«Smarter Medicine»: 5 Interventionen, die in der ambulanten allgemeinen inneren Medizin vermieden werden sollten

Seit 2012 befasst sich die Schweizerische Gesellschaft für Allgemeine Innere Medizin mit der Problematik der Überdiagnostik und Überversorgung in der Medizin. Nun hat sie beschlossen, eine Liste mit fünf Untersuchungen auf dem Gebiet der ambulanten allgemeinen inneren Medizin zusammenzustellen, die ohne oder mit nur geringem Nutzen bei zahlreichen Patienten durchgeführt werden, gleichzeitig jedoch unerwünschte Nebenwirkungen haben können und zum Anstieg der Gesundheitskosten beitragen

Coulomb plasmas in outer envelopes of neutron stars

Outer envelopes of neutron stars consist mostly of fully ionized, strongly coupled Coulomb plasmas characterized by typical densities about 10^4-10^{11} g/cc and temperatures about 10^4-10^9 K. Many neutron stars possess magnetic fields about 10^{11}-10^{14} G. Here we briefly review recent theoretical advances which allow one to calculate thermodynamic functions and electron transport coefficients for such plasmas with an accuracy required for theoretical interpretation of observations.Comment: 4 pages, 2 figures, latex2e using cpp2e.cls (included). Proc. PNP-10 Workshop, Greifswald, Germany, 4-9 Sept. 2000. Accepted for publication in Contrib. Plasma Phys. 41 (2001) no. 2-

Using Genetic Diversity to Understand Susceptibility to Cognitive Decline in Aging and Alzheimer’s Disease

An individual\u27s genetic makeup plays an important role in determining susceptibility to cognitive aging and transition to dementia such as Alzheimer\u27s disease (AD). Identifying the specific genetic variants that contribute to cognitive aging and AD may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we turned to genetically diverse mice from the BXD genetic reference panel (GRP) to overcome some of the barriers traditionally associated with human studies. Using a forward genetics screen, we first identified and validated the gene heterochromatin protein l binding protein 3 (Hp1bp3) as a novel modulator of normal cognitive aging. We then demonstrated that targeted knockdown of Hp1bp3 in the hippocampus by 50-75% was sufficient to induce cognitive deficits and transcriptional changes reminiscent of those observed in aging and AD, namely an increase in inflammatory pathways and decrease in neuronal and synaptically-localized transcripts. We also show Hp1bp3 is a translationally relevant target, as transcriptional changes induced by our targeted knockdown significantly overlapped those observed in the aging human brain. In addition, HPlBP3 itself was decreased in the hippocampus of cognitively impaired aging humans. In summary, our results suggest therapeutics designed to target either Hp1bp3 or its downstream effectors may be useful promoting cognitive longevity. We next expanded on our findings that the BXDs were variably susceptible to cognitive aging and combined the BXD GRP with a well-established transgenic mouse model of AD harboring 5 familial AD mutations, the 5XFAD model. The resulting panel, which we termed the AD-BXDs, consists of genetically diverse yet isogenic Fl mice that all harbor the same high-risk human AD mutations but who differ across the remainder of their genome. We first showed that genetic variation profoundly modified the impact of human AD mutations on both cognitive and pathological phenotypes. We then validated this complex AD model by demonstrating high degrees of genetic, transcriptomic, and phenotypic overlap with human AD. Genetic mapping was used to identify novel genomic loci that modified susceptibility or resilience to cognitive and pathological symptoms of AD. Finally, we used transcriptome profiling to identify gene networks present in the pre-symptomatic mouse brain that predict cognitive performance at an advanced age. Together, the candidates identified through these analyses highlight new potential drivers of susceptibility or resilience to AD and contribute significantly to our understanding of early, potentially causal disease mechanisms. In summary, work here highlights the utility of genetically diverse mice to elucidate mechanisms underlying complex human disease, namely cognitive aging and AD. In addition, we developed a novel AD mouse population as an innovative and reproducible resource for the study of mechanisms underlying AD. Data presented here provides convincing evidence that preclinical models incorporating genetic diversity may better translate to human disease. Due to the reproducible nature of the BXDs and resulting AD-BXDs, this approach creates substantial opportunities to develop improved models of human aging and AD as well as develop a better understanding of precise mechanisms underlying disease. Together, these resources may ultimately enable precision medicine approaches across a diverse population. Finally, our experimental design is likely to be broadly applicable to mouse models of human disease that incorporate a dominantly inherited high-risk genotype in the form of a transgene or other genetic perturbation, enhancing the general utility of results reported here

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations

Study of charmonium production in b -hadron decays and first evidence for the decay Bs0

