An Integrated Passive Phase-Shift Keying Modulator for Biomedical Implants With Power Telemetry Over a Single Inductive Link

This paper presents a passive phase-shift keying (PPSK) modulator for uplink data transmission for biomedical implants with simultaneous power and data transmission over a single 13.56 MHz inductive link. The PPSK modulator provides a data rate up to 1.35 Mbps with a modulation index between 3% and 38% for a variation of the coupling coefficient between 0.05 and 0.26. This modulation scheme is particularly suited for biomedical implants that have high power demand and low coupling coefficients. The PPSK modulator operates in conjunction with on-off-keying downlink communication. The same inductive link is used to provide up to 100 mW of power to a multi-channel stimulator. The majority of the system on the implant side was implemented as an application specific integrated circuit (ASIC), fabricated in 0.6-[Formula: see text] high voltage CMOS technology. The theory of PPSK modulation, simulated and measured performance evaluation, and comparison with other state-of-the-art impedance modulation techniques is presented. The measured bit error rate around critical coupling at 1.35 Mbps is below 6 ×10(-8)

A Versatile Hermetically Sealed Microelectronic Implant for Peripheral Nerve Stimulation Applications

This article presents a versatile neurostimulation platform featuring a fully implantable multi-channel neural stimulator for chronic experimental studies with freely moving large animal models involving peripheral nerves. The implant is hermetically sealed in a ceramic enclosure and encapsulated in medical grade silicone rubber, and then underwent active tests at accelerated aging conditions at 100°C for 15 consecutive days. The stimulator microelectronics are implemented in a 0.6-μm CMOS technology, with a crosstalk reduction scheme to minimize cross-channel interference, and high-speed power and data telemetry for battery-less operation. A wearable transmitter equipped with a Bluetooth Low Energy radio link, and a custom graphical user interface provide real-time, remotely controlled stimulation. Three parallel stimulators provide independent stimulation on three channels, where each stimulator supports six stimulating sites and two return sites through multiplexing, hence the implant can facilitate stimulation at up to 36 different electrode pairs. The design of the electronics, method of hermetic packaging and electrical performance as well as in vitro testing with electrodes in saline are presented

An Implantable Wireless Multi-Channel Neural Prosthesis for Epidural Stimulation

This paper presents a fully implantable multi-channel neural prosthesis for epidural stimulation. The prosthesis features three telemetry-operated independent stimulators providing in total eighteen stimulation channels. The stimulator circuits were implemented in a 0.6-μm CMOS technology. The prosthesis is protected in a hermetically sealed ceramic enclosure and encapsulated in medical grade silicone rubber. In-vitro measured results with electrodes in saline are presented

Populations of high-value predators reflect the traits of their prey

The extent to which prey traits combine to influence the abundance of predators is still poorly understood, particularly for mixed predators in sympatry and in aquatic ecosystems. In this study, we characterise prey use and distribution in iconic bird (grey wagtails and Eurasian dippers) and fish species (brown trout and Atlantic salmon) to assess whether prey traits could predict populations of these four riverine predators. Specifically, we hypothesised that: 1) prey key traits would predict predator populations more effectively than 2) diversity of prey traits, 3) the taxonomic abundance or richness of prey (known as traditional or mass-effect types of biodiversity) or 4) the prevailing environmental conditions. Combined predator population sizes were predicted better by a few key traits – specifically those revealing prey habitat use, size and drifting behaviour – than by prey diversity or prey trait diversity or environmental conditions. Our findings demonstrate that the complex relationships between prey assemblages and multiple predator species can be represented mechanistically when the key prey traits that govern encounter and consumption rates are identified. Given their apparent potential to reveal trophic relationships, and to complement more traditional measures of prey abundance, we advocate further development of trait-based approaches in predator–prey research

Desperately seeking fixedness: practitioners accounts of 'becoming doctoral researchers

