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The accuracy and precision of high-energy spallation models are key issues for the design and development of new applications and experiments. We present a method to estimate model parameters and associated uncertainties by leveraging the Bayesian version of the Generalised Least Squares method, which enables us to incorporate prior knowledge on the parameter values. This approach is designed to adjust parameters based on experimental data, accounting for experimental uncertainty information, and providing uncertainties for all adjusted parameters. This approach is designed in order both to improve the accuracy of models through the modification of free parameters of these models, which results in a better reproduction of experimental data, and to estimate the uncertainties of these parameters and, by extension, their impacts on the model output. We aim at demonstrating the Generalised Least Square method can be applied in the case of Monte Carlo models. We present a proof-of-concept for Monte Carlo models in the specific case of nuclear physics with the model combination INCL/ABLA. We discuss the challenges in the application of this method to high-energy spallation models, notably the large runtime and the stochasticity of the models. Our results indicate this framework can also be applied to analogous situations where parameters of a computationally expensive Monte Carlo code should be inferred/improved. [ABSTRACT FROM AUTHOR]

AbstractObjectivesDesignResultsThis study tests a video intervention to reduce pregnancy smoking stigma among French healthcare students.The participants were randomly selected to watch online either an experimental video (presenting educational content regarding stigma and contact with pregnant smokers) or a control video (presenting standard educational content about the risks of smoking). The students completed scales assessing stigma, intention to address smoking cessation and self-efficacy to do so, before the intervention (T0, n = 252), one week after the intervention (T1, n = 187), and one month after the intervention (T2, n = 131).Compared to the medical students, especially men, the midwifery students reported lower derogative cognitions (η2p = .18), negative behaviours (η2p = .07) and personal distress (η2p = .06). However, the midwifery students also reported lower levels of intention to address smoking (η2p = .02) than the medical students. The experimental video decreased derogative cognitions to a greater extent than the control video (η2p = .23) in both the short and medium term. This study is the first intervention designed to reduce the stigmatisation of pregnant smokers by healthcare students. We recommend that the issue of stigma should receive more attention in the medical curriculum. [ABSTRACT FROM AUTHOR]

Immune senescence is a significant contributor to health problems in the developed world and may be accelerated by chronic viral infections. To date, there have been few studies of immune function in healthy older people in sub-Saharan Africa. We assessed T cell and B cell phenotypes and immune responses to CMV, EBV, and influenza virus in Malawians aged 20-69 y. Notably, the proportion of naive (CCR7+CD45RA+) CD4 and CD8 T cells was only 14% of the lymphoid repertoire even in donors aged under 30 y but did not decrease further with age. A small increase in the late differentiated (CD27-CD28-) CD8 T cell subpopulation was observed in older donors but the CD4/CD8 T cell ratio remained stable in all age groups. Interestingly, the regulatory (CD25hiFOXP3hi) T cell subpopulation was small in all age groups, and we observed no age-associated accumulation of cells expressing the senescence- and exhaustion-associated markers CD57 and PD-1. We assessed functional T cell responses to mitogenic and viral antigenic stimulation by the expression of CD154, IFN-γ, TNF-α, IL-2, and IL-17 and proliferation. All responses were robust across the life course, although we observed an age-associated shift from IFN-γ to TNF-α in the response to EBV. In summary, we found the naive T cell subpopulation of young adult Malawians was smaller than in their contemporaries in high-income settings but remains stable thereafter and that lymphocyte function is retained across the life course. These observations indicate that studies of the genetic and environmental factors influencing immune function in different environments may provide insights into minimizing immune ageing. [ABSTRACT FROM AUTHOR]

In the current set of experiments our goal was to test the hypothesis that individuals avoid courses of action based on a kind of metacognitive evaluation of demand in a Demand Selection Task (DST). Individuals in Experiment 1 completed a DST utilizing visual stimuli known to yield a dissociation between performance and perceived demand. Patterns of demand avoidance followed that of perceived demand. Experiment 2 provided a replication of the aforementioned results, in addition to demonstrating a second dissociation between a peripheral physiological measure of demand (i.e., blink rates) and demand avoidance. Experiment 3 directly tested the assumption that individuals make use of a general metacognitive evaluation of task demand during selections. A DST was utilized in a forced-choice paradigm that required individuals to either select the most effortful, time demanding, or least accurate of 2 choices. Patterns of selections were similar across all rating dimensions, lending credit to this notion. Findings are discussed within a metacognitive framework of demand avoidance and contrasted to current theories. [ABSTRACT FROM AUTHOR]

