Aspects of the biology and behaviour of Lernaeocera branchialis (Linnaeus, 1767) (Copepoda: Pennellidae)

Lernaeocera branchialis (L., 1767) is a parasitic copepod that parasitises a range of gadoids by anchoring in the proximity of the branchial chamber of its host, deriving nutrition from the blood of its host and causing serious pathogenic effects. This study investigates the taxonomy of the juvenile free-swimming stages and host location behaviour in the pre-metamorphosed adult female. The large size and distinctive appearance of the metamorphosed adult female stage, coupled with the wide exploitation and commercial importance of one of its principle final gadoid hosts, the cod (Gadus morhua L.), means that this species has long been recognised in the scientific literature, and here the extensive literature concerning this potentially important and damaging pathogen is re-examined to provide an up to date overview, which includes both aquaculture and wild fisheries perspectives. Due to disagreements between several descriptions of the L. branchialis juvenile stages, and because the majority of the descriptions are over 60 years old, the juvenile free-swimming stages are re-described, using current terminology and a combination of both light and confocal microscopy. The time of hatching and moults in these stages is also examined. Techniques for the automated creation of taxonomic drawings from confocal images using computer software are investigated and the possibilities and implications of this technique are discussed. The method of host location in L. branchialis is unknown but is likely to involve a variety of mechanisms, possibly including chemo-reception, mechano-reception and the use of physical phenomena in the water column, such as haloclines and thermoclines, to search for fish hosts. In this study the role of host-associated chemical cues in host location by adult female L. branchialis is investigated by analysing the parasites behavioural responses to a range of host-derived cues, in both a choice chamber and a 3D tracking arena. To analyse the data from the experiments, specialised computer software (“Paratrack”) was developed to digitise the paths of the parasites’ movements, and calculate a variety of behavioural parameters, allowing behaviour patterns to be identified and compared. The results show that L. branchialis responds to host-associated chemical cues in a similar way to many copepods in the presence of chemical cues. Of the different cues tested, gadoid conditioned water appears to be most attractive to the parasites, although the wide variation in behavioural responses may indicate that other mechanisms are also required for host location. The different behavioural responses of parasites to whiting (Merlangius merlangus L.) and cod (Gadus morhua) conditioned water, which are both definitive hosts, provide some evidence for sub-speciation in L. branchialis. The role of chemical cues in host location of L. branchialis, and the relative importance of chemical and physical cues in host location are discussed. As well as demonstrating several techniques, which show potential for further development, this work has improved our knowledge of the biology and life-cycle of L. branchialis. Further study of this, and other areas of L. branchialis biology and its host-parasite interactions, should assist the development of contingency plans for the effective management and control of this widespread and potentially devastating pathogen.EThOS - Electronic Theses Online ServiceNERCGBUnited Kingdo

A Randomized Placebo-Controlled Trial of Varenicline for Smoking Cessation Allowing Flexible Quit Dates

Introduction: Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication. Methods: In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24. Results: Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively). Conclusions: Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies. © The Author 2011. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco

Sensory Communication

Contains table of contents on Section 2, an introduction, reports on eleven research projects and a list of publications.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Grant 5 R01 DC00270National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00100National Institutes of Health Contract 7 R29 DC00428National Institutes of Health Grant 2 R01 DC00126U.S. Air Force - Office of Scientific Research Grant AFOSR 90-0200U.S. Navy - Office of Naval Research Grant N00014-90-J-1935National Institutes of Health Grant 5 R29 DC00625U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-181

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00126National Institutes of Health Grant R01-DC00270U.S. Air Force - Office of Scientific Research Contract AFOSR-90-0200National Institutes of Health Grant R29-DC00625U.S. Navy - Office of Naval Research Grant N00014-88-K-0604U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-1814U.S. Navy - Naval Training Systems Center Contract N61339-93-M-1213U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0055U.S. Navy - Naval Training Systems Center Contract N61339-93-C-0083U.S. Navy - Office of Naval Research Grant N00014-92-J-4005U.S. Navy - Office of Naval Research Grant N00014-93-1-119

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant R01 DC00117National Institutes of Health Grant R01 DC02032National Institutes of Health/National Institute of Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research Grant N61339-96-K-0002U.S. Navy - Office of Naval Research Grant N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-97-1-0635U.S. Navy - Office of Naval Research Grant N00014-97-1-0655U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202National Institutes of Health Grant RO1 NS33778Massachusetts General Hospital, Center for Innovative Minimally Invasive Therapy Research Fellowship Gran

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fourteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant R01 DC00126National Institutes of Health Grant R01 DC00270National Institutes of Health Contract N01 DC52107U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0176U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-96-K-0002National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-92-J-184

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on fifteen research projects.National Institutes of Health Grant RO1 DC00117National Institutes of Health Grant RO1 DC02032National Institutes of Health Contract P01-DC00361National Institutes of Health Contract N01-DC22402National Institutes of Health/National Institute on Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-94-C-0087U.S. Navy - Office of Naval Research/Naval Air Warfare Center Contract N61339-95-K-0014U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-93-1-1399U.S. Navy - Office of Naval Research/Naval Air Warfare Center Grant N00014-94-1-1079U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-92-J-1814National Institutes of Health Grant R01-NS33778U.S. Navy - Office of Naval Research Grant N00014-88-K-0604National Aeronautics and Space Administration Grant NCC 2-771U.S. Air Force - Office of Scientific Research Grant F49620-94-1-0236U.S. Air Force - Office of Scientific Research Agreement with Brandeis Universit