OECD principles on water governance in practice:an assessment of existing frameworks in Europe, Asia-Pacific, Africa and South America

Through the lens of the 12 OECD Principles on Water Governance, this article examines six water resources and water services frameworks in Europe, Asia-Pacific, Africa and South America to understand enhancing and constraining contextual factors. Qualitative and quantitative methods are used to analyze each framework against four criteria: alignment; implementation; on-ground results; and policy impact. Four main target areas are identified for improving water governance: policy coherence; financing; managing trade-offs; and ensuring integrity and transparency by all decision makers and stakeholders. Suggestions are presented to support practical implementation of the principles through better government action and stakeholder involvement.No Full Tex

A Population Pharmacokinetic Analysis of Milrinone in Pediatric Patients After Cardiac Surgery

The purpose of this study was to ascertain the optimal pharmacokinetic model for milrinone in pediatric patients after cardiac surgery when milrinone was administered as a slow loading dose followed by a constant-rate infusion. The data used for pharmacokinetic analysis were collected in a prospective, randomized, placebo-controlled multi-center trial of milrinone as prophylaxis for the development of low cardiac output syndrome after surgery for repair of complex congenital cardiac defects. Two blood samples were randomly collected from each patient for determination of plasma milrinone concentrations with subsequent population pharmacokinetic modeling. The pharmacokinetics of milrinone in pediatric patients under 6year's age were best described by a weight-normalized one compartment model after a slow loading dose followed by a constant-rate infusion. The volume of distribution was 482mlkg −1 , and was independent of age. Clearance was a linear function of age given by Cl=2.42mlkg −1 min −1 [1+0.0396*age].Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45063/1/10928_2004_Article_485925.pd

Dark Matter Annihilation around Intermediate Mass Black Holes: an update

The formation and evolution of Black Holes inevitably affects the distribution of dark and baryonic matter in the neighborhood of the Black Hole. These effects may be particularly relevant around Supermassive and Intermediate Mass Black Holes (IMBHs), the formation of which can lead to large Dark Matter overdensities, called {\em spikes} and {\em mini-spikes} respectively. Despite being larger and more dense, spikes evolve at the very centers of galactic halos, in regions where numerous dynamical effects tend to destroy them. Mini-spikes may be more likely to survive, and they have been proposed as worthwhile targets for indirect Dark Matter searches. We review here the formation scenarios and the prospects for detection of mini-spikes, and we present new estimates for the abundances of mini-spikes to illustrate the sensitivity of such predictions to cosmological parameters and uncertainties regarding the astrophysics of Black Hole formation at high redshift. We also connect the IMBHs scenario to the recent measurements of cosmic-ray electron and positron spectra by the PAMELA, ATIC, H.E.S.S., and Fermi collaborations.Comment: 12 pages, 7 figures. Invited contribution to NJP Focus Issue on "Dark Matter and Particle Physics

LHC Signatures of a Minimal Supersymmetric Hidden Valley

We investigate the LHC signals of a minimal supersymmetric hidden valley. Our theory consists of the supersymmetric Standard Model along with a light hidden U(1)_x gauge multiplet and a pair of hidden chiral superfields that spontaneously break the new Abelian gauge symmetry near a GeV. The visible and hidden sectors interact exclusively through supersymmetric gauge kinetic mixing. We perform a thorough examination of the hidden decay cascades initiated by the lightest Standard Model superpartner and we study the range of LHC signals they can produce. In particular, we find parameter regions that give rise to missing energy, single and multiple lepton jets, and displaced vertices. Given the simplicity of the underlying theory and the broad range of collider signals it can produce, we propose that this model is a useful benchmark for LHC studies of (supersymmetric) hidden valleys.Comment: 45 pages, 15 figures; typos corrected but conclusions unchange

Kinetically-Enhanced Anomaly Mediation

We investigate a modification of anomaly-mediated supersymmetry breaking (AMSB) with an exotic U(1)_x gauge sector that can solve the tachyonic slepton problem of minimal AMSB scenarios. The new U(1)_x multiplet is assumed to couple directly to the source of supersymmetry breaking, but only indirectly to the minimal supersymmetric Standard Model (MSSM) through kinetic mixing with hypercharge. If the MSSM sector is also sequestered from the source of supersymmetry breaking, the contributions to the MSSM soft terms come from both AMSB and the U(1)_x kinetic coupling. We find that this arrangement can give rise to a flavour-universal, phenomenologically viable, and distinctive spectrum of MSSM superpartners. We also investigate the prospects for discovery and the most likely signatures of this scenario at the Large Hadron Collider (LHC).Comment: 29 pages, 10 figures; Added references, corrected ctau plot in Fig. 4, same general conclusion

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)

Connexin channels and phospholipids: association and modulation

<p>Abstract</p> <p>Background</p> <p>For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood.</p> <p>Results</p> <p>Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred.</p> <p>Conclusion</p> <p>This study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents.</p