Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

The biogeography of abundant and rare bacterioplankton in the lakes and reservoirs of China.

Bacteria play key roles in the ecology of both aquatic and terrestrial ecosystems; however, little is known about their diversity and biogeography, especially in the rare microbial biosphere of inland freshwater ecosystems. Here we investigated aspects of the community ecology and geographical distribution of abundant and rare bacterioplankton using high-throughput sequencing and examined the relative influence of local environmental variables and regional (spatial) factors on their geographical distribution patterns in 42 lakes and reservoirs across China. Our results showed that the geographical patterns of abundant and rare bacterial subcommunities were generally similar, and both of them showed a significant distance-decay relationship. This suggests that the rare bacterial biosphere is not a random assembly, as some authors have assumed, and that its distribution is most likely subject to the same ecological processes that control abundant taxa. However, we identified some differences between the abundant and rare groups as both groups of bacteria showed a significant positive relationship between sites occupancy and abundance, but the abundant bacteria exhibited a weaker distance-decay relationship than the rare bacteria. Our results implied that rare subcommunities were mostly governed by local environmental variables, whereas the abundant subcommunities were mainly affected by regional factors. In addition, both local and regional variables that were significantly related to the spatial variation of abundant bacterial community composition were different to those of rare ones, suggesting that abundant and rare bacteria may have discrepant ecological niches and may play different roles in natural ecosystems

'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology

The Swiss-born medical researcher Karl Friedrich Meyer (1884–1974) is best known as a ‘microbe hunter’ who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer’s 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a ‘reservoir of disease’ as a forerunner of ‘one medicine’ approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer’s other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer—like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet—can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet’s and Smith’s contributions to this scientific field have been widely acknowledged, Meyer’s have been largely ignored. Drawing on Meyer’s published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer’s intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague—exchanges that not only showed how environmental and ecological conditions could ‘tip the balance’ in favor of parasites but which transformed Meyer thinking about resistance to infection and disease

Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and death cell in microglial cells

Excessive Zn2+ causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H2O2/Zn2+-induced Ca2+ signalling and cell death in microglial cells. H2O2/Zn2+ induced concentration-dependent increases in cytosolic Ca2+ concentration ([Ca2+]c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H2O2/Zn2+ induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO. Further analysis indicate that Zn2+ induced ROS production, PARP-1 stimulation, increase in the [Ca2+]c and cell death, which were suppressed by chelerythrine, a protein kinase C inhibitor, DPI, a NADPH-dependent oxidase (NOX) inhibitor, GKT137831, a NOX1/4 inhibitor, and Phox-I2, a NOX2 inhibitor. Furthermore, Zn2+-induced PARP-1 stimulation, increase in the [Ca2+]c and cell death were inhibited by PF431396, a Ca2+-sensitive PYK2 inhibitor, and U0126, a MEK/ERK inhibitor. Taken together, our study shows PKC/NOX-mediated ROS generation and PARP-1 activation as an important mechanism in Zn2+-induced TRPM2 channel activation and, TRPM2-mediated increase in the [Ca2+]c to trigger the PYK2/MEK/ERK signalling pathway as a positive feedback mechanism that amplifies the TRPM2 channel activation. Activation of these TRPM2-depenent signalling mechanisms ultimately drives Zn2+-induced Ca2+ overloading and cell death

