Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes.

Approximately 27-36 million patients in Europe have one of the ~ 5.000-8.000 known rare diseases. These patients often do not receive the care they need or they have a substantial delay from diagnosis to treatment. In March 2017, twenty-four European Reference Networks (ERNs) were launched with the aim to improve the care for these patients through cross border healthcare, in a way that the medical knowledge and expertise travels across the borders, rather than the patients. It is expected that through the ERNs, European patients with a rare disease get access to expert care more often and more quickly, and that research and guideline development will be accelerated resulting in improved diagnostics and therapies. The ERN on Genetic Tumour Risk Syndromes (ERN GENTURIS) aims to improve the identification, genetic diagnostics, prevention of cancer, and treatment of European patients with a genetic predisposition for cancer. The ERN GENTURIS focuses on syndromes such as hereditary breast cancer, hereditary colorectal cancer and polyposis, neurofibromatosis and more rare syndromes e.g. PTEN Hamartoma Tumour Syndrome, Li Fraumeni Syndrome and hereditary diffuse gastric cancer

Stochastic gain in population dynamics

We introduce an extension of the usual replicator dynamics to adaptive learning rates. We show that a population with a dynamic learning rate can gain an increased average payoff in transient phases and can also exploit external noise, leading the system away from the Nash equilibrium, in a reasonance-like fashion. The payoff versus noise curve resembles the signal to noise ratio curve in stochastic resonance. Seen in this broad context, we introduce another mechanism that exploits fluctuations in order to improve properties of the system. Such a mechanism could be of particular interest in economic systems.Comment: accepted for publication in Phys. Rev. Let

Control of wind strength and frequency in the Aral Sea basin during the late Holocene

Changing content of detrital input in laminated sediments traced by XRF scanning and microfacies analyses reflect prominent variations in sedimentation processes in the Aral Sea. A high-resolution record of titanium from a core retrieved in the northwestern Large Aral Sea allows a continuous reconstruction of wind strength and frequency in western Central Asia for the past 1500 yr. During AD 450-700, AD 1210-1265, AD 1350-1750 and AD 1800-1975, detrital inputs (bearing titanium) are high, documenting an enhanced early spring atmospheric circulation associated with an increase in intensity of the Siberian High pressure system over Central Asia. In contrast, lower titanium content during AD 1750-1800 and AD 1980-1985 reflects a diminished influence of the Siberian High during early spring with a reduced atmospheric circulation. A moderate circulation characterizes the time period AD 700-1150. Unprecedented weakened atmospheric circulation over western Central Asia are inferred during ca. AD 1180-1210 and AD 1265-1310 with a considerable decrease in dust storm frequency, sedimentation rates, lamination thickness and detrital inputs (screened at 40-μm resolution). Our results are concurrent with changes in the intensity of the Siberian High during the past 1400 yr as reported in the GISP2 Ice Core from Greenland. © 2007 University of Washington

Analytic Metaphysics versus Naturalized Metaphysics: The Relevance of Applied Ontology

The relevance of analytic metaphysics has come under criticism: Ladyman & Ross, for instance, have suggested do discontinue the field. French & McKenzie have argued in defense of analytic metaphysics that it develops tools that could turn out to be useful for philosophy of physics. In this article, we show first that this heuristic defense of metaphysics can be extended to the scientific field of applied ontology, which uses constructs from analytic metaphysics. Second, we elaborate on a parallel by French & McKenzie between mathematics and metaphysics to show that the whole field of analytic metaphysics, being useful not only for philosophy but also for science, should continue to exist as a largely autonomous field

Multi-basin depositional framework for moisture-balance reconstruction during the last 1300 years at Lake Bogoria, central Kenya Rift Valley

