Modeling extreme wave heights from laboratory experiments with the nonlinear Schrödinger equation

Spatial variation of nonlinear wave groups with different initial envelope shapes is theoretically studied first, confirming that the simplest nonlinear theoretical model is capable of describing the evolution of propagating wave packets in deep water. Moreover, three groups of laboratory experiments run in the wave basin of CEHIPAR (Canal de Experiencias Hidrodinámicas de El Pardo, known also as El Pardo Model Basin) was founded in 1928 by the Spanish Navy. are systematically compared with the numerical simulations of the nonlinear Schrödinger equation. Although a little overestimation is detected, especially in the set of experiments characterized by higher initial wave steepness, the numerical simulation still displays a high degree of agreement with the laboratory experiments. Therefore, the nonlinear Schrödinger equation catches the essential characteristics of the extreme waves and provides an important physical insight into their generation. The modulation instability, resulting from the quasi-resonant four-wave interaction in a unidirectional sea state, can be indicated by the coefficient of kurtosis, which shows an appreciable correlation with the extreme wave height and hence is used in the modified Edgeworth–Rayleigh distribution. Finally, some statistical properties on the maximum wave heights in different sea states have been related with the initial Benjamin–Feir index

Rogue waters

In this essay we give an overview on the problem of rogue or freak wave formation in the ocean. The matter of the phenomenon is a sporadic occurrence of unexpectedly high waves on the sea surface. These waves cause serious danger for sailing and sea use. A number of huge wave accidents resulted in damages, ship losses and people injuries and deaths are known. Now marine researchers do believe that these waves belong to a specific kind of sea waves, not taken into account by conventional models for sea wind waves. This paper addresses to the nature of the rogue wave problem from the general viewpoint based on the wave process ideas. We start introducing some primitive elements of sea wave physics with the purpose to pave the way for the further discussion. We discuss linear physical mechanisms which are responsible for high wave formation, at first. Then, we proceed with description of different sea conditions, starting from the open deep sea, and approaching the sea cost. Nonlinear effects which are able to cause rogue waves are emphasised. In conclusion we briefly discuss the generality of the physical mechanisms suggested for the rogue wave explanation; they are valid for rogue wave phenomena in other media such as solid matters, superconductors, plasmas and nonlinear opticsComment: will be published in Contemporary Physic

Long-term safety and efficacy of patisiran for hereditary transthyretin-mediated amyloidosis with polyneuropathy: 12-month results of an open-label extension study

Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change –4·0, 95 % CI –7·7 to −0·3; phase 2 OLE patisiran –4·7, –11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment −1·4, 95% CI –6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran. Funding: Alnylam Pharmaceuticals

Stress neuropeptide levels in adults with chest pain due to coronary artery disease: potential implications for clinical assessment

: Substance P (SP) and neuropeptide Y (NPY) are neuropeptides involved in nociception. The study of biochemical markers of pain in communicating critically ill coronary patients may provide insight for pain assessment and management in critical care. Purpose of the study was to to explore potential associations between plasma neuropeptide levels and reported pain intensity in coronary critical care adults, in order to test the reliability of SP measurements for objective pain assessment in critical care