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AbstractThe historic processes which have led to the present‐day patterns of genetic structure in the marine coastal fauna of the Northeast Atlantic are still poorly understood. While tectonic uplifts and changes in sea level may have caused large‐scale vicariance, warmer conditions during glacial maxima may have allowed pockets of diversity to persist to a much wider extent than in the Northwestern Atlantic. The large‐scale geographic distribution of deeply divergent lineages of the coastal polychaete tubeworms Pectinaria koreni (two clades) and Owenia fusiformis (three clades) were compared using a fragment of the mitochondrial cytochrome oxidase I gene (mtCOI). All lineages were present along the biogeographic transition zone on the north coast of Brittany (France) and we found evidence pointing towards congruence in the timing of cladogenic events between Pectinaria sp. (P. auricoma/P. belgica and P. koreni) and Owenia sp., suggesting a shared history of vicariant events. More conserved 16SrRNA sequences obtained from four species of Pectinariidae together with mtCOI sequences of P. koreni seem consistent with an initial establishment of pectinariids in the north, and a southward colonization of the Northeast Atlantic. Phylogeographic patterns in O. fusiformis were also consistent with a north/south pattern of lineage splitting and congruent levels of divergence were detected between lineages of both species. We observed signatures of both persistence in small northern glacial refugia, and of northwards range expansion from regions situated closer to the Mediterranean. However, whether the recolonization of the Northeast Atlantic by both species actually reflects separate interglacial periods is unclear with regards to the lack of molecular clock calibration in coastal polychaete species.

The Ophiuchus stream is a short arc-like stellar feature of uncertain origin located $\sim 5$ kpc North of the Galactic centre. New proper motions from the second $Gaia$ data release reconcile the direction of motion of stream members with the stream arc, resolving a puzzling mismatch reported in earlier work. We use N-body simulations to show that the stream is likely only on its second pericentric passage, and thus was formed recently. The simulations suggest that the entire disrupted progenitor is visible in the observed stream today, and that little further tidal debris lies beyond the ends of the stream. The luminosity, length, width, and velocity dispersion of the stream suggest a globular cluster (GC) progenitor substantially fainter and of lower surface brightness than estimated in previous work, and unlike any other known globulars in the Galaxy. This result suggests the existence of clusters that would extend the known GC population to fainter and more weakly bound systems than hitherto known. How such a weakly-bound cluster of old stars survived until it was disrupted so recently, however, remains a mystery. Integrating backwards in time, we find that the orbits of Sagittarius and Ophiuchus passed within $\sim 5$ kpc of each other about $\sim 100$ Myrs ago, an interaction that might help resolve this puzzle. Comment: 11 pages, 7 figures, submitted to MNRAS

Crises test the resilience of public service organizations. Healthcare providers must respond and innovate within tight constraints to address challenges. Presenting COVID-19 as a knowable unknown (black swan event), we adopt information processing theory to investigate how healthcare providers and their suppliers address information asymmetry to support decision-making. Building on primary and secondary datasets, we demonstrate managers were innovating internal structural responses. For black swan events, in-house ‘intelligent clients’ are intrinsic not only in managing information uncertainty associated with early stages of the crisis, but also in addressing information equivocality and joint decision-making with other organizations associated with implementing solutions.

TPS501 Background: Niraparib (N) is an orally selective poly(ADP-ribose) polymerase (PARP)-1/-2 inhibitor approved for maintenance treatment of patients (pt) with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after complete or partial response to platinum-based chemotherapy (CT). Cabozantinib (C) is a tyrosine kinase (TK) inhibitor with activity against TKs including VEGFR2, MET and AXL, approved on kidney cancer pt after TK failure, that has demonstrated clinical activity in heavily pretreated, advanced UC pt. c-Met receptor TK is activated in urothelial carcinoma (UC) cells. c-Met activity can decrease response to PARP inhibitors, whereas treatment with c-Met inhibitors renders cells more sensitive to PARP inhibition. UC pt with tumors overexpressing c-Met may benefit from the combination of c-Met and PARP inhibitors. This multicenter, open-label phase (ph) I-II study is to explore the maximum-tolerated dose (MTD) of N + C combination in pt with advanced genitourinary malignancies (UC and kidney cancer) follow by a preliminary efficacy of the combination in advanced UC. Methods: Eligible pt have confirmed histopathology of UC or clear cell renal cell carcinoma, advanced or metastatic disease, age ≥18 years, ECOG PS ≤1, progressive disease after platinum-based CT, measurable lesions, no prior therapy with PARP or c-Met inhibitors and adequate bone marrow, liver and renal functions. The ph I portion is enrolling ≈24 pt to identify the MTD proposed to use in a ph II (RP2D). Pt will receive N and C p.o. once daily in 28-day cycles: Dose level 1 (DL1) N/C 100/20 mg; DL2 200/20 mg; DL3 200/40 mg; DL4 200/60 mg. Pt will be accrued to each dose level in cohorts of 6 pt until the MTD is achieved (the highest dose at which ≤1 out of 6 pt experience a dose-limiting toxicity [DLT]). DLT will be evaluated during the first 2 cycles. The ph 2 portion will enroll 51 UC pt to receive the RP2D. Tumor response will be assessed per RECIST v1.1. Endpoints of the ph 2 are 6-month PFS (primary), overall response rate, disease control rate, duration of response, PFS and OS. Tissue and plasma sample will be collected for translational study. Clinical trial information: NCT03425201.

