Safety of clonidine used for long-term sedation in paediatric intensive care: A systematic review

AIM: Although not approved, the α-adrenoceptor agonist clonidine is considered an option for long-term sedation protocols in paediatric intensive care. We reviewed adverse effects of clonidine occurring in this indication. METHODS: Relevant literature was systematically identified from PubMed and Embase. We included interventional and observational studies on paediatric patients admitted to intensive care units and systemically long-term sedated with clonidine-containing regimes. In duplicates, we conducted standardised and independent full-text assessment and extraction of safety data. RESULTS: Data from 11 studies with 909 patients were analysed. The studies were heterogeneous regarding patient characteristics (age groups, comorbidity, or comedication) and sedation regimes (dosage, route, duration, or concomitant sedatives). Just four randomised controlled trials (RCTs) and one observational study had comparison groups, using placebo or midazolam. For safety outcomes, our validity evaluation showed low risk of bias only in three studies. All studies focused on haemodynamic problems, particularly bradycardia and hypotension. Observed incidences or subsequent interventions never caused concerns. However, only two RCTs allowed meaningful comparisons with control groups. Odds ratios showed no significant difference between the groups, but small sample sizes (50 and 125 patients) must be considered; pooled analyses were not reasonable. CONCLUSION: All evaluated studies concluded that the use of clonidine in paediatric intensive care units is safe. However, a valid characterisation of the safety profile remains challenging due to limited, biased and heterogeneous data and missing investigation of long-term effects. This evaluation demonstrates the lack of data, which prevents reliable conclusions on the safety of clonidine for long-term sedation in critically ill children. For an evidence-based use, further studies are needed

Black Hole - Neutron Star Mergers as Central Engines of Gamma-Ray Bursts

Hydrodynamic simulations of the merger of stellar mass black hole - neutron star binaries (BH/NS) are compared with mergers of binary neutron stars (NS/NS). The simulations are Newtonian, but take into account the emission and backreaction of gravitational waves. The use of a physical nuclear equation of state allows us to include the effects of neutrino emission. For low neutron star to black hole mass ratios the neutron star transfers mass to the black hole during a few cycles of orbital decay and subsequent widening before finally being disrupted, whereas for ratios near unity the neutron star is already distroyed during its first approach. A gas mass between about 0.3 and about 0.7 solar masses is left in an accretion torus around the black hole and radiates neutrinos at a luminosity of several 10^{53} erg/s during an estimated accretion time scale of about 0.1 s. The emitted neutrinos and antineutrinos annihilate into electron-positron pairs with efficiencies of 1-3% percent and rates of up to 2*10^{52} erg/s, thus depositing an energy of up to 10^{51} erg above the poles of the black hole in a region which contains less than 10^{-5} solar masses of baryonic matter. This could allow for relativistic expansion with Lorentz factors around 100 and is sufficient to explain apparent burst luminosities of up to several 10^{53} erg/s for burst durations of approximately 0.1-1 s, if the gamma emission is collimated in two moderately focussed jets in a fraction of about 1/100-1/10 of the sky.Comment: 8 pages, LaTex, 4 postscript figures, 2 tables. ApJ Letters, accepted; revised and shortened version, Fig. 2 change

Magneto-optical evidence of the percolation nature of the metal-insulator transition in the 2D electron system

We compare the results of the transport and time-resolved magneto-luminescence measurements in disordered 2D electron systems in GaAs-AlGaAs heterostructures in the extreme quantum limit, in particular, in the vicinity of the metal-insulator transition (MIT). At filling factors $\nu <1$, the optical signal has two components: the single-rate exponentially decaying part attributed to a uniform liquid and a power-law long-living tail specific to a microscopically inhomogeneous state of electrons. We interprete this result as a separation of the 2D electron system into a liquid and localized phases, especially because the MIT occurs strikingly close to those filling factors where the liquid occupies ${1\over 2}$ of the sample area (the percollation threshold condition in two-component media).Comment: 5 pages RevTex + 4 fig., to appear in PRB, Rapid Com

Sfermion Pair Production in Polarized and Unpolarized γγ\gamma\gamma Collisions

We calculate total and differential cross sections for the production of sfermion pairs in photon-photon collisions, including contributions from resolved photons and arbitrary photon polarization. Sfermion production in photon collisions depends only on the sfermion mass and charge. It is thus independent of the details of the SUSY breaking mechanism, but highly sensitive to the sfermion charge. We compare the total cross sections for bremsstrahlung, beamstrahlung, and laser backscattering photons to those in $e^+e^-$ annihilation. We find that the total cross section at a polarized photon collider is larger than the $e^+e^-$ annihilation cross section up to the kinematic limit of the photon collider.Comment: 19 pages, Latex, 18 (e)ps-figure

Quantum Hall Effect induced by electron-electron interaction in disordered GaAs layers with 3D spectrum

It is shown that the observed Quantum Hall Effect in epitaxial layers of heavily doped n-type GaAs with thickness (50-140 nm) larger the mean free path of the conduction electrons (15-30 nm) and, therefore, with a three-dimensional single-particle spectrum is induced by the electron-electron interaction. The Hall resistance R_xy of the thinnest sample reveals a wide plateau at small activation energy E_a=0.4 K found in the temperature dependence of the transverse resistance R_xx. The different minima in the transverse conductance G_xx of the different samples show a universal temperature dependence (logarithmic in a large range of rescaled temperatures T/T_0) which is reminiscent of electron-electron-interaction effects in coherent diffusive transport.Comment: 6 pages, 3 figures, 1 tabl

Sfermion Pair Production at μ+μ−\mu^+ \mu^- Colliders

We discuss pair production of stops, sbottoms, staus and tau--sneutrinos at a $\mu^+ \mu^-$ collider. We present the formulae for the production cross sections and perform a detailed numerical analysis within the Minimal Supersymmetric Standard Model. In particular, we consider sfermion production near $\sqrt{s} = m_{H^0}$ and $\sqrt{s} = m_{A^0}$.Comment: 21 pages, Latex, uses Revtex (included), 8 figures (included as PS-files

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Supersymmetric Higgs production in gluon fusion at next-to-leading order

The next-to-leading order (NLO) QCD corrections to the production and decay rate of a Higgs boson are computed within the framework of the Minimal Supersymmetric Standard Model (MSSM). The calculation is based on an effective theory for light and intermediate mass Higgs bosons. We provide a Fortran routine for the numerical evaluation of the coefficient function. For most of the MSSM parameter space, the relative size of the NLO corrections is typically of the order of 5% smaller than the Standard Model value. We exemplify the numerical results for two scenarios: the benchmark point SPS1a, and a parameter region where the gluon-Higgs coupling at leading order is very small due to a cancellation of the squark and quark contributions.Comment: 27 pages, LaTeX, 31 embedded PostScript-files; v2: typos corrected, reformatted in JHEP style; accepted for publication in JHE