Transcranial Doppler ultrasound to assess cerebrovascular reactivity: reliability, reproducibility and effect of posture

Transcranial Doppler ultrasound (TCD) allows measurement of blood flow velocities in the intracranial vessels, and can be used to assess cerebral vasodilator responses to a hypercapnic stimulus. The reliability of this technique has not been established, nor is there agreement about whether the technique should be performed in sitting or lying postures. We tested the intra- and inter-rater reliability of measures of cerebrovascular reactivity (CVR) in 10 healthy adults, in sitting and lying postures. Participants underwent triplicate bilateral ultrasound assessment of flow velocities in the middle cerebral arteries whilst sitting and lying supine prior to and during inhalation of Carbogen (5% CO2, 95% O2) for 2 min. This procedure was performed twice by each of two raters for a total of four sessions. CVR was calculated as the difference between baseline and the peak blood flow velocity attained during CO2 inhalation. Intraclass correlation coefficients (ICCs) for intra-rater reliability were greater sitting than lying for both raters (e.g. Rater 1 ICC sitting = 0.822, lying = 0.734), and inter-rater reliability was also greater in sitting (e.g. sitting ICC = 0.504, lying = 0.081). These results suggest that assessment of CVR using TCD should be performed with participants sitting in order to maximise CVR measurement reliability

False positive and false negative errors in the design and implementation of agri-environmental policies: a case study on water quality and agricultural nutrients

When designing and implementing agri-environmental policies to reduce nutrient loss, action programmes may falsely address areas where the nutrient issue from agricultural activity is not currently important and is not likely to become so in the future (a false positive), or may fail to address areas where the agricultural nutrient issue is currently important or may likely become so in the future (a false negative). Based on a case study of the Louros watershed in Greece, this work identifies database and modelling sources of false positives and negatives and proposes a decision making process aimed at minimizing the possibility of committing such errors. The baseline is well simulated and shows that the Louro’s watershed falls behind a Good Environmental Status, at least marginally. Simulated mitigation measures show that the river’s status can be upgraded to “Good”, at least as concerns nitrates and ammonium. Simulated climate change does not seem to exert an important positive or negative effect. Land use changes forecasting considerably less cultivated area have a significant effect on Total Phosphorous but not on nitrates or ammonium concentrations. The non-linearity between nutrient disposition (inputs) and nutrient concentration in downstream water bodies (output) and the many factors that affect the nutrient disposition-transportation-concentration chain, highlights the importance of simulating the effects of mitigation actions and of future climate and land use changes before adopting and establishing agri-environmental measures

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Climate change and water in the UK: past changes and future prospects

Climate change is expected to modify rainfall, temperature and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper reviews the impact of anthropogenic climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to anthropogenic climate forcing, but over the last 50 years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and water availability. Summer flows may decrease on average, but floods may become larger and more frequent. River and lake water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms in summer, and because of higher flows in the winter. In communicating this important work, researchers should pay particular attention to explaining confidence and uncertainty clearly. Much of the relevant research is either global or highly localized: decision-makers would benefit from more studies that address water and climate change at a spatial and temporal scale appropriate for the decisions they mak

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

Primordial magnetic fields induced by cosmological particle creation

We study the primordial magnetic field generated by stochastic currents produced by scalar charged particles created at the beginning of the radiation dominated epoch. We find that for the mass range 10^(-6)GeV \leq m \leq 10^2 GeV, a field of sufficient intensity to seed different mechanisms of galactic magnetic field generation, while still consistent with observational and theoretical constraints, is created coherently over a galactic scale.Comment: accepted for publication in Phys. Rev.

Second Generation Leptoquark Search in p\bar{p} Collisions at s\sqrt{s} = 1.8 TeV

We report on a search for second generation leptoquarks with the D\O\ detector at the Fermilab Tevatron $p\bar{p}$ collider at $\sqrt{s}$ = 1.8 TeV. This search is based on 12.7 pb$^{-1}$ of data. Second generation leptoquarks are assumed to be produced in pairs and to decay into a muon and quark with branching ratio $\beta$ or to neutrino and quark with branching ratio $(1-\beta)$. We obtain cross section times branching ratio limits as a function of leptoquark mass and set a lower limit on the leptoquark mass of 111 GeV/c$^{2}$ for $\beta = 1$ and 89 GeV/c$^{2}$ for $\beta = 0.5$ at the 95%\ confidence level.Comment: 18 pages, FERMILAB-PUB-95/185-

Process-orientation versus outcome-orientation during organizational change: The role of organizational identification

In this paper we argue that organizational identification is predictive of employee interests and concerns during periods of organizational change. More specifically, we assert that organizational identification may largely determine whether employees may be focused upon the change related outcomes (e.g., salary, expenses, etc.), or on the change processes (e.g., procedures, voice and participation options, etc.). Data of both a scenario experiment and a survey are presented indicating that high and low identifiers indeed are differentially interested in process and outcome information. The results suggest that people who identify less with the organization are more likely to be focused upon the change outcomes then on the change process, while people who identify highly (i.e., deep structure) with the organization are more likely to be focused upon the change processes then on the change outcomes. The benefits of awareness of organizational members' level of identification for organizational change management are discussed. Copyright © 2006 John Wiley & Sons, Ltd

Jet Production via Strongly-Interacting Color-Singlet Exchange in ppˉp\bar{p} Collisions

A study of the particle multiplicity between jets with large rapidity separation has been performed using the D{\O}detector at the Fermilab Tevatron $p\bar{p}$ Collider operating at $\sqrt{s}=1.8$ TeV. A significant excess of low-multiplicity events is observed above the expectation for color-exchange processes. The measured fractional excess is $1.07 \pm 0.10({\rm stat})^{+ 0.25}_{- 0.13}({\rm syst})$, which is consistent with a strongly-interacting color-singlet (colorless) exchange process and cannot be explained by electroweak exchange alone. A lower limit of 0.80% (95% C.L.) is obtained on the fraction of dijet events with color-singlet exchange, independent of the rapidity gap survival probability.Comment: 15 pages (REVTeX), 3 PS figs (uuencoded/tar compressed, epsf.sty) Complete postscript available at http://d0sgi0.fnal.gov/d0pubs/journals.html Submitted to Physical Review Letter