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ObjectiveQuantitative magnetic resonance imaging was used to determine partition coefficients and characteristic time constants for diffusion of MRI contrast agents in disc tissue.Materials and methodsTwenty-two excised equine intervertebral discs were exposed to a range of contrast agents: six to manganese chloride, eight to Magnevist (gadopentetate dimeglumine) and eight to Gadovist (gadobutrol), and uptake into the disc was quantified inT1-weighted images.ResultsDiffusion for all contrast agents was approximately 25% faster in the nucleus than in the outer annulus; disc-average time constants ranged from (2.28 ± 0.23) × 104 s for Gadovist (uncharged, molecular mass 605 g/mol) to (5.07 ± 0.75) × 104 s for the manganese cation (charge + 2). Disc-average partition coefficients ranged from 0.77 ± 0.04 for the anion in Magnevist (charge − 2, molecular mass 548 g/mol) to 5.14 ± 0.43 for the manganese cation.ConclusionThe MRI technique provides high-quality quantitative data which correspond well to theoretical predictions, allowing values for partition coefficient and time constant to be readily determined. These measurements provide information to underpin similar studies in vivo and may be used as a model for the transport of nutrients and pharmaceutical agents in the disc.

An improved model of the Pacinian corpuscle includes corrections for lamellar curvature. Results suggest that outer-zone lamellae produce a focusing effect whereby stimuli are channeled radially inwards. The requirements for this effect (large outer-surface area and thin, closely spaced lamellae) provide a rationale for the complexity of the outer-zone structure.

The acoustic transmittance of two closely spaced solid plates, each perforated with a square array of cylindrical holes, exhibits a band of near-perfect acoustic attenuation originating from hybridization between a resonance in the gap separating the plates and pipe resonances in the holes. Displacement of one plate relative to the other, such that the holes are no longer aligned, or an increase in the plate separation leads to an increased center frequency of the stop band. This ability to easily tune the frequency of the stop band may prove advantageous.

Previous neuroimaging studies of scenarios such as the prisoner’s dilemma and ultimatum game show how brain systems which evolved to process rewarding and aversive stimuli are activated differentially during adherence to and breaches of norms. One theory of how shared social norms evolve is that they arise from mutually rewarding conventions which, through repeated execution, acquire a normative value that sustains social cohesion even when individual self-interest is not served. The authors report an fMRI study of a 2-player coordination game in which players must coordinate on an arbitrary convention (a left or right button press) to obtain monetary rewards. Once this convention has been established, one of the participants is incentivized to deviate from the equilibrium with the offer of extra reward. During the period prior to decisions to violate the convention, activity was observed in regions associated with reward processing, such as the midbrain, caudate, and orbitofrontal cortex. Activations in advance of decisions to continue coordinating included the amygdala and anterior insula–inferior frontal gyrus. The data are discussed in the light of theories which propose the existence of multiple interacting value-based decision-making systems in the human brain.

We report a functional magnetic resonance imaging (fMRI) study which investigated whether brain areas involved in updating task rules within the frontal lobe of the cerebral cortex show activity related to the modality of motor response used in the task. Participants performed a rule switching task using different effector modalities. In some blocks participants responded with left/right button presses, whilst in other blocks left/right saccades were required. The color of a Cue event instructed a left or right response based upon a rule, followed by a Feedback which indicated whether the rule was to stay the same or "Flip" on the next trial. The findings revealed variation in the locus of activity within the ventrolateral frontal cortex dependent upon effector modality. Other frontal areas showed no significant difference in activity between response epochs but changed their pattern of connectivity with posterior cortical areas dependent upon response. Multivariate analysis revealed that the pattern of activity evoked by Flip rule Feedbacks within an apparently supra modal frontal region (dorsolateral frontal cortex) discriminated between response epochs. The results are consistent with the existence of multi-modal representations of stimulus-response (SR) rules within the frontal cerebral cortex.

