Tumour-retained activated CCR7⁺ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.</p

Has charge symmetry breaking been observed in the d d -> alpha pi0 reaction?

Estimates are made of the d d -> alpha gamma gamma production cross sections in a model where each neutron-proton pair in the beam and target initiates an n p -> d gamma reaction. This approach, which successfully reproduces observables in two-pion production at intermediate energies, suggests that direct two-photon production could provide a very significant background to the measurement of the charge-symmetry-breaking (CSB) reaction d d -> alpha pi0. A non-vanishing CSB cross section has been reported which might be confused with such two-photon production under the given experimental conditions.Comment: 9 pages, ReVTEX, 2 figures, submitted to Phys. Rev. Let

A comment on the PCAST report:skip the “match”/“non-match” stage

This letter comments on the report “Forensic science in criminal courts: Ensuring scientific validity of feature-comparison methods” recently released by the President's Council of Advisors on Science and Technology (PCAST). The report advocates a procedure for evaluation of forensic evidence that is a two-stage procedure in which the first stage is “match”/“non-match” and the second stage is empirical assessment of sensitivity (correct acceptance) and false alarm (false acceptance) rates. Almost always, quantitative data from feature-comparison methods are continuously-valued and have within-source variability. We explain why a two-stage procedure is not appropriate for this type of data, and recommend use of statistical procedures which are appropriate

Direct measurements of meltwater runoff on the Greenland ice sheet surface

Meltwater runoff from the Greenland ice sheet surface influences surface mass balance (SMB), ice dynamics, and global sea level rise, but is estimated with climate models and thus difficult to validate. We present a way to measure ice surface runoff directly, from hourly in situ supraglacial river discharge measurements and simultaneous high-resolution satellite/drone remote sensing of upstream fluvial catchment area. A first 72-h trial for a 63.1-km2 moulin-terminating internally drained catchment (IDC) on Greenland?s midelevation (1,207?1,381 m above sea level) ablation zone is compared with melt and runoff simulations from HIRHAM5, MAR3.6, RACMO2.3, MERRA-2, and SEB climate/SMB models. Current models cannot reproduce peak discharges or timing of runoff entering moulins but are improved using synthetic unit hydrograph (SUH) theory. Retroactive SUH applications to two older field studies reproduce their findings, signifying that remotely sensed IDC area, shape, and supraglacial river length are useful for predicting delays in peak runoff delivery to moulins. Applying SUH to HIRHAM5, MAR3.6, and RACMO2.3 gridded melt products for 799 surrounding IDCs suggests their terminal moulins receive lower peak discharges, less diurnal variability, and asynchronous runoff timing relative to climate/SMB model output alone. Conversely, large IDCs produce high moulin discharges, even at high elevations where melt rates are low. During this particular field experiment, models overestimated runoff by +21 to +58%, linked to overestimated surface ablation and possible meltwater retention in bare, porous, low-density ice. Direct measurements of ice surface runoff will improve climate/SMB models, and incorporating remotely sensed IDCs will aid coupling of SMB with ice dynamics and subglacial systemspublishersversionPeer reviewe

Developing priority variables ("ecosystem Essential Ocean Variables" — eEOVs) for observing dynamics and change in Southern Ocean ecosystems

Reliable statements about variability and change in marine ecosystems and their underlying causes are needed to report on their status and to guide management. Here we use the Framework on Ocean Observing (FOO) to begin developing ecosystem Essential Ocean Variables (eEOVs) for the Southern Ocean Observing System (SOOS). An eEOV is a defined biological or ecological quantity, which is derived from field observations, and which contributes significantly to assessments of Southern Ocean ecosystems. Here, assessments are concerned with estimating status and trends in ecosystem properties, attribution of trends to causes, and predicting future trajectories. eEOVs should be feasible to collect at appropriate spatial and temporal scales and are useful to the extent that they contribute to direct estimation of trends and/or attribution, and/or development of ecological (statistical or simulation) models to support assessments. In this paper we outline the rationale, including establishing a set of criteria, for selecting eEOVs for the SOOS and develop a list of candidate eEOVs for further evaluation. Other than habitat variables, nine types of eEOVs for Southern Ocean taxa are identified within three classes: state (magnitude, genetic/species, size spectrum), predator–prey (diet, foraging range), and autecology (phenology, reproductive rate, individual growth rate, detritus). Most candidates for the suite of Southern Ocean taxa relate to state or diet. Candidate autecological eEOVs have not been developed other than for marine mammals and birds. We consider some of the spatial and temporal issues that will influence the adoption and use of eEOVs in an observing system in the Southern Ocean, noting that existing operations and platforms potentially provide coverage of the four main sectors of the region — the East and West Pacific, Atlantic and Indian. Lastly, we discuss the importance of simulation modelling in helping with the design of the observing system in the long term. Regional boundary: south of 30°S

Micropapillary bladder cancer: Current treatment patterns and review of the literature

No guidelines exist for management of micropapillary bladder cancer (MPBC) and the majority of reports of this variant of urothelial carcinoma (UC) are case series comprised of small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature

Vulnerability to climate change of managed stocks in the California Current large marine ecosystem

Introduction: Understanding how abundance, productivity and distribution of individual species may respond to climate change is a critical first step towards anticipating alterations in marine ecosystem structure and function, as well as developing strategies to adapt to the full range of potential changes. Methods: This study applies the NOAA (National Oceanic and Atmospheric Administration) Fisheries Climate Vulnerability Assessment method to 64 federally-managed species in the California Current Large Marine Ecosystem to assess their vulnerability to climate change, where vulnerability is a function of a species’ exposure to environmental change and its biological sensitivity to a set of environmental conditions, which includes components of its resiliency and adaptive capacity to respond to these new conditions. Results: Overall, two-thirds of the species were judged to have Moderate or greater vulnerability to climate change, and only one species was anticipated to have a positive response. Species classified as Highly or Very Highly vulnerable share one or more characteristics including: 1) having complex life histories that utilize a wide range of freshwater and marine habitats; 2) having habitat specialization, particularly for areas that are likely to experience increased hypoxia; 3) having long lifespans and low population growth rates; and/or 4) being of high commercial value combined with impacts from non-climate stressors such as anthropogenic habitat degradation. Species with Low or Moderate vulnerability are either habitat generalists, occupy deep-water habitats or are highly mobile and likely to shift their ranges. Discussion: As climate-related changes intensify, this work provides key information for both scientists and managers as they address the long-term sustainability of fisheries in the region. This information can inform near-term advice for prioritizing species-level data collection and research on climate impacts, help managers to determine when and where a precautionary approach might be warranted, in harvest or other management decisions, and help identify habitats or life history stages that might be especially effective to protect or restore