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

Deglacial Variability in Okhotsk Sea Intermediate Water Ventilation and Biogeochemistry: Implications for North Pacific Nutrient Supply and Productivity

Highlights • Multi-proxy, multi-site reconstruction of Okhotsk Sea palaeo-productivity and mid-depth ventilation changes from 8 to 18 ka. • Link between hinterland river discharge and downstream Okhotsk Sea Intermediate Water (OSIW) ventilation/nutrient signatures. • Surplus Fe, Si(OH)4 export in OSIW during Bølling-Allerød to pelagic Pacific supported transient nutrient-replete conditions. • Subarctic and subtropical Pacific gyres disconnected during Bølling-Allerød, with restricted OSIW flow to lower latitudes. • Deglacial OSIW export and mid-depth Pacific biogeochemistry modulate millennial-scale regional CO2 source/sink conditions. The modern North Pacific plays a critical role in marine biogeochemical cycles, as an oceanic sink of CO2 and by bearing some of the most productive and least oxygenated waters of the World Ocean. The capacity to sequester CO2 is limited by efficient nutrient supply to the mixed layer, particularly from deeper water masses in the Pacific's subarctic and marginal seas. The region is in addition only weakly ventilated by North Pacific Intermediate Water (NPIW), which receives its characteristics from Okhotsk Sea Intermediate Water (OSIW). Here, we present reconstructions of intermediate water ventilation and productivity variations in the Okhotsk Sea that cover the last glacial termination between eight and 18 ka, based on a set of high-resolution sediment cores from sites directly downstream of OSIW formation. In a multi-proxy approach, we use total organic carbon (TOC), chlorin, biogenic opal, and CaCO3 concentrations as indicators for biological productivity. C/N ratios and XRF scanning-derived elemental ratios (Si/K and Fe/K), as well as chlorophycean algae counts document changes in Amur freshwater and sediment discharge that condition the OSIW. Stable carbon isotopes of epi- and shallow endobenthic foraminifera, in combination with 14C analyses of benthic and planktic foraminifera imply decreases in OSIW oxygenation during deglacial warm phases from c. 14.7 to 13 ka (Bølling-Allerød) and c. 11.4 to 9 ka (Preboreal). No concomitant decreases in Okhotsk Sea benthic-planktic ventilation ages are observed, in contrast to nearby, but southerly locations on the Japan continental margin. We attribute Okhotsk Sea mid-depth oxygenation decreases in times of enhanced organic matter supply to maxima in remineralization within OSIW, in line with multi-proxy evidence for maxima in primary productivity and supply of organic matter. Sedimentary C/N and Fe/K ratios indicate more effective entrainment of nutrients into OSIW and thus an increased nutrient load of OSIW during deglacial warm periods. Correlation of palynological and sedimentological evidence from our sites with hinterland reference records suggests that millennial-scale changes in OSIW oxygen and nutrient concentrations were largely influenced by fluvial freshwater runoff maxima from the Amur, caused by a deglacial northeastward propagation of the East Asian Summer Monsoon that increased precipitation and temperatures, in conjunction with melting of permafrost in the Amur catchment area. We suggest that OSIW ventilation minima and the high lateral supply of nutrients and organic matter during the Allerød and Preboreal are mechanistically linked to concurrent maxima in nutrient utilization and biological productivity in the subpolar Northwest Pacific. In this scenario, increased export of nutrients from the Okhotsk Sea during deglacial warm phases supported subarctic Pacific shifts from generally Fe-limiting conditions to transient nutrient-replete regimes through enhanced advection of mid-depth nutrient- and Fe-rich OSIW into the upper ocean. This mechanism may have moderated the role of the subarctic Pacific in the deglacial CO2 rise on millennial timescales by combining the upwelling of old carbon-rich waters with a transient delivery of mid-depth-derived bio-available Fe and silicate

Self-organized critical neural networks

A mechanism for self-organization of the degree of connectivity in model neural networks is studied. Network connectivity is regulated locally on the basis of an order parameter of the global dynamics which is estimated from an observable at the single synapse level. This principle is studied in a two-dimensional neural network with randomly wired asymmetric weights. In this class of networks, network connectivity is closely related to a phase transition between ordered and disordered dynamics. A slow topology change is imposed on the network through a local rewiring rule motivated by activity-dependent synaptic development: Neighbor neurons whose activity is correlated, on average develop a new connection while uncorrelated neighbors tend to disconnect. As a result, robust self-organization of the network towards the order disorder transition occurs. Convergence is independent of initial conditions, robust against thermal noise, and does not require fine tuning of parameters.Comment: 5 pages RevTeX, 7 figures PostScrip