Sensitivity of imaging for multifocal-multicentric breast carcinoma

<p>Abstract</p> <p>Background</p> <p>This retrospective study aims to determine: 1) the sensitivity of preoperative mammography (Mx) and ultrasound (US), and re-reviewed Mx to detect multifocal multicentric breast carcinoma (MMBC), defined by pathology on surgical specimens, and 2) to analyze the characteristics of both detected and undetected foci on Mx and US.</p> <p>Methods</p> <p>Three experienced breast radiologists re-reviewed, independently, digital mammography of 97 women with MMBC pathologically diagnosed on surgical specimens. The radiologists were informed of all neoplastic foci, and blinded to the original mammograms and US reports. With regards to Mx, they considered the breast density, number of foci, the Mx characteristics of the lesions and their BI-RADS classification. For US, they considered size of the lesions, BI-RADS classification and US pattern and lesion characteristics. According to the histological size, the lesions were classified as: index cancer, 2nd lesion, 3rd lesion, and 4th lesion. Any pathologically identified malignant foci not previously described in the original imaging reports, were defined as undetected or missed lesions. Sensitivity was calculated for Mx, US and re-reviewed Mx for detecting the presence of the index cancer as well as additional satellite lesions.</p> <p>Results</p> <p>Pathological examination revealed 13 multifocal and 84 multicentric cancers with a total of 303 malignant foci (282 invasive and 21 non invasive). Original Mx and US reports had an overall sensitivity of 45.5% and 52.9%, respectively. Mx detected 83/97 index cancers with a sensitivity of 85.6%. The number of lesions <it>un</it>detected by original Mx was 165/303. The Mx pattern of breasts with undetected lesions were: fatty in 3 (1.8%); scattered fibroglandular density in 40 (24.3%), heterogeneously dense in 91 (55.1%) and dense in 31 (18.8%) cases. In breasts with an almost entirely fatty pattern, Mx sensitivity was 100%, while in fibroglandular or dense pattern it was reduced to 45.5%. Re-reviewed Mx detected only 3 additional lesions. The sensitivity of Mx was affected by the presence of dense breast tissue which obscured lesions or by an incorrect interpretation of suspicious findings.</p> <p>US detected 73/80 index cancers (sensitivity of 91.2%), US missed 117 malignant foci with a mean tumor diameter of 6.5 mm; the sensitivity was 52.9%</p> <p>Undetected lesions by US were those smallest in size and present in fatty breast or in the presence of microcalcifications without a visible mass.</p> <p>US sensitivity was affected by the presence of fatty tissue or by the extent of calcification.</p> <p>Conclusion</p> <p>Mx missed MMBC malignant foci more often in dense or fibroglandular breasts. US missed small lesions in mainly fatty breasts or when there were only microcalcifications. The combined sensitivity of both techniques to assess MMBC was 58%. We suggest larger studies on multimodality imaging.</p

Psychometric evaluation of a short measure of social capital at work

BACKGROUND: Prior studies on social capital and health have assessed social capital in residential neighbourhoods and communities, but the question whether the concept should also be applicable in workplaces has been raised. The present study reports on the psychometric properties of an 8-item measure of social capital at work. METHODS: Data were derived from the Finnish Public Sector Study (N = 48,592) collected in 2000–2002. Based on face validity, an expert unfamiliar with the data selected 8 questionnaire items from the available items for a scale of social capital. Reliability analysis included tests of internal consistency, item-total correlations, and within-unit (interrater) agreement by r(wg )index. The associations with theoretically related and unrelated constructs were examined to assess convergent and divergent validity (construct validity). Criterion-related validity was explored with respect to self-rated health using multilevel logistic regression models. The effects of individual level and work unit level social capital were modelled on self-rated health. RESULTS: The internal consistency of the scale was good (Cronbach's alpha = 0.88). The r(wg )index was 0.88, which indicates a significant within-unit agreement. The scale was associated with, but not redundant to, conceptually close constructs such as procedural justice, job control, and effort-reward imbalance. Its associations with conceptually more distant concepts, such as trait anxiety and magnitude of change in work, were weaker. In multilevel models, significantly elevated age adjusted odds ratios (ORs) of poor self-rated health (OR = 2.42, 95% confidence interval (CI): 2.24–2.61 for the women and OR = 2.99, 95% CI: 2.56–3.50 for the men) were observed for the employees in the lowest vs. highest quartile of individual level social capital. In addition, low social capital at the work unit level was associated with a higher likelihood of poor self-rated health. CONCLUSION: Psychometric techniques show our 8-item measure of social capital to be a valid tool reflecting the construct and displaying the postulated links with other variables

When One Size Does Not Fit All: A Simple Statistical Method to Deal with Across-Individual Variations of Effects

In science, it is a common experience to discover that although the investigated effect is very clear in some individuals, statistical tests are not significant because the effect is null or even opposite in other individuals. Indeed, t-tests, Anovas and linear regressions compare the average effect with respect to its inter-individual variability, so that they can fail to evidence a factor that has a high effect in many individuals (with respect to the intra-individual variability). In such paradoxical situations, statistical tools are at odds with the researcher’s aim to uncover any factor that affects individual behavior, and not only those with stereotypical effects. In order to go beyond the reductive and sometimes illusory description of the average behavior, we propose a simple statistical method: applying a Kolmogorov-Smirnov test to assess whether the distribution of p-values provided by individual tests is significantly biased towards zero. Using Monte-Carlo studies, we assess the power of this two-step procedure with respect to RM Anova and multilevel mixed-effect analyses, and probe its robustness when individual data violate the assumption of normality and homoscedasticity. We find that the method is powerful and robust even with small sample sizes for which multilevel methods reach their limits. In contrast to existing methods for combining p-values, the Kolmogorov-Smirnov test has unique resistance to outlier individuals: it cannot yield significance based on a high effect in one or two exceptional individuals, which allows drawing valid population inferences. The simplicity and ease of use of our method facilitates the identification of factors that would otherwise be overlooked because they affect individual behavior in significant but variable ways, and its power and reliability with small sample sizes (<30–50 individuals) suggest it as a tool of choice in exploratory studies