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The distribution of the sand eel stretches in the Northeast Atlantic from 490 N to 730 N (Reay, 1970) with a tendency to inhabit in well-defined areas on shallow banks (Macer, 1966). The substrate must be conductive to burrowing (Meyer et al., 1979) with the choice of habitat probably determined by the type of sediment and the hydrodynamic processes affecting the sediment (Pinto et al., 1984). Wright et al., 1998 found that the sand eel was absent from sediment with a silt content less than 10% which together with depth and tide influenced habitat choice. The depth maximum for sand eel abundance is about 100m (Pedersen et al., 1999), and the water flow must be above 0.6 ms-1 (Wright et al., 1998). These constraints leads to a very restricted distribution of sand eels, i.e. they are found in sandy areas where tides and wave action is expected to scour the bottom giving rise to coarse sand and well-aerated substrate. These areas appear to coincide with the areas of the North Sea influenced by tidal front activity. The distribution of fishing areas clearly matches the san eel preferred habitat (figure 1). Due to the stationary habit of post-settled sand eels, a patchy distribution of the sand eel habitat, and a limited interchange of the planktonic stages between the spawning areas the sand eel stock in IV consist of a number of sub-populations (Proctor et al. 1998, Pedersen et al. 1999). Due to a to coarse spatial aggregation level of the fisheries data that is used in the sand eel assessment and a lack of biological information for defining the limits of each of the reproductively isolated population units, it is presently not possible to make an assessment that take account of the sub-population structure of sand eels (ICES 2006). The catches of sand eels in area IV consist mainly of the lesser sand eel Ammodytes marinus. However, other species of sand eels is also caught. At some of the grounds in the Dogger Bank area the smooth sand eel Gymnammodytes semisquamatus can be important, and in the catches from more coastal grounds the other Ammodytes species Ammodytes tobianus can be important. The greater sand eel Hyperoplus lanceolatus appears in the catches from all grounds, but usually in insignificant numbers compared to A. marinus. The population dynamics of A. tobianus, G. semisquamatus, and H. lanceolatus are largely unknown, and so are the possible effects on these species of commercial fisheries. Figure 2 shows the total catch of sand eel over the past 50 years in the North Sea area (ICES 2006). ICES expert group PGCCDBS have recommended a further investigation of the age estimation of sand eel (ICES 2005) and the present report gives the results from a workshop hosted by DIFRES aiming at securing consistent age readings at different laboratories. Prior to the workshop an exchange was carried out between Denmark, Norway and Scotland, results indicating a limited inconsistency among international sand eel age readers (discussed in a separate section of the present report). The objectives of the workshop were manifold; apart from the overall goal of securing consistency in age estimation of sand eel; updating and assembling age readers from all national laboratories handling sand eel from the North Sea to exchanged views on methods and experiences was among the objectives. This had not been done for more than a decade among the participating laboratories. The aim of such an exchange of experiences was to start the process of the creation of a training manual/DVD to be used as both quality assurance for trained readers and as a guide for new readers. The workshop had one day of calibration exercise where a traditional age calibration exercise was combined with an image analysis system approach

Section HeadClinical/translational cancer immunotherapyBackgroundThe goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non–small-cell lung cancer (NSCLC).MethodsUtomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored. Tumor responses by RECIST1.1 were assessed by baseline and on-treatment scans. Tumor biopsies were collected for detection of programmed cell death ligand 1, CD8, 4-1BB, perforin, and granzyme B, and gene expression analyzed by next-generation sequencing. CD8+ T cells from healthy donors were stimulated with anti-CD3 ± utomilumab and compared with control.ResultsPatients with melanoma (n=43) and NSCLC (n=20) received utomilumab 0.24 mg/kg (n=36), 1.2 mg/kg (n=26), or 10 mg/kg (n=1). Treatment-emergent AEs (TEAEs) occurred in 55 (87.3%) patients and serious TEAEs in 18 (28.6%). Five (7.9%) patients discontinued owing to TEAEs. Thirty-two (50.8%) patients experienced treatment-related AEs, mostly grade 1–2. Objective response rate: 2.3% in patients with melanoma; no confirmed responses for patients with NSCLC. Ten patients each with melanoma (23.3%) or NSCLC (50%) had stable disease; respective median (95% confidence interval, CI) progression-free survival was 1.8 (1.7–1.9) and 3.6 (1.6–6.5) months. Utomilumab exposure increased with dose. The incidences of antidrug and neutralizing antibodies were 46.3% and 19.4%, respectively. Efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity appeared to be blunted at higher doses.ConclusionsUtomilumab was well tolerated, but antitumor activity was low in patients who previously progressed on ICIs. The potential of 4-1BB agonists requires additional study to optimize efficacy while maintaining the tolerable safety profile.

