Wave intensity analysis: A novel non-invasive method for determining arterial wave transmission

Wave intensity analysis is a novel technique for assessing wavelet transmission in the cardiovascular system. Using this tool, we have developed non-invasive techniques to study wave transmission in both central & peripheral arteries in man. The aim of this study was to determine the reproducibility of various haemodynamic measures in the carotid, brachial and radial arteries. 12 treated hypertensive men underwent applanation tonometry and pulsed Doppler ultrasound studies of the carotid, brachial and radial arteries on 2 occasions. Coefficients of variation for the local wave speed, cardiac compression wave intensity and main reflected wave intensity ranged between 3.7-6.6%, 8.2-11.4% and 12.5-19.6% respectively. We conclude that non-invasive methods used for wave intensity analysis are reproducible & provide additional information regarding the complex phenomenon of arterial wave transmission in man

Site α Is Crucial for Two Routes of IFNγ-Induced MHC Class I Transactivation: The ISRE-Mediated Route and a Novel Pathway Involving CIITA

AbstractThe constitutive and cytokine-induced levels of major histocompatibility (MHC) class I expression are tightly controlled at the transcriptional level. In this study, it is shown that the cis-acting regulatory element site α of the MHC class I promoter is essential for the IFNγ-induced transactivation of MHC class I gene expression through the ISRE. Moreover, it was discovered that the class II transactivator (CIITA), which is itself under the control of the IFNγ induction pathway, strongly transactivates MHC class I gene expression and exerts its activity through site α. Therefore, site α is a crucial regulatory element, mediating the classic route of IFNγ induction via the ISRE as well as a novel route of MHC class I transactivation involving CIITA

Limitations of augmentation index in the assessment of wave reflection in normotensive healthy individuals

Objectives Augmentation index (AIx) is widely used as a measure of wave reflection. We compared the relationship between AIx and age, height and sex with ‘gold standard’ measures of wave reflection derived from measurements of pressure and flow to establish how well AIx measures wave reflection. Materials and Methods Measurements of carotid pressure and flow velocity were made in the carotid artery of 65 healthy normotensive individuals (age 21–78 yr; 43 male) and pulse wave analysis, wave intensity analysis and wave separation was performed; waveforms were classified into type A, B or C. AIx, the time of the first shoulder (Ts), wave reflection index (WRI) and the ratio of backward to forward pressure (Pb/Pf) were calculated. Results AIx did not correlate with log WRI or Pb/Pf. When AIx was restricted to positive values AIx and log WRI were positively correlated (r = 0.33; p = 0.04). In contrast log WRI and Pb/Pf were closely correlated (r = 0.66; p<0.001). There was no correlation between the Ts and the timing of Pb or the reflected wave identified by wave intensity analysis. Wave intensity analysis showed that the morphology of type C waveforms (negative AIx) was principally due to a forward travelling (re-reflected) decompression wave in mid-systole. AIx correlated positively with age, inversely with height and was higher in women. In contrast log WRI and Pb/Pf showed negative associations with age, were unrelated to height and did not differ significantly by gender. Conclusions AIx has serious limitations as a measure of wave reflection. Negative AIx values derived from Type C waves should not be used as estimates of wave reflection magnitude

Multiphysics Modelling and Simulation of Thrombolysis via Activated Platelet-Targeted Nanomedicine

PURPOSE: This study establishes a multiphysics simulation platform for both conventional and targeted thrombolysis using tissue plasminogen activator (tPA). Based on our computational results, the effects of therapeutic parameters on the dynamics of thrombolysis and the risk of side effects are investigated. METHODS: The model extends our previously developed one-dimensional(1D) mathematical models for fibrinolysis by incorporating targeted thrombolysis. It consists of two parts: (i) a coupled mathematical model of systemic pharmacokinetics (PK) and pharmacodynamics (PD) and local PD in a 1D occluded artery, and (ii) a mechanistic model for a targeted thrombolytic system via activated platelet-targeted tPA-loaded nanovesicles (tPA-NV), with model parameters derived from our in vitro experiments. A total of 16 therapeutic scenarios are simulated by varying the clot location and composition as well as the dosing regimen with free tPA or tPA-NV. RESULTS: Our simulation results indicate that tPA-NV offers several advantages over free tPA for thrombolysis. It reduces systemic exposure of tPA, thereby minimising the risk of bleeding complications. Simulations with different tPA-NV doses reveal that tPA-NV at 10% of the recommended dose can be as effective as the standard regimen with the full recommended dose of free tPA, demonstrating the potential of our tPA-NV as a new thrombolytic strategy with a reduced tPA dose. Moreover, faster recanalisation can be achieved with tPA-NV, especially for platelet-rich(or fibrin-poor) clots. CONCLUSIONS: Our simulation platform for thrombolysis with well-tuned model parameters can be used to evaluate and optimise treatment regimens of existing and new thrombolytic therapies via benefit/risk assessment under various therapeutic scenarios

A novel 60 GHz wideband coupled half-mode/quarter-mode substrate integrated waveguide antenna

A novel wideband substrate integrated waveguide (SIW) antenna topology, consisting of coupled half-mode and quarter-mode SIW resonant cavities, is proposed for operation in the 60 GHz band. This innovative topology combines a considerable bandwidth enhancement and a low form factor with compatibility with low-cost printed circuit board manufacturing processes, making it excellently suited for the next generation, high data rate wireless applications. Moreover, exploiting SIW technology, a high antenna-platform isolation is obtained, enabling dense integration with active electronics without harmful coupling. The computer-aided design process yields an antenna that covers the entire 57-64 GHz IEEE 802.11ad band with a measured fractional impedance bandwidth of 11.7% (7 GHz). The measured maximum gain and radiation efficiency of the prototype are larger than 5.1 dBi and 65%, respectively, within the entire impedance bandwidth

