Dependence of residual amplitude noise in electro-optic phase modulators on the intensity distribution of the incident field

Our results demonstrate that photorefractive residual amplitude modulation (RAM) noise in electro-optic modulators (EOMs) can be reduced by modifying the incident beam intensity distribution. Here we report an order of magnitude reduction in RAM when beams with uniform intensity (flat-top) profiles, generated with an LCOS-SLM, are used instead of the usual fundamental Gaussian mode (TEM00). RAM arises from the photorefractive amplified scatter noise off the defects and impurities within the crystal. A reduction in RAM is observed with increasing intensity uniformity (flatness), which is attributed to a reduction in space charge field on the beam axis. The level of RAM reduction that can be achieved is physically limited by clipping at EOM apertures, with the observed results agreeing well with a simple model. These results are particularly important in applications where the reduction of residual amplitude modulation to 10^-6 is essential.

Do drinking and riding mix? Effects of legal doses of alcohol on balance ability in experienced motorcyclists

The appropriateness of applying drink driving legislation to motorcycle riding has been questioned as there may be fundamental differences in the effects of alcohol on these two activities. For example, while the distribution of blood alcohol content (BAC) levels among fatally injured male drivers compared to riders is similar, a greater proportion of motorcycle fatalities involve levels in the lower (0 to .10% BAC) range. Several psychomotor and higher-order cognitive skills underpinning riding performance appear to be significantly influenced by low levels of alcohol. For example, at low levels (.02 to .046% BAC), riders show significant increases in reaction time to hazardous stimuli, inattention to the riding task, performance errors such as leaving the roadway and a reduced ability to complete a timed course. It has been suggested that alcohol may redirect riders’ focus from higher-order cognitive skills to more physical skills such as maintaining balance. As part of a research program to investigate the potential benefits of introducing a zero, or reduced, BAC for all riders in Queensland regardless of their licence status, the effects of low doses of alcohol on balance ability were investigated in a laboratory setting. The static balance of ten experienced riders was measured while they performed either no secondary task, a visual search task, or a cognitive (arithmetic) task following the administration of alcohol (0; 0.02, and 0.05% BAC). Subjective ratings of intoxication and balance impairment increased in a dose-dependent manner; however, objective measures of static balance were negatively affected only at the .05% BAC dose. Performance on a concurrent secondary visual search task, but not a purely cognitive (arithmetic) task, improved postural stability across all BAC levels. Finally, the .05% BAC dose was associated with impaired performance on the cognitive (arithmetic) task, but not the visual search task, when participants were balancing, but neither task was impaired by alcohol when participants were standing on the floor. Implications for road safety and future ‘drink riding’ policy considerations are discussed.

Low formalin concentrations induce fine-tuned responses that are sex and age-dependent : a developmental study

The formalin test is increasingly applied as a model of inflammatory pain using high formalin concentrations (5–15%). However, little is known about the effects of low formalin concentrations on related behavioural responses. To examine this, rat pups were subjected to various concentrations of formalin at four developmental stages: 7, 13, 22, and 82 days of age. At postnatal day (PND) 7, sex differences in flinching but not licking responses were observed with 0.5% formalin evoking higher flinching in males than in females. A dose response was evident in that 0.5% formalin also produced higher licking responses compared to 0.3% or 0.4% formalin. At PND 13, a concentration of 0.8% formalin evoked a biphasic response. At PND 22, a concentration of 1.1% evoked higher flinching and licking responses during the late phase (10–30 min) in both males and females. During the early phase (0–5 min), 1.1% evoked higher licking responses compared to 0.9% or 1% formalin. 1.1% formalin produced a biphasic response that was not evident with 0.9 or 1%. At PND 82, rats displayed a biphasic pattern in response to three formalin concentrations (1.25%, 1.75% and 2.25%) with the presence of an interphase for both 1.75% and 2.25% but not for 1.25%. These data suggest that low formalin concentrations induce fine-tuned responses that are not apparent with the high formalin concentration commonly used in the formalin test. These data also show that the developing nociceptive system is very sensitive to subtle changes in formalin concentrations.

Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis

Quantity and timing of protein ingestion are major factors regulating myofibrillar protein synthesis (MPS). However, the effect of specific ingestion patterns on MPS throughout a 12 h period is unknown. We determined how different distributions of protein feeding during 12 h recovery after resistance exercise affects anabolic responses in skeletal muscle. Twenty-four healthy trained males were assigned to three groups (n = 8/group) and undertook a bout of resistance exercise followed by ingestion of 80 g of whey protein throughout 12 h recovery in one of the following protocols: 8 × 10 g every 1.5 h (PULSE); 4 × 20 g every 3 h (intermediate: INT); or 2 × 40 g every 6 h (BOLUS). Muscle biopsies were obtained at rest and after 1, 4, 6, 7 and 12 h post exercise. Resting and post-exercise MPS (l-[ring-(13)C6] phenylalanine), and muscle mRNA abundance and cell signalling were assessed. All ingestion protocols increased MPS above rest throughout 1-12 h recovery (88-148%, P < 0.02), but INT elicited greater MPS than PULSE and BOLUS (31-48%, P < 0.02). In general signalling showed a BOLUS>INT>PULSE hierarchy in magnitude of phosphorylation. MuRF-1 and SLC38A2 mRNA were differentially expressed with BOLUS. In conclusion, 20 g of whey protein consumed every 3 h was superior to either PULSE or BOLUS feeding patterns for stimulating MPS throughout the day. This study provides novel information on the effect of modulating the distribution of protein intake on anabolic responses in skeletal muscle and has the potential to maximize outcomes of resistance training for attaining peak muscle mass.

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

Better understanding of food material on the basis of water distribution using Thermogravimetric analysis

The prime objective of drying is to enhance shelf life of perishable food materials. As the process is very energy intensive in nature, researchers are trying to minimise energy consumption in the drying process. In order to determine the exact amount of energy needed for drying a food product, understanding the physics of moisture distribution and bond strength of water within the food material is essential. In order understand the critical moisture content, moisture distribution and water bond strength in food material, Thermogravimetric analysis (TGA) can be properly utilised. This work has been conducted to investigate moisture distribution and water bond strength in selected food materials; apple, banana and potato. It was found that moisture distribution and water bond strength influence moisture migration from the food materials. In addition, proportion of different types of water (bound, free, surface water) has been simply identified using TGA. This study provides a better understanding of water contents and its role in drying rate and energy consumption.

Platinum-based chemotherapy in metastatic breast cancer : current status

Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently ∼60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer. © 2003 Elsevier Ltd. All rights reserved.

A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma

Background: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2-deoxyuridine-5- monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of I mM for six or more hours, significantly enhances the efficacy of 5-FU. Patients and methods: 5-FU/FA was given as follows: days 1 and 2 - FA 250 mg/m 2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m 2 by intravenous bolus (ivb) over 15 minutes and subsequently 5-FU 400 mg/m 2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g ivb over 15 minutes followed by 12 g ivi over 12 hours. Results: Thirty patients were entered into the study. Median survival was nine months (range 1-51 + months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. Conclusion: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m 2. Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m 2, the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m 2. Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m 2 and grade 2 in two, one who received a cumulative dose of 960 mg m 2 and the other a cumulative dose of 600 mg m 2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m 2. Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard non-anthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m 2, we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated. © 2002 Cancer Research UK.

Characteristics of nontuberculous mycobacteria from a municipal water distribution system and their relevance to human infections

This thesis documented pathogenic species of nontuberculous mycobacteria in the Brisbane water distribution system. When water and shower aerosol strains were compared with human strains of mycobacteria, the study found that the likelihood of acquiring infection from municipal water was specific for four main species. The method for isolation of mycobacteria from water was refined, followed by sampling from 220 sites across Brisbane. A variety of species (incl 15 pathogens) were identified and genotypically compared to human strains. For M. abscessus and M. lentiflavum, water strains clustered with human strains. Pathogenic strains of M. kansasii were found, though non-pathogenic strains dominated. Waterborne strains of M. fortuitum differed to human strains. Extensive home sampling of 20 patients with NTM disease, supported the theory that the risk of acquiring NTM from water or shower aerosols appears species specific for M. avium, M. kansasii, M. lentiflavum and M. abscessus.

Gemcitabine and paclitaxel associated pneumonitis in non-small cell lung cancer : report of a phase I/II dose-escalating study

The aim of this phase I/II dose escalating study was to establish the maximum tolerated dose (MTD) of gemcitabine and paclitaxel given in combination in non-small cell lung cancer (NSCLC). 12 patients with stage IIIB and IV NSCLC received paclitaxel administered intravenously over 1 h followed by gemcitabine given over 30 min on days 1, 8 and 15 every 28 days. Pneumonitis was the principal side-effect observed with 4 patients affected. Of these, 1 experienced grade 3 toxicity after one cycle of treatment and the others had grade 2 toxicity. All 4 cases responded to prednisolone. No other significant toxicities were observed. Of the 8 evaluable patients, 3 had a partial response and 2 had minor responses. The study was discontinued due to this dose-limiting toxicity. The combination of paclitaxel and gemcitabine shows promising antitumour activity in NSCLC, however, this treatment schedule may predispose to pneumonitis. (C) 2000 Elsevier Science Ltd.

Changes in the site distribution of common melanoma subtypes in Queensland, Australia over time: implications for public health campaigns

Abstract BACKGROUND: An examination of melanoma incidence according to anatomical region may be one method of monitoring the impact of public health initiatives. OBJECTIVES:   To examine melanoma incidence trends by body site, sex and age at diagnosis or body site and morphology in a population at high risk. MATERIALS AND METHODS:   Population-based data on invasive melanoma cases (n = 51473) diagnosed between 1982 and 2008 were extracted from the Queensland Cancer Registry. Age-standardized incidence rates were calculated using the direct method (2000 world standard population) and joinpoint regression models were used to fit trend lines. RESULTS:   Significantly decreasing trends for melanomas on the trunk and upper limbs/shoulders were observed during recent years for both sexes under the age of 40 years and among males aged 40-59years. However, in the 60 and over age group, the incidence of melanoma is continuing to increase at all sites (apart from the trunk) for males and on the scalp/neck and upper limbs/shoulders for females. Rates of nodular melanoma are currently decreasing on the trunk and lower limbs. In contrast, superficial spreading melanoma is significantly increasing on the scalp/neck and lower limbs, along with substantial increases in lentigo maligna melanoma since the late 1990s at all sites apart from the lower limbs. CONCLUSIONS:   In this large study we have observed significant decreases in rates of invasive melanoma in the younger age groups on less frequently exposed body sites. These results may provide some indirect evidence of the impact of long-running primary prevention campaigns.

A novel real time pricing scheme for demand response in residential distribution systems

Price based technique is one way to handle increase in peak demand and deal with voltage violations in residential distribution systems. This paper proposes an improved real time pricing scheme for residential customers with demand response option. Smart meters and in-home display units are used to broadcast the price and appropriate load adjustment signals. Customers are given an opportunity to respond to the signals and adjust the loads. This scheme helps distribution companies to deal with overloading problems and voltage issues in a more efficient way. Also, variations in wholesale electricity prices are passed on to electricity customers to take collective measure to reduce network peak demand. It is ensured that both customers and utility are benefitted by this scheme.

Local stress-strain distribution and load transfer across cartilage matrix at micro-scale using combined microscopy-based finite element method

Articular cartilage is the load-bearing tissue that consists of proteoglycan macromolecules entrapped between collagen fibrils in a three-dimensional architecture. To date, the drudgery of searching for mathematical models to represent the biomechanics of such a system continues without providing a fitting description of its functional response to load at micro-scale level. We believe that the major complication arose when cartilage was first envisaged as a multiphasic model with distinguishable components and that quantifying those and searching for the laws that govern their interaction is inadequate. To the thesis of this paper, cartilage as a bulk is as much continuum as is the response of its components to the external stimuli. For this reason, we framed the fundamental question as to what would be the mechano-structural functionality of such a system in the total absence of one of its key constituents-proteoglycans. To answer this, hydrated normal and proteoglycan depleted samples were tested under confined compression while finite element models were reproduced, for the first time, based on the structural microarchitecture of the cross-sectional profile of the matrices. These micro-porous in silico models served as virtual transducers to produce an internal noninvasive probing mechanism beyond experimental capabilities to render the matrices micromechanics and several others properties like permeability, orientation etc. The results demonstrated that load transfer was closely related to the microarchitecture of the hyperelastic models that represent solid skeleton stress and fluid response based on the state of the collagen network with and without the swollen proteoglycans. In other words, the stress gradient during deformation was a function of the structural pattern of the network and acted in concert with the position-dependent compositional state of the matrix. This reveals that the interaction between indistinguishable components in real cartilage is superimposed by its microarchitectural state which directly influences macromechanical behavior.