Exclusion of PINK1 as candidate gene for the late-onset form of Parkinson's disease in two European populations

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recently, mutations in the PINK1 (PARK6) gene were shown to rarely cause autosomal-recessively transmitted, early-onset parkinsonism. In order to evaluate whether PINK1 contributes to the risk of common late-onset PD we analysed PINK1 sequence variations. A German (85 patients) and a Norwegian cohort (90 patients) suffering from late-onset PD were screened for mutations and single nucleotide polymorphisms (SNPs) in the PINK1 gene. Both cohorts consist of well-characterized patients presenting a positive family history of PD in ~17%. Investigations were performed by single strand conformation polymorphism (SSCP), denaturating high performance liquid chromatography (DHPLC) and sequencing analyses. SNP frequencies were compared by the χ(2 )test RESULTS: Several common SNPs were identified in our cohorts, including a recently identified coding variant (Q115L) in exon 1. Genotyping of the Q115L variation did not reveal significant frequency differences between patients and controls. Pathogenic mutations in the PINK1 gene were not identified, neither in the German nor in the Norwegian cohort. CONCLUSION: Sequence variation in the PINK1 gene appears to play a marginal quantitative role in the pathogenesis of the late-onset form of PD, in German and Norwegian cohorts, if at all

Dispersion relations for hadronic light-by-light scattering and the muon g

The largest uncertainties in the Standard Model calculation of the anomalous magnetic moment of the muon (g – 2)μ come from hadronic effects, and in a few years the subleading hadronic light-by-light (HLbL) contribution might dominate the theory error. We present a dispersive description of the HLbL tensor, which is based on unitarity, analyticity, crossing symmetry, and gauge invariance. This opens up the possibility of a data-driven determination of the HLbL contribution to (g – 2)μ with the aim of reducing model dependence and achieving a reliable error estimate. Our dispersive approach defines unambiguously the pion-pole and the pion-box contribution to the HLbL tensor. Using Mandelstam double-spectral representation, we have proven that the pion-box contribution coincides exactly with the one-loop scalar-QED amplitude, multiplied by the appropriate pion vector form factors. Using dispersive fits to high-statistics data for the pion vector form factor, we obtain αμπ-box=−15.92×10−11. A first model-independent calculation of effects of ππ intermediate states that go beyond the scalar-QED pion loop is also presented. We combine our dispersive description of the HLbL tensor with a partial-wave expansion and demonstrate that the known scalar-QED result is recovered after partial-wave resummation. After constructing suitable input for the γ*γ* → ππ helicity partial waves based on a pion-pole left-hand cut (LHC), we find that for the dominant charged-pion contribution this representation is consistent with the two-loop chiral prediction and the COMPASS measurement for the pion polarizability. This allows us to reliably estimate S-wave rescattering effects to the full pion box and leads to αμπ-box+αμ,J=0ππ,π-pole LHC=−241×10−11

Robotic ubiquitous cognitive ecology for smart homes

Robotic ecologies are networks of heterogeneous robotic devices pervasively embedded in everyday environments, where they cooperate to perform complex tasks. While their potential makes them increasingly popular, one fundamental problem is how to make them both autonomous and adaptive, so as to reduce the amount of preparation, pre-programming and human supervision that they require in real world applications. The project RUBICON develops learning solutions which yield cheaper, adaptive and efficient coordination of robotic ecologies. The approach we pursue builds upon a unique combination of methods from cognitive robotics, machine learning, planning and agent- based control, and wireless sensor networks. This paper illustrates the innovations advanced by RUBICON in each of these fronts before describing how the resulting techniques have been integrated and applied to a smart home scenario. The resulting system is able to provide useful services and pro-actively assist the users in their activities. RUBICON learns through an incremental and progressive approach driven by the feed- back received from its own activities and from the user, while also self-organizing the manner in which it uses available sensors, actuators and other functional components in the process. This paper summarises some of the lessons learned by adopting such an approach and outlines promising directions for future work