Virtual textiles, generated in response to exploratory movements, are presented to the fingertip via a 24-contactor vibrotactile array. Software models are based on surface-roughness profiles from real textiles. Results suggest that distinguishable “textile-like” surfaces are produced, but these lack the necessary accuracy for reliable matching to real textiles.

While moving our fingertip over a fine surface we experience a sensation that gives us an idea of its properties. A satisfactory simulation of this feeling is still an unsolved problem. In this paper, we describe a rendering strategy based on vibrations that play an important role in the tactile exploration of fine surfaces. To produce appropriate excitation patterns we use an array of vibrating contactor pins. Similar to the colour model in computer graphics, we simulate arbitrary vibrations as a superposition of only two sinewaves. Each sinewave is intended for the excitation of a specific population of mechanoreceptors. We carried out first tests of our rendering strategy on Brownian surfaces of different fractal dimensions.

A stimulator array is described which can deliver a wide range of displacement waveforms from each contactor, allowing vibratory stimuli to be targeted towards different populations of mechanoreceptors in the skin. The array has a working bandwidth of 20-400 Hz and 100 moving contactors covering an area of 1 cm2 on the fingertip. The array was validated with two experiments on the perception of moving vibratory targets within a uniform background vibration. In the first experiment, with target and background at the same frequency, equivalent discrimination of target movement was obtained at higher values of target/background amplitude ratio for 40-Hz stimuli than for 320-Hz stimuli. In the second experiment, discrimination of target movement within a different-frequency background (320-Hz target and 40-Hz background, or vice versa) was found to be much easier than within a same-frequency background. These results suggest that tactile spatial acuity is better at 320 Hz than 40 Hz and that it is possible to target different receptor populations in the skin by using these frequencies. However, there are problems with this interpretation: on the basis of characterization of touch receptors in previous studies, spatial acuity is expected to be worse at 320 Hz than at 40 Hz.

The acoustic transmission of a closely spaced pair of patterned and perforated rigid plates is explored in air. The structure resembles an acoustic double fishnet design, with each plate modified such that the gap between them acts as an array of Helmholtz resonators. This allows the center frequency of the stop band to be reduced by a factor greater than 2 from the value obtained for the conventional acoustic double fishnet design. Experimental results accord well with the predictions of a finite element model.

This paper describes an evaluation of a simple electronic simulation of sensorineural hearing loss intended to raise the awareness of mainstream trainee teachers during role play as both teacher and hearing-impaired pupil. In the wake of the continuing commitment to integration, it is hoped that such a device can improve the preparation of mainstream trainee teachers for their role as teachers of the hearing impaired. Twenty-four trainee teachers experienced both roles during the simulation, and their comments were scored by an expert panel for their importance. It was found that participants achieved a significant increase in awareness during their two five-minute simulated experiences of being a hearing pupil and teaching a hearing-impaired pupil. The experience of learning as a pupil with a simulated impairment was demonstrated to be as valuable as teaching a pupil with a simulated impairment, although there were differences with respect to the types of issues highlighted.

Cardiac arrest is a major cause of unexpected sudden death in adults. In the majority of cases an arrhythmia is the primary cause. A multitude of agents have been used in the treatment of ventricular fibrillation and asystole during cardiac arrest. At present there is no evidence to indicate that any of these agents ultimately improve the final outcome in humans. Prevention, competent basic life support and rapid defibrillation for patients in ventricular fibrillation remain the mainstays of treatment for cardiac arrest.

Investigation of the cause of image artifacts generated by a magnetization transfer (MT) sequence using binomial-pulse trains led to findings of imperfections in the pulses. These imperfections caused anomalous direct saturation of the free water, which was localized due to the static magnetic field inhomogeneity. In the case of single binomial pulses a loss of overall MT response across the field of view results. Two methods of correcting the imperfections and removing the artifact have been established using interactive adjustment of sub-pulse lobes and phase swapping of pulse trains. These imperfections may be present in many systems and may have led to erroneous judgements of the value of binomial pulses for MT imaging. A technique for interrogating the frequency spectrum of the binomial-pulse train has been utilized, allowing its optimization. The use of accurate and optimized binomial pulses may yet prove to be preferable to pulsed off-resonance methods for quantitative, clinical MT imaging. J. Magn. Reson. Imaging 2000;11:539–548. © 2000 Wiley-Liss, Inc.