Precessional pacing of tropical ocean carbon export during the Late Cretaceous

The marine biological carbon pump, which exports organic carbon out of the surface ocean, plays an essential role in sequestering carbon from the atmosphere, thus impacting climate and affecting marine ecosystems. Orbital variations in solar insolation modulate these processes, but their influence on the tropical Pacific during the Late Cretaceous is unknown. Here we present a high-resolution composite record of elemental barium from deep-sea sediments as a proxy for organic carbon export out of the surface oceans (i.e., export production) from Shatsky Rise in the tropical Pacific. Variations in export production in the Pacific during the Maastrichtian, from 71.5 to 66 million years ago, were dominated by precession and less so by eccentricity modulation or obliquity, confirming that tropical surface-ocean carbon dynamics were influenced by seasonal insolation in the tropics during this greenhouse period. We suggest that precession paced primary production in the tropical Pacific and recycling in the euphotic zone by changing water column stratification, upwelling intensity, and continental nutrient fluxes. Benthic foraminiferal accumulation rates covaried with export production, providing evidence for bentho-pelagic coupling of the marine biological carbon pump across these high-frequency changes in a cool greenhouse planet.</p

The Effects of COVID-19 on the Placenta During Pregnancy.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission

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

Evidence for weathering and volcanism during the PETM from Arctic Ocean and Peri-Tethys osmium isotope records

Sudden global warming during the Paleocene–Eocene Thermal Maximum (PETM, 55.9 Ma) occurred because of the rapid release of several thousand gigatonnes of isotopically light carbon into the oceans and atmosphere; however, the cause of this release is not well understood. Some studies have linked carbon injection to volcanic activity associated with the North Atlantic Igneous Province (NAIP), while others have emphasised carbon cycle feedbacks associated with orbital forcing. This study presents the osmium isotope compositions of mudrocks that were deposited during the PETM at four locations (one from the Arctic Ocean, and three from the Peri-Tethys). The Os-isotope records all exhibit a shift of similar magnitude towards relatively radiogenic values across the PETM. This observation confirms that there was a transient, global increase in the flux of radiogenic Os from the weathering of continental rocks in response to elevated temperatures at that time. The tectonic effects of NAIP volcanic emplacement near the onset of the PETM is recorded by anomalously radiogenic Os-isotope compositions of PETM-age Arctic Ocean samples, which indicate an interval of hydrographic restriction that can be linked tectonic uplift due to hotspot volcanism in the North Atlantic seaway. The Peri-Tethys data also document a transient, higher flux of unradiogenic osmium into the ocean near the beginning of the PETM, most likely from the weathering of young mafic rocks associated with the NAIP. These observations support the hypothesis that volcanism played a major role in triggering the cascade of environmental changes during the PETM, and highlight the influence of paleogeography on the Os isotope characteristics of marine water masses

Enhanced terrestrial carbon export from East Antarctica during the early Eocene

Terrestrial organic carbon (TerrOC) acts as an important CO2 sink when transported via rivers to the ocean and sequestered in coastal marine sediments. This mechanism might help to modulate atmospheric CO2 levels over short- and long timescales (103 to 106 years), but its importance during past warm climates remains unknown. Here we use terrestrial biomarkers preserved in coastal marine sediment samples from Wilkes Land, East Antarctica (~67°S) to quantify TerrOC burial during the early Eocene (~54.4 to 51.5 Ma). Terrestrial biomarker distributions indicate the delivery of plant-, soil- and peat-derived organic carbon (OC) into the marine realm. Mass accumulation rates of plant- (long-chain n-alkane) and soil-derived (hopane) biomarkers dramatically increase between the earliest Eocene (~54 Ma) and the early Eocene Climatic Optimum (EECO; ~53 Ma). This coincides with increased OC mass accumulation rates and indicates enhanced TerrOC burial during the EECO. Leaf wax δ 2H values indicate that the EECO was characterised by wetter conditions relative to the earliest Eocene, suggesting that hydroclimate exerts a first-order control on TerrOC export. Our results indicate that TerrOC burial in coastal marine sediments UOB Open could have acted as an important negative feedback mechanism during the early Eocene, but also during other warm climate intervals

A High-Fidelity Benthic Stable Isotope Record of Late Cretaceous-Early Eocene Climate Change and Carbon-Cycling

The Late Cretaceous–Early Paleogene is the most recent period in Earth history that experienced sustained global greenhouse warmth on multimillion year timescales. Yet, knowledge of ambient climate conditions and the complex interplay between various forcing mechanisms are still poorly constrained. Here we present a 14.75 million‐year‐long, high‐resolution, orbitally tuned record of paired climate change and carbon‐cycling for this enigmatic period (~67–52 Ma), which we compare to an up‐to‐date compilation of atmospheric pCO2 records. Our climate and carbon‐cycling records, which are the highest resolution stratigraphically complete records to be constructed from a single marine site in the Atlantic Ocean, feature all major transient warming events (termed “hyperthermals”) known from this time period. We identify eccentricity as the dominant pacemaker of climate and the carbon cycle throughout the Late Maastrichtian to Early Eocene, through the modulation of precession. On average, changes in the carbon cycle lagged changes in climate by ~23,000 years at the long eccentricity (405,000‐year) band, and by ~3,000–4,500 years at the short eccentricity (100,000‐year) band, suggesting that light carbon was released as a positive feedback to warming induced by orbital forcing. Our new record places all known hyperthermals of the Late Maastrichtian–Early Eocene into temporal context with regards to evolving ambient climate of the time. We constrain potential carbon cycle influences of Large Igneous Province volcanism associated with the Deccan Traps and North Atlantic Igneous Province, as well as the sensitivity of climate and the carbon‐cycle to the 2.4 million‐year‐long eccentricity cycle

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