CV19017

This report provides the results of the seventh underwater television on the ‘Porcupine Bank Nephrops grounds’ ICES assessment area; Functional Unit 16. The survey was multi-disciplinary in nature collecting UWTV, CTD and other ecosystem data. In total 65 UWTV stations were successfully completed in a randomised 6 nautical mile isometric grid covering the full spatial extent of the stock. The mean burrow density observed in 2019, adjusted for edge effect, was 0.14 burrows/m². The final krigged abundance estimate was 1010 million burrows with a relative standard error of 5% and an estimated stock area of 7,130 km2. The 2019 abundance estimate was 9.5% lower than in 2018. Using the 2019 estimate of abundance and updated stock data implies catches between 2127 and 2637 tonnes in 2020 that correspond to the F ranges in the EU multi annual plan for Western Waters (assuming that all catch is landed). Four species of sea-pen; Virgularia mirabilis, Funiculina quadrangularis, Pennatula phosphorea and the deepwater sea-pen Kophobelemnon stelliferum were observed during the survey. Trawl marks were also observed on 31% of the stations surveyed

In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments

Detection of an intergalactic meteor particle with the 6-m telescope

On July 28, 2006 the 6-m telescope of the Special Astrophysical Observatory of the Russian Academy of Sciences recorded the spectrum of a faint meteor. We confidently identify the lines of FeI and MgI, OI, NI and molecular-nitrogen N_2 bands. The entry velocity of the meteor body into the Earth's atmosphere estimated from radial velocity is equal to 300 km/s. The body was several tens of a millimeter in size, like chondrules in carbon chondrites. The radiant of the meteor trajectory coincides with the sky position of the apex of the motion of the Solar system toward the centroid of the Local Group of galaxies. Observations of faint sporadic meteors with FAVOR TV CCD camera confirmed the radiant at a higher than 96% confidence level. We conclude that this meteor particle is likely to be of extragalactic origin. The following important questions remain open: (1) How metal-rich dust particles came to be in the extragalactic space? (2) Why are the sizes of extragalactic particles larger by two orders of magnitude (and their masses greater by six orders of magnitude) than common interstellar dust grains in our Galaxy? (3) If extragalactic dust surrounds galaxies in the form of dust (or gas-and-dust) aureoles, can such formations now be observed using other observational techniques (IR observations aboard Spitzer satellite, etc.)? (4) If inhomogeneous extragalactic dust medium with the parameters mentioned above actually exists, does it show up in the form of irregularities on the cosmic microwave background (WMAP etc.)?Comment: 9 pages, 6 EPS figure

The use of toxicokinetics and exposure studies to show that carprofen in cattle tissue could lead to secondary toxicity and death in wild vultures

Veterinary medicines can be extremely damaging to the environment, as seen with the catastrophic declines in Gyps vulture in South Asia due to their secondary exposure to diclofenac in their primary food source. Not surprisingly, concern has been raised over other similar drugs. In this study, we evaluate the toxicity of carprofen to the Gyps vulture clade through plasma pharmacokinetics evaluations in Bos taurus cattle (their food source) and Gyps africanus (a validated model species); tissue residues in cattle; and the effect of carprofen as a secondary toxicant as both tissue-bound residue or pure drug at levels expected in cattle tissues. Carprofen residues were highest in cattle kidney (7.72 ± 2.38 mg/kg) and injection site muscle (289.05 ± 98.96 mg/kg of dimension of 5 × 5 × 5 cm). Vultures exposed to carprofen as residues in the kidney tissue or pure drug equivalents showed no toxic signs. When exposed to average injection site concentrations (64 mg/kg) one of two birds died with evidence of severe renal and liver damage. Toxicokinetic analysis revealed a prolonged drug half-life of 37.75 h in the dead bird as opposed to 13.99 ± 5.61 h from healthy birds dosed intravenously at 5 mg/kg. While carprofen may generally be harmless to Gyps vultures, its high levels at the injection site in treated cattle can result in lethal exposure in foraging vultures, due to relative small area of tissue it is found therein. We thus suggest that carprofen not be used in domesticated ungulates in areas where carcasses are accessible or provided to vultures at supplementary feeding sites.The Royal Society for the Protection of Birds and the Chester Zoo.http://www.elsevier.com/locate/chemosphere2019-01-01hj2018Paraclinical Science

Trends in the availability of the vulture-toxic drug, diclofenac, and other NSAIDs in South Asia, as revealed by covert pharmacy surveys

SummaryThe catastrophic declines of three species of ‘Critically Endangered’ Gyps vultures in South Asia were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Despite a ban on its veterinary use in 2006 (India, Nepal, Pakistan) and 2010 (Bangladesh), residues of diclofenac have continued to be found in cattle carcasses and in dead wild vultures. Another NSAID, meloxicam, has been shown to be safe to vultures. From 2012 to 2018, we undertook covert surveys of pharmacies in India, Nepal and Bangladesh to investigate the availability and prevalence of NSAIDs for the treatment of livestock. The purpose of the study was to establish whether diclofenac continued to be sold for veterinary use, whether the availability of meloxicam had increased and to determine which other veterinary NSAIDs were available. The availability of diclofenac declined in all three countries, virtually disappearing from pharmacies in Nepal and Bangladesh, highlighting the advances made in these two countries to reduce this threat to vultures. In India, diclofenac still accounted for 10–46% of all NSAIDs offered for sale for livestock treatment in 2017, suggesting weak enforcement of existing regulations and a continued high risk to vultures. Availability of meloxicam increased in all countries and was the most common veterinary NSAID in Nepal (89.9% in 2017). Although the most widely available NSAID in India in 2017, meloxicam accounted for only 32% of products offered for sale. In Bangladesh, meloxicam was less commonly available than the vulture-toxic NSAID ketoprofen (28% and 66%, respectively, in 2018), despite the partial government ban on ketoprofen in 2016. Eleven different NSAIDs were recorded, several of which are known or suspected to be toxic to vultures. Conservation priorities should include awareness raising, stricter implementation of current bans, bans on other vulture-toxic veterinary NSAIDs, especially aceclofenac and nimesulide, and safety-testing of other NSAIDs on Gyps vultures to identify safe and toxic drugs.</jats:p

Excitability and synaptic transmission in the enteric nervous system: Does diet play a role?