In normal hearts, myocardial perfusion is fairly well matched to regional metabolic demand, although both are distributed heterogeneously. Nonuniform regional metabolic vulnerability during coronary stenosis would help to explain nonuniform necrosis during myocardial infarction. In the present study, we investigated whether metabolismperfusion correlation diminishes during coronary stenosis, indicating increasing mismatch of regional oxygen supply to demand. Thirty anesthetized male pigs were studied: controls without coronary stenosis (n = 11); group I, left anterior descending (LAD) coronary stenosis leading to coronary perfusion pressure reduction to 70 mmHg (n = 6); group II, stenosis with perfusion pressure of about 35 mmHg (n = 6); and group III, stenosis with perfusion pressure of 45 mmHg combined with adenosine infusion (n = 7). [2-13C]- and [1,2-13C]acetate infusion was used to calculate regional O2 consumption from glutamate NMR spectra measured for multiple tissue samples of about 100 mg dry mass in the LAD region. Blood flow was measured with microspheres in the same regions. In control hearts without stenosis, regional oxygen extraction did not correlate with basal blood flow. Average myocardial O2 delivery and consumption decreased during coronary stenosis, but vasodilation with adenosine counteracted this. Regional oxygen extraction was on average decreased during stenosis, suggesting adaptation of metabolism to lower oxygen supply after half an hour of ischemia. Whereas regional O2 delivery correlated with O2 consumption in controls, this relation was progressively lost with graded coronary hypotension but partially reestablished by adenosine infusion. Therefore, coronary stenosis leads to heterogeneous metabolic stress indicated by decreasing regional O2 supply to demand matching in myocardium during partial coronary obstruction. [ABSTRACT FROM AUTHOR]

Background Excessive ethanol (Et OH) drinking is associated with white matter loss in the brain at all stages of life. Myelin-forming oligodendrocytes ( OLs) are a major component of white matter, but their involvement in Et OH-mediated white matter loss is unclear. Myelination continues throughout the life with highest rates during fetal development and adolescence. However, little is known about the effects of Et OH and its principal metabolite acetaldehyde ( ACD) on OLs at the cellular level. Methods We compared the responses to different concentrations of Et OH or ACD by primary OLs in culture. Results Et OH did not cause significant cell death at concentrations lower than 120 mM, even after 24 hours. In comparison, ACD was highly lethal at doses above 50 μM. High concentrations of Et OH (120 mM) and ACD (500 μM) for 24 hours did not reduce myelin in mature OLs. Myelin production and OL differentiation were significantly impaired by 7 days exposure to 500 or 50 μM ACD but not 120 mM EtOH. Conclusions This study shows that OLs are relatively resistant to Et OH, even at a concentration more than 4 times the typical blood Et OH concentrations associated with social drinking (10 to 30 mM). In contrast, OLs are much more sensitive to ACD than Et OH, particularly with long-term exposure. This suggests that part of white matter loss in response to Et OH, especially during high rates of myelin formation, may be due in part to the effects of its principal metabolite ACD. [ABSTRACT FROM AUTHOR]

Organizational states of turbulence are identified through novel analysis of large scale pipe flow experiments at a Reynolds number of 35 000. The distinct states are revealed by an azimuthal decomposition of the two-point spatial correlation of the streamwise velocity fluctuation. States with dominant azimuthal wave numbers corresponding to kϑ = 2,3,4,5,6 are discovered and their structure revealed as a series of alternately rotating quasistreamwise vortices. Such organizational states are highly reminiscent of the nonlinear traveling wave solutions previously identified at Reynolds numbers an order of magnitude lower. [ABSTRACT FROM AUTHOR]

The UK has seen periodic attempts to develop large district heating (DH) networks to make use of residual heat from industry and power generation. Under concerns about climate change and energy security, DH has recently re-emerged in policy visions for future heat systems with small decentralised combined heat and power (CHP) generators playing a key role in the establishment of such networks. This paper draws on Stewart Russell's accounts of earlier DH programmes, asking to what extent the reasons he concluded CHP and DH were systematically excluded continue to marginalise the technologies. In spite of governance changes which ostensibly open new opportunities for experimentation, key structural issues challenge the development of decentralised energy, particularly the alignment of the electricity sector to a centralised system and the dependency of local governments with limited capacity on central government. The reluctance of central government to engage in system planning and the failure to integrate policies related to energy production and energy consumption limit the effectiveness of support for DH. [ABSTRACT FROM AUTHOR]

Background: The aerobic energy metabolism of cardiac muscle cells is of major importance for the contractile function of the heart. Because energy metabolism is very heterogeneously distributed in heart tissue, especially during coronary disease, a method to quantify metabolic fluxes in small tissue samples is desirable. Taking tissue biopsies after infusion of substrates labeled with stable carbon isotopes makes this possible in animal experiments. However, the appreciable noise level in NMR spectra of extracted tissue samples makes computational estimation of metabolic fluxes challenging and a good method to define confidence regions was not yet available. Results: Here we present a computational analysis method for nuclear magnetic resonance (NMR) measurements of tricarboxylic acid (TCA) cycle metabolites. The method was validated using measurements on extracts of single tissue biopsies taken from porcine heart in vivo. Isotopic enrichment of glutamate was measured by NMR spectroscopy in tissue samples taken at a single time point after the timed infusion of 13C labeled substrates for the TCA cycle. The NMR intensities for glutamate were analyzed with a computational model describing carbon transitions in the TCA cycle and carbon exchange with amino acids. The model dynamics depended on five flux parameters, which were optimized to fit the NMR measurements. To determine confidence regions for the estimated fluxes, we used the Metropolis-Hastings algorithm for Markov chain Monte Carlo (MCMC) sampling to generate extensive ensembles of feasible flux combinations that describe the data within measurement precision limits. To validate our method, we compared myocardial oxygen consumption calculated from the TCA cycle flux with in vivo blood gas measurements for 38 hearts under several experimental conditions, e.g. during coronary artery narrowing. Conclusions: Despite the appreciable NMR noise level, the oxygen consumption in the tissue samples, estimated from the NMR spectra, correlates with blood-gas oxygen uptake measurements for the whole heart. The MCMC method provides confidence regions for the estimated metabolic fluxes in single cardiac biopsies, taking the quantified measurement noise level and the nonlinear dependencies between parameters fully into account. [ABSTRACT FROM AUTHOR]

Economic development in Africa is expected to increase levels of bushmeat hunting through rising demand for meat and improved transport infrastructure. However, few studies have tracked long-term changes in hunter behavior as a means of testing this prediction. We evaluated changes in hunter behavior in a rural community in Equatorial Guinea over a period of rapid national economic growth, during which time road access to the regional capital greatly improved. We conducted offtake surveys (Supporting Information) over 3 7-week periods at the same time of year in 1998, 2003, and 2010 and conducted hunter and household interviews (Supporting Information) in 2003 and 2010. We tested whether relations existed among catch, hunting effort, hunting strategy, and income earned through hunting and other livelihoods in 2003 and 2010. Although village offtake increased from 1775 kg in 1998 to 4172 kg in 2003, it decreased in 2010 to 1361 kg. Aggregate catch per unit effort (i.e., number of carcasses caught per hunter and per trap) decreased from 2003 to 2010, and the majority of hunters reported a decrease in abundance of local fauna. Although these results are indicative of unsustainable hunting, cumulative changes in offtake and catch per unit effort were driven by a contraction in the total area hunted following an out-migration of 29 of the village's hunters, most of whom left to gain employment in the construction industry, after 2003. Hunters operating in both 2003 and 2010 hunted closer to the village because an increased abundance of elephants posed a danger and because they desired to earn income through other activities. Our study provides an example of national economic development contributing to a reduction in the intensity and extent of hunting. Factores de Cambio en la Captura de Cazadores y Estrategias de Caza en Sendje, Guinea Ecuatorial [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Heterogeneity of regional coronary blood flow is caused in part by heterogeneity in O2 demand in the normal heart. We investigated whether myocardial O2 supply/demand mismatching is associated with the myocardial depression of sepsis. Regional blood flow (microspheres) and O2 uptake ([13C]acetate infusion and analysis of resultant NMR spectra) were measured in about nine contiguous tissue samples from the left ventricle (LV) in each heart. Endotoxemic pigs (n = 9) showed hypotension at unchanged cardiac output with a fall in LV stroke work and first derivative of LV pressure relative to controls (n = 4). Global coronary blood flow and O2 delivery were maintained. Lactate accumulated in arterial blood, but net lactate extraction across the coronary bed was unchanged during endotoxemia. When LV O2 uptake based on blood gas versus NMR data were compared, the correlation was 0.73 (P = 0.007). While stable over time in controls, regional blood flows were strongly redistributed during endotoxin shock, with overall flow heterogeneity unchanged. A stronger redistribution of blood flow with endotoxin was associated with a larger fall in LV function parameters. Moreover, the correlation of regional O2 delivery to uptake fell from r = 0.73 (P < 0.001) in control to r = 0.18 (P = 0.25, P = 0.009 vs. control) in endotoxemic hearts. The results suggest a redistribution of LV regional coronary blood flow during endotoxin shock in pigs, with regional O2 delivery mismatched to O2 demand. Mismatching may underlie, at least in part, the myocardial depression of sepsis. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines. Methodology/Principal Findings: Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses. Conclusions: The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV. [ABSTRACT FROM AUTHOR]

Motivation: Quantitative determination of metabolic fluxes in single tissue biopsies is difficult. We report a novel analysis approach and software package for in vivo flux quantification using stable isotope labeling. [ABSTRACT FROM PUBLISHER]

Human immunodeficiency virus (HIV)-negative infants born to HIV-positive mothers frequently exhibit a range of immunological abnormalities. We tested the hypothesis that HIV during pregnancy affects the ability of CD4 T cells of HIV-negative infants to respond to vaccine challenge by recruiting HIV-negative infants born to HIV-negative and HIV-positive mothers and measuring their responses to Bacille Calmette-Guérin (BCG) vaccine given at birth. At 2 weeks, maternal HIV status did not influence CD4 T-cell counts or differentiation, but by 10 weeks CD4 counts of infants born to HIV-positive mothers fell to a level characteristic of HIV-positive infants. Among the CD4 T-cell populations, markers of differentiation (CCR7− CD45RA− CD27−) and senescence (CD57, PD-1) were more common among infants born to HIV-positive mothers than among infants born to HIV-negative mothers. At 2 weeks of age, we assessed the effector response to heat-killed BCG and tuberculin purified protein derivative (PPD) by overnight interferon (IFN)-γ enzyme-linked immunosorbent spot-forming cell assay (ELISpot), but found no measurable effect of maternal HIV status. At 10 weeks, we assessed CD4 T-cell memory by measuring proliferation in response to the same antigens. We observed a bimodal response that allowed infants to be classified as high or low responders and found that fewer infants born to HIV-positive mothers were able to mount a robust proliferative response, suggesting that their reduced CD4 counts and increased differentiation indicated a deficiency in their ability to develop immunological memory. [ABSTRACT FROM AUTHOR]

Background: Infection with Plasmodium falciparum during pregnancy contributes substantially to the disease burden in both mothers and offspring. Placental malaria may lead to intrauterine growth restriction or preterm delivery resulting in low birth weight (LBW), which, in general, is associated with increased infant morbidity and mortality. However, little is known about the possible direct impact of the specific disease processes occurring in PM on longer term outcomes such as subsequent retarded growth development independent of LBW. Methods: In an existing West-African cohort, 783 healthy infants with a birth weight of at least 2,000 g were followed up during their first year of life. The aim of the study was to investigate if Plasmodium falciparum infection of the placenta, assessed by placental histology, has an impact on several anthropometric parameters, measured at birth and after three, six and 12 months using generalized estimating equations models adjusting for moderate low birth weight. Results: Independent of LBW, first to third born infants who were exposed to either past, chronic or acute placental malaria during pregnancy had significantly lower weight-for-age (-0.43, 95% CI: -0.80;-0.07), weight-forlength (-0.47, 95% CI: -0.84; -0.10) and BMI-for-age z-scores (-0.57, 95% CI: -0.84; -0.10) compared to infants born to mothers who were not diagnosed with placental malaria (p = 0.019, 0.013, and 0.012, respectively). Interestingly, the longitudinal data on histology-based diagnosis of PM also document a sharp decline of PM prevalence in the Sukuta cohort from 16.5% in 2002 to 5.4% in 2004. Conclusions: It was demonstrated that PM has a negative impact on the infant's subsequent weight development that is independent of LBW, suggesting that the longer term effects of PM have been underestimated, even in areas where malaria transmission is declining. [ABSTRACT FROM AUTHOR]

The purpose of this safety study, carried out within the EURISOL Design Study, was to characterize the radiation environment and design the appropriate shielding of the new-generation radioactive ion beam postaccelerator. Both variants of linac layouts--without stripper (L#1) and with stripper (L#2)--were analyzed using the 132Sn25+ radioactive beam of unprecedented intensity, namely, up to -1013 particles/s, as reference for simulations. In this work two scenarios were analyzed: (a) an accidental full beam loss during I s every day and (b) continuous beam loss of 10-4 m-1, representing normal operation conditions. Representative loss positions along the accelerator at variable energies of 21, 45.5, 76, 115, and 150 MeVu-1 were investigated. The lost ions were assumed to strike a stopping copper target. Dedicated simulations were performed by means of the PHITS code. The induced radioactivity in the accelerator components, concrete walls, and air inside the tunnel were estimated using the DCHA/N-SP-2001 code based on an external neutron source and spallation products derived from PHITS. Ambient dose equivalent rates due to the residual radiation were calculated with the MCNPX code using photon sources resulting from DCHAIN. The effect of implanted radioactive ions at low energies in the accelerator structure was also assessed. [ABSTRACT FROM AUTHOR]

Selection methods that require only a single-switch input, such as a button click or blink, are potentially useful for individuals with motor impairments, mobile technology users, and individuals wishing to transmit information securely. We present a single-switch selection method, ''Nomon,'' that is general and efficient. Existing single-switch selection methods require selectable options to be arranged in ways that limit potential applications. By contrast, traditional operating systems, web browsers, and free-form applications (such as drawing) place options at arbitrary points on the screen. Nomon, however, has the flexibility to select any point on a screen. Nomon adapts automatically to an individual's clicking ability; it allows a person who clicks precisely to make a selection quickly and allows a person who clicks imprecisely more time to make a selection without error. Nomon reaps gains in information rate by allowing the specification of beliefs (priors) about option selection probabilities and by avoiding tree-based selection schemes in favor of direct (posterior) inference. We have developed both a Nomon-based writing application and a drawing application. To evaluate Nomon's performance, we compared the writing application with a popular existing method for single-switch writing (row-column scanning). Novice users wrote 35% faster with the Nomon interface than with the scanning interface. An experienced user (author TB, with > 10 hours practice) wrote at speeds of 9.3 words per minute with Nomon, using 1.2 clicks per character and making no errors in the final text. [ABSTRACT FROM AUTHOR]

Background: In a previously published study, we found that large differentiated subpopulations of CD8 T-cells emerged rapidly after CMV infection in young infants and persisted throughout the following year. Here we describe a follow-up study conducted on the same infants to establish whether the differentiated subpopulations continued through the second year post-infection. Methodology / Principal Findings: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population. The large subpopulation of differentiated cytotoxic (CD28-CD62L-Bcl-2lowCD95+perforin+) cells that emerged rapidly after infection remained stable after two years. No similar subpopulation was found in CMV-uninfected infants indicating that two years after infection, CMV remained a major factor in driving CD8 T-cell differentiation. Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly. The age-related increase in IFNγ response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially. Conclusions / Significance: The large differentiated subpopulations of CD8 T-cells that had emerged immediately after CMV infection persisted through the second year post-infection, while levels of activation and functional capacity remained fairly constant. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection induces profound differentiation of T cells, and is associated with impaired responses to other immune challenges. We therefore considered whether CMV infection and the consequent T-cell differentiation in Gambian infants was associated with impaired specific responses to measles vaccination or polyclonal responses to the superantigen staphylococcal enterotoxin B (SEB). While the concentration of undifferentiated (CD27+ CD28+ CCR7+) T-cells in peripheral blood was unaffected by CMV, there was a large increase in differentiated (CD28− CD57+) CD8 T-cells and a smaller increase in differentiated CD4 cells. One week post-vaccination, the CD4 cell interferon-γ (IFN-γ) response to measles was lower among CMV-infected infants, but there were no other differences between the cytokine responses, or between the cytokine or proliferative responses 4 months post-vaccination. However, the CD8 T cells of CMV-infected infants proliferated more in response to SEB and the antibody response to measles correlated with the IFN-γ response to CMV, indicating that CMV infection actually enhances some immune responses in infancy. [ABSTRACT FROM AUTHOR]

