Functional brain maps of Tower of London performance : a positron emission tomography and functional magnetic resonance imaging study

Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD) contrasts represent different physiological measures of brain activation. The present study aimed to compare two functional brain imaging techniques (functional magnetic resonance imaging versus [15O] positron emission tomography) when using Tower of London (TOL) problems as the activation task. A categorical analysis (task versus baseline) revealed a significant BOLD increase bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for the cerebellum. A parametric haemodynamic response model (or regression analysis) confirmed a task-difficulty-dependent increase of BOLD and rCBF for the cerebellum and the left dorsolateral prefrontal cortex. In line with previous studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also detected for the premotor cortex, cingulate, precuneus, and globus pallidus. These results imply consistency across the two neuroimaging modalities, particularly for the assessment of prefrontal brain function when using a parametric TOL adaptation.

Exploration of the fundamental equilibrium behaviour of calcium exchange with weak acid cation resins

This study evaluated the complexity of calcium ion exchange with sodium exchanged weak acid cation resin (DOW MAC-3). Exchange equilibria recorded for a range of different solution normalities revealed profiles which were represented by conventional “L” or “H” type isotherms at low values of equilibrium concentration (Ce) of calcium ions, plus a superimposed region of increasing calcium uptake was observed at high Ce values. The loading of calcium ions was determined to be ca. 53.5 to 58.7 g/kg of resin when modelling only the sorption curve created at low Ce values,which exhibited a well-defined plateau. The calculated calcium ion loading capacity for DOWMAC-3 resin appeared to correlate with the manufacturer's recommendation. The phenomenon of super equivalent ion exchange (SEIX) was observed when the “driving force” for the exchange process was increased in excess of 2.25 mmol calcium ions per gram of resin in the starting solution. This latter event was explained in terms of displacement of sodium ions from sodium hydroxide solution which remained in the resin bead following the initial conversion of the as supplied “H+” exchanged resin sites to the “Na+” version required for softening studies. Evidence for hydrolysis of a small fraction of the sites on the sodium exchanged resin surface was noted. The importance of carefully choosing experimental parameters was discussed especially in relation to application of the Langmuir–Vageler expression. This latter model which compared the ratio of the initial calcium ion concentration in solution to resin mass, versus final equilibrium loading of the calcium ions on the resin; was discovered to be an excellent means of identifying the progress of the calcium–sodium ion exchange process. Moreover, the Langmuir–Vageler model facilitated standardization of various calcium–sodium ion exchange experiments which allowed systematic experimental design.

Autologous human kidney proximal tubule epithelial cells (PTEC) modulate dendritic cell (DC), T cell and B cell responses

This is a comprehensive study of human kidney proximal tubular epithelial cells (PTEC) which are known to respond to and mediate the pathological process of a range of kidney diseases. It identifies various molecules expressed by PTEC and how these molecules participate in down-regulating the inflammatory process, thereby highlighting the clinical potential of these molecules to treat various kidney diseases. In the disease state, PTEC gain the ability to regulate the immune cell responses present within the interstitium. This down-regulation is a complex interaction of contact dependent/independent mechanisms involving various immuno-regulatory molecules including PD-L1, sHLA-G and IDO. The overall outcome of this down-regulation is suppressed DC maturation, decreased number of antibody producing B cells and low T cell responses. These manifestations within a clinical setting are expected to dampen the ongoing inflammation, preventing the damage caused to the kidney tissue.

Do instructional attributes pose multicollinearity problems? An empirical exploration

It is commonly perceived that variables ‘measuring’ different dimensions of teaching (construed as instructional attributes) used in student evaluation of teaching (SET) questionnaires are so highly correlated that they pose a serious multicollinearity problem for quantitative analysis including regression analysis. Using nearly 12000 individual student responses to SET questionnaires and ten key dimensions of teaching and 25 courses at various undergraduate and postgraduate levels for multiple years at a large Australian university, this paper investigates whether this is indeed the case and if so under what circumstances. This paper tests this proposition first by examining variance inflation factors (VIFs), across courses, levels and over time using individual responses; and secondly by using class averages. In the first instance, the paper finds no sustainable evidence of multicollinearity. While, there were one or two isolated cases of VIFs marginally exceeding the conservative threshold of 5, in no cases did the VIFs for any of the instructional attributes come anywhere close to the high threshold value of 10. In the second instance, however, the paper finds that the attributes are highly correlated as all the VIFs exceed 10. These findings have two implications: (a) given the ordinal nature of the data ordered probit analysis using individual student responses can be employed to quantify the impact of instructional attributes on TEVAL score; (b) Data based on class averages cannot be used for probit analysis. An illustrative exercise using level 2 undergraduate courses data suggests higher TEVAL scores depend first and foremost on improving explanation, presentation, and organization of lecture materials.

Can perceptual indices estimate physiological strain across a range of environments and metabolic workloads when wearing explosive ordnance disposal and chemical protective clothing?

Objective Explosive ordnance disposal (EOD) often requires technicians to wear multiple protective garments in challenging environmental conditions. The accumulative effect of increased metabolic cost coupled with decreased heat dissipation associated with these garments predisposes technicians to high levels of physiological strain. It has been proposed that a perceptual strain index (PeSI) using subjective ratings of thermal sensation and perceived exertion as surrogate measures of core body temperature and heart rate, may provide an accurate estimation of physiological strain. Therefore, this study aimed to determine if the PeSI could estimate the physiological strain index (PSI) across a range of metabolic workloads and environments while wearing heavy EOD and chemical protective clothing. Methods Eleven healthy males wore an EOD and chemical protective ensemble while walking on a treadmill at 2.5, 4 and 5.5 km·h− 1 at 1% grade in environmental conditions equivalent to wet bulb globe temperature (WBGT) 21, 30 and 37 °C. WBGT conditions were randomly presented and a maximum of three randomised treadmill walking trials were completed in a single testing day. Trials were ceased at a maximum of 60-min or until the attainment of termination criteria. A Pearson's correlation coefficient, mixed linear model, absolute agreement and receiver operating characteristic (ROC) curves were used to determine the relationship between the PeSI and PSI. Results A significant moderate relationship between the PeSI and the PSI was observed [r = 0.77; p < 0.001; mean difference = 0.8 ± 1.1 a.u. (modified 95% limits of agreement − 1.3 to 3.0)]. The ROC curves indicated that the PeSI had a good predictive power when used with two, single-threshold cut-offs to differentiate between low and high levels of physiological strain (area under curve: PSI three cut-off = 0.936 and seven cut-off = 0.841). Conclusions These findings support the use of the PeSI for monitoring physiological strain while wearing EOD and chemical protective clothing. However, future research is needed to confirm the validity of the PeSI for active EOD technicians operating in the field.

Different correlation of Sphingosine-1-Phosphate receptor 1 with receptor activator of nuclear factor kappa B ligand and regulatory T cells in rat periapical lesions

Introduction Sphingosine-1-phosphate receptor 1 (S1P1) is crucial for regulation of immunity and bone metabolism. This study aimed to investigate the expression of S1P1 in rat periapical lesions and its relationship with receptor activator of nuclear factor kappa B ligand (RANKL) and regulatory T (Treg) cells. Methods Periapical lesions were induced by pulp exposure in the first lower molars of 55 Wistar rats. Thirty rats were killed on days 0, 7, 14, 21, 28, and 35, and their mandibles were harvested for x-ray imaging, micro–computed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. The remaining 25 rats were killed on days 0, 14, 21, 28, and 35, and mandibles were harvested for flow cytometry. Results The volume and area of the periapical lesions increased from day 0 to day 21 and then remained comparably stable after day 28. S1P1-positive cells were observed in the inflammatory periapical regions; the number of S1P1-positive cells peaked at day 14 and then decreased from day 21 to day 35. The distribution of S1P1-positive cells was positively correlated with the dynamics of RANKL-positive cells but was negatively correlated with that of Treg cells. Conclusions S1P1 expression was differentially correlated with RANKL and Treg cell infiltration in the periapical lesions and is therefore a contributing factor to the pathogenesis of such lesions.

Association between single-nucleotide polymorphisms in growth factor genes and quality of life in men with prostate cancer and the general population

Purpose Improved survival for men with prostate cancer has led to increased attention to factors influencing quality of life (QOL). As protein levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) have been reported to be associated with QOL in people with cancer, we sought to identify whether single-nucleotide polymorphisms (SNPs) of these genes were associated with QOL in men with prostate cancer. Methods Multiple linear regression of two data sets (including approximately 750 men newly diagnosed with prostate cancer and 550 men from the general population) was used to investigate SNPs of VEGF and IGF-1 (10 SNPs in total) for associations with QOL (measured by the SF-36v2 health survey). Results Men with prostate cancer who carried the minor ‘T’ allele for IGF-1 SNP rs35767 had higher mean Role-Physical scale scores (≥0.3 SD) compared to non-carriers (p < 0.05). While this association was not identified in men from the general population, one IGF-1 SNP rs7965399 was associated with higher mean Bodily Pain scale scores in men from the general population that was not found in men with prostate cancer. Men from the general population who carried the rare ‘C’ allele had higher mean Bodily Pain scale scores (≥0.3 SD) than non-carriers (p < 0.05). Conclusions Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes. Future research may identify biomarkers associated with increased risk of poor QOL that could assist in the provision of pre-emptive support for those identified at risk.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Pituitary volume and early treatment response in drug-naïve first-episode psychosis patients

BACKGROUND: An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome. However, factors that predict treatment response are not well understood. The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis (FEP) patients. METHODS: We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate. Logistic regression was used to examine predictors of treatment response. Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial. RESULTS: Larger pituitary volume was associated with less improvement in overall psychotic symptoms (Brief Psychiatric Rating Scale (BPRS) P=0.031) and positive symptoms (BPRS positive symptom subscale P=0.010). Regardless of gender, patients with a pituitary volume at the 25th percentile (413 mm(3)) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile (635 mm(3)) (odds ratio=3.07, CI: 0.90-10.48). CONCLUSION: The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis. Potential implications for treatment strategies in early psychosis are discussed.

Size-resolved particle distribution and gaseous concentrations by real-world road tunnel measurement

Measurements of aerosol particle number size distributions (15-700 nm), CO and NOx were performed in a bus tunnel, Australia. Daily mean particle size distributions of mixed diesel/CNG (Compressed Natural Gas) buses traffic flow were determined in 4 consecutive measurement days. EFs (Emission Factors) of Particle size distribution of diesel buses and CNG buses were obtained by MLR (Multiple Linear Regression) methods, particle distributions of diesel buses and CNG buses were observed as single accumulation mode and nuclei-mode separately. Particle size distributions of mixed traffic flow were decomposed by two log-normal fitting curves for each 30 minutes interval mean scans, all the mix fleet PSD emission can be well fitted by the summation of two log-normal distribution curves, and these were composed of nuclei mode curve and accumulation curve, which were affirmed as the CNG buses and diesel buses PN emission curves respectively. Finally, particle size distributions of diesel buses and CNG buses were quantified by statistical whisker-box charts. For log-normal particle size distribution of diesel buses, accumulation mode diameters were 74.5～87.5nm, geometric standard deviations were 1.89～1.98. As to log-normal particle size distribution of CNG buses, nuclei-mode diameters were 21～24 nm, geometric standard deviations were 1.27～1.31.

B-adrenoceptor determinants of contractility in the human heart: The role of phosphodiesterase enzymes

This thesis investigated how enzymes called phosphodiesterases control changes in contractility mediated by noradrenaline and adrenaline through activation of β1- and β2-adrenoceptors in live human heart tissue from patients with advanced heart failure undergoing transplantation. The study compared patients who had been administered β-blocker medicines metoprolol or carvedilol or no β-blocker treatment. This work helped to further elucidate the complex roles of target receptors and enzymes that are integral to the progression of heart failure, to compare the mechanisms of action of β-blockers currently used to manage heart failure and to identify new drug targets for heart failure treatment.

A computer-controlled hyperthermia system

Hyperthermia, raised temperature, has been used as a means of treating cancer for centuries. Hippocrates (400 BC) and Galen (200 BC) used red-hot irons to treat small tumours. Much later, after the Renaissance, there are many reports of spontaneous tumour regression in patients with fevers produced by erysipelas, malaria, smallpox, tuberculosis and influenza. These illnesses produce fevers of about 40 °C which last for several days. Temperatures of at least 40 °C were found to be necessary for tumour regression. Towards the end of the nineteenth century pyrogenic bacteria were injected into patients with cancer. In 1896, Coly used a mixture of erysipelas and B. prodigeosus, with some success...

Gender-specific differences of interaction between obesity and air pollution on stroke and cardiovascular diseases in Chinese adults from a high pollution range area: A large population based cross sectional study

Background Little information exists regarding the interaction effects of obesity with long-term air pollution exposure on cardiovascular diseases (CVDs) and stroke in areas of high pollution. The aim of the present study is to examine whether obesity modifies CVD-related associations among people living in an industrial province of northeast China. Methods We studied 24,845 Chinese adults, aged 18 to 74 years old, from three Northeastern Chinese cities in 2009 utilizing a cross-sectional study design. Body weight and height were measured by trained observers. Overweight and obesity were defined as a body mass index (BMI) between 25–29.9 and ≥ 30 kg/m2, respectively. Prevalence rate and related risk factors of cardiovascular and cerebrovascular diseases were investigated by a questionnaire. Three-year (2006–2008) average concentrations of particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxides (NO2), and ozone (O3) were measured by fixed monitoring stations. All the participants lived within 1 km of air monitoring sites. Two-level logistic regression (personal level and district-specific pollutant level) was used to examine these effects, controlling for covariates. Results We observed significant interactions between exposure and obesity on CVDs and stroke. The associations between annual pollutant concentrations and CVDs and stroke were strongest in obese subjects (OR 1.15–1.47 for stroke, 1.33–1.59 for CVDs), less strong in overweight subjects (OR 1.22–1.35 for stroke, 1.07–1.13 for CVDs), and weakest in normal weight subjects (OR ranged from 0.98–1.01 for stroke, 0.93–1.15 for CVDs). When stratified by gender, these interactions were significant only in women. Conclusions Study findings indicate that being overweight and obese may enhance the effects of air pollution on the prevalence of CVDs and stroke in Northeastern metropolitan China. Further studies will be needed to investigate the temporality of BMI relative to exposure and onset of disease.