Stage is not a reliable indicator of tumor volume in non-small cell lung cancer: a preliminary analysis of the trans-tasman radiation oncology group 99-05 database

Background: Tumor volume has been shown to be a prognostic factor for the response of some tumors to radiotherapy. TNM stage has prognostic value for patients treated surgically for non-small cell lung cancer (NSCLC), but its value is less clear for patients treated by nonsurgical means. This may be because tumor size is not a consistent determinant of T stage or stage group. As part of the preliminary analyses for the Trans-Tasman Radiation Oncology Group 99-05 study, the authors performed this analysis to determine to what extent stage reflects tumor volume. Methods: In this prospective multicenter observational study, patients had to have histologically proven NSCLC, no evidence of disease beyond the primary site or thoracic lymph nodes, and been planned for radical radiotherapy with or without chemotherapy. Tumor volume measurements were based on computed tomography-based treatment planning images. Results: Four hundred four patients were available for analysis. There was a strong correlation between (log) maximum tumor diameter and (log) tumor volume (r = 0.93, p < 0.001). Although there was a highly significant trend of increasing volume with increasing T stage and stage group, when tumors were categorized into four groups according to increasing volume, there was only 55% concordance with T stage and 67% concordance with stage group. Conclusions: There is limited correlation between tumor size and disease stage in patients with NSCLC. This justifies documentation and investigation of size as a potential prognostic factor independent of stage. Maximum tumor diameter may be an adequate substitute for volume as a measurement of size.

Quadriceps activity and movement reactions in response to unpredictable sagittal support-surface translations in women with patellofemoral pain

Patellofemoral pain (PFP) may be related to unfavorable knee joint loading. Delayed and/or reduced activity of vastus medialis obliquus (VMO) and different movement patterns have been identified in individuals with PFP in some studies, whereas other studies have failed to show a difference compared to non-affected controls. The discrepancy between study results may depend on the different tasks that have been investigated. No previous study has investigated these variables in postural responses to unpredictable perturbations in PFP. Whole body three dimensional kinematics and surface EMG of quadriceps muscles activation was studied in postural responses to unpredictable support surface translations in 17 women with PFP who were pain free at the time of testing, and 17 matched healthy controls. The results of the present study showed earlier onset of VMO activity and associated changes in kinematics to anterior platform translation in the PFP subjects. We suggest that the relative timing between the portions quadriceps muscles may be task specific and part of an adapted response in attempt to reduce knee joint loading. This learned response appears to remain even when the pain is no longer present.

Correlation of T-cell immune response with spontaneous resolution and subsequent relapse of Hodgkin's lymphoma

To our knowledge, there has been no report of spontaneous regression in a non-immunocompromised adult with classical Hodgkin's lymphoma (HL) in the absence of chemotherapy. We describe spontaneous regression and subsequent relapse of Epstein - Barr virus (EBV)-positive HL in an otherwise healthy male adult. The clinical course was associated with an increase in regulatory T-cell markers within the peripheral blood and diseased lymph node at the time of relapse and with a concomitant reduction in cellular immunity against relevant EBV latent membrane protein tumor-associated antigens. Our findings are in keeping with previous observations that implicate impaired cellular immunity in the immunopathogenesis of EBV-positive HL.

Inhibition, encoding specificity, and response availability revisited

In the think/no-think paradigm people practice “suppressing” a learned response to a cue. Practice at suppression appears to produce a long-lasting inhibition of the suppressed response, as evidenced by a subsequent failure to recall the response to an extralist (associatively related, non-studied) cue. Critical to this interpretation is the assumption that suppression practice is necessary. A series of interference paradigms, which do not involve suppression practice and which are structurally similar to the think/no-think paradigm, provide evidence against the inhibition interpretation. Additional evidence against inhibition derives from our demonstrations herewith that the findings from the think/no-think paradigm can be replicated without any apparent suppression requirement. Furthermore, the results from all of these paradigms can be explained by the same simple principle. Namely, that when an item exists in an extended associative network, strengthening the item makes it interfere with the recall of other items in the network.

Humpback whale social sounds: Sources levels and response to playback

Humpback whale ‘‘social sounds’’ appear to be used in communication when whales interact but they have received little study in comparison to the song. During experiments as part of the Humpback whale Acoustics Research Collaboration (HARC), whales migrating past the study site on the east coast of Australia produced a wide range of social sounds. Whales were tracked visually using a theodolite and singers were tracked acoustically using an array of five widely spaced hydrophones. Source levels of social sounds were calculated from the received level of the sounds, corrected for measured propagation loss. Playbacks of social sounds were made using a J11 transducer and the consequent reactions were recorded in terms of the change in direction of the migrating whales in relation to the playback position. In one playback, a DTAG was place on a female with calf. Playback of social sounds resulted in significant changes in the course of the migrating whales, in some cases towards the transducer while in others it was away from the transducer. From the estimates of source levels it is possible to assess the effectiveness of the playback and the range of influence of social sounds. [Work supported by ONR and DSTO.]

