A Review of Agent Emotion Architectures

This paper attempts to highlight some of the research that has been conducted worldwide in the area of computational models of emotions, with a particular emphasis on agent emotions suitable for simulations and games. The intended outcome is to both review some of the more prominent research in the field, and to also ascertain the level of formal psychology that may underpin such work with a view to proposing that there is scope for an architecture built from the ground up, that arises from non-conflicting theories of emotion

Influence of oral contrast type and volume on patient experience and quality of luminal distension at MR Enterography in Crohn's disease:an observational study of patients recruited to the METRIC trial

OBJECTIVES: To compare the distention quality and patient experience of oral mannitol and polyethylene glycol (PEG) for MRE. METHODS: This study is a retrospective, observational study of a subset of patients enrolled in a multicentre, prospective trial evaluating the diagnostic accuracy of MRE for small bowel Crohn’s. Overall and segmental MRE small bowel distention, from 105 patients (64 F, mean age 37) was scored from 0 = poor to 4 = excellent by two experienced observers (68 [65%] mannitol and 37 [35%] PEG). Additionally, 130 patients (77 F, mean age 34) completed a questionnaire rating tolerability of various symptoms immediately and 2 days after MRE (85 [65%] receiving mannitol 45 [35%] receiving PEG). Distension was compared between agents and between those ingesting ≤ 1 L or > 1 L of mannitol using the test of proportions. Tolerability grades were collapsed into “very tolerable,” “moderately tolerable,” and “not tolerable.” RESULTS: Per patient distension quality was similar between agents (“excellent” or “good” in 54% [37/68] versus 46% [17/37]) with mannitol and PEG respectively. Jejunal distension was significantly better with mannitol compared to PEG (40% [27/68] versus 14% [5/37] rated as excellent or good respectively). There was no significant difference according to the volume of mannitol ingested. Symptom tolerability was comparable between agents, although fullness following MRE was graded as “very tolerable” in 27% (12/45) of patients ingesting PEG, verses 44% (37/84) ingesting mannitol, difference 17% (95% CI 0.6 to 34%). CONCLUSION: Mannitol-based solutions and PEG generally achieve comparable distension quality and side effect profiles, although jejunal distension is better quality with mannitol. Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol. KEY POINTS: • Mannitol-based and PEG-based oral preparation agents generally achieve comparable distension quality for MRE with the exception of the jejunum which is better distended with mannitol. • Mannitol-based and PEG-based oral preparation agents used for MRE have similar side effect profiles. • Neither distension quality nor side-effect profile is altered by ingestion of more than 1 L of mannitol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00330-022-08614-9

Diagnostic performance of sonographic activity scores for adult terminal ileal Crohn’s disease compared to magnetic resonance and histological reference standards:experience from the METRIC trial

Objectives: The simple ultrasound activity score for Crohn’s disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial. Methods: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies. Sensitivity and specificity of SUS-CD and BUSS for TI CD activity were calculated with 95% confidence intervals (CI), from the prospective observations of the original METRIC trial sonographers against the histological activity index (HAI) and the simplified magnetic resonance index of activity (sMARIA). Results: We included 284 patients (median 31.5 years, IQR 23–46) from 8 centres, who underwent IUS and MRE. Of these, 111 patients had available terminal ileal biopsies with HAI scoring. Against histology, sensitivity and specificity for active disease were 79% (95% CI 69–86%) and 50% (31–69%) for SUS-CD, and 66% (56–75%) and 68% (47–84%) for BUSS, respectively. Compared to sMARIA, the sensitivity and specificity for active CD were 81% (74–86%) and 75% (66–83%) for SUS-CD, and 68% (61–74%) and 85% (76–91%) for BUSS, respectively. The sensitivity of SUS-CD was significantly greater than that of BUSS against HAI and sMARIA (p &lt; 0.001), but its specificity was significantly lower than of BUSS against the MRE reference standard (p = 0.003). Conclusions: Particularly when compared to MRE activity scoring, SUS-CD and BUSS are promising tools in a real-world clinical setting.Clinical relevance statement: When tested using data from a multicentre, multireader diagnostic accuracy trial, the simple ultrasound activity score for Crohn’s disease (SUS-CD) and bowel ultrasound score (BUSS) were clinically viable intestinal ultrasound indices that were reasonably sensitive and specific for terminal ileal Crohn’s disease, especially when compared to a magnetic resonance reference standard.</p

Diagnostic performance of sonographic activity scores for adult terminal ileal Crohn's disease compared to magnetic resonance and histological reference standards: experience from the METRIC trial

OBJECTIVES: The simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) are promising intestinal ultrasound (IUS) indices of CD, but studied mainly in small settings with few sonographers. We compared SUS-CD and BUSS against histological and magnetic resonance enterography (MRE) reference standards in a post hoc analysis of a prospective multicentre, multireader trial. METHODS: Participants recruited to the METRIC trial (ISRCTN03982913) were studied, including those with available terminal ileal (TI) biopsies. Sensitivity and specificity of SUS-CD and BUSS for TI CD activity were calculated with 95% confidence intervals (CI), from the prospective observations of the original METRIC trial sonographers against the histological activity index (HAI) and the simplified magnetic resonance index of activity (sMARIA). RESULTS: We included 284 patients (median 31.5 years, IQR 23-46) from 8 centres, who underwent IUS and MRE. Of these, 111 patients had available terminal ileal biopsies with HAI scoring. Against histology, sensitivity and specificity for active disease were 79% (95% CI 69-86%) and 50% (31-69%) for SUS-CD, and 66% (56-75%) and 68% (47-84%) for BUSS, respectively. Compared to sMARIA, the sensitivity and specificity for active CD were 81% (74-86%) and 75% (66-83%) for SUS-CD, and 68% (61-74%) and 85% (76-91%) for BUSS, respectively. The sensitivity of SUS-CD was significantly greater than that of BUSS against HAI and sMARIA (p < 0.001), but its specificity was significantly lower than of BUSS against the MRE reference standard (p = 0.003). CONCLUSIONS: Particularly when compared to MRE activity scoring, SUS-CD and BUSS are promising tools in a real-world clinical setting. CLINICAL RELEVANCE STATEMENT: When tested using data from a multicentre, multireader diagnostic accuracy trial, the simple ultrasound activity score for Crohn's disease (SUS-CD) and bowel ultrasound score (BUSS) were clinically viable intestinal ultrasound indices that were reasonably sensitive and specific for terminal ileal Crohn's disease, especially when compared to a magnetic resonance reference standard. KEY POINTS: The simple ultrasound activity score for Crohn's disease and bowel ultrasound score are promising intestinal ultrasound indices of Crohn's disease but to date studied mainly in small settings with few sonographers. Compared to histology and the magnetic resonance reference standard in a multicentre, multireader setting, the sensitivity of simple ultrasound activity score for Crohn's disease is significantly greater than that of bowel ultrasound score. The specificity of simple ultrasound activity score for Crohn's disease was significantly lower than that of bowel ultrasound score compared to the magnetic resonance enterography reference standard. The specificity of both indices was numerically higher when the magnetic resonance enterography reference standard was adopted

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Genomic evidence of widespread admixture from polar bears into brown bears during the last ice age

Recent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has mainly been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, when brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomics to reveal patterns of evolutionary change that are otherwise masked in contemporary data

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study

Background: Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods: TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings: Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation: Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding: Cancer Research UK