Calibration of insulin pumps based on discrete doses at given cycle times.

One application in the medical treatment at very small flow rates is the usage of an Insulin pump that delivers doses of insulin at constant cycle times for a specific basal rate as quasi-continuous insulin delivery, which is an important cornerstone in diabetes management. The calibration of these basal rates are performed by either gravimetric or optical methods, which have been developed within the European Metrology Program for Innovation and Research (EMPIR) Joint Research Project (JRP) 18HLT08 Metrology for drug delivery II (MeDDII). These measurement techniques are described in this paper, and an improved approach of the analytical procedure given in the standard IEC 60601-2-24:2012 for determining the discrete doses and the corresponding basal rates is discussed in detail. These improvements allow detailed follow up of dose cycle time and delivered doses as a function of time to identify some artefacts of the measurement method or malfunctioning of the insulin pump. Moreover, the calibration results of different basal rates and bolus deliveries for the gravimetric and the optical methods are also presented. Some analysis issues that should be addressed to prevent misinterpreting of the calibration results are discussed. One of the main issues is the average over a period of time which is an integer multiple of the cycle time to determine the basal rate with the analytical methods described in this paper.

Calibration Uncertainty of Non-Catching Precipitation Gauges.

Precipitation is among the most important meteorological variables for, e.g., meteorological, hydrological, water management and climate studies. In recent years, non-catching precipitation gauges are increasingly adopted in meteorological networks. Despite such growing diffusion, calibration procedures and associated uncertainty budget are not yet standardized or prescribed in best practice documents and standards. This paper reports a metrological study aimed at proposing calibration procedures and completing the uncertainty budgets, to make non-catching precipitation gauge measurements traceable to primary standards. The study is based on the preliminary characterization of different rain drop generators, specifically developed for the investigation. Characterization of different models of non-catching rain gauges is also included.

Carbon nanotube electrodes for retinal implants: A study of structural and functional integration over time.

The choice of electrode material is of paramount importance in neural prosthetic devices. Electrodes must be biocompatible yet able to sustain repetitive current injections in a highly corrosive environment. We explored the suitability of carbon nanotube (CNT) electrodes to stimulate retinal ganglion cells (RGCs) in a mouse model of outer retinal degeneration. We investigated morphological changes at the bio-hybrid interface and changes in RGC responses to electrical stimulation following prolonged in vitro coupling to CNT electrodes. We observed gradual remodelling of the inner retina to incorporate CNT assemblies. Electrophysiological recordings demonstrate a progressive increase in coupling between RGCs and the CNT electrodes over three days, characterized by a gradual decrease in stimulation thresholds and increase in cellular recruitment. These results provide novel evidence for time-dependent formation of viable bio-hybrids between CNTs and the retina, demonstrating that CNTs are a promising material for inclusion in retinal prosthetic devices.

Near-field electromagnetic holography for high-resolution analysis of network interactions in neuronal tissue.

BACKGROUND: Brain function is dependent upon the concerted, dynamical interactions between a great many neurons distributed over many cortical subregions. Current methods of quantifying such interactions are limited by consideration only of single direct or indirect measures of a subsample of all neuronal population activity. NEW METHOD: Here we present a new derivation of the electromagnetic analogy to near-field acoustic holography allowing high-resolution, vectored estimates of interactions between sources of electromagnetic activity that significantly improves this situation. In vitro voltage potential recordings were used to estimate pseudo-electromagnetic energy flow vector fields, current and energy source densities and energy dissipation in reconstruction planes at depth into the neural tissue parallel to the recording plane of the microelectrode array. RESULTS: The properties of the reconstructed near-field estimate allowed both the utilization of super-resolution techniques to increase the imaging resolution beyond that of the microelectrode array, and facilitated a novel approach to estimating causal relationships between activity in neocortical subregions. COMPARISON WITH EXISTING METHODS: The holographic nature of the reconstruction method allowed significantly better estimation of the fine spatiotemporal detail of neuronal population activity, compared with interpolation alone, beyond the spatial resolution of the electrode arrays used. Pseudo-energy flow vector mapping was possible with high temporal precision, allowing a near-realtime estimate of causal interaction dynamics. CONCLUSIONS: Basic near-field electromagnetic holography provides a powerful means to increase spatial resolution from electrode array data with careful choice of spatial filters and distance to reconstruction plane. More detailed approaches may provide the ability to volumetrically reconstruct activity patterns on neuronal tissue, but the ability to extract vectored data with the method presented already permits the study of dynamic causal interactions without bias from any prior assumptions on anatomical connectivity.