The evidence relating feeding and mating to hormonal control of egg production in Rhodnius prolixus is reviewed from two perspectives. It identifies crucial areas in which information is lacking, and it attempts to relate the findings, most of which have been obtained on laboratory colonies isolated for many years, to the sylvan life of the insect as an opportunistic micropredator.

The purpose of this study was to compare the combined effects of creatine monohydrate (Cr) and beta-alanine (BA) with their isolated use on performance and physiological parameters during repeated sprint sequences (RSS). Forty-four male (n=34) and female (n=10) amateur team- and racket sport players (25.1±3.1 years; 175.2±9.8 cm; 76.0±10.3 kg; 15.2±6.8% body fat) performed ten repetitions of 6-s sprints with departure every 30 s, before and after a 28-day supplementation period with either Cr (n=11, 5 g‧day-1), BA (n=10, 6 g‧day-1), combined Cr and BA (n=12, 5 g‧day-1 of Cr plus 6g‧day-1 of BA) or placebo (11 g‧day-1 of rice flour). Peak (PP) and mean power (MP), performance decrement (%Dec), heart rate (HR), blood lactate concentration (LA) and perceived exertion (RPE) were measured. Analyses of variance (ANOVA) were used to determine the effects of groups (Cr, BA, CrBA, P), sprint number (1 to 10), and time (pre- vs. post-supplementation) on all variables. A significant increase in PP was shown in the post- compared to the pre-supplementation in Cr (+5.2%) and BA (+5.2%) groups only (p<.05), and significant decreases in MP in all groups (3.7% to 6.4%, p<.05), except BA. %Dec was significantly decreased post-supplementation in the Cr group only (17.4%, p<.05). No effects were shown on HR, RPE and LA (p<.05). These results show no additional benefits of the combination of Cr and BA on RSS performance and suggest that longer sprint or total exercise duration might be necessary to observe the benefits of the combined supplementation.

Knowledge of the molecular virology of the hepatitis viruses and the responses they elicit has emphasised the importance of host immunity in resolving infection and mediating liver damage. Many viruses cause cytolytic infections in which viral replication occurs at the expense of host cell viability. However this is a shortsighted strategy for the virus as it provides a clear “danger signal”1 that alerts the host’s innate and adaptive immune defences to eliminate the virus and terminate the infection. Such a life cycle requires a high rate of transmission from host to host, causes acute tissue damage and is unlikely to result in persistent infection. In order to cause chronic infection viruses must use strategies that enable them to evade or modify host immune responses sufficiently to prevent clearance. Of the hepatitis viruses only hepatitis B (HBV) and hepatitis C (HCV) viruses cause chronic infections and in order to do so they must evade host immune responses. Neither hepatitis A virus nor hepatitis E virus cause chronic infection and must be assumed to lack the ability to escape immune responses. Understanding the mechanisms used by HBV and HCV to evade host immunity is central to understanding their pathogenicity and necessary for the development of effective therapeutic strategies. Although knowledge of the mechanisms of immune escape by hepatitis viruses is increasing, considerable insight has come from the study of other viruses, some of which can cause hepatitis such as Epstein-Barr virus (EBV), HIV, and model systems such as murine lymphocytic choriomeningitis virus (LCMV), as well as transgenic mouse models of HBV infection. In both acute HBV and HCV infection a vigorous antiviral T lymphocyte response is associated with viral clearance. In chronic hepatitis B and hepatitis C virus specific T lymphocyte responses are weak or absent. The mechanisms leading to ineffectual …