Preclinical platforms to study therapeutic efficacy of human γδT‐cells for oncology indications

In this commentary, we discuss recent advances in the study of γδT cell-based immunotherapeutics. As an allo-compatible cell therapy chassis without clear functional homologs in mice, γδT cells represent a challenge and an opportunity for preclinical modelling. We discuss some of the techniques and approaches that can be used to demonstrate and characterise γδT cell behaviour in biomimetic systems

A search for technosignatures from 14 planetary systems in the Kepler field with the Green Bank Telescope at 1.15-1.73 GHz

Analysis of Kepler mission data suggests that the Milky Way includes billions of Earth-like planets in the habitable zone of their host star. Current technology enables the detection of technosignatures emitted from a large fraction of the Galaxy. We describe a search for technosignatures that is sensitive to Arecibo-class transmitters located within ~420 ly of Earth and transmitters that are 1000 times more effective than Arecibo within ~13 000 ly of Earth. Our observations focused on 14 planetary systems in the Kepler field and used the L-band receiver (1.15-1.73 GHz) of the 100 m diameter Green Bank Telescope. Each source was observed for a total integration time of 5 minutes. We obtained power spectra at a frequency resolution of 3 Hz and examined narrowband signals with Doppler drift rates between +/-9 Hz/s. We flagged any detection with a signal-to-noise ratio in excess of 10 as a candidate signal and identified approximately 850 000 candidates. Most (99%) of these candidate signals were automatically classified as human-generated radio-frequency interference (RFI). A large fraction (>99%) of the remaining candidate signals were also flagged as anthropogenic RFI because they have frequencies that overlap those used by global navigation satellite systems, satellite downlinks, or other interferers detected in heavily polluted regions of the spectrum. All 19 remaining candidate signals were scrutinized and none were attributable to an extraterrestrial source.Comment: 15 pages, 5 figures, accepted for publication in the Astronomical Journa

Variability in IC5070: two young stars with deep recurring eclipses

Investigating the structure and properties of the innermost parts of protoplanetary accretion disks on sub-AU scales is currently only possible via indirect methods. One option to map the planet-forming zone is to search for occultations of the central young stellar object (YSO) by circumstellar material, e.g., warps or clumps in the inner disks. Such disk eclipses typically last hours to days (Cody et al. 2014) and have been identified in massive HAeBe stars such as UX Ori (Herbst & Shevchenko 1999) and lower mass objects such as AA Tau (Bouvier et al. 1999). Of particular interest are quasi-periodic dimming events. They allow distance determinations of the occulting material from the central star. In such cases the actual azimuthal physical extent of the material can be determined from the duration of the dimming event relative to the period. Observations over several periods enable investigations into temporal changes in the line of sight column density distribution, and multi-wavelength data allows us to probe the dust scattering properties. Our citizen science project HOYS-CAPS (Froebrich et al. 2018) aims to identify such periodic dimming events around YSOs. We used this data-set to search for periodic signatures in light-curves from YSOs in the Pelican nebula (IC 5070). For this field we have ~200 individual observations in the V, R, and I-band filters, distributed over ~800 days. Hence, the average cadence is 4 days, but the most frequent gap (30%) between subsequent observations is 2 days. Observations are usually taken as 8 × 2 minutes integrations in all filters to achieve a consistent S/N

Modelling visual-vestibular integration and behavioural adaptation in the driving simulator

It is well established that not only vision but also other sensory modalities affect drivers’ control of their vehicles, and that drivers adapt over time to persistent changes in sensory cues (for example in driving simulators), but the mechanisms underlying these behavioural phenomena are poorly understood. Here, we consider the existing literature on how driver steering in slalom tasks is affected by down-scaling of vestibular cues, and propose, for the first time, a computational model of driver behaviour that can, based on neurobiologically plausible mechanisms, explain the empirically observed effects, namely: decreased task performance and increased steering effort during initial exposure, followed by a partial reversal of these effects as task exposure is prolonged. Unexpectedly, the model also reproduced another previously unexplained empirical finding: a local optimum for motion down-scaling, where path-tracking is better than when one-to-one motion cues are available. Overall, our findings suggest that: (1) drivers make direct use of vestibular information as part of determining appropriate steering actions, and (2) motion down-scaling causes a yaw rate underestimation phenomenon, where drivers behave as if the simulated vehicle is rotating more slowly than it is. However, (3) in the slalom task, a certain degree of such underestimation brings a path-tracking performance benefit. Furthermore, (4) behavioural adaptation in simulated slalom driving tasks may occur due to (a) down-weighting of vestibular cues, and/or (b) increased sensitivity in timing and magnitude of steering corrections, but (c) seemingly not in the form of a full compensatory rescaling of the received vestibular input. The analyses presented here provide new insights and hypotheses about simulated driving and simulator design, and the developed models can be used to support research on multisensory integration and behavioural adaptation in both driving and other task domains

Ecological Meltdown in the Firth of Clyde, Scotland: Two Centuries of Change in a Coastal Marine Ecosystem

BACKGROUND: The Firth of Clyde is a large inlet of the sea that extends over 100 km into Scotland\u27s west coast. METHODS: We compiled detailed fisheries landings data for this area and combined them with historical accounts to build a picture of change due to fishing activity over the last 200 years. FINDINGS: In the early 19th century, prior to the onset of industrial fishing, the Firth of Clyde supported diverse and productive fisheries for species such as herring (Clupea harengus, Clupeidae), cod (Gadus morhua, Gadidae), haddock (Melanogrammus aeglefinus, Gadidae), turbot (Psetta maxima, Scophthalmidae) and flounder (Platichthys flesus, Pleuronectidae). The 19th century saw increased demand for fish, which encouraged more indiscriminate methods of fishing such as bottom trawling. During the 1880s, fish landings began to decline, and upon the recommendation of local fishers and scientists, the Firth of Clyde was closed to large trawling vessels in 1889. This closure remained in place until 1962 when bottom trawling for Norway lobster (Nephrops norvegicus, Nephropidae) was approved in areas more than three nautical miles from the coast. During the 1960s and 1970s, landings of bottomfish increased as trawling intensified. The trawl closure within three nautical miles of the coast was repealed in 1984 under pressure from the industry. Thereafter, bottomfish landings went into terminal decline, with all species collapsing to zero or near zero landings by the early 21st century. Herring fisheries collapsed in the 1970s as more efficient mid-water trawls and fish finders were introduced, while a fishery for mid-water saithe (Pollachius virens, Gadidae) underwent a boom and bust shortly after discovery in the late 1960s. The only commercial fisheries that remain today are for Nephrops and scallops (Pecten maximus, Pectinidae). SIGNIFICANCE: The Firth of Clyde is a marine ecosystem nearing the endpoint of overfishing, a time when no species remain that are capable of sustaining commercial catches. The evidence suggests that trawl closures helped maintain productive fisheries through the mid-20th century, and their reopening precipitated collapse of bottomfish stocks. We argue that continued intensive bottom trawling for Nephrops with fine mesh nets will prevent the recovery of other species. This once diverse and highly productive environment will only be restored if trawl closures or other protected areas are re-introduced. The Firth of Clyde represents at a small scale a process that is occurring ocean-wide today, and its experience serves as a warning to others

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research