Hypothermia in a surgical intensive care unit

BACKGROUND: Inadvertent hypothermia is not uncommon in the immediate postoperative period and it is associated with impairment and abnormalities in various organs and systems that can lead to adverse outcomes. The aim of this study was to estimate the prevalence, the predictive factors and outcome of core hypothermia on admission to a surgical ICU. METHODS: All consecutive 185 adult patients who underwent scheduled or emergency noncardiac surgery admitted to a surgical ICU between April and July 2004 were admitted to the study. Tympanic membrane core temperature (Tc) was measured before surgery, on arrival at ICU and every two hours until 6 hours after admission. The following variables were also recorded: age, sex, body weight and height, ASA physical status, type of surgery, magnitude of surgical procedure, anesthesia technique, amount of intravenous fluids administered during anesthesia, use of temperature monitoring and warming techniques, duration of the anesthesia, ICU length of stay, hospital length of stay and SAPS II score. Patients were classified as either hypothermic (Tc ≤ 35°C) or normothermic (Tc> 35°C). Univariate analysis and multiple regression binary logistic with an odds ratio (OR) and its 95% Confidence Interval (95%CI) were used to compare the two groups of patients and assess the relationship between each clinical predictor and hypothermia. Outcome measured as ICU length of stay and mortality was also assessed. RESULTS: Prevalence of hypothermia on ICU admission was 57.8%. In univariate analysis temperature monitoring, use of warming techniques and higher previous body temperature were significant protective factors against core hypothermia. In this analysis independent predictors of hypothermia on admission to ICU were: magnitude of surgery, use of general anesthesia or combined epidural and general anesthesia, total intravenous crystalloids administrated and total packed erythrocytes administrated, anesthesia longer than 3 hours and SAPS II scores. In multiple logistic regression analysis significant predictors of hypothermia on admission to the ICU were magnitude of surgery (OR 3.9, 95% CI, 1.4–10.6, p = 0.008 for major surgery; OR 3.6, 95% CI, 1.5–9.0, p = 0.005 for medium surgery), intravenous administration of crystalloids (in litres) (OR 1.4, 95% CI, 1.1–1.7, p = 0.012) and SAPS score (OR 1.0, 95% CI 1.0–1.7, p = 0.014); higher previous temperature in ward was a significant protective factor (OR 0.3, 95% CI 0.1–0.7, p = 0.003). Hypothermia was neither a risk factor for hospital mortality nor a predictive factor for staying longer in ICU. CONCLUSION: The prevalence of patient hypothermia on ICU arrival was high. Hypothermia at time of admission to the ICU was not an independent factor for mortality or for staying longer in ICU

Insights into molecular mechanisms of disease in Neurodegeneration with Brain Iron Accumulation; unifying theories.

Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterised by dystonia, parkinsonism and spasticity. Iron accumulates in the basal ganglia and may be accompanied by Lewy bodies, axonal swellings and hyperphosphorylated tau depending on NBIA subtype. Mutations in 10 genes have been associated with NBIA that include Ceruloplasmin (Cp) and Ferritin Light Chain (FTL), both directly involved in iron homeostasis, as well as Pantothenate Kinase 2 (PANK2), Phospholipase A2 group 6 (PLA2G6), Fatty acid hydroxylase 2 (FA2H), Coenzyme A synthase (COASY), C19orf12, WDR45 and DCAF17 (C2orf37). These genes are involved in seemingly unrelated cellular pathways, such as lipid metabolism, Coenzyme A synthesis and autophagy. A greater understanding of the cellular pathways that link these genes and the disease mechanisms leading to iron dyshomeostasis is needed. Additionally, the major overlap seen between NBIA and more common neurodegenerative diseases may highlight conserved disease processes. In this review, we will discuss clinical and pathological findings for each NBIA-related gene, discuss proposed disease mechanisms such as mitochondrial health, oxidative damage, autophagy/mitophagy and iron homeostasis and speculate potential overlap between NBIA subtypes

The ASY-EOS experiment at GSI: investigating the symmetry energy at supra-saturation densities

The elliptic-flow ratio of neutrons with respect to protons in reactions of neutron rich heavy-ions systems at intermediate energies has been proposed as an observable sensitive to the strength of the symmetry term in the nuclear Equation Of State (EOS) at supra-saturation densities. The recent results obtained from the existing FOPI/LAND data for $^{197}$Au+$^{197}$Au collisions at 400 MeV/nucleon in comparison with the UrQMD model allowed a first estimate of the symmetry term of the EOS but suffer from a considerable statistical uncertainty. In order to obtain an improved data set for Au+Au collisions and to extend the study to other systems, a new experiment was carried out at the GSI laboratory by the ASY-EOS collaboration in May 2011.Comment: Talk given by P. Russotto at the 11th International Conference on Nucleus-Nucleus Collisions (NN2012), San Antonio, Texas, USA, May 27-June 1, 2012. To appear in the NN2012 Proceedings in Journal of Physics: Conference Series (JPCS

Multiphoton Quantum Optics and Quantum State Engineering

We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromnagnetic field, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.Comment: 198 pages, 36 eps figure

Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis

Triglycerides (TG) are one of the most common excipients used in oral lipid-based formulations. The chain length of the TG plays an important role in the oral bioavailability of the co-administered drug. Fatty acid (FA) chain-length specificity of porcine pancreatic lipase was studied by means of an in vitro lipolysis model under bio-relevant conditions at pH 6.80. In order to determine the total extent of lipolysis, back-titration experiments at pH 11.50 were performed. Results suggest that there is a specific chain length range (C2–C8) for which pancreatic lipase shows higher activity. This specificity could result from a combination of physicochemical properties of TGs, 2-monoglycerides (2-MGs) and FAs, namely the droplet size of the TGs, the solubility of 2-MGs within mixed micelles, and the relative stability of the FAs as leaving groups in the hydrolysis reaction. During experimentation, it was evident that an optimisation of lipolysis conditions was needed for tighter control over pH levels so as to better mimic in vivo conditions. 1 M NaOH, 3.5 mL/min maximum dosing rate, and 3 μL/min minimum dosing rate were the optimised set of conditions that allowed better pH control, as well as the differentiation of the lipolysis of different lipid loads