Signatures of slope failures and river-delta collapses in a perialpine lake (Lake Lucerne, Switzerland)

Historical reports from the 17th Century document two destructive tsunamis with runups exceeding 5 m, affecting proximal basins of Lake Lucerne (Switzerland). One event in AD 1601 is coeval with a strong nearby earthquake (MW ca 5.9), which caused extensive slope failures in many parts of the lake. The second event in AD 1687 is associated with an apparently spontaneous partial collapse of the Muota river delta. This study combines high-resolution bathymetry, reflection seismic and lithological data in order to document the sedimentary and morphological signatures of the two subaqueous mass movements that probably generated the observed tsunamis. Such mass movements are significant as a common sedimentation process and as natural hazard in fjord-type lakes and similar environments. The deposits, covering large parts of the basins with thicknesses reaching >10 m, consist of two subunits: A lower ‘massflow deposit’ contains variably deformed sediments from the source areas. Its emplacement affected pre-existing sediments, incorporating thin sediment slices into the deposit and increasing its volume. Deep-reaching deformation near This is an Accepted Article that has been peer-reviewed and approved for publication in the Sedimentology, but has yet to undergo copy-editing and proof correction.

Sediment dynamics in the subaquatic channel of the Rhone delta (Lake Geneva, France/Switzerland)

bstract With its smaller size, well-known boundary conditions, and the availability of detailed bathymetric data, Lake Geneva’s subaquatic canyon in the Rhone Delta is an excellent analogue to understand sedimentary pro- cesses in deep-water submarine channels. A multidisciplinary research effort was undertaken to unravel the sediment dynamics in the active canyon. This approach included innovative coring using the Russian MIR sub- mersibles, in situ geotechnical tests, and geophysical, sedimentological, geochemical and radiometric analysis techniques. The canyon floor/levee complex is character- ized by a classic turbiditic system with frequent spillover events. Sedimentary evolution in the active canyon is controlled by a complex interplay between erosion and sedimentation processes. In situ profiling of sediment strength in the upper layer was tested using a dynamic penetrometer and suggests that erosion is the governing mechanism in the proximal canyon floor while sedimen- tation dominates in the levee structure. Sedimentation rates progressively decrease down-channel along the levee structure, with accumulation exceeding 2.6 cm/year in the proximal levee. A decrease in the frequency of turbidites upwards along the canyon wall suggests a progressive confinement of the flow through time. The multi-proxy methodology has also enabled a qualitative slope-stability assessment in the levee structure. The rapid sediment loading, slope undercutting and over-steepening, and increased pore pressure due to high methane concentrations hint at a potential instability of the proximal levees. Fur- thermore, discrete sandy intervals show very high methane concentrations and low shear strength and thus could cor- respond to potentially weak layers prone to scarp failures.

Combined systemic and local morpholino treatment rescues the phenotype of the SMA Delta 7 mouse model

Spinal muscular atrophy (SMA) is a childhood fatal motor neuron disease caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, currently without effective treatment. One possible therapeutic approach is the use of antisense oligonucleotides (ASOs) to redirect the splicing of a paralogous gene, SMN2, to increase the production of functional SMN protein. A range of ASOs with different chemical properties is suitable for these applications, including a morpholino (MO) variant, which has a particularly excellent safety, and efficacy profile. We used a 25- nt MO oligomer sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D(-10-34)) with superior efficacy to previously described sequences also in transgenic SMA Δ7 mice. The combined local and systemic administration of MO (bare or conjugated to octa-guanidine) is necessary to increase full-length SMN expression, leading to robust neuropathological features improvement and survival rescue. Additionally, several snRNA levels that are dysregulated in SMA mice could be restored by MO treatment. These results demonstrate that MO therapy is efficacious and can result in phenotypic rescue. These data provide important insights for the development of therapeutic strategies in SMA patients.

Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD

An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN).

A pilot study for targeted surveillance of bovine spongiform encephalopathy in Nigeria.