Measurements have been made on the discrimination of speech contrasts on the basis of single-channel vibrotactile presentation of a variety of speech-derived signals, coded as amplitude- and frequency-modulated pulse trains. Stimulation was at the index fingertip. The signals chosen for tactile presentation were the speech amplitude envelope, the voice fundamental frequency FO and the zero-crossing frequency in the 1.3-6.6 kHz band. "Two-feature' codings, which present two of these signals simultaneously (one coded as stimulus frequency and one coded as stimulus amplitude), were found to be no more effective than "single feature' codings which present only one signal (coded as both amplitude and frequency). Scores for consonant discrimination were highest for the single-feature coding of zero-crossing frequency, although differences between the codings were not, in general, significant. Scores for emphatic-stress discrimination were highest for the single-feature coding of F0, and this coding produced best results overall. A practical wrist-worn device, whose design is influenced by these experimental results is briefly described.

The design of a radiofrequency coil of U-shaped geometry, specifically intended to image individual knuckle joints of the hand, has been investigated. The coil geometry is that of a "split and opened" birdcage coil. The optimum leg positions for such a U-shaped coil have been theoretically predicted using a novel technique that considers both the signal-to-noise ratio and the homogeneity of the field-of-view. Two particular coils of this type have been constructed, each optimum for a different size of image space and assuming a different source of image noise (sample-dominated or coil-dominated). The experimentally determined radiofrequency fields produced by the coils correspond well to theory. Either coil can be used to obtain good-quality, high-resolution (130 microns x 130 microns in-plane) images in vivo of the first, second, or fifth metacarpophalangeal joints of the hand, sites of particular interest in the study of arthritis.

The “acoustic double fishnet” is a structure with holes running from its front to back faces, yet at a characteristic frequency it transmits very little sound. The transmittance of this structure, which is comprised of a pair of closely spaced, periodically perforated plates, is determined experimentally and analytically. The surprising acoustic properties are due to hybridization between a two-dimensional resonance within the gap between the plates, and pipe modes within the holes. At the center of the stop band the input impedance is imaginary, interpreted as a negative product of effective bulk modulus and density.

To the Editor: Functional MRI (fMRI) using a blood oxygen level dependent (BOLD) sequence provides a tool to measure the effects of alterations in blood glucose on the patterns and magnitudes of neuronal activation in the human brain [1]. Previous experiments using a glucose load have suggested that it is possible in humans to identify changes in the BOLD signal from areas within the hypothalamus [2–6]; however, the results have been contradictory. This study involved seven healthy participants aged 27– 38 years (three female, four male; mean±SD BMI 23.6± 1.3 kg/m), who gave informed consent. The study was approved by the local research ethics committee. Each participant attended for two studies in random order: one involving ingestion of a glucose load and the other water. After anatomical scans and a 5 min baseline period of fMRI acquisition, participants were either given 75 g glucose diluted with 200 ml water or the same volume of water only. fMRI acquisition continued for a further 25 min after the start of drinking. Blood samples for measurement of plasma glucose were taken 5 min before the start of drinking and 25 min after the start of drinking. There was no difference in mean glucose levels between conditions at baseline, but significantly higher values in the glucose arm at the end of the study (4.41±0.31 mmol/l for the water arm vs 5.36± 0.28 mmol/l for the glucose arm, p00.001). With the use of a six-channel head coil at 1.5 T, fMRI variables were: repetition time04 s (three-shot echo planar imaging, volume acquisition in 12 s); echo time045 ms; 50 sagittal slices; 2 mm slice thickness; 0.2 mm interslice gap; 2×2 mm in-plane resolution. The 30 min fMRI measurement produced a sequence of 150 volume acquisitions, which were aligned to the 80th volume using SPM5 software (Wellcome Trust Centre for Neuroimaging, London, UK). The position of the hypothalamus was identified on a near-midline sagittal slice of the 80th fMRI volume acquisition on the basis of landmarks: the anterior commissure (AC), the optic chiasm (OC) and the mammillary body (MM). The MarsBaR toolbox for SPM5 (available from http://marsbar.sourceforge.net/) was used to specify the overall region of interest (ROI)—a parallelogram with three D. E. Flanagan (*) :B. Krishnan :A. Watt Department of Endocrinology, Level 9, Derriford Hospital, Plymouth PL6 8DH, UK e-mail: danielflanagan@nhs.net

