nanohole array sensors could have sufficient spatial resolution to determine enthalpy of reaction.

Nanohole arrays of mixed designs and microwriting for simultaneous and multiple protein binding studies.

We demonstrate using nanohole arrays of mixed designs and a microwriting process based on dip-pen nanolithography to monitor multiple, different protein binding events simultaneously in real-time based on the intensity of Extraordinary Optical Transmission of nanohole arrays. The microwriting process and small footprint of the individual nanohole arrays enabled us to observe different binding events located only 16 microm apart, achieving high spatial resolution. We also present a novel concept that incorporates nanohole arrays of different designs to improve confidence and accuracy of binding studies. For proof of concept, two types of nanohole arrays, designed to exhibit opposite responses to protein bindings, were fabricated on one transducer. Initial studies indicate that the mixed designs could help to screen out artifacts such as protein intrinsic signals, providing improved accuracy of binding interpretation.

Multiplexed plasmonic sensing based on small-dimension nanohole arrays and intensity interrogation.

We performed multiplexed sensing on nanohole array devices to simultaneously obtain information on molecular absorption, scattering, and refractive-index change, which were distinguished by using different array structures with distinct optical behavior. Up to 25 arrays were fabricated within a 65 microm x 50 microm area to provide real-time information of the local surface environment. The performance of multiplexed sensing was examined by flowing NaCl, Coomassie blue, bovine serum albumin, and liposome solutions that exhibit different visible light absorption/scattering properties and different refractive indices. Experimental artifacts from light source fluctuation, sample injections, and light scattering induced by aggregates in solutions were detected by monitoring superwavelength holes or nanohole arrays with different periodicity and hole diameters.

Metallic nanohole arrays on fluoropolymer substrates as small label-free real-time bioprobes.

We describe a nanoplasmonic probing platform that exploits small-dimension (

High-throughput nanohole array based system to monitor multiple binding events in real time.

We have developed an integrated label-free, real-time sensing system that is able to monitor multiple biomolecular binding events based on the changes in the intensity of extraordinary optical transmission (EOT) through nanohole arrays. The core of the system is a sensing chip containing multiple nanohole arrays embedded within an optically thick gold film, where each array functions as an independent sensor. Each array is a square array containing 10 x 10 nanoholes (150 nm in diameter), occupying a total area of 3.3 mum x 3.3 mum. The integrated system includes a laser light source, a temperature-regulated flow cell encasing the sensing chip, motorized optics, and a charge-coupled detector (CCD) camera. For demonstration purposes, sensing chips containing 25 nanohole arrays were studied for their use in multiplexed detection, although the sensing chip could be easily populated to contain up to 20 164 nanohole arrays within its 0.64 cm2 sensing area. Using this system, we successfully recorded 25 separate binding curves between glutathione S-transferase (GST) and anti-GST simultaneously in real time with good sensitivity. The system responds to binding events in a concentration-dependent manner, showing a sharp linear response to anti-GST at concentrations ranging from 13 to 290 nM. The EOT intensity-based approach also enables the system to monitor multiple bindings simultaneously and continuously, offering a temporal resolution on milliseconds scale that is decided only by the camera speed and exposure time. The small footprint of the sensing arrays combined with the EOT intensity-based approach enables the system to resolve binding events that occurred on nanohole sensing arrays spaced 96 mum apart, with a reasonable prediction of resolving binding events spaced 56 mum apart. This work represents a new direction that implements nanohole arrays and EOT intensity to meet high-throughput, spatial and temporal resolution, and sensitivity requirements in drug discovery and proteomics studies.

Breaking the diffraction barrier outside of the optical near-field with bright, collimated light from nanometric apertures.

The optical diffraction limit has been the dominant barrier to achieving higher optical resolution in the fields of microscopy, photolithography, and optical data storage. We present here an approach toward imaging below the diffraction barrier. Through the exposure of photosensitive films placed a finite and known distance away from nanoscale, zero-mode apertures in thin metallic films, we show convincing, physical evidence that the propagating component of light emerging from these apertures shows a very strong degree of collimation well past the maximum extent of the near-field (lambda(0)/4n-lambda(0)/2n). Up to at least 2.5 wavelengths away from the apertures, the transmitted light exhibits subdiffraction limit irradiance patterns. These unexpected results are not explained by standard diffraction theory or nanohole-based "beaming" rationalizations. This method overcomes the diffraction barrier and makes super-resolution fluorescence imaging practical.

Effects of a program for coordinated care of advanced illness on patients, surrogates, and healthcare costs: a randomized trial.

OBJECTIVE: To evaluate the Advanced Illness Coordinated Care Program (AICCP), delivered by allied health personnel to improve care for patients coping with advanced illness and in need of preparation for end-of-life (EOL) care. STUDY DESIGN: Clinical trial involving 275 patients and 143 surrogates in 6 settings who were randomly assigned to the AICCP or usual care (UC). METHODS: The AICCP participants met with a care coordinator for assistance with provider communication, care coordination, and support. The AICCP was evaluated for effects on satisfaction with care, advance planning, consistency of care with patient preferences, and healthcare costs. RESULTS: The AICCP increased patient satisfaction with care and communication (P = .03), and AICCP surrogates reported fewer problems with provider support (P = .03). More AICCP than UC participants completed an advance directive (AD) (69.4% vs 48.4%; P = .006), and the AICCP group completed more ADs per participant (P = .01). Median time to AD documentation was 46 days for AICCP and 238 days for UC (P = .02). There was no difference in survival (AICCP 43% vs UC 42%). Six-month costs were lower with AICCP than with UC (12,123 US dollars vs 16,295 US dollars); however, the difference did not reach statistical significance. CONCLUSIONS: The AICCP improved satisfaction with care and helped patients develop and revise more ADs, sooner, without affecting mortality. This program may be delivered in a range of managed care, fee-for-service, and group-model settings.

Point-of-care biosensor systems for cancer diagnostics/prognostics.

With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments--DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.

Emerging tools for real-time label-free detection of interactions on functional protein microarrays.

The availability of extensive genomic information and content has spawned an era of high-throughput screening that is generating large sets of functional genomic data. In particular, the need to understand the biochemical wiring within a cell has introduced novel approaches to map the intricate networks of biological interactions arising from the interactions of proteins. The current technologies for assaying protein interactions--yeast two-hybrid and immunoprecipitation with mass spectrometric detection--have met with considerable success. However, the parallel use of these approaches has identified only a small fraction of physiologically relevant interactions among proteins, neglecting all nonprotein interactions, such as with metabolites, lipids, DNA and small molecules. This highlights the need for further development of proteome scale technologies that enable the study of protein function. Here we discuss recent advances in high-throughput technologies for displaying proteins on functional protein microarrays and the real-time label-free detection of interactions using probes of the local index of refraction, carbon nanotubes and nanowires, or microelectromechanical systems cantilevers. The combination of these technologies will facilitate the large-scale study of protein interactions with proteins as well as with other biomolecules.

Becky's legacy: more lessons.

In this commentary on Werth's (this issue) article, the author attempts to continue the work of "meaning making" by describing 10 lessons that were evident to him, based on 25 years of experience as an end-of-life researcher and clinician. He highlights the impact of stress, the importance of communication, the idiosyncratic definition of a "good death," the role of patient-centered care, the power of self-efficacy, the need to integrate theory and experience, the use of interdisciplinary teams, the impact of altruism and having a sense of purpose, the need to listen, and the healing effects of communicating about loss.