In vitro verification of a 3-D regenerative neural interface design: examination of neurite growth and electrical properties within a bifurcating microchannel structure

Toward the development of neuroprosthesis, we propose a 3-D regenerative neural interface design for connecting with the peripheral nervous system. This approach relies on bifurcating microstructures to achieve defasciculated ingrowth patterns and, consequently, high selectivity. In vitro studies were performed to validate this design by showing that fasciculation during nerve regeneration can be influenced by providing a scaffold to guide growth appropriately. With this approach, neurites can be separated from one another and guided toward specific electrode sites to create a highly selective interface. The neurite separation characteristics were examined for smaller microchannel structures (2.5 and 5 ¿m wide) and larger microchannels (10 and 20 ¿m wide), with smaller microchannels shown to be statistically more effective at initiating separation. Electrodes incorporated at different locations within the microchannels allowed for the recording and tracking of action potential propagation. Microchannel size was also found to play an important role in this regard, with smaller microchannels amplifying the recordable extracellular signal; a twofold increase in the signal to noise ratio was found for 5 ¿m wide microchannels

Development of a national medical leadership competency framework: The Dutch approach

Background: The concept of medical leadership (ML) can enhance physicians' inclusion in efforts for higher quality healthcare. Despite ML's spiking popularity, only a few countries have built a national taxonomy to facilitate ML competency education and training. In this paper we discuss the development of the Dutch ML competency framework with two objectives: to account for the framework's making and to complement to known approaches of developing such frameworks. Methods: We designed a research approach and analyzed data from multiple sources based on Grounded Theory. Facilitated by the Royal Dutch Medical Association, a group of 14 volunteer researchers met over a period of 2.5 years to perform: 1) literature review; 2) individual interviews; 3) focus groups; 4) online surveys; 5) international framework comparison; and 6) comprehensive data synthesis. Results: The developmental processes that led to the framework provided a taxonomic depiction of ML in Dutch perspective. It can be seen as a canonical 'knowledge artefact' created by a community of practice and comprises of a contemporary definition of ML and 12 domains, each entailing four distinct ML competencies. Conclusions: This paper demonstrates how a new language for ML can be created in a healthcare system. The success of our approach to capture insights, expectations and demands relating leadership by Dutch physicians depended on close involvement of the Dutch national medical associations and a nationally active community of practice; voluntary work of diverse researchers and medical practitioners and an appropriate research design that used multiple methods and strategies to circumvent reverberation of established opinions and conventionalisms. Implications: The experiences reported here may provide inspiration and guidance for those anticipating similar work in other countries to develop a tailored approach to create a ML framework

Prediction of clinically relevant adverse drug events in surgical patients

Background Risk stratification of hospital patients for adverse drug events would enable targeting patients who may benefit from interventions aimed at reducing drug-related morbidity. It would support clinicians and hospital pharmacists in selecting patients to deliver a more efficient health care service. This study aimed to develop a prediction model that helps to identify patients on the day of hospital admission who are at increased risk of developing a clinically relevant, preventable adverse drug event during their stay on a surgical ward. Methods Data of the pre-intervention measurement period of the P-REVIEW study were used. This study was designed to assess the impact of a multifaceted educational intervention on clinically relevant, preventable adverse drug events in surgical patients. Thirty-nine variables were evaluated in a univariate and multivariate logistic regression analysis, respectively. Model performance was expressed in the Area Under the Receiver Operating Characteristics. Bootstrapping was used for model validation. Results 6780 admissions of patients at surgical wards were included during the pre-intervention period of the PREVIEW trial. 102 patients experienced a clinically relevant, adverse drug event during their hospital stay. The prediction model comprised five variables: age, number of biochemical tests ordered, heparin/LMWH in therapeutic dose, use of opioids, and use of cardiovascular drugs. The AUROC was 0.86 (95% CI 0.83–0.88). The model had a sensitivity of 80.4% and a specificity of 73.4%. The positive and negative predictive values were 4.5% and 99.6%, respectively. Bootstrapping generated parameters in the same boundaries. Conclusions The combined use of a limited set of easily ascertainable patient characteristics can help physicians and pharmacists to identify, at the time of admission, surgical patients who are at increased risk of developing ADEs during their hospital stay. This may serve as a basis for taking extra precautions to ensure medication safety in those patients

GRB 011121: A massive star progenitor

Of the cosmological gamma-ray bursts, GRB 011121 has the lowest redshift, z = 0.36. More importantly, the multicolor excess in the afterglow detected in the Hubble Space Telescope (HST) light curves is compelling observational evidence of an underlying supernova. Here we present near-infrared and radio observations of the afterglow, and from our comprehensive afterglow modeling, we find evidence favoring a wind-fed circumburst medium. Lacking X-ray data, we are unable to conclusively measure the mass-loss rate, M, but obtain an estimate, M ∼ 2 × 10-7/νw3 M⊙yr-1, where νw3 is the speed of the wind from the progenitor in units of 103 km s-1. This M is similar to that inferred for the progenitor of the Type Ibc supernova SN 1998bw that has been associated with the peculiar burst GRB 980425. Our data, taken in conjunction with the HST results of Bloom et al., provide a consistent picture: the long-duration GRB 011121 had a massive star progenitor that exploded as a supernova at about the same time as the gamma-ray burst event. Finally, we note that the gamma-ray profile of GRB 011121 is similar to that of GRB 980425

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs