Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49oC) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid- cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.

Measuring the impact of observations on the predictability of the Kuroshio Extension in a shallow-water model

In this paper sequential importance sampling is used to assess the impact of observations on a ensemble prediction for the decadal path transitions of the Kuroshio Extension (KE). This particle filtering approach gives access to the probability density of the state vector, which allows us to determine the predictive power — an entropy based measure — of the ensemble prediction. The proposed set-up makes use of an ensemble that, at each time, samples the climatological probability distribution. Then, in a post-processing step, the impact of different sets of observations is measured by the increase in predictive power of the ensemble over the climatological signal during one-year. The method is applied in an identical-twin experiment for the Kuroshio Extension using a reduced-gravity shallow water model. We investigate the impact of assimilating velocity observations from different locations during the elongated and the contracted meandering state of the KE. Optimal observations location correspond to regions with strong potential vorticity gradients. For the elongated state the optimal location is in the first meander of the KE. During the contracted state of the KE it is located south of Japan, where the Kuroshio separates from the coast.

Connectivity measures for internet topologies on the level of autonomous systems

Classical measures of network connectivity are the number of disjoint paths between a pair of nodes and the size of a minimum cut. For standard graphs, these measures can be computed efficiently using network flow techniques. However, in the Internet on the level of autonomous systems (ASs), referred to as AS-level Internet, routing policies impose restrictions on the paths that traffic can take in the network. These restrictions can be captured by the valley-free path model, which assumes a special directed graph model in which edge types represent relationships between ASs. We consider the adaptation of the classical connectivity measures to the valley-free path model, where it is -hard to compute them. Our first main contribution consists of presenting algorithms for the computation of disjoint paths, and minimum cuts, in the valley-free path model. These algorithms are useful for ASs that want to evaluate different options for selecting upstream providers to improve the robustness of their connection to the Internet. Our second main contribution is an experimental evaluation of our algorithms on four types of directed graph models of the AS-level Internet produced by different inference algorithms. Most importantly, the evaluation shows that our algorithms are able to compute optimal solutions to instances of realistic size of the connectivity problems in the valley-free path model in reasonable time. Furthermore, our experimental results provide information about the characteristics of the directed graph models of the AS-level Internet produced by different inference algorithms. It turns out that (i) we can quantify the difference between the undirected AS-level topology and the directed graph models with respect to fundamental connectivity measures, and (ii) the different inference algorithms yield topologies that are similar with respect to connectivity and are different with respect to the types of paths that exist between pairs of ASs.

A randomised crossover study investigating the effects of galacto-oligosaccharides on the faecal microbiota in men and women over 50 years of age

Faecal microbial changes associated with ageing include reduced bifidobacteria numbers. These changes coincide with an increased risk of disease development. Prebiotics have been observed to increase bifidobacteria numbers within humans. The present study aimed to determine if prebiotic galacto-oligosaccharides (GOS) could benefit a population of men and women of 50 years and above, through modulation of faecal microbiota, fermentation characteristics and faecal water genotoxicity. A total of thirty-seven volunteers completed this randomised, double-blind, placebo-controlled crossover trial. The treatments – juice containing 4 g GOS and placebo – were consumed twice daily for 3 weeks, preceded by 3-week washout periods. To study the effect of GOS on different large bowel regions, three-stage continuous culture systems were conducted in parallel using faecal inocula from three volunteers. Faecal samples were microbially enumerated by quantitative PCR. In vivo, following GOS intervention, bifidobacteria were significantly more compared to post-placebo (P = 0·02). Accordingly, GOS supplementation had a bifidogenic effect in all in vitro system vessels. Furthermore, in vessel 1 (similar to the proximal colon), GOS fermentation led to more lactobacilli and increased butyrate. No changes in faecal water genotoxicity were observed. To conclude, GOS supplementation significantly increased bifidobacteria numbers in vivo and in vitro. Increased butyrate production and elevated bifidobacteria numbers may constitute beneficial modulation of the gut microbiota in a maturing population.

The impact of a seasonally ice free Arctic Ocean on the temperature, precipitation and surface mass balance of Svalbard

The observed decline in summer sea ice extent since the 1970s is predicted to continue until the Arctic Ocean is seasonally ice free during the 21st Century. This will lead to a much perturbed Arctic climate with large changes in ocean surface energy flux. Svalbard, located on the present day sea ice edge, contains many low lying ice caps and glaciers and is expected to experience rapid warming over the 21st Century. The total sea level rise if all the land ice on Svalbard were to melt completely is 0.02 m. The purpose of this study is to quantify the impact of climate change on Svalbard’s surface mass balance (SMB) and to determine, in particular, what proportion of the projected changes in precipitation and SMB are a result of changes to the Arctic sea ice cover. To investigate this a regional climate model was forced with monthly mean climatologies of sea surface temperature (SST) and sea ice concentration for the periods 1961–1990 and 2061–2090 under two emission scenarios. In a novel forcing experiment, 20th Century SSTs and 21st Century sea ice were used to force one simulation to investigate the role of sea ice forcing. This experiment results in a 3.5 m water equivalent increase in Svalbard’s SMB compared to the present day. This is because over 50 % of the projected increase in winter precipitation over Svalbard under the A1B emissions scenario is due to an increase in lower atmosphere moisture content associated with evaporation from the ice free ocean. These results indicate that increases in precipitation due to sea ice decline may act to moderate mass loss from Svalbard’s glaciers due to future Arctic warming.

Effect of architecture on the phase behavior of AB-type block copolymer melts

Equilibrium phase diagrams are calculated for a selection of two-component block copolymer architectures using self-consistent field theory (SCFT). The topology of the phase diagrams is relatively unaffected by differences in architecture, but the phase boundaries shift significantly in composition. The shifts are consistent with the decomposition of architectures into constituent units as proposed by Gido and coworkers, but there are significant quantitative deviations from this principle in the intermediate-segregation regime. Although the complex phase windows continue to be dominated by the gyroid (G) phase, the regions of the newly discovered Fddd (O^70) phase become appreciable for certain architectures and the perforated-lamellar (PL) phase becomes stable when the complex phase windows shift towards high compositional asymmetry.

Social and material influences on the Kelabit dwelt environment

Relations with the environment are key to the ways in which people pursue their dwelling practices. The complex processes of globalisation challenge the isolation of rural groups, consequently affecting their perception and use of the environment. One such place where this can be seen is the Kelabit Highlands of northern Sarawak (Malaysian Borneo), where the recent arrival of commercial logging has allowed local people to make wider connections via the logging roads. Cultural and historic traditions are reconstituted in the light of new material relations with a dynamic environment, which can be seen reflected in changing customs of housebuilding.

Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

BACKGROUND: Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. METHODS: With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. RESULTS: Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. CONCLUSIONS: This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior.

Assessing wind profile effects on the global atmospheric torque

The impact of a new approach to the evaluation of surface gravity wave drag (GWD) is assessed. This approach uses linear theory, but incorporates the effects of wind profile shear and curvature, by means of a second-order WKB approximation. While the theory predicts the possibility of either drag enhancement or reduction, depending on the wind profile, results obtained with the ERA-40 reanalysis data clearly indicate the predominance of local drag enhancement. However, the global impact of shear on the atmospheric axial GWD torque comes mostly from regions with predominantly easterly flow, contributing to a slight reduction of the bias found in different studies of the global angular momentum budget. The relative correction due to shear on linear GWD is found not to depend too strongly on the levels chosen for the computation of the low-level wind derivatives.

The impact of installer business models on the uptake of residential microgeneration in the UK: Evidence from a nation-wide survey

This paper arises from a doctoral thesis comparing the impact of alternative installer business models on the rate at which microgeneration is taken up in homes and installation standards across the UK. The paper presents the results of the first large-scale academic survey of businesses certified to install residential microgeneration. The aim is to systematically capture those characteristics which define the business model of each surveyed company, and relate these to the number, location and type of technologies that they install, and the quality of these installations. The methodology comprised a pilot web survey of 235 certified installer businesses, which was carried out in June last year and achieved a response rate of 30%. Following optimisation of the design, the main web survey was emailed to over 2000 businesses between October and December 2011, with 317 valid responses received. The survey is being complemented during summer 2012 by semi-structured interviews with a representative sample of installers who completed the main survey. The survey results are currently being analysed. The early results indicate an emerging and volatile market where solar PV, solar hot water and air source heat pumps are the dominant technologies. Three quarters of respondents are founders of their installer business, while only 22 businesses are owned by another company. Over half of the 317 businesses have five employees or less, while 166 businesses are no more than four years old. In addition, half of the businesses stated that 100% of their employees work on microgeneration-related activities. 85% of the surveyed companies have only one business location in the UK. A third of the businesses are based either in the South West or South East regions of England. This paper outlines the interim results of the survey combined with the outcomes from additional interviews with installers to date. The research identifies some of the business models underpinning microgeneration installers and some of the ways in which installer business models impact on the rate and standards of microgeneration uptake. A tentative conclusion is that installer business models are profoundly dependent on the levels and timing of support from the UK Feed-in Tariffs and Renewable Heat Incentive.

Climate on the Southern Black Sea coast during the Holocene: implications from the Sofular Cave record

We present the updated Holocene section of the Sofular Cave record from the southernBlackSeacoast (northern Turkey); an area with considerably different present-day climate compared to that of the neighboring Eastern Mediterranean region. Stalagmite δ13C, growth rates and initial (234U/238U) ratios provide information about hydrological changes above the cave; and prove to be more useful than δ18O for deciphering Holocene climatic variations. Between ∼9.6 and 5.4 ka BP (despite a pause from ∼8.4 to 7.8 ka BP), the Sofular record indicates a remarkable increase in rainfall amount and intensity, in line with other paleoclimate studies in the Eastern Mediterranean. During that period, enhanced summertime insolation either produced much stronger storms in the following fall and winter through high sea surface temperatures, or it invoked a regional summer monsoon circulation and rainfall. We suggest that one or both of these climatic mechanisms led to a coupling of the BlackSea and the Mediterranean rainfall regimes at that time, which can explain the observed proxy signals. However, there are discrepancies among the Eastern Mediterranean records in terms of the timing of this wet period; implying that changes were probably not always occurring through the same mechanism. Nevertheless, the Sofular Cave record does provide hints and bring about new questions about the connection between regional and large scale climates, highlighting the need for a more extensive network of high quality paleoclimate records to better understand Holoceneclimate.

Effect of triclosan or a phenolic farm disinfectant on the selection of antibiotic-resistant Salmonella enterica

Objective: To determine the effect of growth of five strains of Salmonella enterica and their isogenic multiply antibiotic-resistant (MAR) derivatives with a phenolic farm disinfectant or triclosan (biocides) upon the frequency of mutation to resistance to antibiotics or cyclohexane. Methods: Strains were grown in broth with or without the biocides and then spread on to agar containing ampicillin, ciprofloxacin or tetracycline each at 4x MIC or agar overlaid with cyclohexane. Incubation was for 24 and 48 h and the frequency of mutation to resistance was calculated for strains with and without prior growth with the biocides. MICs were determined and the presence of mutations in the acrR and marR regions was determined by sequencing and the presence of mutations in gyrA by light-cycler analysis, for a selection of the mutants that arose. Results: The mean frequency of mutation to antibiotic or cyclohexane resistance was increased similar to10- to 100-fold by prior growth with the phenolic disinfectant or triclosan. The increases were statistically significant for all antibiotics and cyclohexane following exposure to the phenolic disinfectant (P less than or equal to 0.013), and for ampicillin and cyclohexane following exposure to triclosan (P less than or equal to 0.009). Mutants inhibited by >1 mg/L ciprofloxacin arose only from strains that were MAR. Reduced susceptibility to ciprofloxacin (at 4x MIC for parent strains) alone was associated with mutations in gyrA. MAR mutants did not contain mutations in the acrR or marR region. Conclusions: These data renew fears that the use of biocides may lead to an increased selective pressure towards antibiotic resistance.

Influence of geographical origin, host animal and stx gene on the virulence characteristics of Escherichia coli O26 strains

The influence of geographical origin, host animal and presence of the stx gene on the virulence of Escherichia coli O26 strains from ruminants was determined in this study. A clear association was found between the virulence profile and geographical origin of Shiga-toxigenic E. coli (STEC) O26 strains, with UK STEC O26 strains harbouring virtually identical profiles, whilst central European strains showed considerable heterogeneity in plasmid-encoded genes. The former group were also more likely to be non-motile and katP gene positive. Comparison of UK STEC and atypical enteropathogenic E. coli (aEPEC O26 strains showed that the presence of the stx1 gene was positively correlated with the presence of espP and katP genes and negatively associated with the presence of the yagP-yagT region and with rhamnose fermentation. In contrast to the uniform profiles of STEC O26 strains from ruminants in the UK, aEPEC O26 strains of bovine and ovine origin showed diverse profiles both within and between groups, and could not be separated into discrete groups. These results indicate that the characteristics of UK O26 strains from ruminants are distinct from those of O26 strains from ruminants and humans in other regions in central Europe. Such differences are expected to influence the zoonotic potential of this pathogen and the subsequent incidence of O26-associated human disease.

On the seasonal onset of polar mesospheric clouds and the breakdown of the stratospheric polar vortex in the Southern Hemisphere

Southern Hemisphere (SH) polar mesospheric clouds (PMCs), also known as noctilucent clouds, have been observed to be more variable and, in general, dimmer than their Northern Hemisphere (NH) counterparts. The precise cause of these hemispheric differences is not well understood. This paper focuses on one aspect of the hemispheric differences: the timing of the PMC season onset. Observations from the Aeronomy of Ice in the Mesosphere satellite indicate that in recent years the date on which the PMC season begins varies much more in the SH than in the NH. Using the Canadian Middle Atmosphere Model, we show that the generation of sufficiently low temperatures necessary for cloud formation in the SH summer polar mesosphere is perturbed by year‐to‐year variations in the timing of the late‐spring breakdown of the SH stratospheric polar vortex. These stratospheric variations, which persist until the end of December, influence the propagation of gravity waves up to the mesosphere. This adds a stratospheric control to the temperatures in the polar mesopause region during early summer, which causes the onset of PMCs to vary from one year to another. This effect is much stronger in the SH than in the NH because the breakdown of the polar vortex occurs much later in the SH, closer in time to the PMC season.

A diagnostic study of waves on the tropopause

The spatial structure and phase velocity of tropopause disturbances localized around the subpolar jet in the Southern Hemisphere are investigated using 6-hourly European Centre for Medium-Range Weather Forecasts reanalysis data covering 15 yr (1979–93). The phase velocity and phase structure of the tropopause disturbances are in good agreement with those of an edge wave vertically trapped at the tropopause. However, the vertical distribution of the ratio of potential to kinetic energy exhibits maxima above and below the tropopause and a minimum around the tropopause, in contradiction to edge wave theory for which the ratio is unity throughout the troposphere and stratosphere. This difference in vertical structure between the observed tropopause disturbances and edge wave theory is attributed to the effects of a finite-depth tropopause together with the next-order corrections in Rossby number to quasigeostrophic dynamics