Bovine spongiform encephalopathy (BSE), popularly known as 'mad cow disease', led to an epidemic in Europe that peaked in the mid-1990s. Its impact on developing countries, such as Nigeria, has not been fully established as information on livestock and surveillance has eluded those in charge of this task. The BSE risk to Nigeria's cattle population currently remains undetermined, which has resulted in international trade restrictions on commodities from the cattle population. This is mainly because of a lack of updated BSE risk assessments and disease surveillance data. To evaluate the feasibility of BSE surveillance in Nigeria, we carried out a pilot study targeting cattle that were presented for emergency or casualty slaughter. In total, 1551 cattle of local breeds, aged 24 months and above were clinically examined. Ataxia, recumbency and other neurological signs were topmost on our list of criteria. A total of 96 cattle, which correspond to 6.2%, presented clinical signs that supported a suspect of BSE. The caudal brainstem tissues of these animals were collected post-mortem and analysed for the disease-specific form of the prion protein using a rapid test approved by the International Animal Health Organization (OIE). None of the samples were positive for BSE. Although our findings do not exclude the presence of BSE in Nigeria, they do demonstrate that targeted sampling of clinically suspected cases of BSE is feasible in developing countries. In addition, these findings point to the possibility of implementing clinical monitoring schemes for BSE and potentially other diseases with grave economic and public health consequences.

Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control.

International air travel has already spread Ebola virus disease (EVD) to major cities as part of the unprecedented epidemic that started in Guinea in December 2013. An infected airline passenger arrived in Nigeria on July 20, 2014 and caused an outbreak in Lagos and then Port Harcourt. After a total of 20 reported cases, including 8 deaths, Nigeria was declared EVD free on October 20, 2014. We quantified the impact of early control measures in preventing further spread of EVD in Nigeria and calculated the risk that a single undetected case will cause a new outbreak. We fitted an EVD transmission model to data from the outbreak in Nigeria and estimated the reproduction number of the index case at 9.0 (95% confidence interval [CI]: 5.2-15.6). We also found that the net reproduction number fell below unity 15 days (95% CI: 11-21 days) after the arrival of the index case. Hence, our study illustrates the time window for successful containment of EVD outbreaks caused by infected air travelers.

Intravenous Delta-9-Tetrahydrocannabinol to Prevent Postoperative Nausea and Vomiting: A Randomized Controlled Trial.

BACKGROUND Evidence suggests that cannabinoids can prevent chemotherapy-induced nausea and vomiting. The use of tetrahydrocannabinol (THC) has also been suggested for the prevention of postoperative nausea and vomiting (PONV), but evidence is very limited and inconclusive. To evaluate the effectiveness of IV THC in the prevention of PONV, we performed this double-blind, randomized, placebo-controlled trial with patient stratification according to the risk of PONV. Our hypothesis was that THC would reduce the relative risk of PONV by 25% compared with placebo. METHODS With IRB approval and written informed consent, 40 patients at high risk for PONV received either 0.125 mg/kg IV THC or placebo at the end of surgery before emergence from anesthesia. The primary outcome parameter was PONV during the first 24 hours after emergence. Secondary outcome parameters included early and late nausea, emetic episodes and PONV, and side effects such as sedation or psychotropic alterations. RESULTS The relative risk reduction of overall PONV in the THC group was 12% (95% confidence interval, -37% to 43%), potentially less than the clinically significant 25% relative risk reduction demonstrated by other drugs used for PONV prophylaxis. Calculation of the effect of treatment group on overall PONV by logistic regression adjusted for anesthesia time gave an odds ratio of 0.97 (95% confidence interval, 0.21 to 4.43, P = 0.97). Psychotropic THC side effects were clinically relevant and mainly consisted of sedation and confusion that were not tampered by the effects of anesthesia. The study was discontinued after 40 patients because of the inefficacy of THC against PONV and the finding of clinically unacceptable side effects that would impede the use of THC in the studied setting. CONCLUSIONS Because of an unacceptable side effect profile and uncertain antiemetic effects, IV THC administered at the end of surgery before emergence from anesthesia cannot be recommended for the prevention of PONV in high-risk patients.