αα'-trehalose 6,6'-dibehenate in non-phospholipid-based liposomes enables direct interaction with trehalose, offering stability during freeze-drying

Trehalose is a well known protector of biostructures like liposomes and proteins during freeze-drying, but still today there is a big debate regarding its mechanism of action. In previous experiments we have shown that trehalose is able to protect a non-phospholipid-based liposomal adjuvant (designated CAF01) composed of the cationic dimethyldioctadecylammonium (DDA) and trehalose 6,6-dibehenate (TDB) during freeze-drying [D. Christensen, C. Foged, I. Rosenkrands, H.M. Nielsen, P. Andersen, E.M. Agger, Trehalose preserves DDA/TDB liposomes and their adjuvant effect during freeze-drying, Biochim. Biophys. Acta, Biomembr. 1768 (2007) 2120-2129]. Furthermore it was seen that TDB is required for the stabilizing effect of trehalose. Herein, we show using the Langmuir-Blodgett technique that a high concentration of TDB present at the water-lipid interface results in a surface pressure around 67 mN/m as compared to that of pure DDA which is approximately 47 mN/m in the compressed state. This indicates that the attractive forces between the trehalose head group of TDB and water are greater than those between the quaternary ammonium head group of DDA and water. Furthermore, addition of trehalose to a DDA monolayer containing small amounts of TDB also increases the surface pressure, which is not observed in the absence of TDB. This suggests that even small amounts of trehalose groups on TDB present at the water-lipid interface associate free trehalose to the liposome surface, presumably by hydrogen bonding between the trehalose head groups of TDB and the free trehalose molecules. Hence, for CAF01 the TDB component not only stabilizes the cationic liposomes and enhances the immune response but also facilitates the cryo-/lyoprotection by trehalose through direct interaction with the head group of TDB. Furthermore the results indicate that direct interaction with liposome surfaces is necessary for trehalose to enable protection during freeze-drying.

Imaging the dynamics of the auditory steady-state evoked response

This study used magnetoencephalography (MEG) to examine the dynamic patterns of neural activity underlying the auditory steady-state response. We examined the continuous time-series of responses to a 32-Hz amplitude modulation. Fluctuations in the amplitude of the evoked response were found to be mediated by non-linear interactions with oscillatory processes both at the same source, in the alpha and beta frequency bands, and in the opposite hemisphere. © 2005 Elsevier Ireland Ltd. All rights reserved.

GLM-beamformer method demonstrates stationary field, alpha ERD and gamma ERS co-localisation with fMRI BOLD response in visual cortex

Recently, we introduced a new 'GLM-beamformer' technique for MEG analysis that enables accurate localisation of both phase-locked and non-phase-locked neuromagnetic effects, and their representation as statistical parametric maps (SPMs). This provides a useful framework for comparison of the full range of MEG responses with fMRI BOLD results. This paper reports a 'proof of principle' study using a simple visual paradigm (static checkerboard). The five subjects each underwent both MEG and fMRI paradigms. We demonstrate, for the first time, the presence of a sustained (DC) field in the visual cortex, and its co-localisation with the visual BOLD response. The GLM-beamformer analysis method is also used to investigate the main non-phase-locked oscillatory effects: an event-related desynchronisation (ERD) in the alpha band (8-13 Hz) and an event-related synchronisation (ERS) in the gamma band (55-70 Hz). We show, using SPMs and virtual electrode traces, the spatio-temporal covariance of these effects with the visual BOLD response. Comparisons between MEG and fMRI data sets generally focus on the relationship between the BOLD response and the transient evoked response. Here, we show that the stationary field and changes in oscillatory power are also important contributors to the BOLD response, and should be included in future studies on the relationship between neuronal activation and the haemodynamic response. © 2005 Elsevier Inc. All rights reserved.

Motion sharpening and contrast:Gain control precedes compressive non-linearity?

Blurred edges appear sharper in motion than when they are stationary. We (Vision Research 38 (1998) 2108) have previously shown how such distortions in perceived edge blur may be accounted for by a model which assumes that luminance contrast is encoded by a local contrast transducer whose response becomes progressively more compressive as speed increases. If the form of the transducer is fixed (independent of contrast) for a given speed, then a strong prediction of the model is that motion sharpening should increase with increasing contrast. We measured the sharpening of periodic patterns over a large range of contrasts, blur widths and speeds. The results indicate that whilst sharpening increases with speed it is practically invariant with contrast. The contrast invariance of motion sharpening is not explained by an early, static compressive non-linearity alone. However, several alternative explanations are also inconsistent with these results. We show that if a dynamic contrast gain control precedes the static non-linear transducer then motion sharpening, its speed dependence, and its invariance with contrast, can be predicted with reasonable accuracy. © 2003 Elsevier Science Ltd. All rights reserved.

Fast response static var generator for improving the power system performance of an electric arc furnace (EAF)

Cascaded multilevel inverters-based Static Var Generators (SVGs) are FACTS equipment introduced for active and reactive power flow control. They eliminate the need for zigzag transformers and give a fast response. However, with regard to their application for flicker reduction in using Electric Arc Furnace (EAF), the existing multilevel inverter-based SVGs suffer from the following disadvantages. (1) To control the reactive power, an off-line calculation of Modulation Index (MI) is required to adjust the SVG output voltage. This slows down the transient response to the changes of reactive power; and (2) Random active power exchange may cause unbalance to the voltage of the d.c. link (HBI) capacitor when the reactive power control is done by adjusting the power angle d alone. To resolve these problems, a mathematical model of 11-level cascaded SVG, was developed. A new control strategy involving both MI (modulation index) and power angle (d) is proposed. A selected harmonics elimination method (SHEM) is taken for switching pattern calculations. To shorten the response time and simplify the controls system, feed forward neural networks are used for on-line computation of the switching patterns instead of using look-up tables. The proposed controller updates the MI and switching patterns once each line-cycle according to the sampled reactive power Qs. Meanwhile, the remainder reactive power (compensated by the MI) and the reactive power variations during the line-cycle will be continuously compensated by adjusting the power angles, d. The scheme senses both variables MI and d, and takes action through the inverter switching angle, qi. As a result, the proposed SVG is expected to give a faster and more accurate response than present designs allow. In support of the proposal there is a mathematical model for reactive powered distribution and a sensitivity matrix for voltage regulation assessment, MATLAB simulation results are provided to validate the proposed schemes. The performance with non-linear time varying loads is analysed and refers to a general review of flicker, of methods for measuring flickers due to arc furnace and means for mitigation.

Influence of blur on the visual evoked magnetic response to a pattern reversal stimulus

Blurring a pattern reversal stimulus increases the latency and decreases the amplitude of the visual evoked potential (VEP) P100 peak. Recording the visual evoked magnetic response (VEMR) is some subjects may therefore be difficult because their spectacles create excessive magnetic noise. Hence, the effect of varying degrees of blur (-5 to +5 D) on the VEMR was investigated in three subjects with 6/6 vision to determine whether refraction with non-magnetic frames and lenses was necessary before magnetic recording. Small (32') and larger (70') checks were studied since there is evidence that blurring small checks has a more significant effect on the VEP compared with large checks. The VEMR was recorded using a single channel dc-SQUID, second order gradiometer in an unshielded laboratory. The latency (ms) and amplitude (fT) of the most prominant positive peak within the first 130 ms (P100M) were measured. Blurring the 32' checks significantly increased latency aand reduced the amplitude of the P100M peak. The resulting response curves were parabolic with minimum latency and maximum amplitude recorded at 0 D. Blurring the 70' check had no significant effect on latency or amplitude. Hence, the magnetic P100M responds similarly to the electrical P100 in response to blur. It would be essential when recording the VEMR that vision is corrected with non-magnetic spectacles especially when small checks are used.

Non-Linear oil firm force coefficients for a journal bearing operating under aligned and misaligned conditions

It is well established that hydrodynamic journal bearings are responsible for self-excited vibrations and have the effect of lowering the critical speeds of rotor systems. The forces within the oil film wedge, generated by the vibrating journal, may be represented by displacement and velocity coefficient~ thus allowing the dynamical behaviour of the rotor to be analysed both for stability purposes and for anticipating the response to unbalance. However, information describing these coefficients is sparse, misleading, and very often not applicable to industrial type bearings. Results of a combined analytical and experimental investigation into the hydrodynamic oil film coefficients operating in the laminar region are therefore presented, the analysis being applied to a 120 degree partial journal bearing having a 5.0 in diameter journal and a LID ratio of 1.0. The theoretical analysis shows that for this type of popular bearing, the eight linearized coefficients do not accurately describe the behaviour of the vibrating journal based on the theory of small perturbations, due to them being masked by the presence of nonlinearity. A method is developed using the second order terms of Taylor expansion whereby design charts are provided which predict the twentyeight force coefficients for both aligned, and for varying amounts of journal misalignment. The resulting non-linear equations of motion are solved using a modified Newton-Raphson method whereby the whirl trajectories are obtained, thus providing a physical appreciation of the bearing characteristics under dynamically loaded conditions.