These figures contain details of the study population, elastic net model parameters, and CytoPro method validation.These tables report results from statistical analyses of biomarker associations with overall survival in JAVELIN Bladder 100.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

Additional file 1 Supplementary Figures and Tables.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

Additional file 2. Descriptive summary of serum mogamulizumab pharmacokinetic parameter values for Cycle 5 (biweekly dosing). Table of PK values after multiple dosing.

Additional file 1. Descriptive summary of serum mogamulizumab pharmacokinetic parameter values for Cycle 1, single dose. Table of PK values after one dose.

Jenkins, Tanner, Hoback, W. Wyatt, Leasure, Doug, Mulder, Phillip, Davis, Craig (2018): Distribution of the Endangered American Burying Beetle at the Northwestern Limit of its Range. Insect Systematics and Diversity 2 (1): 1-8, DOI: 10.1093/isd/ixx011, URL: http://dx.doi.org/10.1093/isd/ixx011

Hip fractures are a common type of fragility fracture that afflict 293,000 Americans (over 5,000 per week) and 35,000 Canadians (over 670 per week) annually. Despite the large population impact the optimal fixation technique for low energy femoral neck fractures remains controversial. The primary objective of the FAITH study is to assess the impact of cancellous screw fixation versus sliding hip screws on rates of revision surgery at 24 months in individuals with femoral neck fractures. The secondary objective is to determine the impact on health-related quality of life, functional outcomes, health state utilities, fracture healing, mortality and fracture-related adverse events. FAITH is a multi-centre, multi-national randomized controlled trial utilizing minimization to determine patient allocation. Surgeons in North America, Europe, Australia, and Asia will recruit a total of at least 1,000 patients with low-energy femoral neck fractures. Using central randomization, patients will be allocated to receive surgical treatment with cancellous screws or a sliding hip screw. Patient outcomes will be assessed at one week (baseline), 10 weeks, 6, 12, 18, and 24 months post initial fixation. We will independently adjudicate revision surgery and complications within 24 months of the initial fixation. Outcome analysis will be performed using a Cox proportional hazards model and likelihood ratio test. This study represents major international efforts to definitively resolve the treatment of low-energy femoral neck fractures. This trial will not only change current Orthopaedic practice, but will also set a benchmark for the conduct of future Orthopaedic trials. The FAITH trial is registered at ClinicalTrials.gov (Identifier NCT00761813 ).

An ongoing LADWP project requires appropriate seismic earth pressure for designing a buried concrete reservoir. The century old Mononobe-Okabe (M-O) method of estimating seismic earth pressure on cantilever retaining walls, and many methods developed later based on the original M-O method, are not applicable to the case of underground restrained structures. Centrifuge model tests on rectangular structures buried in unsaturated soils are being conducted to study the mechanism of soil-structure-interaction (SSI) and seismic earth pressure for this problem. The centrifuge testing program consists of a total of 116 shaking tests on a total of 12 models, varying in roof burial depths, structural stiffness, soil properties, and backfill soil geometry and subject to varying input motions with different amplitude and predominate frequencies. In order to compare the centrifuge testing results with soil-structure-interaction (SSI) results and seismic earth pressures from a numerical modeling approach that would commonly be used for practical design, pre-centrifuge testing Class A predictions have been performed to facilitate a comparison of the “blind” numerical modeling with the centrifuge testing results. This allows identifying potential analysis issues with commonly-used numerical modeling approaches for designing underground box structures. This paper focuses on Class A prediction results conducted using a SSI numerical modeling approach. Structural bending moment and earth pressure diagrams were derived at a) static conditions; b) when the maximum total peak moment occurred in the walls; and c) when the maximum peak total lateral earth pressure occurred on the walls. Note that these maximum values of moment and pressure peaks may occur at different time steps during shaking. Furthermore, the contributions to the moment diagram from static earth pressure, seismic incremental earth pressure and wall inertial force were de-coupled to understand each individual effect on structural moment. The calculated earth pressures were also compared with pressures derived with M-O method. Further studies are being performed to compare the numerical simulation to the centrifuge testing results that will be published elsewhere.

An immunosuppressed rat model was used to determine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic surfactant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in lungs of rats infected with P. carinii. When atovaquone was combined with surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in lung were achieved. Aerosolized synthetic surfactant alone significantly increased survival of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of the drug and eradication of the organism.