This paper details a pilot study done to assess the effectiveness of a tactile rendering strategy. The rendering strategy addresses the tactile receptors in the skin via stimuli consisting of superimposed sine waves. To assess the validity of this strategy, subjects were presented with sets of four virtual textiles and asked to rate them in terms of similarity to a real textile. The results showed that 38.1±3.1% of textiles were accurately identified as the most similar, with systematic error patterns in the identification of textiles. We conclude that the virtual textiles are discriminable to test subjects, with 4.54±0.13 of the subjects consistently choosing the same textile, but in many cases none of the virtual textiles is a good match to the real textiles.

Using a 100-element tactile stimulator on the fingertip during functional-magnetic-resonance imaging, brain areas were identified that were selectively activated by a moving vibrotactile stimulus (the sensation of a moving line being dragged over the fingertip). Activation patterns elicited by tactile motion, contrasted to an equivalent stationary stimulus, were compared in six human subjects with those generated by a moving visual stimulus, contrasted to an equivalent stationary stimulus. Results provide further evidence for a neuroanatomical convergence of tactile-motion processing and visual-motion processing in humans. The sites of this convergence are found to lie in the middle temporal complex (hMT+V5), an area with known specialization for visual-motion processing, and in the intraparietal area of the posterior parietal cortex. In an advance on previous studies, the present study includes separate delineation of activations for moving tactile stimuli and activations for moving visual stimuli. Results suggest that the two sets of activations are not entirely collocated. Compared to the visual-motion activations, the tactile-motion activations are found to lie nearer the midline of the brain and further superior.

The EU funded RTD project "HAPTEX" addresses the challenge of developing a Virtual Reality (VR) system for the realistic and accurate rendering of the physical interactions of humans with textiles, through the real-time generation of artificial visual and haptic stimuli. This challenge concerns the development of both the SW and the HW components of the VR system, as well as it implies a substantial advancement in the understanding of the mechanisms underlying the human haptic perception of fine physical properties like those of textiles. This paper reports some important details relating to the technical implementation of the developed HW and SW components with special emphasis on the issues related to their integration into a single VR system. Furthermore some preliminary results relating to the functional tests carried out on the integrated system are also reported.

This study investigates the discrimination of small changes of interval size in short sequences of musical tones. Major, minor and neutral thirds were varied in increments of 15 cents. The nine subjects had varying degrees of amateur musical experience-their level of musical training was lower than that of professional musicians. In some experiments the stimuli were presented purely melodically and in others they were presented together with a sustained tone at a higher pitch. Some subjects were able to make use of the additional cues from beats in the latter case. Category widths for identification were measured at around 70 cents and just-noticeable differences in frequency were measured at around 10 cents. Little significant variation of inter-stimulus sensitivity index d' was observed across the stimulus sets, i.e., there was little evidence for "anchors" or "landmarks" within the range of tunings employed. However, for major thirds, discrimination of the 15 cent increment between 400 and 415 cents was reduced compared to discrimination of other 15 cent increments within the stimulus sets.