Multi-proxy analysis of sediment cores from five key locations in hypersaline, alkaline Lake Bogoria (central Kenya Rift Valley) has allowed reconstruction of its history of depositional and hydrological change during the past 1300years. Analyses including organic matter and carbonate content, granulometry, mineralogical composition, charcoal counting and high-resolution scanning of magnetic susceptibility and elemental geochemistry resulted in a detailed sedimentological and compositional characterization of lacustrine deposits in the three lake basins and on the two sills separating them. Thesepalaeolimnological data were supplemented with information on present-day sedimentation conditions based on seasonal sampling of settling particles and on measurement of physicochemical profiles through the water column. A new age model based on Pb-210, Cs-137 and C-14 dating captures the sediment chronology of this hydrochemically complex and geothermally fed lake. An extensive set of chronological tie points between the equivalent high-resolution proxy time series of the five sediment sequences allowed transfer of radiometric dates between the basins, enabling interbasin comparison of sedimentation dynamics through time. The resulting reconstruction demonstrates considerable moisture-balance variability through time, reflecting regional hydroclimate dynamics over the past 1300years. Between ca 690 and 950AD, the central and southern basins of Lake Bogoria were reduced to shallow and separated brine pools. In the former, occasional near-complete desiccation triggered massive trona precipitation. Between ca 950 and 1100AD, slightly higher water levels allowed the build-up of high pCO(2) leading to precipitation of nahcolite still under strongly evaporative conditions. Lake Bogoria experienced a pronounced highstand between ca 1100 and 1350AD, only to recede again afterwards. For a substantial part of the time between ca 1350 and 1800AD, the northern basin was probably disconnected from the united central and southern basins. Throughout the last two centuries, lake level has been relatively high compared to the rest of the past millennium. Evidence for increased terrestrial sediment supply in recent decades, due to anthropogenic soil erosion in the wider Bogoria catchment, is a reason for concern about possible adverse impacts on the unique ecosystem of Lake Bogoria

Optical techniques for 3D surface reconstruction in computer-assisted laparoscopic surgery

One of the main challenges for computer-assisted surgery (CAS) is to determine the intra-opera- tive morphology and motion of soft-tissues. This information is prerequisite to the registration of multi-modal patient-specific data for enhancing the surgeon’s navigation capabilites by observ- ing beyond exposed tissue surfaces and for providing intelligent control of robotic-assisted in- struments. In minimally invasive surgery (MIS), optical techniques are an increasingly attractive approach for in vivo 3D reconstruction of the soft-tissue surface geometry. This paper reviews the state-of-the-art methods for optical intra-operative 3D reconstruction in laparoscopic surgery and discusses the technical challenges and future perspectives towards clinical translation. With the recent paradigm shift of surgical practice towards MIS and new developments in 3D opti- cal imaging, this is a timely discussion about technologies that could facilitate complex CAS procedures in dynamic and deformable anatomical regions

Discovery of the Lanthipeptide Curvocidin and Structural Insights into its Trifunctional Synthetase CuvL

Lanthipeptides are ribosomally-synthesized natural products from bacteria featuring stable thioether-crosslinks and various bioactivities. Herein, we report on a new clade of tricyclic class-IV lanthipeptides with curvocidin from Thermomonospora curvata as its first representative. We obtained crystal structures of the corresponding lanthipeptide synthetase CuvL that showed a circular arrangement of its kinase, lyase and cyclase domains, forming a central reaction chamber for the iterative substrate processing involving nine catalytic steps. The combination of experimental data and artificial intelligence-based structural models identified the N-terminal subdomain of the kinase domain as the primary site of substrate recruitment. The ribosomal precursor peptide of curvocidin employs an amphipathic α-helix in its leader region as an anchor to CuvL, while its substrate core shuttles within the central reaction chamber. Our study thus reveals general principles of domain organization and substrate recruitment of class-IV and class-III lanthipeptide synthetases.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Research Training Group RTG 2473 "Bioactive Peptides"RTG 2473 "Bioactive Peptides"Peer Reviewe

On impact and volcanism across the Cretaceous-Paleogene boundary

The cause of the end-Cretaceous mass extinction is vigorously debated, owing to the occurrence of a very large bolide impact and flood basalt volcanism near the boundary. Disentangling their relative importance is complicated by uncertainty regarding kill mechanisms and the relative timing of volcanogenic outgassing, impact, and extinction. We used carbon cycle modeling and paleotemperature records to constrain the timing of volcanogenic outgassing. We found support for major outgassing beginning and ending distinctly before the impact, with only the impact coinciding with mass extinction and biologically amplified carbon cycle change. Our models show that these extinction-related carbon cycle changes would have allowed the ocean to absorb massive amounts of carbon dioxide, thus limiting the global warming otherwise expected from postextinction volcanism