We draw upon the concept of liminality to explore the experiences of practitioners enrolled on a UK Doctor of Business Administration (DBA) programme. We analyse twenty practitioners’ reflective journals to detail how the DBA liminal space was negotiated. More specifically, we describe how practitioners deal with their struggles of identity incoherence or ‘monsters of doubt’ which are amplified in the DBA context owing to the complex nature of the separation phase of liminality. We identify three broad methods deployed in this endeavour: ‘scaffolding’; ‘putting the past to work’ and ‘bracketing’- which evidence practitioners ‘desperately seeking fixedness’. We make three contributions – first, we provide empirical insights into the experiences of the increasingly significant, but still under researched, DBA student. Second, we develop our understandings of monsters of doubt through illustrating how these are negotiated for learning to progress. Finally, we contribute to wider discussions of ‘becoming’ to demonstrate the simultaneous and paradoxical importance of movement and fixedness in order to learn and become

Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>The development and evaluation of rapid and accurate new diagnostic tools is essential to improve tuberculosis (TB) control in developing countries. In a previous study, the first release of a urine LAM-ELISA by Chemogen (Portland, USA) has been evaluated with a promising sensitivity and specificity for the diagnosis of pulmonary TB. In the present study, the now commercially available assay has been clinically assessed regarding its diagnostic value alone and in combination with clinical co-factors.</p> <p>Methods</p> <p>The test was applied to two urine samples from 291 consecutively enrolled Tanzanian patients with suspected pulmonary tuberculosis. The participants were subsequently assigned to classification groups according to microbiological, clinical and radiological findings at recruitment and during a maximum follow up period of 56 days.</p> <p>Results</p> <p>Only 35 out of 69 pulmonary TB cases -confirmed by smear microscopy and/or solid culture and/or liquid culture- showed at least one positive LAM-ELISA result (sensitivity 50.7%). The sensitivity was noticeably higher in females (66.7%) and in HIV positive participants (62.0%). The specificity amounted to 87.8% and was determined in participants with negative results in all microbiological tests and with sustained recovery under antibiotic treatment at day 56. Correlation with urinalysis revealed that proteinuria was significantly and positively associated with LAM-positivity (<it>P </it>= 0.026).</p> <p>Conclusion</p> <p>This commercially available generation of LAM-ELISA does not appear to be useful as an independent diagnostic test for pulmonary tuberculosis. The question whether the assay is suitable as a supplemental device in the diagnosis of HIV-associated TB, requires further investigations.</p

A pilot study evaluating the use of ABCD2 score in pre-hospital assessment of patients with suspected transient ischaemic attack: experience and lessons learned

Background: Suspected transient ischaemic attack (TIA) is a common presentation to emergency medical services (EMS) in the United Kingdom (UK). Several EMS systems have adopted the ABCD2 score to aid pre-hospital risk stratification and decision-making on patient disposition, such as direct referral to an Emergency Department or specialist TIA clinic. However, the ABCD2 score, developed for hospital use, has not been validated for use in the pre-hospital context of EMS care. Methods: We conducted a pilot study to assess eligibility criteria, recruitment rates, protocol compliance, consent and follow-up procedures to inform the development of a definitive study to validate the ABCD2 tool in pre-hospital evaluation of patients with suspected TIA. Results: From 1st May–1st September 2013, nine patients with an EMS suspected diagnosis of TIA had the TIA diagnosis later confirmed by a specialist from five participating sites. This recruitment rate is comparable to stroke trials in the EMS setting. Bureaucratic obstacles and duplication of approval processes across participating sites took 13 months to resolve before recruitment commenced. Due to the initial difficulty in recruitment, a substantial amendment was approved to modify inclusion criteria, allowing patients with atrial fibrillation and/or taking anticoagulant therapy to participate in the study. Conclusions: It is possible to identify, recruit and follow up patients with suspected TIA in the EMS setting. Training large numbers of EMS staff is required as exposure to TIA patients is infrequent. Significant insight was gained into the complexity of NHS research governance mechanisms in the UK. This knowledge will facilitate the planning of a future adequately powered study to validate the ABCD2 tool in a pre-hospital setting

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins