• Absence of nonlinear responses in cells and tissues exposed to RF energy at mobile phone frequencies using a doubly resonant cavity

      Kowalczuk, C.; Yarwood, G.; Blackwell, R.; Priestner, M.; Sienkiewicz, Z.; Bouffler, S.; Ahmed, I.; Abd-Alhameed, Raed A.; Excell, Peter S.; Hodzic, V.; et al. (2010)
      A doubly resonant cavity was used to search for nonlinear radiofrequency (RF) energy conversion in a range of biological preparations, thereby testing the hypothesis that living tissue can demodulate RF carriers and generate baseband signals. The samples comprised high-density cell suspensions (human lymphocytes and mouse bone marrow cells); adherent cells (IMR-32 human neuroblastoma, G361 human melanoma, HF-19 human fibroblasts, N2a murine neuroblastoma (differentiated and non-differentiated) and Chinese hamster ovary (CHO) cells) and thin sections or slices of mouse tissues (brain, kidney, muscle, liver, spleen, testis, heart and diaphragm). Viable and non-viable (heat killed or metabolically impaired) samples were tested. Over 500 cell and tissue samples were placed within the cavity, exposed to continuous wave (CW) fields at the resonant frequency (f) of the loaded cavity (near 883 MHz) using input powers of 0.1 or 1 mW, and monitored for second harmonic generation by inspection of the output at 2f. Unwanted signals were minimised using low pass filters (</= 1 GHz) at the input to, and high pass filters (>/= 1 GHz) at the output from, the cavity. A tuned low noise amplifier allowed detection of second harmonic signals above a noise floor as low as -169 dBm. No consistent second harmonic of the incident CW signals was detected. Therefore, these results do not support the hypothesis that living cells can demodulate RF energy, since second harmonic generation is the necessary and sufficient condition for demodulation.
    • Cine cerebrospinal fluid imaging in multiple sclerosis

      Magnano, C.R.; Schirda, C.V.; Weinstock-Guttman, B.; Wack, D.S.; Lindzen, E.; Hojnacki, D.; Bergsland, N.; Kennedy, C.; Belov, P.; Dwyer, Michael G.; et al. (2012)
      PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius in multiple sclerosis (MS) patients and healthy controls (HC) using cine phase contrast imaging. MATERIALS AND METHODS: In all, 67 MS patients (48 relapsing-remitting [RR] and 19 secondary-progressive [SP]), nine patients with clinically isolated syndrome (CIS), and 35 age- and sex-matched HC were examined. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and magnetic resonance imaging (MRI) disease outcomes. RESULTS: Significantly decreased CSF net flow was detected in MS patients compared to HC (-3.7 vs. -7.1 muL/beat, P = 0.005). There was a trend for increased net positive flow between SP, RR, and CIS patients. Altered CSF flow and velocity measures were associated with more severe T1 and T2 lesion volumes, lateral and fourth ventricular volumes, and third ventricular width in MS and CIS patients (P < 0.01 for all). In CIS patients, conversion to clinically definite MS in the following year was related to decreased CSF net flow (P = 0.007). There was a trend between increased annual relapse rate and altered CSF flow/velocity measures in RRMS patients (P < 0.05). CONCLUSION: CSF flow dynamics are altered in MS patients. More severe clinical and MRI outcomes in RRMS and CIS patients relate to altered CSF flow and velocity measures.
    • Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency

      Zivadinov, R.; Poloni, G.U.; Marr, K.; Schirda, C.V.; Magnano, C.R.; Carl, E.; Bergsland, N.; Hojnacki, D.; Kennedy, C.; Beggs, Clive B.; et al. (2011)
      BACKGROUND: The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC). METHODS: 59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: < .3 mm, .3-.6 mm, .6-.9 mm and > .9 mm. RESULTS: CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p < .0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter < .3 mm, and increased DFV compared to HC (all p < .0001). Subjects diagnosed with CCSVI had significantly increased DFV (p < .0001), decreased overall ATVV and ATVV of veins with a diameter < .3 mm (p < .003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p < .0001) on pre- and post-contrast SWI, but not in HC. CONCLUSIONS: MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS.
    • Development of a novel liquid crystal based cell traction force transducer system

      Soon, Chin Fhong; Youseffi, Mansour; Berends, Rebecca F.; Blagden, Nicholas; Denyer, Morgan C.T. (2013)
      Keratinocyte traction forces play a crucial role in wound healing. The aim of this study was to develop a novel cell traction force (CTF) transducer system based on cholesteryl ester liquid crystals (LC). Keratinocytes cultured on LC induced linear and isolated deformation lines in the LC surface. As suggested by the fluorescence staining, the deformation lines appeared to correlate with the forces generated by the contraction of circumferential actin filaments which were transmitted to the LC surface via the focal adhesions. Due to the linear viscoelastic behavior of the LC, Hooke's equation was used to quantify the CTFs by associating Young's modulus of LC to the cell induced stresses and biaxial strain in forming the LC deformation. Young's modulus of the LC was profiled by using spherical indentation and determined at approximately 87.1+/-17.2kPa. A new technique involving cytochalasin-B treatment was used to disrupt the intracellular force generating actin fibers, and consequently the biaxial strain in the LC induced by the cells was determined. Due to the improved sensitivity and spatial resolution ( approximately 1mum) of the LC based CTF transducer, a wide range of CTFs was determined (10-120nN). These were found to be linearly proportional to the length of the deformations. The linear relationship of CTF-deformations was then applied in a bespoke CTF mapping software to estimate CTFs and to map CTF fields. The generated CTF map highlighted distinct distributions and different magnitude of CTFs were revealed for polarized and non-polarized keratinocytes.
    • Imaging of the cell surface interface using objective coupled widefield surface plasmon microscopy

      Jamil, M. Mahadi Abdul; Denyer, Morgan C.T.; Youseffi, Mansour; Britland, Stephen T.; Liu, S.; See, C.W.; Somekh, M.G.; Zhang, J. (2008)
      We report on the development and on the first use of the widefield surface plasmon (WSPR) microscope in the examination of the cell surface interface at submicron lateral resolutions. The microscope is Kohler illuminated and uses either a 1.45 numerical aperture (NA) oil immersion lens, or a 1.65 NA oil immersion lens to excite surface plasmons at the interface between a thin gold layer and a glass or sapphire cover slip. Like all surface plasmon microscope systems the WSPR has been proven in previous studies to also be capable of nanometric z-scale resolutions. In this study we used the system to image the interface between HaCaT cells and the gold layer. Imaging was performed in air using fixed samples and the 1.45 NA objective based system and also using live cells in culture media using the 1.65 NA based system. Imaging in air enabled the visualisation of high resolution and high-contrast submicron features identified by vinculin immunostaining as component of focal contacts and focal adhesions. In comparison, imaging in fluid enabled cell surface interfacial interactions to be tracked by time-lapse video WSPR microscopy. Our results indicate that the cell surface interface and thus cell signalling mechanisms may be readily interrogated in live cells without the use of labelling techniques.
    • Jugular venous reflux and white matter abnormalities in Alzheimer's disease: a pilot study

      Chung, C.P.; Beggs, Clive B.; Wang, P.N.; Bergsland, N.; Shepherd, Simon J.; Cheng, C.Y.; Ramasamy, D.P.; Dwyer, Michael G.; Hu, H.H.; Zivadinov, R. (2014)
      To determine whether jugular venous reflux (JVR) is associated with cerebral white matter changes (WMCs) in individuals with Alzheimer's disease (AD), we studied 12 AD patients 24 mild cognitive impairment (MCI) patients, and 17 elderly age- and gender-matched controls. Duplex ultrasonography and 1.5T MRI scanning was applied to quantify cerebral WMCs [T2 white matter (WM) lesion and dirty-appearing-white-matter (DAWM)]. Subjects with severe JVR had more frequently hypertension (p = 0.044), more severe WMC, including increased total (p = 0.047) and periventricular DAWM volumes (p = 0.008), and a trend for increased cerebrospinal fluid volumes (p = 0.067) compared with the other groups. A significantly decreased (65.8%) periventricular DAWM volume (p = 0.01) in the JVR-positive AD individuals compared with their JVR-negative counterparts was detected. There was a trend for increased periventricular and subcortical T2 WMC lesion volumes in the JVR-positive AD individuals compared with their JVR-negative counterparts (p = 0.073). This phenomenon was not observed in either the control or MCI groups. In multiple regression analysis, the increased periventricular WMC lesion volume and decreased DAWM volume resulted in 85.7% sensitivity and 80% specificity for distinguishing between JVR-positive and JVR-negative AD patients. These JVR-WMC association patterns were not seen in the control and MCI groups. Therefore, this pilot study suggests that there may be an association between JVR and WMCs in AD patients, implying that cerebral venous outflow impairment might play a role in the dynamics of WMCs formation in AD patients, particularly in the periventricular regions. Further longitudinal studies are needed to confirm and validate our findings.
    • The acoustic and visual factors influencing the construction of tranquil space in urban and rural environments tranquil spaces-quiet places?

      Pheasant, Robert J.; Horoshenkov, Kirill V.; Watts, Gregory R.; Barrett, Brendan T. (2008)
      Prior to this work no structured mechanism existed in the UK to evaluate the tranquillity of open spaces with respect to the characteristics of both acoustic and visual stimuli. This is largely due to the fact that within the context of "tranquil" environments, little is known about the interaction of the audio-visual modalities and how they combine to lead to the perception of tranquillity. This paper presents the findings of a study in which visual and acoustic data, captured from 11 English rural and urban landscapes, were used by 44 volunteers to make subjective assessments of both their perceived tranquillity of a location, and the loudness of five generic soundscape components. The results were then analyzed alongside objective measurements taken in the laboratory. It was found that the maximum sound pressure level (L(Amax)) and the percentage of natural features present at a location were the key factors influencing tranquillity. Engineering formulas for the tranquillity as a function of the noise level and proportion of the natural features are proposed.