An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it’s needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug-delivery systems

MusA: Using Indoor Positioning and Navigation to Enhance Cultural Experiences in a museum

In recent years there has been a growing interest into the use of multimedia mobile guides in museum environments. Mobile devices have the capabilities to detect the user context and to provide pieces of information suitable to help visitors discovering and following the logical and emotional connections that develop during the visit. In this scenario, location based services (LBS) currently represent an asset, and the choice of the technology to determine users' position, combined with the definition of methods that can effectively convey information, become key issues in the design process. In this work, we present MusA (Museum Assistant), a general framework for the development of multimedia interactive guides for mobile devices. Its main feature is a vision-based indoor positioning system that allows the provision of several LBS, from way-finding to the contextualized communication of cultural contents, aimed at providing a meaningful exploration of exhibits according to visitors' personal interest and curiosity. Starting from the thorough description of the system architecture, the article presents the implementation of two mobile guides, developed to respectively address adults and children, and discusses the evaluation of the user experience and the visitors' appreciation of these application

Electrophoretic drug delivery for seizure control.

The persistence of intractable neurological disorders necessitates novel therapeutic solutions. We demonstrate the utility of direct in situ electrophoretic drug delivery to treat neurological disorders. We present a neural probe incorporating a microfluidic ion pump (μFIP) for on-demand drug delivery and electrodes for recording local neural activity. The μFIP works by electrophoretically pumping ions across an ion exchange membrane and thereby delivers only the drug of interest and not the solvent. This "dry" delivery enables precise drug release into the brain region with negligible local pressure increase. The therapeutic potential of the μFIP probe is tested in a rodent model of epilepsy. The μFIP probe can detect pathological activity and then intervene to stop seizures by delivering inhibitory neurotransmitters directly to the seizure source. We anticipate that further tailored engineering of the μFIP platform will enable additional applications in neural interfacing and the treatment of neurological disorders

Precision tomography of a three-qubit electron-nuclear quantum processor in silicon

Nuclear spins were among the first physical platforms to be considered for quantum information processing, because of their exceptional quantum coherence and atomic-scale footprint. However, their full potential for quantum computing has not yet been realized, due to the lack of methods to link nuclear qubits within a scalable device combined with multi-qubit operations with sufficient fidelity to sustain fault-tolerant quantum computation. Here we demonstrate universal quantum logic operations using a pair of ion-implanted $^{31}$P nuclei in a silicon nanoelectronic device. A nuclear two-qubit controlled-Z gate is obtained by imparting a geometric phase to a shared electron spin, and used to prepare entangled Bell states with fidelities up to 94.2(2.7)%. The quantum operations are precisely characterised using gate set tomography (GST), yielding one-qubit gate fidelities up to 99.93(3)%, two-qubit gate fidelity of 99.21(14)% and two-qubit preparation/measurement fidelities of 98.95(4)%. These three metrics indicate that nuclear spins in silicon are approaching the performance demanded in fault-tolerant quantum processors. We then demonstrate entanglement between the two nuclei and the shared electron by producing a Greenberger-Horne-Zeilinger three-qubit state with 92.5(1.0)% fidelity. Since electron spin qubits in semiconductors can be further coupled to other electrons or physically shuttled across different locations, these results establish a viable route for scalable quantum information processing using nuclear spins.Comment: 27 pages, 14 figures, plus 20 pages supplementary information. v2 includes new and updated references, and minor text change

Predictors of reading literacy for first and second language learners

In this study an attempt was made to construct a multi-factor model predicting the development of reading literacy in the upper grades of primary school in the Netherlands for subgroups of 729 first language (L1) learners and 93 second language (L2) learners. Following a longitudinal design, it was explored to what extent the variation in reading literacy development in L1 and L2 from grade 4 to grade 6 can be explained from children’s word decoding, language, mathematics and nonverbal reasoning skills, reading motivation and self confidence as well as their home reading resources. The results showed that L1 and L2 learners differed in reading literacy skills, language, mathematics, and reasoning skills. Structural equation modelling showed that the reading literacy development in both L1 and L2 learners could be explained from decoding, language, mathematics and reasoning skills, as well as their motivation and self-confidence. A striking difference was the fact that home reading resources had an impact on reading literacy in L1 learners but not in L2 learners

Activation of Hypoxia Inducible Factor 1 Is a General Phenomenon in Infections with Human Pathogens

Background: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Methodology/Principal Findings: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Conclusions/Significance: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections

Implementation salvage experiences from the Melbourne diabetes prevention study

Background Many public health interventions based on apparently sound evidence from randomised controlled trials encounter difficulties when being scaled up within health systems. Even under the best of circumstances, implementation is exceedingly difficult. In this paper we will describe the implementation salvage experiences from the Melbourne Diabetes Prevention Study, which is a randomised controlled trial of the effectiveness and cost-effectiveness nested in the state-wide Life! Taking Action on Diabetes program in Victoria, Australia.Discussion The Melbourne Diabetes Prevention Study sits within an evolving larger scale implementation project, the Life! program. Changes that occurred during the roll-out of that program had a direct impact on the process of conducting this trial. The issues and methods of recovery the study team encountered were conceptualised using an implementation salvage strategies framework. The specific issues the study team came across included continuity of the state funding for Life! program and structural changes to the Life! program which consisted of adjustments to eligibility criteria, referral processes, structure and content, as well as alternative program delivery for different population groups. Staff turnover, recruitment problems, setting and venue concerns, availability of potential participants and participant characteristics were also identified as evaluation roadblocks. Each issue and corresponding salvage strategy is presented.Summary The experiences of conducting such a novel trial as the preliminary Melbourne Diabetes Prevention Study have been invaluable. The lessons learnt and knowledge gained will inform the future execution of this trial in the coming years. We anticipate that these results will also be beneficial to other researchers conducting similar trials in the public health field. We recommend that researchers openly share their experiences, barriers and challenges when conducting randomised controlled trials and implementation research. We encourage them to describe the factors that may have inhibited or enhanced the desired outcomes so that the academic community can learn and expand the research foundation of implementation salvage.<br /

EXPORTS Measurements and Protocols for the NE Pacific Campaign

EXport Processes in the Ocean from Remote Sensing (EXPORTS) is a large-scale NASA-led and NSF co-funded field campaign that will provide critical information for quantifying the export and fate of upper ocean net primary production (NPP) using satellite information and state of the art technology

Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour