Ministry emphasises quality of medical training

One proposed mechanism of tumour escape from immune surveillance is tumour up-regulation of the cell surface ligan FasL, whichcan lead to apoptosis of Fas receptor (Fas) positive lymphocytes. Based upon this `coun-- rattack', we have developed a mathematical model inelAin tumour cell--lymphocyte ineA-- ction cell surface expression of Fas/FasL,an d their secreted soluble forms. The model predicts that (a) the production of soluble forms of Fas an d FasL will lead to thedown regulation of theimmun respon --fi (b) matrix metallopr otein se (MMP)ink'PTfiA ion should lead toin'x# sed membran FasLan result in a higher rate of Fas-mediated apoptosis for lymphocytesthan for tumour cells. Recen studieson can--# patient len support for theseprediction s. TheclinP-- l implication are two-fold. Firstly, the use of broad spectrum MMPin'#x tors asan`fi-- n`fi--'` cagenP may be compromised by their adverse e#ecton tumour FasL up-regulation Also, Fas/FasL insL action may havean impact on the outcome ofnA--x`#B onA in immunBB`fiAw`P-- ic trialssin` the finA common pathway of all these approaches is thetran - duction of deathsign-- swithin the tumour cell

Magnitude effects for experienced rewards at short delays in the escalating interest task

A first-person shooter video game was adapted for the study of choice between smaller sooner and larger later rewards. Participants chose when to fire a weapon that increased in damage potential over a short interval. When the delay to maximum damage was shorter (5 – 8 s), people showed greater sensitivity to the consequences of their choices than when the delay was longer (17 – 20 s). Participants also evidenced a magnitude effect by waiting proportionally longer when the damage magnitudes were doubled for all rewards. The experiment replicated the standard magnitude effect with this new video game preparation over time scales similar to those typically used in nonhuman animal studies and without complications due to satiation or cost

The Broadband XMM-Newton and NuSTAR X-ray Spectra of Two Ultraluminous X-ray Sources in the Galaxy IC 342

We present results for two Ultraluminous X-ray Sources (ULXs), IC 342 X-1 and IC 342 X-2, using two epochs of XMM-Newton and NuSTAR observations separated by $\sim$7 days. We observe little spectral or flux variability above 1 keV between epochs, with unabsorbed 0.3--30 keV luminosities being $1.04^{+0.08}_{-0.06} \times 10^{40}$ erg s$^{-1}$ for IC 342 X-1 and $7.40\pm0.20 \times 10^{39}$ erg s$^{-1}$ for IC 342 X-2, so that both were observed in a similar, luminous state. Both sources have a high absorbing column in excess of the Galactic value. Neither source has a spectrum consistent with a black hole binary in low/hard state, and both ULXs exhibit strong curvature in their broadband X-ray spectra. This curvature rules out models that invoke a simple reflection-dominated spectrum with a broadened iron line and no cutoff in the illuminating power-law continuum. X-ray spectrum of IC 342 X-1 can be characterized by a soft disk-like black body component at low energies and a cool, optically thick Comptonization continuum at high energies, but unique physical interpretation of the spectral components remains challenging. The broadband spectrum of IC 342 X-2 can be fit by either a hot (3.8 keV) accretion disk, or a Comptonized continuum with no indication of a seed photon population. Although the seed photon component may be masked by soft excess emission unlikely to be associated with the binary system, combined with the high absorption column, it is more plausible that the broadband X-ray emission arises from a simple thin blackbody disk component. Secure identification of the origin of the spectral components in these sources will likely require broadband spectral variability studies.Comment: 12 pages, 11 figures, 5 Tables, Accepted for publication in The Astrophysical Journa

The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette-Guérin immunization.

Bacille Calmette-Guérin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n = 53) and cellular (n = 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml(-1) [3300-11 050] in cord blood) and six weeks (0.00 ng ml(-1) [0-288]). Frequencies of PPD-specific IFN-γ-expressing CD4(+)T cells increased at one week and declined between one and six weeks (p = 0.031). Frequencies of IL-2- and TNF-α-expressing PPD-specific CD4(+)T cells increased between one and six weeks (p = 0.019, p = 0.009, respectively). At one week, the frequency of PPD-specific CD4(+)T cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses (p = 0.002) and after adjusting for confounders (mean difference, 95% CI -0.041% (-0.082, -0.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCG immunization. These findings are being explored further in a larger study

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant

Anticipating the prevalence of avian influenza subtypes H9 and H5 in live-bird markets.

An ability to forecast the prevalence of specific subtypes of avian influenza viruses (AIV) in live-bird markets would facilitate greatly the implementation of preventative measures designed to minimize poultry losses and human exposure. The minimum requirement for developing predictive quantitative tools is surveillance data of AIV prevalence sampled frequently over several years. Recently, a 4-year time series of monthly sampling of hemagglutinin subtypes 1–13 in ducks, chickens and quail in live-bird markets in southern China has become available. We used these data to investigate whether a simple statistical model, based solely on historical data (variables such as the number of positive samples in host X of subtype Y time t months ago), could accurately predict prevalence of H5 and H9 subtypes in chickens. We also examined the role of ducks and quail in predicting prevalence in chickens within the market setting because between-species transmission is thought to occur within markets but has not been measured. Our best statistical models performed remarkably well at predicting future prevalence (pseudo-R2 = 0.57 for H9 and 0.49 for H5), especially considering the multi-host, multi-subtype nature of AIVs. We did not find prevalence of H5/H9 in ducks or quail to be predictors of prevalence in chickens within the Chinese markets. Our results suggest surveillance protocols that could enable more accurate and timely predictive statistical models. We also discuss which data should be collected to allow the development of mechanistic models.published_or_final_versio

Paschen-alpha Emission in the Gravitationally Lensed Galaxy SMM J163554.2+661225

We report the detection of the Paschen-alpha emission line in the z=2.515 galaxy SMM J163554.2+661225 using Spitzer spectroscopy. SMM J163554.2+661225 is a sub-millimeter-selected infrared (IR)-luminous galaxy maintaining a high star-formation rate (SFR), with no evidence of an AGN from optical or infrared spectroscopy, nor X-ray emission. This galaxy is lensed gravitationally by the cluster Abell 2218, making it accessible to Spitzer spectroscopy. Correcting for nebular extinction derived from the H-alpha and Pa-alpha lines, the dust-corrected luminosity is L(Pa-alpha) = (2.57+/-0.43) x 10^43 erg s^-1, which corresponds to an ionization rate, Q = (1.6+/-0.3) x 10^55 photons s^-1. The instantaneous SFR is 171+/-28 solar masses per year, assuming a Salpeter-like initial mass function. The total IR luminosity derived using 70, 450, and 850 micron data is L(IR) = (5-10) x 10^11 solar luminosities, corrected for gravitational lensing. This corresponds to a SFR=90-180 solar masses per year, where the upper range is consistent with that derived from the Paschen-alpha luminosity. While the L(8 micron) / L(Pa-alpha) ratio is consistent with the extrapolated relation observed in local galaxies and star-forming regions, the rest-frame 24 micron luminosity is significantly lower with respect to local galaxies of comparable Paschen-alpha luminosity. Thus, SMM J163554.2+661225 arguably lacks a warmer dust component (T ~ 70 K), which is associated with deeply embedded star formation, and which contrasts with local galaxies with comparable SFRs. Rather, the starburst is consistent with star-forming local galaxies with intrinsic luminosities, L(IR) ~ 10^10 solar luminosities, but "scaled-up" by a factor of 10-100.Comment: Published in the Astrophysical Journal. 14 pages in emulateapj format, 9 figures (many in color

The analysis of European lacquer : optimization of thermochemolysis temperature of natural resins

In order to optimize chromatographic analysis of European lacquer, thermochemolysis temperature was evaluated for the analysis of natural resins. Five main ingredients of lacquer were studied: sandarac, mastic, colophony, Manila copal and Congo copal. For each, five temperature programs were tested: four fixed temperatures (350, 480, 550, 650 degrees C) and one ultrafast thermal desorption (UFD), in which the temperature rises from 350 to 660 degrees C in 1 min. In total, the integrated signals of 27 molecules, partially characterizing the five resins, were monitored to compare the different methods. A compromise between detection of compounds released at low temperatures and compounds formed at high temperatures was searched. 650 degrees C is too high for both groups, 350 degrees C is best for the first, and 550 degrees C for the second. Fixed temperatures of 480 degrees C or UFD proved to be a consensus in order to detect most marker molecules. UFD was slightly better for the molecules released at low temperatures, while 480 degrees C showed best compounds formed at high temperatures

A theory-based online health behaviour intervention for new university students (U@Uni): results from a randomised controlled trial

BACKGROUND Too few young people engage in behaviours that reduce the risk of morbidity and premature mortality, such as eating healthily, being physically active, drinking sensibly and not smoking. This study sought to assess the efficacy and cost-effectiveness of a theory-based online health behaviour intervention (based on self-affirmation theory, the Theory of Planned Behaviour and implementation intentions) targeting these behaviours in new university students, in comparison to a measurement-only control. METHODS Two-weeks before starting university all incoming undergraduates at the University of Sheffield were invited to take part in a study of new students' health behaviour. A randomised controlled design, with a baseline questionnaire, and two follow-ups (1 and 6 months after starting university), was used to evaluate the intervention. Primary outcomes were measures of the four health behaviours targeted by the intervention at 6-month follow-up, i.e., portions of fruit and vegetables, metabolic equivalent of tasks (physical activity), units of alcohol, and smoking status. RESULTS The study recruited 1,445 students (intervention n = 736, control n = 709, 58% female, Mean age = 18.9 years), of whom 1,107 completed at least one follow-up (23% attrition). The intervention had a statistically significant effect on one primary outcome, smoking status at 6-month follow-up, with fewer smokers in the intervention arm (8.7%) than in the control arm (13.0%; Odds ratio = 1.92, p = .010). There were no significant intervention effects on the other primary outcomes (physical activity, alcohol or fruit and vegetable consumption) at 6-month follow-up. CONCLUSIONS The results of the RCT indicate that the online health behaviour intervention reduced smoking rates, but it had little effect on fruit and vegetable intake, physical activity or alcohol consumption, during the first six months at university. However, engagement with the intervention was low. Further research is needed before strong conclusions can be made regarding the likely effectiveness of the intervention to promote health lifestyle habits in new university students. TRIAL REGISTRATION Current Controlled Trials, ISRCTN67684181