Using decays to φ-meson pairs, the inclusive production of charmonium states in b-hadron decays is studied with pp collision data corresponding to an integrated luminosity of 3.0 fb−1, collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. Denoting byBC ≡ B(b → C X) × B(C → φφ) the inclusive branching fraction of a b hadron to a charmonium state C that decays into a pair of φ mesons, ratios RC1C2 ≡ BC1 /BC2 are determined as Rχc0ηc(1S) = 0.147 ± 0.023 ± 0.011, Rχc1ηc(1S) =0.073 ± 0.016 ± 0.006, Rχc2ηc(1S) = 0.081 ± 0.013 ± 0.005,Rχc1 χc0 = 0.50 ± 0.11 ± 0.01, Rχc2 χc0 = 0.56 ± 0.10 ± 0.01and Rηc(2S)ηc(1S) = 0.040 ± 0.011 ± 0.004. Here and below the first uncertainties are statistical and the second systematic.Upper limits at 90% confidence level for the inclusive production of X(3872), X(3915) and χc2(2P) states are obtained as RX(3872)χc1 < 0.34, RX(3915)χc0 < 0.12 andRχc2(2P)χc2 < 0.16. Differential cross-sections as a function of transverse momentum are measured for the ηc(1S) andχc states. The branching fraction of the decay B0s → φφφ is measured for the first time, B(B0s → φφφ) = (2.15±0.54±0.28±0.21B)×10−6. Here the third uncertainty is due to the branching fraction of the decay B0s → φφ, which is used for normalization. No evidence for intermediate resonances is seen. A preferentially transverse φ polarization is observed.The measurements allow the determination of the ratio of the branching fractions for the ηc(1S) decays to φφ and p p asB(ηc(1S)→ φφ)/B(ηc(1S)→ p p) = 1.79 ± 0.14 ± 0.32

BB flavour tagging using charm decays at the LHCb experiment

An algorithm is described for tagging the flavour content at production of neutral $B$ mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a $B$ meson with the charge of a reconstructed secondary charm hadron from the decay of the other $b$ hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes $B^+ \to J/\psi \, K^+$ and $B^0 \to J/\psi \, K^{*0}$ using $3.0\mathrm{\,fb}^{-1}$ of data collected by the LHCb experiment at $pp$ centre-of-mass energies of $7\mathrm{\,TeV}$ and $8\mathrm{\,TeV}$. Its tagging power on these samples of $B \to J/\psi \, X$ decays is $(0.30 \pm 0.01 \pm 0.01) \%$.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

A model-independent confirmation of the Z(4430)−Z(4430)^- state

The decay $B^0\to \psi(2S) K^+\pi^-$ is analyzed using $\rm 3~fb^{-1}$ of $pp$ collision data collected with the LHCb detector. A model-independent description of the $\psi(2S) \pi$ mass spectrum is obtained, using as input the $K\pi$ mass spectrum and angular distribution derived directly from data, without requiring a theoretical description of resonance shapes or their interference. The hypothesis that the $\psi(2S)\pi$ mass spectrum can be described in terms of $K\pi$ reflections alone is rejected with more than 8$\sigma$ significance. This provides confirmation, in a model-independent way, of the need for an additional resonant component in the mass region of the $Z(4430)^-$ exotic state.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-038.htm

Model-independent evidence for J/ψpJ/\psi p contributions to Λb0→J/ψpK−\Lambda_b^0\to J/\psi p K^- decays

The data sample of $\Lambda_b^0\to J/\psi p K^-$ decays acquired with the LHCb detector from 7 and 8~TeV $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$, is inspected for the presence of $J/\psi p$ or $J/\psi K^-$ contributions with minimal assumptions about $K^- p$ contributions. It is demonstrated at more than 9 standard deviations that $\Lambda_b^0\to J/\psi p K^-$ decays cannot be described with $K^- p$ contributions alone, and that $J/\psi p$ contributions play a dominant role in this incompatibility. These model-independent results support the previously obtained model-dependent evidence for $P_c^+\to J/\psi p$ charmonium-pentaquark states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the end

Measurement of the mass and lifetime of the Ωb−\Omega_b^- baryon

A proton-proton collision data sample, corresponding to an integrated luminosity of 3 fb$^{-1}$ collected by LHCb at $\sqrt{s}=7$ and 8 TeV, is used to reconstruct $63\pm9$ $\Omega_b^-\to\Omega_c^0\pi^-$, $\Omega_c^0\to pK^-K^-\pi^+$ decays. Using the $\Xi_b^-\to\Xi_c^0\pi^-$, $\Xi_c^0\to pK^-K^-\pi^+$ decay mode for calibration, the lifetime ratio and absolute lifetime of the $\Omega_b^-$ baryon are measured to be \begin{align*} \frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\ \tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the uncertainties are statistical, systematic and from the calibration mode (for $\tau_{\Omega_b^-}$ only). A measurement is also made of the mass difference, $m_{\Omega_b^-}-m_{\Xi_b^-}$, and the corresponding $\Omega_b^-$ mass, which yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2. \end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm

Search for the rare decays B0→J/ψγB^{0}\to J/\psi \gamma and Bs0→J/ψγB^{0}_{s} \to J/\psi \gamma

A search for the rare decay of a $B^{0}$ or $B^{0}_{s}$ meson into the final state $J/\psi\gamma$ is performed, using data collected by the LHCb experiment in $pp$ collisions at $\sqrt{s}=7$ and $8$ TeV, corresponding to an integrated luminosity of 3 fb$^{-1}$. The observed number of signal candidates is consistent with a background-only hypothesis. Branching fraction values larger than $1.7\times 10^{-6}$ for the $B^{0}\to J/\psi\gamma$ decay mode are excluded at 90% confidence level. For the $B^{0}_{s}\to J/\psi\gamma$ decay mode, branching fraction values larger than $7.4\times 10^{-6}$ are excluded at 90% confidence level, this is the first branching fraction limit for this decay.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-044.htm