© Springer International Publishing Switzerland 2016. Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption. The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission. Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imaging techniques using voltage- or calcium-sensitive dyes to record neuronal activity promise to overcome many limitations inherent to electrophysiological approaches. Imaging techniques allow access to a wide range of ENS phenotypes and to the changes they undergo during dietary challenges. These sorts of studies have shown that dietary variation or obesity can change how the ENS processes information-in effect reprogramming the ENS. In this review, the data gathered from intracellular recordings will be compared with measurements made using imaging techniques in an effort to determine if the lessons learnt from inflammatory changes are relevant to the understanding of diet-induced reprogramming

Factors influencing job preferences of health workers providing obstetric care : results from discrete choice experiments in Malawi, Mozambique and Tanzania

BACKGROUND: Task shifting from established health professionals to mid-level providers (MLPs) (professionals who undergo shorter training in specific procedures) is one key strategy for reducing maternal and neonatal deaths. This has resulted in a growth in cadre types providing obstetric care in low and middle-income countries. Little is known about the relative importance of the different factors in determining motivation and retention amongst these cadres. METHODS: This paper presents findings from large sample (1972 respondents) discrete choice experiments to examine the employment preferences of obstetric care workers across three east African countries. RESULTS: The strongest predictors of job choice were access to continuing professional development and the presence of functioning human resources management (transparent, accountable and consistent systems for staff support, supervision and appraisal). Consistent with similar works we find pay and allowances significantly positively related to utility, but financial rewards are not as fundamental a factor underlying employment preferences as many may have previously believed. Location (urban vs rural) had the smallest average effect on utility for job choice in all three countries. CONCLUSIONS: These findings are important in the context where efforts to address the human resources crisis have focused primarily on increasing salaries and incentives, as well as providing allowances to work in rural areas

Sequence-Based Association and Selection Scans Identify Drug Resistance Loci in the Plasmodium Falciparum Malaria Parasite

Through rapid genetic adaptation and natural selection, the Plasmodium falciparum parasite—the deadliest of those that cause malaria—is able to develop resistance to antimalarial drugs, thwarting present efforts to control it. Genome-wide association studies (GWAS) provide a critical hypothesis-generating tool for understanding how this occurs. However, in P. falciparum, the limited amount of linkage disequilibrium hinders the power of traditional array-based GWAS. Here, we demonstrate the feasibility and power improvements gained by using whole-genome sequencing for association studies. We analyzed data from 45 Senegalese parasites and identified genetic changes associated with the parasites’ in vitro response to 12 different antimalarials. To further increase statistical power, we adapted a common test for natural selection, XP-EHH (cross-population extended haplotype homozygosity), and used it to identify genomic regions associated with resistance to drugs. Using this sequence-based approach and the combination of association and selection-based tests, we detected several loci associated with drug resistance. These loci included the previously known signals at pfcrt, dhfr, and pfmdr1, as well as many genes not previously implicated in drug-resistance roles, including genes in the ubiquitination pathway. Based on the success of the analysis presented in this study, and on the demonstrated shortcomings of array-based approaches, we argue for a complete transition to sequence-based GWAS for small, low linkage-disequilibrium genomes like that of P. falciparum.Molecular and Cellular BiologyOrganismic and Evolutionary Biolog

Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT(4 )agonist – tegaserod

BACKGROUND: Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT(4 )receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. METHODS: The effects of a high cholesterol (1%) diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX). Two groups of animals, fed either low (0.03%) or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. RESULTS: The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod-treatment removed the effects of a high cholesterol diet on neuronal muscarinic receptors, as the potentiating effect of TTX on carbachol-elicited contractions was maintained in these animals. CONCLUSION: A high cholesterol diet causes significant changes to cholinergic neurotransmission in the enteric nerves of the jejunum. The mechanisms by which these effects of cholesterol are reversed by tegaserod are unknown, but relate to removal of an inhibitory effect of cholesterol on enteric nerves

The impact of a supportive supervision intervention on health workers in Niassa, Mozambique: a cluster-controlled trial

BACKGROUND: Regular supportive supervision is critical to retaining and motivating staff in resource-constrained settings. Previous studies have shown the particular contribution that supportive supervision can make to improving job satisfaction amongst over-stretched health workers in such settings. METHODS: The Support, Train and Empower Managers (STEM) study designed and implemented a supportive supervision intervention and measured its' impact on health workers using a controlled trial design with a three-arm pre- and post-study in Niassa Province in Mozambique. Post-intervention interviews with a small sample of health workers were also conducted. RESULTS: The quantitative measurements of job satisfaction, emotional exhaustion and work engagement showed no statistically significant differences between end-line and baseline. The qualitative data collected from health workers post the intervention showed many positive impacts on health workers not captured by this quantitative survey. CONCLUSIONS: Health workers perceived an improvement in their performance and attributed this to the supportive supervision they had received from their supervisors following the intervention. Reports of increased motivation were also common. An unexpected, yet important consequence of the intervention, which participants directly attributed to the supervision intervention, was the increase in participation and voice amongst health workers in intervention facilities