Abstract: We measured integral thin target cross sections for the proton-induced production of He-, Ne-, Ar-, Kr- and Xe-isotopes from bismuth (Bi) from the respective reaction thresholds up to 2.6GeV. Here we present 275 cross sections for 23 nuclear reactions. The production of noble gas isotopes from Bi is of special importance for design studies of accelerator driven systems (EA/ADS) and nuclear spallation sources. For experiments with proton energies above 200MeV the mini-stack approach was used instead of the stacked-foil technique in order to minimise the influences of secondary particles on the residual nuclide production. Comparing the cross sections for Bi to the data published recently for Pb indicates that for 4He the cross sections for Bi below 200MeV are up to a factor of 2–3 higher than the Pb data, which can be explained by the production of α-decaying Po-isotopes from Bi but not from Pb. Some of the cross sections for the production of 21Ne from Bi are affected by recoil effects from neighboured Al-foils, which compromises a study of a possible lowering of the effective Coulomb-barrier. The differences in the excitation functions between Pb and Bi for Kr- and Xe-isotopes can be explained by energy-dependent higher fission cross sections for Bi compared to Pb. The experimental data are compared to results from the theoretical nuclear model codes INCL4/ABLA and TALYS. The INCL4/ABLA system describes the cross sections for the production of 4He-, Kr- and Xe-isotopes reasonably well, i.e. mostly within a factor of a few. In contrast, the model completely fails describing 21Ne, 22Ne, 36Ar and 38Ar, which are produced via spallation and/or multifragmentation. The TALYS code is only able to accurately predict reaction thresholds. The absolute values are either significantly over- or underestimated. Consequently, the comparison of measured and modelled thin target cross sections clearly indicates that experimental data are still needed because the predictive power of nuclear model codes, though permanently improving, does still not allow to reliably predict the cross sections needed for most applications and irradiation experiments remain indispensable. [Copyright &y& Elsevier]

We compared cytomegalovirus (CMV)-specific interferon-γ (IFN-γ), interleukin 2 (IL-2), and CD154 CD4+ T cell responses of infants to those from chronically infected adults and from children aged 4-5 years. Magnitudes of the re- sponses were similar, although coexpression of IFN-γ plus CD154 occurred more than coexpression of IFN-γ plus IL-2 or IL-2 plus CD154. Responses remained constant during infancy, although the proportion of IFN-γ-producing cells increased from infancy to adulthood. Most responding cells in infants were undifferentiated (i.e., CD27+CD28+), although IFN-γ-producing cells were disproportionately CD27-. By 12 months after diagnosis, viremia was rarely detectable, indicating that CMV was controlled despite the slow development of CMV-specific CD4+ T cell responses. [ABSTRACT FROM AUTHOR]

In 2005, the ACS Green Chemistry Institute (GCI) and the global pharmaceutical corporations developed the ACS GCI Pharmaceutical Roundtable to encourage the integration of green chemistry and green engineering into the pharmaceutical industry. The Roundtable has developed a list of key research areas. The purpose of this perspective is to summarise how that list was agreed, provide an assessment of the current state of the art in those areas and to highlight areas for future improvement. [ABSTRACT FROM AUTHOR]

Myocardial blood flow and oxygen consumption are heterogeneously distributed. Perfusion and myocardial oxygen consumption are closely correlated in the normal heart. It is unknown how this metabolism–perfusion relation is influenced by sympathetic denervation. We investigated this question in seven chloralose-anaesthetized dogs, 3–4 weeks after regional sympathetic denervation of the left circumflex coronary artery area of supply of the left ventricle. Measurements were made of local myocardial blood flow (MBF, in ml min−1 (g dry wt)−1), measured with microspheres, and myocardial oxygen consumption ( , in μmol min−1 (g dry wt)−1) in the same location, calculated from the 13C spectrum of tissue extracts after intracoronary infusion of 3–13C-lactate. Since both innervated and denervated regions are subject to the same arterial pressure, lower blood flow indicates higher resistance. Mean MBF was 5.56 ml min−1 (g dry wt)−1 (heterogeneity of 3.47 ml min−1 (g dry wt)−1) innervated, 7.48 ml min−1 (g dry wt)−1 (heterogeneity of 3.62 ml min−1 (g dry wt)−1) denervated (n.s.). Significant linear relations were found between MBF and of individual samples within the innervated and denervated regions. The slopes of these relations were not significantly different, but the adjusted mean was significantly higher in the denervated regions (+1.92 ml min−1 (g dry wt)−1, an increase of 38% of the mean MBF at the pooled mean , P= 0.028, ANCOVA). The ratio (in ml μmol−1) was significantly higher, being 0.296 ± 0.167 ml μmol−1 in the denervated region compared with the innervated region, 0.216 ± 0.126 ml μmol−1, P= 0.0182, Mann–Whitney U test. These results indicate that sympathetic tone under chloralose anaesthesia imposes a moderate vasoconstrictive effect in the myocardium that is not detected by comparison of the mean blood flow or resistance. [ABSTRACT FROM AUTHOR]

Sparse-graph codes appropriate for use in quantum error-correction are presented. Quantum error-correcting codes based on sparse graphs are of interest for three reasons. First, the best codes currently known for classical channels are based on sparse graphs. Second, sparse-graph codes keep the number of quantum interactions associated with the quantum error-correction process small: a constant number per quantum bit, independent of the block length. Third, sparse-graph codes often offer great flexibility with respect to block length and rate. We believe some of the codes we present are unsurpassed by previously published quantum error-correcting codes. [ABSTRACT FROM AUTHOR]

Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a pharmaceutical compound used for the treatment of depression, social anxiety disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of the parent compound being excreted as metabolites through the urine and feces of patients. Therefore PA and metabolites have the potential to be discharged into wastewater treatment systems after therapeutic use. PA and its major human metabolite (PM) were investigated using studies designed to describe physical/chemical characteristics and determine their fate and effects in the aquatic environment. A significant portion of the PM entering a wastewater treatment plant would be expected to biodegrade given the higher activated sludge solids concentrations present in a typical wastewater treatment plant. The potential for direct photolysis of PM is also possible based on photolysis results for PA itself. These results provide strong support for expecting that PA and PM residuals will not persist in the aquatic environment after discharge from a wastewater treatment facility. This conclusion is also supported by the results of a USGS monitoring study, where no PM was detected in any of the samples at the 260 ng/L reporting limit The results presented here also demonstrate the importance of understanding the human metabolism of a pharmaceutical so that the appropriate molecule(s) is used for fate and effects studies. In addition to the PA fate studies, PM was investigated using studies designed to determine potential environmental effects and a predicted no effect level (PNEC). The average measured activated sludge respiration inhibition value (EC50) for PM was 82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Dap/inia magna EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 µg/L. Fate data were then used in a new watershed-based environmental risk assessment model, PhATE, to predict environmental concentrations (PECs). Comparison of the calculated PECs with the PNEC allows an assessment of potential environmental risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from ∼3 × 10-8 to ∼3 × 10-8, indicating a wide margin of safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk to the environment. In addition, Microtox studies carried out on PM biodegradation byproducts indicated no detectable residual toxicity. Any compounds in the environment as a result of the biodegradation of PM should be innocuous polar byproducts that should not exert any toxic effects. [ABSTRACT FROM AUTHOR]

Introduces a code which is capable of correcting multiple insertion, deletion and substitution errors. Outline of watermark codes for synchronization; Channel model; Encoding and decoding.

Presents information on a study which focused on the application of variational methods to Gaussian processes to produce an efficient Bayesian binary classifier. Features of the variational Gaussian process classifier; Results and discussion; Conclusions.

Provides information on a study which examined the theoretical and practical properties of error-correcting codes based on very sparse matrices. Limits of optimal decoding; Practical decoding by the sum-product algorithm; Experimental results; Conclusions.

I examine two approximate methods for computational implementation of Bayesian hierarchical models, that is, models that include unknown hyperparameters such as regularization constants and noise levels. In the evidence framework, the model parameters are integrated over, and the resulting evidence is maximized over the hyperparameters. The optimized hyperparameters are used to define a gaussian approximation to the posterior distribution. In the alternative MAP method, the true posterior probability is found by integrating over the hyperparameters. The true posterior is then maximized over the model parameters, and a gaussian approximation is made. The similarities of the two approaches and their relative merits are discussed, and comparisons are made with the ideal hierarchical Bayesian solution. In moderately ill–posed problems, integration over hyperparameters yields a probability distribution with a skew peak, which causes significant biases to arise in the MAP method. In contrast, the evidence framework is shown to introduce negligible predictive error under straightforward conditions. General lessons are drawn concerning inference in many dimensions. [ABSTRACT FROM AUTHOR]

Presents information on a study which compared alternative methods for constructing irregular Gallager codes. Information on Gallager codes; Discussion on Poison method; Fast-encoding Gallager codes; Discussion.

Isolation into pure culture was attempted on 1183 species (2233 specimens) of lichen-forming and lichenicolous fungi from diverse ecosystems and systematic groups (covering 14 ascomycete orders, 77 families and 280 genera), in 20 countries. Four hundred and ninety three species (42%) were successfully isolated either from ascospores (or basidiospores, or conidia) or photobiont-free fragments from thallus macerates. Of the total number of isolation attempts from ascospores (1609) and thallus fragments (719), 30% and 32% respectively were successful. The reasons for failure to isolate from ascospores were: ascospores did not germinate (43%) > ascospores were not discharged (30%) > ascospores germinated but growth was not sustained (19%) > discharged spores were heavily contaminated (8%). 59% of isolation failures with fragments were due to lack of growth and 41% were due to contamination. The orders from which mycobionts were most readily isolated were the Ostropales (70% of species attempted were isolated), Dothideales (63%), Pertusariales (53%) and Lecanorales (45%); those orders least readily yielding isolates were Verrucariales (10%), Gyalectales (20%), Arthoniales (30%), Lichinales (29%) and Peltigerales (27%) . Members of the Lecanorales comprised ) c. 60% of species collected of which Porpidiaceae (80% of species successfully isolated), Cladoniaceae (69%), Lecideaceae (67%), Rhizocarpaceae (62%), Umbilicariaceae (60%), Ramalinaceae (60%) and Lecanoraceae (54%) were comparatively successful families and Alectoriaceac (18%), Catillariaceae (8%), Pannariaceac (8%) Collemataceae (7%), and Micareaceac (6%) were least successful. Of those species containing a cyanobacteriurn (either as the primary photobiont or in cephalodia), only 22% yielded isolates compared with 46% and 43%, of lichens containing only a chlorococcoid photobiont or Trentepohlia, respectively. Success was even lower (17%) in species containing a cyanobacterium as the primary photobiont. Among non-cyanobacterial lichens, isolation of mycohionts was achieved in 56% of fruticose species collected compared with 43% and 40% for crustose/squamulose and foliose taxa respectively. Mycobionts of fruticose lichens cultured particularly readily from fragments, with 56% of green algal species to which this method was applied coming into culture compared to 37% of non-cyanobacterial foliose species. Lichenicolous fungi cultured less readily, with only 31% of species yielding isolates. In many species viability of ascospores varied between collections. Weather conditions at the time of collection, environmental conditions during transportation, and developmental stage of ascomata of pyrenocarpous lichens might partly explain this variation. [ABSTRACT FROM AUTHOR]

Corynebacterium pseudotuberculosis or caseous lymphadenitis is a common condition in sheep and goats. Two cases are described involving otitis media-interna and, in one case, cerebellar abscessation. The first case began with otitis externa and progressed to cerebellar abscessation, presumably as a result of C. pseudotuberculosis infection based on the macroscopic appearance of the abscess. The second case of otitis media-interna involved C. pseudotuberculosis with parasitic encephalitis or secondary meningo-encephalitis. Caseous lymphadenitis is a worldwide problem in livestock and also has zoonotic implications. Antimicrobial therapy of abscesses is often unrewarding due to the thick encapsulation of the abscesses and the extremely contagious nature of the organism. Alternative measures of treating this condition must be sought. In flocks or herds where caseous lymphadenitis has been diagnosed, it should be considered as a differential diagnosis for neurological conditions. The potential for spread must be kept in mind when it is suspected to be the cause of otitis in livestock. [ABSTRACT FROM AUTHOR]

The capabilities of the new version of the Liège intranuclear cascade model (labeled INCL++6 from now on) are presented in detail. This new version of INCL is able to handle strange particles, such as kaons and the Λ and Σ hyperons, and the associated reactions and also allows extending nucleon-nucleon collisions up to about 15-20 GeV incident energy. Compared to the previous version, new observables can be studied, e.g., kaon, hyperon, and hypernuclei production cross sections (with the use of a suitable de-excitation code) as well as aspects of kaon-induced spallation reactions. The main purpose of this paper is to present the specific ingredients of the new INCL version and its new features, notably the newly implemented variance reduction scheme. We also compare, for some illustrative strangeness production cases, theoretical results calculated using this version of INCL with experimental data. [ABSTRACT FROM AUTHOR]

Ticker is a probabilistic stereophonic single-switch text entry method for visually-impaired users with motor disabilities who rely on single-switch scanning systems to communicate. Such scanning systems are sensitive to a variety of noise sources, which are inevitably introduced in practical use of single-switch systems. Ticker uses a novel interaction model based on stereophonic sound coupled with statistical models for robust inference of the user's intended text in the presence of noise. As a consequence of its design, Ticker is resilient to noise and therefore a practical solution for single-switch scanning systems. Ticker's performance is validated using a combination of simulations and empirical user studies. [ABSTRACT FROM AUTHOR]

Combining and separating fluid streams at the microscale has many scientific, industrial, and medical applications. This numerical and experimental study explores inertial instabilities in so-called mixing-separating micro-geometries. The geometry consists of two straight square parallel channels with flow from opposite directions and a central gap that allows the streams to interact, mix, or remain separate (often also referred to as the H-geometry). Under creeping-flow conditions (the Reynolds number tending to zero), the flow is steady, two-dimensional, and produces a sharp interface between fluid streams entering the geometry from opposite directions. When Re exceeds a critical value, one of two different supercritical, inertial instabilities appears which leads to significant changes in the flow pattern and an increased level of interaction between the two streams, although the flow remains steady. The exact form of the instability is dependent on the gap size and the Reynolds number, and we identify two distinct instabilities, one of which appears in devices with large gaps and another which appears in devices with small gaps. At intermediate gap sizes, both instabilities can occur in the same device (at different onset Re). The experimental results for one gap size are used to validate our numerical method, which is then applied to a wider range of gap sizes. The results suggest that the gap size is of primary importance in determining the type of instability that occurs. With a judicious choice of gap size, the instabilities can be exploited (or avoided) in scientific, medical, or other microfluidic applications. [ABSTRACT FROM AUTHOR]

