Distribution of Polycyclic Aromatic Hydrocarbons (PAHs) in a tropical coastal lagoon (Grand-Lahou lagoon, Côte d’Ivoire)

The distribution of 8 polycyclic aromatic hydrocarbons (PAHs) in the surface sediments of the Grand-Lahou lagoon (Côte d’Ivoire) was investigated using a high performance liquid chromatography (HPLC). The total concentrations of PAHs were between 1.55 and 437.52 μg/g in the dry season. Pyrene, benzo (b) fluoranthene and fluoranthene have the highest concentrations. In the rainy season, the total PAHs concentrations varied between 46.35 and 1222.73 μg/g. Pyrene, benzo (a) pyrene and benzo (a) anthracene were the most present in the sediments of the lagoon of Grand-Lahou during the wet season. Possible sources of PAHs in the  lagoon of Grand-Lahou are oil and fuel spills from ships and fishing boats, combustion of waste, domestic waste disposal and especially the production of charcoal on the Grand-Lahou lagoon shores. A clear dominance of high molecular weight (HMW) PAHs (pyrene, Benzo (k) fluoranthene, Benzo (a) pyrene, indeno (1,2,3-cd) pyrilène, Benzo (g, h, i) pyrilene, Benzo (a) anthracene , Benzo (b) fluoranthene) was observed compared to low molecular weight (LMW) PAHs (fluoranthene).Keywords: Polycyclic Aromatic Hydrocarbon (PAH), coastal lagoon, pollution, West Africa

Anchor geotechnics for floating offshore wind: Current technologies and future innovations

A rapid expansion of the anchor market is required to meet the increasing demand for floating offshore wind. This paper, which is aimed at a broad readership within and beyond geotechnical engineering, summarises the current state-of-the-art and discusses future developments of anchor types and geotechnical design methods.Current anchor technologies are presented via comparative analytical assessments of performance across a range of practical scales and seabed conditions. This analysis demonstrates the relative merits and performance of different anchor types, using simplified cost-performance indicators for each anchor technology. An example outcome is the large differences in anchor efficiency (capacity per unit weight), that are linked to the different ways anchors achieve their holding capacity.Potential improvements in the performance-cost response for each anchor type, through future enhancements, are then explored. These enhancements are categorised as (1) unlocking higher anchor performance through improved design methods with a better understanding of the geotechnical response, (2) upscaling or (3) commoditising of the anchor type, by making larger versions or enabling more efficient mass production and installation, or (4) invention of new anchor technologies. Finally, findings of the different sections are summarised within a single table to enable a quick selection of anchoring solutions

Forging Links between Human Mental Retardation–Associated CNVs and Mouse Gene Knockout Models

Rare copy number variants (CNVs) are frequently associated with common neurological disorders such as mental retardation (MR; learning disability), autism, and schizophrenia. CNV screening in clinical practice is limited because pathological CNVs cannot be distinguished routinely from benign CNVs, and because genes underlying patients' phenotypes remain largely unknown. Here, we present a novel, statistically robust approach that forges links between 148 MR–associated CNVs and phenotypes from ∼5,000 mouse gene knockout experiments. These CNVs were found to be significantly enriched in two classes of genes, those whose mouse orthologues, when disrupted, result in either abnormal axon or dopaminergic neuron morphologies. Additional enrichments highlighted correspondences between relevant mouse phenotypes and secondary presentations such as brain abnormality, cleft palate, and seizures. The strength of these phenotype enrichments (>100% increases) greatly exceeded molecular annotations (<30% increases) and allowed the identification of 78 genes that may contribute to MR and associated phenotypes. This study is the first to demonstrate how the power of mouse knockout data can be systematically exploited to better understand genetically heterogeneous neurological disorders

Making ethnic tourism good for the poor

Ministry of Education, Singapore under its Academic Research Funding Tier

Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m−2) and etoposide (2 × 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80–98%) with a median survival time of 19.5 months (95% CI 12.8–29.2). The 1-, 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence

Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment

FXS is the most common genetic cause of intellectual (ID) and autism spectrum disorders (ASD). FXS is caused by loss of FMRP, an RNA-binding protein involved in the translational regulation of a large number of neuronal mRNAs. Absence of FMRP has been shown to lead to elevated protein synthesis and is thought to be a major cause of the synaptic plasticity and behavioural deficits in FXS. The increase in protein synthesis results in part from abnormal activation of key protein translation pathways downstream of ERK1/2 and mTOR signalling. Pharmacological and genetic interventions that attenuate hyperactivation of these pathways can normalize levels of protein synthesis and improve phenotypic outcomes in animal models of FXS. Several efforts are currently underway to trial this strategy in patients with FXS. To date, elevated global protein synthesis as a result of FMRP loss has not been validated in the context of human neurons. Here, using an isogenic human stem cell-based model, we show that de novo protein synthesis is elevated in FMRP-deficient neural cells. We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment. Finally, we examined the effect of normalizing protein synthesis on phenotypic abnormalities in FMRP-deficient neural cells. We find that treatment with metformin attenuates the increase in proliferation of FMRP-deficient neural progenitor cells but not the neuronal deficits in neurite outgrowth. The elevated level of protein synthesis and the normalization of neural progenitor proliferation by metformin treatment were validated in additional control and FXS patient-derived hiPSC lines. Overall, our results validate that loss of FMRP results in elevated de novo protein synthesis in human neurons and suggest that approaches targeting this abnormality are likely to be of partial therapeutic benefit in FXS.Peer reviewe