Understanding the Spatial Clustering of Severe Acute Respiratory Syndrome (SARS) in Hong Kong

We applied cartographic and geostatistical methods in analyzing the patterns of disease spread during the 2003 severe acute respiratory syndrome (SARS) outbreak in Hong Kong using geographic information system (GIS) technology. We analyzed an integrated database that contained clinical and personal details on all 1,755 patients confirmed to have SARS from 15 February to 22 June 2003. Elementary mapping of disease occurrences in space and time simultaneously revealed the geographic extent of spread throughout the territory. Statistical surfaces created by the kernel method confirmed that SARS cases were highly clustered and identified distinct disease “hot spots.” Contextual analysis of mean and standard deviation of different density classes indicated that the period from day 1 (18 February) through day 16 (6 March) was the prodrome of the epidemic, whereas days 86 (15 May) to 106 (4 June) marked the declining phase of the outbreak. Origin-and-destination plots showed the directional bias and radius of spread of superspreading events. Integration of GIS technology into routine field epidemiologic surveillance can offer a real-time quantitative method for identifying and tracking the geospatial spread of infectious diseases, as our experience with SARS has demonstrated

Formation of superdense hadronic matter in high energy heavy-ion collisions

We present the detail of a newly developed relativistic transport model (ART 1.0) for high energy heavy-ion collisions. Using this model, we first study the general collision dynamics between heavy ions at the AGS energies. We then show that in central collisions there exists a large volume of sufficiently long-lived superdense hadronic matter whose local baryon and energy densities exceed the critical densities for the hadronic matter to quark-gluon plasma transition. The size and lifetime of this matter are found to depend strongly on the equation of state. We also investigate the degree and time scale of thermalization as well as the radial flow during the expansion of the superdense hadronic matter. The flow velocity profile and the temperature of the hadronic matter at freeze-out are extracted. The transverse momentum and rapidity distributions of protons, pions and kaons calculated with and without the mean field are compared with each other and also with the preliminary data from the E866/E802 collaboration to search for experimental observables that are sensitive to the equation of state. It is found that these inclusive, single particle observables depend weakly on the equation of state. The difference between results obtained with and without the nuclear mean field is only about 20\%. The baryon transverse collective flow in the reaction plane is also analyzed. It is shown that both the flow parameter and the strength of the ``bounce-off'' effect are very sensitive to the equation of state. In particular, a soft equation of state with a compressibility of 200 MeV results in an increase of the flow parameter by a factor of 2.5 compared to the cascade case without the mean field. This large effect makes it possible to distinguish the predictions from different theoretical models and to detect the signaturesComment: 55 pages, latex, + 39 figures available upon reques

Two-dimensional one-component plasma on a Flamm's paraboloid

We study the classical non-relativistic two-dimensional one-component plasma at Coulomb coupling Gamma=2 on the Riemannian surface known as Flamm's paraboloid which is obtained from the spatial part of the Schwarzschild metric. At this special value of the coupling constant, the statistical mechanics of the system are exactly solvable analytically. The Helmholtz free energy asymptotic expansion for the large system has been found. The density of the plasma, in the thermodynamic limit, has been carefully studied in various situations

Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer.

Drug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique with a population-based stochastic search algorithm to navigate through the large parametric space of nine angiostatic drugs at four concentrations to identify optimal low-dose drug combinations. This implied an iterative approach of in vitro testing of endothelial cell viability and algorithm-based analysis. The optimal synergistic drug combination, containing erlotinib, BEZ-235 and RAPTA-C, was reached in a small number of iterations. Final drug combinations showed enhanced endothelial cell specificity and synergistically inhibited proliferation (p < 0.001), but not migration of endothelial cells, and forced enhanced numbers of endothelial cells to undergo apoptosis (p < 0.01). Successful translation of this drug combination was achieved in two preclinical in vivo tumor models. Tumor growth was inhibited synergistically and significantly (p < 0.05 and p < 0.01, respectively) using reduced drug doses as compared to optimal single-drug concentrations. At the applied conditions, single-drug monotherapies had no or negligible activity in these models. We suggest that FSC can be used for rapid identification of effective, reduced dose, multi-drug combinations for the treatment of cancer and other diseases