Many complex tasks require us to flexibly switch between behavioral rules, associations, and strategies. The prefrontal cerebral cortex is thought to be critical to the performance of such behaviors, although the relative contribution of different components of this structure and associated subcortical regions are not fully understood. We used functional magnetic resonance imaging to measure brain activity during a simple task which required repeated reversals of a rule linking a colored cue and a left/right motor response. Each trial comprised three discrete events separated by variable delay periods. A colored cue instructed which response was to be executed, followed by a go signal which told the subject to execute the response and a feedback instruction which indicated whether to “hold” or “flip” the rule linking the colored cue and response. The design allowed us to determine which brain regions were recruited by the specific demands of preparing a rule contingent motor response, executing such a response, evaluating the significance of the feedback, and reconfiguring stimulus-response (SR) associations. The results indicate that an increase in neural activity occurs within the anterior cingulate gyrus under conditions in which SR associations are labile. In contrast, lateral frontal regions are activated by unlikely/unexpected perceptual events regardless of their significance for behavior. A network of subcortical structures, including the mediodorsal nucleus of the thalamus and striatum were the only regions showing activity that was exclusively correlated with the neurocognitive demands of reversing SR associations. We conclude that lateral frontal regions act to evaluate the behavioral significance of perceptual events, whereas medial frontal-thalamic circuits are involved in monitoring and reconfiguring SR associations when necessary.

Two experiments on the discrimination of time-varying tactile stimuli were performed, with comparison of stimulus delivery to the distal pad of the right index finger and to the right wrist (palmar surface). Subjects were required to perceive differences in short sequences of computer-generated stimulus elements (experiment 1) or differences in short tactile stimuli derived from a speech signal (experiment 2). The pulse-train stimuli were distinguished by differences in frequency (i.e., pulse repetition rate) and amplitude, and by the presence/absence of gaps (approximately 100-ms duration). Stimulation levels were 10 dB higher at the wrist than at the fingertip, to compensate for the lower vibration sensitivity at the wrist. Results indicate similar gap detection at wrist and fingertip and similar perception of frequency differences. However, perception of amplitude differences was found to be better at the wrist than at the fingertip. Maximum information transfer rates for the stimuli in experiment 1 were estimated at 7 bits s(-1) at the wrist and 5 bits s(-1) at the fingertip.

The aim of this fMRI investigation was to identify those areas of the brain associated with approaching a story generation task creatively and to investigate the effects upon these correlates of incorporating a set of words that were unrelated to each other—a strategy considered to encourage semantic divergence. Preliminary experiments were undertaken to investigate the possible confounding effects of the scanner environment upon creativity and to reveal the effects of creative effort and word relatedness upon the creativity of those who would be participating in the fMRI scan. In the final part of the investigation, a factorial fMRI design was used to elucidate brain regions involved in increased creative effort and also the effect upon activity in these regions when participants incorporated words that bore little semantic relationship with each other. Results support the notion that areas of the right prefrontal cortex are critical to the types of divergent semantic processing involved with creativity in this context.

This study investigates the relation between objective and subjective parameters which relate to the quality of magnetic-resonance images, with a view to developing procedures for minimizing imaging time. The investigation uses high-resolution images of the thumb as example. Detection thresholds for an artificial lesion and ratings of image quality were obtained for a variety of images, with several experienced observers. In addition, the information content was calculated for each image, using the method developed by Fuderer (1988 IEEE Tralns. Med. Imaging 7 368-80). Results suggest that information content can be used as a predictor of either detection threshold or quality rating, with a critical information content beyond which there is no significant improvement in either of these aspects of image quality. Since it is possible to estimate the effect of imaging variables on information content, it is possible to predict the effect of time-saving imaging strategies on image quality. A procedure is suggested for determining the combination of imaging variables which gives the shortest possible imaging time whilst retaining image quality.