Automatic optic disc detection in colour fundus images by means of multispectral analysis and information content

The optic disc (OD) in retinal fundus images is widely used as a reference in computer-based systems for the measurement of the severity of retinal disease. A number of algorithms have been published in the past 5 years to locate and measure the OD in digital fundus images. Our proposed algorithm, automatically: (i) uses the three channels (RGB) of the digital colour image to locate the region of interest (ROI) where the OD lies, (ii) measures the Shannon information content per channel in the ROI, to decide which channel is most appropriate for searching for the OD centre using the circular Hough transform. A series of evaluations were undertaken to test our hypothesis that using the three channels gives a better performance than a single channel. Three different databases were used for evaluation purposes with a total of 2,371 colour images giving a misdetection error of 3% in the localisation of the centre of the OD. We find that the area determined by our algorithm which assumes that the OD is circular, is similar to that found by other algorithms that detected the shape of the OD. Five metrics were measured for comparison with other recent studies. Combining the two databases where expert delineation of the OD is available (1,240 images), the average results for our multispectral algorithm are: TPR = 0.879, FPR = 0.003, Accuracy = 0.994, Overlap = 80.6% and Dice index = 0.878

Effect of a carotenoid-producing Bacillus strain on intestinal barrier integrity and systemic delivery of carotenoids : a randomised trial in animals and humans

The aim of the present study was to investigate effects of the carotenoid-producing Bacillus indicus strain PD01 on intestinal barrier function and its ability to survive passage through the gastrointestinal tract and to assess systemic bioavailability of these carotenoids in vivo. As model for impaired barrier function, 16 early weaned piglets were randomly assigned to a control diet or control diet with PD01 for 23 days. In addition, 67 overweight/obese, otherwise healthy individuals were randomly assigned to groups receiving PD01 or placebo for 6 weeks. PD01 survived passage through the gastrointestinal tract in piglets and human subjects and resulted in significant accumulation of PD01 derived carotenoids (methyl-glycosyl-apo-8'-lycopenoate and glycosyl-apo-8'- lycopene) in human plasma after 3- and 6-weeks supplementation versus baseline (0.044 and 0.076 vs 0 mu M, respectively; p = 0.104). In summary, PD01 survived transit through the gastrointestinal tract, resulted in systemic carotenoid accumulation and improved compromised barrier function outcomes

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

A hybrid integration strategy for compact, broadband, and highly efficient millimeter-wave on-chip antennas

A novel hybrid integration strategy for compact, broadband, and highly efficient millimeter-wave (mmWave) on-chip antennas is demonstrated by realizing a hybrid on-chip antenna, operating in the [27.5-29.5] GHz band. A cavity-backed stacked patch antenna is implemented on a 600 mu m thick silicon substrate by using air-filled substrate-integrated-waveguide technology. A hybrid on-chip approach is adopted in which the antenna feed and an air-filled cavity are integrated on-chip, and the stacked patch configuration is implemented on a high-frequency printed circuit board (PCB) laminate that supports the chip. A prototype of the hybrid on-chip antenna is validated, demonstrating an impedance bandwidth of 3.7 GHz. In free-space conditions, a boresight gain of 7.3 dBi and a front-to-back ratio of 20.3 dB at 28.5GHz are achieved. Moreover, the antenna is fabricated using standard silicon fabrication techniques and features a total antenna efficiency above 90% in the targeted frequency band of operation. The high performance, in combination with the compact antenna footprint of 0.49 lambda(min) x 0.49 lambda(min), makes it an ideal building block to construct broadband antenna arrays with a broad steering range

Re-Treatment Tuberculosis Cases Categorised as “Other”: Are They Properly Managed?

BACKGROUND: Although the World Health Organization (WHO) provides information on the number of TB patients categorised as "other", there is limited information on treatment regimens or treatment outcomes for "other". Such information is important, as inappropriate treatment can lead to patients remaining infectious and becoming a potential source of drug resistance. Therefore, using a cohort of TB patients from a large registration centre in Lilongwe, Malawi, our study determined the proportion of all TB re-treatment patients who were registered as "other", and described their characteristics and treatment outcomes. METHODS: This retrospective observational study used routine program data to determine the proportion of all TB re-treatment patients who were registered as "other" and describe their characteristics and treatment outcomes between January 2006 and December 2008. RESULTS: 1,384 (12%) of 11,663 TB cases were registered as re-treatment cases. Of these, 898 (65%) were categorised as "other": 707 (79%) had sputum smear-negative pulmonary TB and 191 (21%) had extra pulmonary TB. Compared to the smear-positive relapse, re-treatment after default (RAD) and failure cases, smear-negative "other" cases were older than 34 years and less likely to have their HIV status ascertained. Among those with known HIV status, "other" TB cases were more likely to be HIV positive. Of TB patients categorised as "other", 462 (51%) were managed on the first-line regimen with a treatment success rate of 63%. CONCLUSION: A large proportion of re-treatment patients were categorised as "other". Many of these patients were HIV-infected and over half were treated with a first-line regimen, contrary to national guidelines. Treatment success was low. More attention to recording, diagnosis and management of these patients is warranted as incorrect treatment regimen and poor outcomes could lead to the development of drug resistant forms of TB