The effect of haem limitation and iron restriction on outer membrane proteins and on respiratory systems of non typable Haemophilus influenzae

The effects of haem limitation and iron restriction on cells of non typable Haemophilus influenzae were investigated. Haem limitation was achieved by adding concentrations of haem to growth media which resulted in substantial decreases in final cell yields. Iron restriction was achieved by substituting protoporphyrin IX (PPIX) for haem in the growth medium and adding an iron chelator to the system. The effect of these nutrient limitations on a) outer membrane composition, and b) respiratory systems of non typable H.influenzae was investigated. Several of the strains examined produced new PPIX-specific outer membrane proteins when cultured utilising PPIX as a porphyrin source. The immune response of patients with bronchiectasis to outer membrane antigens of H.influenzae cultured under iron-restricted conditions was analysed by ELISA and immunoblotting techniques. ELISA analysis revealed that individuals with severe bronchiectasis had high titres of antibodies directed against H.influenzae OMs in both serum and sputum. Immunoblotting with homologous serum showed that where PPIX-specific OMPs were produced they were antigenic and were recognised by patients' serum. This suggested that these H.influenzae OMPs may be expressed in vivo. Additionally, the development of the immune responses to non typable H.influenzae outer membrane antigens was investigated using a rat lung model. Bacteria encased in agar beads were inoculated intratracheally into rat lungs, infection was established, and the immune response monitored for 6 weeks. The animals developed antibodies to PPIX-specific OMPs during the course of infection, providing further evidence that H.influenzae express these novel OMP antigens when growing in vivo. Studies in vitro on respiratory systems of phenotypically altered H.influenzae showed that bacteria grown utilising PPIX as a porphyrin source, or under conditions of iron-restriction produced ten fold fewer cytochromes than cells grown in nutrient excess, while haem limited H.influenzae produced no detectable cytochromes. Respiration of various substrates was depressed in haem limited and in PPIX-grown cultures as compared with cells grown in nutrient excess.

Influence of microbial antigen formulation and delivery route on the immune response

Recent technological advances have resulted in the production of safe subunit and synthetic small peptide vaccines. Unfortunately, these vaccines are weakly or non-immunogenic in the absence of an immunological adjuvant (agents that can induce strong immunity to antigens). In addition, in order to prevent and/or control infection at the mucosal surface, stimulation of the mucosal immune system is essential. This may be achieved via the common mucosal immune system by exposure to antigen at a mucosal surface remote from the area of infection. Initial studies investigated the potential of multiple emulsions in effecting oral absorption and the subsequent immune responses to a lipopolysaccharide vaccine (LPS) after immunisation. Nasal delivery of LPS was carried out in parallel work using either aqueous solution or gel formulations. Tetanus toxoid vaccine in simple solution was delivered to guinea pigs as free antigen or entrapped in DSPC liposomes. In addition, adsorbed tetanus toxoid vaccine was delivered nasally free or in an aerosil gel formulation. This work was extended to investigate guinea pigs immunised by various mucosal routes with a herpes simplex virus subunit vaccine prepared from virus infected cells and delivered in gels, multiple emulsions and liposomes. Comparable serum antibody responses resulted but failed to produce enhanced protection against vaginal challenge when compared to subcutaneous immunisation with alhydrogel adjuvanted vaccine. Thus, immunisation of the mucosal surface by these methods may have been inadequate. These studies were extended in an attempt to protect against HSV genital challenge by construction of an attenuated Salmonella typhimurium HWSH aroA mutant expressing a cloned glycoprotein D-l gene fused to the Es-cherichia coli lac z promoter. Preliminary work on the colonisation of guinea pigs with S. typhimurium HWSH aroA mutants were carried out, with the aim of using the guinea pig HSV vaginal model to investigate protection.

Ocular response to silicone-hydrogel contact lenses

The thesis investigates the ocular response to silicone-hydrogel (SiH) contact lens wear, a relatively new contact lens material that has a higher modulus of rigidity and different surface coating than used in conventional hydrogel materials. The properties of SiH materials differ significantly from conventional hydrogels and, using subjective and objective means of assessment, the thesis examines how these properties affect reflection and biometry, ocular physiology, tear film characteristics, symptomatology, adverse events and complications. A range of standard and newly designed investigative techniques were employed, and latter involving novel imaging techniques, for the objective assessment of physiological changes which occur with contact lens wear. The study is the first to combine these techniques with biochemical analyses of the tear film composition. Forty-seven subjects were fitted with SiH lenses and randomly allocated to one of the two materials currently on the market (Lotrafilcon A or Balafilcon A) on an either daily or continuous wear basis. An additional control group of 14 age-matched non-contact lens wearers were monitored over the same period. Measurements were taken before and 1, 3, 6, 12 and 18 months after initial fitting. The findings reported in this thesis will enable contact lens practitioners and manufacturers to understand further the optical, physiological and biochemical nature of the ocular response to SiH contact lenses and hence facilitate the development of this important generation of contact lens material.