Knowledge of the state of tissue hydration in patients suffering from peripheral vascular disease and neuropathy as a result of diabetes is important in their treatment. Further, because magnetic resonance imaging (MRI) is uniquely able to generate information about soft tissues and their water content, it is ideal for studying disorders of this kind. The feet and hands, often affected in diabetes, are ideal for studying fundamental aspects of the disease state and the response of patients to treatment. In this preliminary study, two related areas are reported: the measurement of diffusion coefficients in the finger and the visualization of the distribution of edema and muscle atrophy in the feet of people suffering from diabetes. Diffusion coefficients of water have been measured in the normal finger as a baseline study for a current patient study. It was found that the measured diffusion coefficient increased with subject age; this is not consistent with a direct-hydration model and it is conjectured that this could be linked to structural changes in proteins. Linked to this study, we have also imaged the feet of patients suffering from diabetes. Magnetization transfer has clearly demonstrated changes in muscle tissue with atrophy caused by motor neuropathy—in general, the amount of tissue water is increased as muscle volume decreases. Further, it is evident that these changes can be related to changes in cross-linking of protein and collagen molecules as muscle fibers become thinned, thus relating these studies to the diffusion coefficient measurements. The studies of the feet have also revealed artifacts in the images, consistent with the deposition of ferrous material in tissues. It is surmised that this is caused by hemosiderin deposits at ulcer sites associated with progress of the disease. MRI could be a useful tool for monitoring the distribution of ulcers below the skin surface and provide a means of determining the response of patients to treatment.

Arthritis is intimately associated with the destruction of cartilage. High-resolution (100–200-μm)in vivo images of the finger joints have been obtained using a targeted magnetic resonance imaging (MRI) system. The study of asymptomatic subjects has enabled the normal anatomical zones of cartilage as visualised by MRI to be identified. In patients with advanced osteoarthritis features such as osteophytes and loss of cartilage are clearly demonstrated. An obvious question is whether MRI can be used to measure cartilage thickness and then whether this parameter can be utilized to quantify cartilage loss during the evolution of disease processes or response to therapy. However, there are a number of difficulties with this measurement which are discussed. It is possible that more valuable insights may be gained by careful choice of specific arthropathies to be studied—for example, acromegaly, which can lead to osteoarthritis—offers a way of observing subtle early changes that occur in the cartilage and subchondral bone.

To report the development of high-resolution targeted magnetic-resonance imaging (MRI) techniques (not using injections of contrast media) to investigate and monitor rheumatoid arthritis (RA) in the metacarpophalangeal (MCP) joints.A total of 25 RA patients (age range 30-68 years) with varying degrees of disease severity ranging from early onset through active disease to the burnt-out stage, were imaged. (One patient subsequently underwent surgery and histological data was obtained.) A series of 10 control subjects were also studied--two for each 10-year age range. All the RA subjects were assessed for disease activity using standard clinical criteria and radiography as part of normal procedures. MRI was carried out using a targeted system and novel radiofrequency coil. Images of the MCP were performed at very high resolution with 1.5 mm slice thickness and in-plane resolution 130 microns. Standard gradient-echo (GE) sequences were used for anatomical imaging, multiple-echo GE sequences used to produce effective spin-spin relaxation time (T2*) maps and optimised binomialpulse presaturation used in conjunction with a GE sequence to generate magnetization-transfer (MT) ratio maps.High-quality high-resolution images of the MCP joints were obtained which highlighted normal anatomy and key features characterising the disease state (e.g. pannus, bone erosions, vascularity). Accurate measurements of T2* and MT with variations of +/- 4% and +/- 2% respectively were achieved. In active disease, variations in T2* and MT could be determined throughout areas of pannus, clearly demonstrating the heterogeneity of this erosive tissue. Pannus in MCP joints with active destruction was found to have high values of T2* varying from 25 ms to 40 ms with pockets up to 100 ms, whereas pannus present in chronic destruction, or burnt-out disease, had T2* values ranging from 21 to 29 ms. MT-active tissue was uniformly distributed in burnt-out disease, which was confirmed histologically in one case, compared with a more heterogeneous distribution in active disease.The MRI sequences and targeted system developed allow high-resolution studies of RA disease progression and activity. The data confirm the variable pattern of the disease and, in particular, heterogeneity of pannus.

Magnetic resonance imaging (MRI) has been used to explore acoustic streaming caused in water under ultrasonic exposure conditions similar to those used for diagnostic applications. Streaming was established in an enclosed tube with acoustically transparent end windows, using a pulsed, weakly-focused transducer of acoustic frequency 3.5 MHz. Phase-detection MRI was used to image and quantify streaming profiles in the region of the acoustic focus. Acoustic powers in the range 0.4 mW to 100 mW were used. The sensitivity of the technique enabled streaming velocities down to 0. 1 mm s(-1) to be measured, generated by acoustic power less than 1 mW. In addition, acoustic streaming generated within open meshes with minimum pore dimensions of 3.0 mm and 2.0 mm was measured. The flow velocity in the coarser mesh reached 0.9 mm s(-1) at 95 mW total acoustic power. These observations demonstrate that acoustic streaming is probably a much more general phenomenon in diagnostic ultrasound (ultrasound) than previously recognised. The combination of magnetic resonance and ultrasound shows promise as a diagnostic method for the differentiation of cystic lesions in vivo, and for their characterisation, with sensitivity significantly greater than using ultrasound alone.

Experiments have been carried out to investigate the information transfer available via a single vibrator on the fingertip. In a first experiment, for stimuli with durations 80 to 320 ms, discrimination of a one-octave step change in frequency at the halfway point was investigated. Results were similar for three stimulus types--sinewave, monophasic pulse and tetraphasic pulse--suggesting temporal cues are more important than spectral cues in this task. In a second experiment, subjects were required to perceive changes in a sequence of stimulus elements. A presentation rate of 6.25 elements s-1 was found to give better results than a rate of 12.5 elements s-1. In the former case, the potential information transfer per element was estimated to be approximately 1.0 bits, corresponding to an information transfer rate of around 6 bits s-1. Implications for the design of a tactile aid to lipreading are discussed.

Abstract The therapy of brain cancers such as Glioblastoma multiforme (GBM) is often hampered by the blood-brain-barrier, which limits the access of drugs to the brain. High blood concentrations of a drug can increase transport into the brain but in the case of cytotoxic drugs often lead to dose-limiting peripheral toxicity, typically myelosuppression. In the current study we explore the potential of Nanomerics’ Molecular Envelope Technology (MET) nanoparticles to enhance transport of the cytotoxic drug lomustine to the brain while avoiding dose-limiting peripheral bone marrow toxicity. We have previously shown that these particles increase the brain activity of drugs such as the intravenous anaesthetic propofol by a factor of ten. MET nanoparticles were prepared from a self-assembling amphiphilic chitosan based polymer - quaternary ammonium palmitoyl glycol chitosan. Lomustine, a poorly water soluble alkylating nitrosourea (CCNU), was encapsulated within these particles at a concentration of 2mg mL−1, 20x higher than what is achievable with conventional ethanolic- polysorbate 80 formulations. In order to determine the therapeutic efficacy of the formulations, orthotopic intracranial human glioblastomas (U87- MG cells) were studied in female CD-1 nude mice. Established tumours were treated at the maximal achievable lomustine concentrations using MET lomustine (13 mg kg−1/day) and the conventional formulation (1.2 mg kg−1/day) for 10 days. The mean survival time for animals that received the MET formulation was significantly (p Animal white blood cell and femoral cell counts were not affected by any of the lomustine formulations, however both treated groups of animals showed a transient drop in the platelet count on Day 7 with recovery by day 22. The MET lomustine particulate formulation thus enabled the administration of a more than ten times higher dose of lomustine which dramatically improved therapeutic outcome with little evidence of any additional toxicity or dose limiting toxic effects. The results of this study suggest that MET nanoparticles may provide a safe means to improve therapeutic outcomes in brain cancer using current cytotoxic drugs. Citation Format: Funmilola A. Fisusi, Ahmed Alzharani, Ian Summers, Julian Morger, Omotunde Okubanjo, Kar wai Chooi, Andreas G. Schätzlein, Ijeoma F. Uchegbu. Lomustine nanoparticles are effective brain cancer treatments. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4519. doi:10.1158/1538-7445.AM2013-4519