Open charm and charmonium production at relativistic energies

We calculate open charm and charmonium production in $Au+Au$ reactions at $\sqrt{s}$ = 200 GeV within the hadron-string dynamics (HSD) transport approach employing open charm cross sections from $pN$ and $\pi N$ reactions that are fitted to results from PYTHIA and scaled in magnitude to the available experimental data. Charmonium dissociation with nucleons and formed mesons to open charm ($D+\bar{D}$ pairs) is included dynamically. The 'comover' dissociation cross sections are described by a simple phase-space model including a single free parameter, i.e. an interaction strength $M_0^2$, that is fitted to the $J/\Psi$ suppression data for $Pb+Pb$ collisions at SPS energies. As a novel feature we implement the backward channels for charmonium reproduction by $D \bar{D}$ channels employing detailed balance. From our dynamical calculations we find that the charmonium recreation is comparable to the dissociation by 'comoving' mesons. This leads to the final result that the total $J/\Psi$ suppression at $\sqrt{s}$ = 200 GeV as a function of centrality is slightly less than the suppression seen at SPS energies by the NA50 Collaboration, where the 'comover' dissociation is substantial and the backward channels play no role. Furthermore, even in case that all directly produced $J/\Psi$ mesons dissociate immediately (or are not formed as a mesonic state), a sizeable amount of charmonia is found asymptotically due to the $D+\bar{D} \to J/\Psi$ + meson channels in central collisions of $Au+Au$ at $\sqrt{s}$ = 200 GeV which, however, is lower than the $J/\Psi$ yield expected from binary scaling of $pp$ collisions.Comment: 42 pages, including 14 eps figures, discussions extended and references added, to be published in Phys. Rev.

Scoping review : intergenerational resource transfer and possible enabling factors

We explore the intergenerational pattern of resource transfer and possible associated factors. A scoping review was conducted of quantitative, peer-reviewed, English-language studies related to intergenerational transfer or interaction. We searched AgeLine, PsycINFO, Social Work Abstracts, and Sociological Abstracts for articles published between Jane 2008 and December 2018. Seventy-five studies from 25 countries met the inclusion criteria. The scoping review categorised resource transfers into three types: financial, instrumental, and emotional support. Using an intergenerational solidarity framework, factors associated with intergenerational transfer were placed in four categories: (1) demographic factors (e.g., age, gender, marital status, education, and ethno-cultural background); (2) needs and opportunities factors, including health, financial resources, and employment status; (3) family structures, namely, family composition, family relationship, and earlier family events; and (4) cultural-contextual structures, including state policies and social norms. Those factors were connected to the direction of resource transfer between generations. Downward transfers from senior to junior generations occur more frequently than upward transfers in many developed countries. Women dominate instrumental transfers, perhaps influenced by traditional gender roles. Overall, the pattern of resource transfer between generations is shown, and the impact of social norms and social policy on intergenerational transfers is highlighted. Policymakers should recognise the complicated interplay of each factor with different cultural contexts. The findings could inform policies that strengthen intergenerational solidarity and support.</jats:p

Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy

Antigen specific immunotherapy aims to tolerise patients to specific autoantigens that are responsible for the pathology of an autoimmune disease. Immune tolerance is generated in conditions where the immune response is suppressed and thus gold nanoparticles (AuNPs) are an attractive drug delivery platform due to their anti-inflammatory effects and their potential to facilitate temporal and spatial delivery of a peptide autoantigen in conjunction with pro-tolerogenic elements. In this study we have covalently attached an autoantigen, currently under clinical evaluation for the treatment of type 1 diabetes (PIC19-A3 peptide), to AuNPs to create nanoscale (<5 nm), negatively charged (−40 to −60 mV) AuNP-peptide complexes for immunotherapy. We also employ a clinically approved microneedle delivery system, MicronJet600, to facilitate minimally-invasive intradermal delivery of the nanoparticle constructs to target skin-resident antigen presenting cells, which are known to be apposite target cells for immunotherapy. The AuNP-peptide complexes remain physically stable upon extrusion through microneedles and when delivered into ex vivo human skin they are able to diffuse rapidly and widely throughout the dermis (their site of deposition) and, perhaps more surprisingly, the overlying epidermal layer. Intracellular uptake was extensive, with Langerhans cells proving to be the most efficient cells at internalising the AuNP-peptide complex (94% of the local population within the treated region of skin). In vitro studies showed that uptake of the AuNP-peptide complexes by dendritic cells reduced the capacity of these cells to activate naïve T cells. This indicator of biological functionality encourages further development of the AuNP-peptide formulation, which is now being evaluated in clinical trials

Thermal and Chemical Equilibration in Relativistic Heavy Ion Collisions

We investigate the thermalization and the chemical equilibration of a parton plasma created from Au+Au collision at LHC and RHIC energies starting from the early moment when the particle momentum distributions in the central region become for the first time isotropic due to longitudinal cooling. Using the relaxation time approximation for the collision terms in the Boltzmann equations for gluons and for quarks and the real collision terms constructed from the simplest QCD interactions, we show that the collision times have the right behaviour for equilibration. The magnitude of the quark (antiquark) collision time remains bigger than the gluon collision time throughout the lifetime of the plasma so that gluons are equilibrating faster than quarks both chemically and kinetically. That is we have a two-stage equilibration scenario as has been pointed out already by Shuryak sometimes ago. Full kinetic equilibration is however slow and chemical equilibration cannot be completed before the onset of the deconfinement phase transition assumed to be at $T_c=200$ MeV. By comparing the collision entropy density rates of the different processes, we show explicitly that inelastic processes, and \emph{not} elastic processes as is commonly assumed, are dominant in the equilibration of the plasma and that gluon branching leads the other processes in entropy generation. We also show that, within perturbative QCD, processes with higher power in \alpha_s need not be less important for the purpose of equilibration than those with lower power. The state of equilibration of the system has also a role to play. We compare our results with those of the parton cascade model.Comment: 17 pages, revtex+psfig style with 14 embedded postscript figures, to appear in Phys. Rev.

Real-time nonequilibrium dynamics in hot QED plasmas: dynamical renormalization group approach

We study the real-time nonequilibrium dynamics in hot QED plasmas implementing a dynamical renormalization group and using the hard thermal loop (HTL) approximation. The focus is on the study of the relaxation of gauge and fermionic mean fields and on the quantum kinetics of the photon and fermion distribution functions. For semihard photons of momentum eT << k << T we find to leading order in the HTL that the gauge mean field relaxes in time with a power law as a result of infrared enhancement of the spectral density near the Landau damping threshold. The dynamical renormalization group reveals the emergence of detailed balance for microscopic time scales larger than 1/k while the rates are still varying with time. The quantum kinetic equation for the photon distribution function allows us to study photon production from a thermalized quark-gluon plasma (QGP) by off-shell effects. We find that for a QGP at temperature T ~ 200 MeV and of lifetime 10 < t < 50 fm/c the hard (k ~ T) photon production from off-shell bremsstrahlung (q -> q \gamma and \bar{q} -> \bar{q}\gamma) at O(\alpha) grows logarithmically in time and is comparable to that produced from on-shell Compton scattering and pair annihilation at O(\alpha \alpha_s). Fermion mean fields relax as e^{-\alpha T t ln(\omega_P t)} with \omega_P=eT/3 the plasma frequency, as a consequence of the emission and absorption of soft magnetic photons. A quantum kinetic equation for hard fermions is obtained directly in real time from a field theoretical approach improved by the dynamical renormalization group. The collision kernel is time-dependent and infrared finite.Comment: RevTeX, 46 pages, including 5 EPS figures, published versio