Sustainable Fisheries Management and the Welfare of Bycaught and Entangled Cetaceans.

The incidental capture of cetaceans and other protected marine wildlife in fishing gear has significant welfare implications. Many thousands of cetaceans are bycaught in fishing gear in European waters and hundreds of thousands die globally. We can expect many more to survive, but suffer from such interactions. As marine policy focuses on "population level" impact assessments and "sustainability" of fishing to preserve fish populations, the impacts to the bycaught individual, and their wider social group, are often largely underestimated, despite the large numbers affected. The wide range of recorded injuries, including abrasions, cuts, bruising, and broken bones, along with the potential for panic associated with forced submersion, indicate that the welfare of bycaught cetaceans is, individually and collectively, very poor. Commercial fishing is the last human activity targeting wildlife (fish) on a grand scale where slaughter includes incidental killing of other large sapient wildlife on such a regular basis. Here, we review the compelling evidence of the short and long term welfare impacts of bycatch, and the progress made toward implementation of measures to understand and solve this significant welfare issue. We argue that policy decisions surrounding fishing do not adequately consider cetacean bycatch, including welfare impacts. Ultimately, there are welfare issues in all bycatch situations and suffering cannot plausibly be reduced without preventing bycatch. The well-documented welfare implications provide a strong argument for zero tolerance of cetacean bycatch and provide a compelling case for immediate action in fisheries where bycatch is taking place. The only way to reduce the suffering of bycaught cetaceans is to decrease, or ideally eliminate, the number of animals caught in fishing gear. Uncertainties around the scale of bycatch should not delay management, even where individual bycatch estimates are considered "sustainable." Lack of monitoring of sub-lethal impacts on populations may result in flawed impact assessments. We urge that animal welfare considerations should become an integral part of management decision-making in relation to bycatch globally. Enhanced, robust and transparent management systems are urgently required for the range of fisheries within which cetacean bycatch occurs, with the aim to better document and most importantly, work toward eliminating cetacean bycatch altogether.

Fulfilling EU Laws to Ensure Marine Mammal Protection During Marine Renewable Construction Operations in Scotland.

Large-scale offshore renewable energy infrastructure construction in Scottish waters is anticipated in coming decades. An approach being pursued, with a view to preventing short-range marine mammal injury, is the introduction of additional noise sources to intentionally disturb and displace animals from renewable sites over the construction period. To date, no full and transparent consideration has been given to the long-term cost benefits of noise reduction compared with noise-inducing mitigation techniques. It has yet to be determined if the introduction of additional noise is consistent with the objectives of the EU Habitats Directive and the Marine Strategy Framework Directive.

Summary Report Panel 2: Regulatory Issues.

The Effects of Noise on Aquatic Life 2013 Conference convened four panels to discuss specific topics related to the effects of anthropogenic noise on aquatic ecosystems. The second of these four panels, the Regulatory Issues Panel, brought together several different perspectives: representatives of agencies responsible for regulating activities that introduce anthropogenic noise into aquatic ecosystems: representatives of the regulated industries, agencies, and consultancies that advise regulators and regulated industries; and nongovernmental organizations and other stakeholders with an interest in anthropogenic noise. The goal of the panel was to help develop a more productive relationship between these groups.

Synthesis of the HCV protease inhibitor Vaniprevir (MK-7009) using ring-closing metathesis strategy.

A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.

Renin inhibitors for the treatment of hypertension: design and optimization of a novel series of tertiary alcohol-bearing piperidines.

The design and optimization of a novel series of renin inhibitor is described herein. Strategically, by committing the necessary resources to the development of synthetic sequences and scaffolds that were most amenable for late stage structural diversification, even as the focus of the SAR campaign moved from one end of the molecule to another, highly potent renin inhibitors could be rapidly identified and profiled.

Magnetically driven agitation in a tube mixer affords clog-resistant fast mixing independent of linear velocity.

An economical and simple flow mixer based on magnetically driven agitation in a tube (MDAT) is reported. Mixing via MDAT compared favorably to both Tee and multilaminar mixers at low flow and was successfully used to screen and optimize two challenging organometallic reactions at low temperature without clogging or the need for high dilution.

Active sonar, beaked whales and European regional policy.

Various reviews, resolutions and guidance from international and regional fora have been produced in recent years that acknowledge the significance of marine noise and its potential impacts on cetaceans. Within Europe, ACCOBAMS and ASCOBANS have shown increasing attention to the issue. The literature highlights concerns surrounding the negative impacts of active sonar on beaked whales in particular, where concerns primarily relate to the use of mid-frequency active sonar (1-10kHz), as used particularly in military exercises. The authors review the efforts that European regional policies have undertaken to acknowledge and manage possible negative impacts of active sonar and how these might assist the transition from scientific research to policy implementation, including effective management and mitigation measures at a national level.

A practical synthesis of 5-lipoxygenase inhibitor MK-0633.

Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesulfonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of vinyl hydroxy-acid 22 followed by a robust end-game featuring a through-process hydrazide acylation/1,3,4-oxadiazole ring closure/salt formation sequence to afford MK-0633 p-toluenesulfonate (1).

Scalable synthesis of a prostaglandin EP4 receptor antagonist.

The evolution of scalable, economically viable synthetic approaches to the potent and selective prostaglandin EP4 antagonist 1 is presented. The chromatography-free synthesis of multikilogram quantities of 1 using a seven-step sequence (six in the longest linear sequence) is described. This approach has been further modified in an effort to identify a long-term manufacturing route. Our final synthesis involves no step requiring cryogenic (< -25 degrees C) conditions; comprises a total of four steps, only three of which are in the longest linear synthesis; and features the use of two consecutive iron-catalyzed Friedel-Crafts substitutions.

Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438).

A series of stearoyl-CoA desaturase 1 (SCD1) inhibitors were developed. Investigations of enzyme potency and metabolism led to the identification of the thiadiazole-pyridazine derivative MF-438 as a potent SCD1 inhibitor. MF-438 exhibits good pharmacokinetics and metabolic stability, thereby serving as a valuable tool for further understanding the role of SCD inhibition in biological and pharmacological models of diseases related to metabolic disorders.

A critique of the UK's JNCC seismic survey guidelines for minimising acoustic disturbance to marine mammals: best practise?

The United Kingdom's statutory conservation agency, the Joint Nature Conservation Committee (JNCC), developed guidelines in 1995 to minimise acoustic disturbance of marine mammals by oil and gas industry seismic surveys. These were the first national guidelines to be developed and have subsequently become the standard, or basis, of international mitigation measures for noise pollution during seismic surveys. However, relatively few aspects of these measures have a firm scientific basis or proven efficacy. Existing guidelines do not offer adequate protection to marine mammals, given the complex propagation of airgun pulses; the difficulty of monitoring in particular the smaller, cryptic, and/or deep-diving species, such as beaked whales and porpoises; limitations in monitoring requirements; lack of baseline data; and other biological and acoustical complications or unknowns. Current guidelines offer a 'common sense' approach to noise mitigation, but in light of recent research and ongoing concerns, they should be updated, with broader measures needed to ensure adequate species protection and to address data gaps.

Synthesis of 3-aminoisoxazoles via the addition-elimination of amines on 3-bromoisoxazolines.

A novel two-step procedure for the synthesis of 3-amino-5-substituted-isoxazoles is described. In the presence of a base, readily available 3-bromoisoxazolines react with amines to afford 3-aminoisoxazolines. An oxidation protocol was developed for these heterocycles to provide 3-aminoisoxazoles in consistently high yield.

Comparative review of marine mammal guidance implemented during naval exercises.

This article reviews the types and effectiveness of marine mammal mitigation measures used during some naval activities worldwide. The three main standard methods used to mitigate the potential impacts of naval sonar sound on marine mammals are (1) time/area planning (of exercises/active sonar use) to avoid marine mammals; (2) implementation of operational procedures (e.g. 'soft start' - where sound levels are gradually increased over time); and (3) monitoring of animals for the purpose of maintaining an 'exclusion zone' around the sound source. Suggestions towards a minimum worldwide mitigation standard are made.

Navy sonar and cetaceans: just how much does the gun need to smoke before we act?

Cetacean mass stranding events associated with naval mid-frequency sonar use have raised considerable conservation concerns. These strandings have mostly involved beaked whales, with common pathologies, including "bubble lesions" similar to decompression sickness symptoms and acoustic traumas. However, other cetacean species have also stranded coincident with naval exercises. Possible mechanisms for the strandings include a behavioral response that causes deep divers to alter their diving behavior, which then results in decompression sickness-like impacts. Current mitigation measures during military exercises are focused on preventing auditory damage (hearing loss), but there are significant flaws with this approach. Behavioral responses, which occur at lower sound levels than those that cause hearing loss, may be more critical. Thus, mitigation measures should be revised. A growing number of international bodies recognize this issue and have urged increasing scrutiny of sound-producing activities, but many national jurisdictions have resisted calls for increased protection.

Isothiocyanates from tosyl chloride mediated decomposition of in situ generated dithiocarbamic acid salts.

A facile and general protocol for the preparation of isothiocyanates from alkyl and aryl amines is reported. This method relies on a tosyl chloride mediated decomposition of a dithiocarbamate salt that is generated in situ by treatment of an amine with carbon disulfide and triethylamine. Utilizing this protocol, we have prepared 19-alkyl- and arylisothiocyanates in moderate to excellent yield.

Superior reactivity of thiosemicarbazides in the synthesis of 2-amino-1,3,4-oxadiazoles.

A facile and general protocol for the preparation of 2-amino-1,3,4-oxadiazoles is reported. This method relies on a tosyl chloride/pyridine-mediated cyclization of a thiosemicarbazide, which is readily prepared by acylation of a given hydrazide with the appropriate isothiocyanate. Cyclization of the thiosemicarbazide consistently outperforms the analogous semicarbazide cyclization under these conditions, for 18 distinct examples. Utilizing this protocol, we have prepared 5-alkyl- and 5-aryl-2-amino-1,3,4-oxadiazoles in 78-99% yield.

Supported chiral Mo-based complexes as efficient catalysts for enantioselective olefin metathesis.

Syntheses and catalytic activities of seven new polymer-supported chiral Mo-based complexes are disclosed. Four of the complexes are polystyrene-based, and three involve polynorbornene supports. Studies concerning the ability of the polymer-bound chiral complexes to promote an assortment of asymmetric ring-closing (ARCM) and ring-opening (AROM) metathesis reactions are detailed. In many instances, levels of reactivity and enantioselectivity are competitive with those of the analogous homogeneous catalysts. The positive effect of lower cross-linking within the polymer backbone on reaction efficiency and asymmetric induction is detailed. The optically enriched products obtained through the use of the supported complexes, after simple filtration and removal of the supported Mo catalysts, contain significantly lower levels of metal impurities as compared to products synthesized with the corresponding homogeneous catalysts.