Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment

Emplacement mechanisms of submarine landslides and their effect on ocean circulation and climate

Submarine landslides are some of the largest-scale geological events on the surface of the planet. They can generate dangerous tsunamis posing serious geohazards. They move large (up to 3,000 km3) amounts of material and can disintegrate to form large clouds of sediment. The main aim of this thesis is to use global circulation models to study the effect of these sediment clouds on the ocean circulation and climate. A driver for this question is the coincidence in time of the largest submarine landslide in the geological record, the Storegga Slide, and the last major extreme climatic event, the 8.2 ka cold event.Arctic regional ocean circulation models are set up to simulate a large and dense water mass at the bottom of the Norwegian Basin. A mechanism for the dense mud cloud to influence the circulation is shown. The main driver for the perturbation is the strong steric effect generated, i.e. changes in density generating changes in surface height; this increases incoming fluxes of water into the Nordic Seas, increasing the freshwater content. Subsequently we observe a reduction in convection in the Nordic Seas and ex- ported deep water through Denmark Strait, thus affecting the Meridional Overturning Circulation (MOC).This climate influencing mechanism proves to be robust under a number of different parameter choices ranging from the size and concentration of the perturbation to the horizontal resolution of the model to the timescale of the perturbation. It is therefore suggested that the Storegga Slide might have played a major role in the 8.2ka cold event.Finally, a case study from the Norwegian Margin is presented, using a newly collected high resolution multibeam bathymetry dataset together with a recompilation of sites on the Norwegian coasts to study landslide frequency and tsunamigenesis. It is shown that multiple large (>400 km3) landslides can occur during a single glacial period over the same area, contrasting with previously suggested theories that only one slide can occur during each glacial period. Moreover, it is concluded that not all large submarine landslides generate large and widespread tsunamis

Direct monitoring reveals initiation of turbidity currents from extremely dilute river plumes

Rivers (on land) and turbidity currents (in the ocean) are the most important sediment transport processes on Earth. Yet, how rivers generate turbidity currents as they enter the coastal ocean remains poorly understood. The current paradigm, based on laboratory experiments, is that turbidity currents are triggered when river plumes exceed a threshold sediment concentration of ~1 kg.m‐3. Here we present direct observations of an exceptionally dilute river‐plume, with sediment concentrations one order of magnitude below this threshold (0.07 kg.m‐3), which generated a fast (1.5 m.s‐1), erosive, short‐lived (6 min) turbidity current. However, no turbidity current occurred during subsequent river‐plumes. We infer that turbidity currents are generated when fine‐sediment, accumulating in a tidal turbidity maximum, is released during spring tide. This means that very dilute river‐plumes can generate turbidity currents more frequently and in a wider range of locations, than previously thought

Key future directions for research on turbidity currents and their deposits

Turbidity currents, and other types of submarine sediment density flow, redistribute more sediment across the surface of the Earth than any other sediment flow process, yet their sediment concentration has never been measured directly in the deep ocean. The deposits of these flows are of societal importance as imperfect records of past earthquakes and tsunamogenic landslides and as the reservoir rocks for many deep-water petroleum accumulations. Key future research directions on these flows and their deposits were identified at an informal workshop in September 2013. This contribution summarizes conclusions from that workshop, and engages the wider community in this debate. International efforts are needed for an initiative to monitor and understand a series of test sites where flows occur frequently, which needs coordination to optimize sharing of equipment and interpretation of data. Direct monitoring observations should be combined with cores and seismic data to link flow and deposit character, whilst experimental and numerical models play a key role in understanding field observations. Such an initiative may be timely and feasible, due to recent technological advances in monitoring sensors, moorings, and autonomous data recovery. This is illustrated here by recently collected data from the Squamish River delta, Monterey Canyon, Congo Canyon, and offshore SE Taiwan. A series of other key topics are then highlighted. Theoretical considerations suggest that supercritical flows may often occur on gradients of greater than ??0.6°. Trains of up-slope-migrating bedforms have recently been mapped in a wide range of marine and freshwater settings. They may result from repeated hydraulic jumps in supercritical flows, and dense (greater than approximately 10% volume) near-bed layers may need to be invoked to explain transport of heavy (25 to 1,000 kg) blocks. Future work needs to understand how sediment is transported in these bedforms, the internal structure and preservation potential of their deposits, and their use in facies prediction. Turbulence damping may be widespread and commonplace in submarine sediment density flows, particularly as flows decelerate, because it can occur at low (<?0.1%) volume concentrations. This could have important implications for flow evolution and deposit geometries. Better quantitative constraints are needed on what controls flow capacity and competence, together with improved constraints on bed erosion and sediment resuspension. Recent advances in understanding dilute or mainly saline flows in submarine channels should be extended to explore how flow behavior changes as sediment concentrations increase. The petroleum industry requires predictive models of longer-term channel system behavior and resulting deposit architecture, and for these purposes it is important to distinguish between geomorphic and stratigraphic surfaces in seismic datasets. Validation of models, including against full-scale field data, requires clever experimental design of physical models and targeted field programs

Direct monitoring reveals initiation of turbidity currents from extremely dilute river plumes

Rivers (on land) and turbidity currents (in the ocean) are the most important sediment transport processes on Earth. Yet, how rivers generate turbidity currents as they enter the coastal ocean remains poorly understood. The current paradigm, based on laboratory experiments, is that turbidity currents are triggered when river plumes exceed a threshold sediment concentration of ~1 kg.m‐3. Here we present direct observations of an exceptionally dilute river‐plume, with sediment concentrations one order of magnitude below this threshold (0.07 kg.m‐3), which generated a fast (1.5 m.s‐1), erosive, short‐lived (6 min) turbidity current. However, no turbidity current occurred during subsequent river‐plumes. We infer that turbidity currents are generated when fine‐sediment, accumulating in a tidal turbidity maximum, is released during spring tide. This means that very dilute river‐plumes can generate turbidity currents more frequently and in a wider range of locations, than previously thought