Direct ink writing (DIW) is a three-dimensional (3D) printing technique exploited by researchers working in fields from scaffolds for energy applications to bioprinting. DIW's main strength is that it enables shaping advanced materials, if these materials can be formulated into complex fluids that meet the demands of the printing process. They must be extremely shear thinning soft solids, able to flow through narrow nozzles, recovering their structure upon deposition and retaining the predesigned 3D shape. Formulation design and rheology are critical, but these aspects can be overlooked due to the high specialization required. This work provides insight on the rheology and printability of complex yield-stress fluids through the study of linear and nonlinear behaviors using large-amplitude oscillatory shear rheology. We refine previous protocols and develop tools to understand the behaviors of formulations for DIW. We apply an existing mathematical framework to a library of carbon-based formulations for energy applications. Fourier transform analysis enables quantifying the onset and rising of higher harmonic contributions. Quantitative comparisons between different formulations are established using 3D harmonics maps, stress–strain plots, and material measures of nonlinearities [Fourier and Chebyshev coefficients, elastic moduli (G M ′ , G L ′ ), and dimensionless index of nonlinearity (S)]. 3D Lissajous plots provide a qualitative alternative to interpretate the yielding transition. We create Ashby-type printability maps to guide formulation design and elucidate that non-printable formulations show distinctive features. This insight on yield-stress fluids for DIW is relevant to other applications and technologies: drilling fluids, gels, colloids, and foods. [ABSTRACT FROM AUTHOR]

In this review article we present some of the major applications for cosmogenic nuclide studies; extraterrestrial applications on meteorites, lunar surface samples but also on interstellar grains and terrestrial applications ranging from ages for exposure and burial over erosion and denudation rates to uplift and soil dynamics. For all the applications a good knowledge of the cosmogenic nuclide production rates is indispensable. Since it is neither possible nor feasible measuring production rates for all possible set-ups and geometries they are usually calculated using the particle spectra for primary and secondary particles and the cross sections for the relevant nuclear reactions. Considering the reacting particles we also discuss in some detail the basic properties of solar and galactic cosmic rays, especially we focus on the temporal variability. With a good understanding of the projectile types, a very relevant step is to understand and model the induced nuclear reactions. In doing so, we will briefly discuss the basic properties of spallation reactions and we especially focus on the recent very impressive improvements. We finish with a short outlook of the next possible steps for further improvements. [ABSTRACT FROM AUTHOR]

Background: Human immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect.Methods: Thirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants.Results: We demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants.Conclusions: In the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants. [ABSTRACT FROM AUTHOR]

Following our goal to devise a unified green chemistry metric that inspires innovation in sustainable drug manufacturing across the pharmaceutical industry, we herein disclose joint efforts by IQ, the ACS GCI PR and academia, leading to the significantly improved ‘innovation Green Aspiration Level’ (iGAL) methodology. Backed by the statistical analysis of 64 drug manufacturing processes encompassing 703 steps across 12 companies, we find that iGAL affords an excellent proxy for molecular complexity and presents a valuable molecular weight-based ‘fixed’ goal. iGAL thereby accurately captures the impact of green process inventiveness and improvements, making it a useful innovation-driven green metric. We conclude by introducing the comprehensive, yet easy-to-use and readily adaptable Green Chemistry Innovation Scorecard web calculator, whose graphical output clearly and effectively illustrates the impact of innovation on waste reduction during drug manufacture. [ABSTRACT FROM AUTHOR]

The new version of the Liège intranuclear-cascade model (INCL), recently extended to the production of strange particles and hypernuclei, is used to investigate the Λ-nucleus potential in a broad range of nuclear masses from Si to Pb. The combination of the INCL calculation results with experimental cross sections of Λ hypernuclei, obtained from (π+,K+) reaction studies, allows us to constrain the Λ-nucleus potential depth with an accuracy of about 0.9 MeV. Our results show that the potential depth increases with the mass number (A) from 28 MeV in the region of medium-mass hypernuclei up to a maximum of 39.6 MeV in the region of heavy hypernuclei around A=208. This deviation could be related to the nucleon-isospin dependence of the three-body Λ-nucleon-nucleon force in asymmetry matter whose contribution is more relevant in hyperneutron matter due to a strong contribution from Λnn interactions. [ABSTRACT FROM AUTHOR]

The authors argue on the need for nations to agree on a common goal that is in everyone's self-interest in forging a strong climate accord in Paris, France in December 2015. They comment on how the lack of an enforcement mechanism was only partly responsible for the failure of the Kyoto Protocol and suggest a common commitment is also required. They recommend the use of a global carbon price instead of a global cap-and-trade scheme as carbon pricing lets nations keep all carbon revenues.

We measured the isotopic concentrations of long-lived and stable He, Ne, Ar, Kr, and Xe isotopes in a sample from a lead-bismuth eutectic target irradiated with 1.0 and 1.4 GeV protons. Our data indicate for most noble gases nearly complete release with retention fractions in the range of percent or less. Higher retention fractions result from the decay of long-lived radioactive progenitors from groups 1, 2, or 7 of the periodic table. From the data we can calculate a retention fraction for 3 H of 2–3%. For alkaline metals we find retention fractions of about 10%, 30%, and 50% for Na, Rb, and Cs, respectively. For the alkaline earth metal Ba we found complete retention. Finally, the measured Kr and Xe concentrations indicate that there was some release of the halogens Br and I during and/or after the irradiation. [ABSTRACT FROM AUTHOR]

Major, rapid performance improvements in perceptual training are often dismissed as 'task' or 'procedural' learning because they are fast and generalize within a task. We assessed the contributions of perceptual and procedural learning to improvement in an auditory tone frequency learning task in humans and found that perceptual learning accounted for between 76% and 98% of the rapid early performance improvement. [ABSTRACT FROM AUTHOR]