A neocortical delta rhythm facilitates reciprocal interlaminar interactions via nested theta rhythms.

Delta oscillations (1-4 Hz) associate with deep sleep and are implicated in memory consolidation and replay of cortical responses elicited during wake states. A potent local generator has been characterized in thalamus, and local generators in neocortex have been suggested. Here we demonstrate that isolated rat neocortex generates delta rhythms in conditions mimicking the neuromodulatory state during deep sleep (low cholinergic and dopaminergic tone). The rhythm originated in an NMDA receptor-driven network of intrinsic bursting (IB) neurons in layer 5, activating a source of GABAB receptor-mediated inhibition. In contrast, regular spiking (RS) neurons in layer 5 generated theta-frequency outputs. In layer 2/3 principal cells, outputs from IB cells associated with IPSPs, whereas those from layer 5 RS neurons related to nested bursts of theta-frequency EPSPs. Both interlaminar spike and field correlations revealed a sequence of events whereby sparse spiking in layer 2/3 was partially reflected back from layer 5 on each delta period. We suggest that these reciprocal, interlaminar interactions may represent a "Helmholtz machine"-like process to control synaptic rescaling during deep sleep.

Ascertaining year of birth/age at death in forensic cases: A review of conventional methods and methods allowing for absolute chronology.

Based on an actual case, where we were able to ascertain the year of birth of three dead babies found in a deep-freezer to within 1-2 years (1986, 1988 and 2004, respectively), we review the current state of forensic age determination/year of birth determination. The age of an individual (year of birth) is often a fundamental piece of data in connection with forensic identification of unidentified bodies. The methods most often used are based on determining various morphological, age-related, changes on the skeleton (or teeth, although odontological methods are not reviewed in this paper). As such, these methods are all relative, i.e. they do not furnish calendar ages or years, but an estimate of the age at death, with a rather large range, i.e. the methods rely on biological aging following the chronological aging. More recently, methods have been proposed using more direct ascertainment of age at death, e.g. protein racemisation, or, as in our case, radiocarbon methods. Especially the latter method may in fact yield absolute ages (years of birth), because (14)C activity, as measured in specific proteins in specific cells or tissues in the body, were in equilibrium with the so-called bomb-pulse, when these proteins were formed (at birth). The bomb pulse reflects a dramatic change in atmospheric (14)C content due to nuclear bomb testing, and these dramatic changes can be rather tightly related to single calendar years.

Radiocarbon dating of the human eye lens crystallines reveal proteins without carbon turnover throughout life.

BACKGROUND: Lens crystallines are special proteins in the eye lens. Because the epithelial basement membrane (lens capsule) completely encloses the lens, desquamation of aging cells is impossible, and due to the complete absence of blood vessels or transport of metabolites in this area, there is no subsequent remodelling of these fibers, nor removal of degraded lens fibers. Human tissue ultimately derives its (14)C content from the atmospheric carbon dioxide. The (14)C content of the lens proteins thus reflects the atmospheric content of (14)C when the lens crystallines were formed. Precise radiocarbon dating is made possible by comparing the (14)C content of the lens crystallines to the so-called bomb pulse, i.e. a plot of the atmospheric (14)C content since the Second World War, when there was a significant increase due to nuclear-bomb testing. Since the change in concentration is significant even on a yearly basis this allows very accurate dating. METHODOLOGY/PRINCIPAL FINDINGS: Our results allow us to conclude that the crystalline formation in the lens nucleus almost entirely takes place around the time of birth, with a very small, and decreasing, continuous formation throughout life. The close relationship may be further expressed as a mathematical model, which takes into account the timing of the crystalline formation. CONCLUSIONS/SIGNIFICANCE: Such a life-long permanence of human tissue has hitherto only been described for dental enamel. In confront to dental enamel it must be held in mind that the eye lens is a soft structure, subjected to almost continuous deformation, due to lens accommodation, yet its most important constituent, the lens crystalline, is never subject to turnover or remodelling once formed. The determination of the (14)C content of various tissues may be used to assess turnover rates and degree of substitution (for example for brain cell DNA). Potential targets may be nervous tissues in terms of senile or pre-senile degradation, as well as other highly specialised structures of the eyes. The precision with which the year of birth may be calculated points to forensic uses of this technique.