To establish the best strategy for transmitting speech-derived information via a single tactile channel, measurements were made on the perception of frequency- and/or amplitude-modulated pulse-train stimuli, with a comparison of the electrotactile and vibrotactile modalities. In one experiment, vibrotactile perception of 2-oct step changes in stimulus frequency was found to be significantly better than electrotactile on a time-scale appropriate for the transmission of speech features (e.g., with practiced subjects, information transfer of 69% with 200-ms vibrotactile stimuli, 32% with 200-ms electrotactile stimuli). Perception of step changes in stimulus amplitude was similar in the two modalities when changes in amplitude were tailored to match the different dynamic ranges available. In a second experiment, vibrotactile-perception of voice fundamental frequency with various codings was investigated. Both experiments showed information transfer for vibrotactile stimuli to be greater when frequency and amplitude modulation were used together rather than with one or the other in isolation (sentence-stress identification scores: 66% for FM stimuli, 69% for AM stimuli, 80% for FM/AM stimuli). It is concluded that frequency- and amplitude-modulated vibratory stimulation is a good choice in a practical device for the profoundly hearing impaired.

Diffusion coefficients of water have been measured in the fingers of humans by magnetic resonance imaging. It was found that the measured diffusion coefficients increased with subject age in certain regions of the finger but that these regions differed between males and females. The observation of an increased diffusion coefficient with age appears to be inconsistent with a direct-hydration model and possible explanations are given using other models. It is conjectured that the measured diffusion coefficient of water increases with age as a result of structural changes to proteins.

Measurements have been made on the ability of normally hearing subjects to identify the stressed word in simple sentences, using only tactile information. Vibrotactile stimuli were presented to the distal pad of the second finger via a single vibrator. A range of coding strategies was investigated, voice pitch or speech amplitude being represented as stimulus frequency and/or intensity. Test results show that, even without specific training, subjects can be quite successful in identifying stress patterns. The most effective coding strategies were (i) voice frequency presented as continuously variable stimulus frequency over the range 40-220 Hz, with a correlated modulation of stimulus amplitude, (ii) speech amplitude presented as two discrete levels of stimulus amplitude.

Profoundly deaf subjects were given information about sound level in their environment by means of a body-worn unit coupled to a small vibrator worn on the finger. Results of trials on 19 adults are discussed. The Tactile Acoustic Monitor was found to be useful for identifying domestic sounds by means of their distinctive timing patterns. No significant overall improvement in subject's control of voice level was observed, although some subjects found that having a voice level monitor gave them greater confidence to join conversations. Various design improvements were suggested by the trials. Modifications which have been incorporated into an improved unit are described.

Sound level monitoring apparatus for a deaf person comprises a microphone, a discriminator connected to the microphone to provide an output signal in response to the attainment of a predetermined sound level threshold in the ambient sound detected by the microphone, and a sensory transducer responsive to the discriminator to provide a representation of the output signal. In use the threshold suitably represents the normal speech level of the user, and may be adjustable, and the transducer accordingly indicates whether the user should raise or lower his speech level in a given environment. The apparatus can operate in association with several thresholds with the lowest denoting normal speech and with one or more transducers providing respectively, mutually distinctive representations. The transducer or transducers can be of visual form, with use of differently colored light outputs or of vibratory tactile form, with different operating frequencies.