East Chisenbury Midden 2015−17: further investigations of the late prehistoric midden deposits, enclosure and associated settlement

After a gap of almost two decades further investigations were initiated at this remarkable late prehistoric midden site, supported by Operation Nightingale/Breaking Ground Heritage. Geophysical survey clarified the extent of the broadly contemporary enclosure surrounding the midden, as well as other related features, while subsequent excavations provided new information on the midden, the enclosure and settlement. Two small trenches in the northeast half of the midden revealed a different sequence and produced far fewer finds than the 1992−3 excavations in the southwest half, demonstrating that it is not a homogeneous mound. A substantial ditch and associated bank, largely levelled by the late Roman period, may have been contemporary with or pre-dated the early development of the midden, while some 150 postholes attested to the presence of numerous roundhouses and other structures within the enclosure. Overall, a date range of c. 1000−500 cal. BC and possibly later is suggested from radiocarbon dating and pottery, the main phase of midden development perhaps later than the majority of the settlement. Furthermore, recent results of radiocarbon dating of material from the earlier excavations suggest the site sequence may continue as late as c. 400 cal. BC. Radiocarbon dating of the few human remains has also highlighted the likelihood that some were curated, the probable intervals between the dates of death and deposition ranging from a few decades to three centuries. Finds and environmental assemblages are generally consistent with those previously found, but a few sherds of scratch cordoned bowl represent a significant new discovery, as does a unique copper alloy ‘pendant’ of possible continental origin. Evidence now indicates that cattle, as well as sheep and pigs, were intensively managed and slaughtered on site, with the isotope data suggesting local origins for most of the animals, though some cattle may have been raised on pasturage further afield

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Learning Hierarchical Task Models by Defining and Refining Examples

this paper, we present a development environment that can ease the task model acquisition process. The environment combines direct model editing, machine learning based upon annotated examples, and model verification through regression testing. The learning techniques and most of the other major components of this environment are in place; however, the graphical front-end is still under developmen

Learning Hierarchical Task Models by Defining and Refining Examples

Task models are used in many areas of computer science including planning, intelligent tutoring, plan recognition, interface design, and decision theory. However, developing task models is a significant practical challenge. We present a task model development environment centered around a machine learning engine that infers task models from examples. A novel aspect of the environment is support for a domain expert to refine past examples as he or she develops a clearer understanding of how to model the domain. Collectively, these examples constitute a “test suite ” that the development environment manages in order to verify that changes to the evolving task model do not have unintended consequences

Regarding Docket No. FR-6111-P-02, HUD’s Implementation of the Fair Housing Act’s Disparate Impact Standard

The is a Comment on the Department of Housing and Urban Development (HUD) Proposed Rule: FR-6111-P-02 HUD’s Implementation of the Fair Housing Act’s Disparate Impact Standard . This comment examines how algorithms in housing applications may be inherently biased against certain groups of people. Their arguments against the proposed legislation: 1. To ensure that an algorithm does not have disparate impact, it is not enough to show that individual input factors are not “substitutes or close proxies” for protected characteristics. 2. It is impossible to audit an algorithm for bias without an adequate level of transparency or access to the algorithm. 3. Allowing defendants to deflect responsibility to proprietary third-party algorithms effectively destroys disparate impact liability. 4. The proposed regulation fails to take into account the cumulative impact of multiple users of algorithms that result in disparate impact on protected classes where no individual user has liability under the proposed regulation. TO VIEW OR LEAVE COMMENTS VISIT THE FEDERAL REGISTE

A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non-small-cell Lung Cancer: SWOG 1206 (8811)

BACKGROUND: We conducted a 2-part study to evaluate the incorporation of veliparib, a PARP inhibitor, into chemoradiotherapy (CRT) for stage III non-small-cell lung cancer. PATIENTS AND METHODS: In the phase I part, patients were treated successively at 3 dose levels of veliparib (40, 80, and 120 mg) twice daily during CRT. In the phase II part, patients were randomized to receive veliparib or placebo during thoracic radiotherapy with concurrent weekly carboplatin and paclitaxel, followed by 2 cycles of consolidation carboplatin and paclitaxel with veliparib or placebo. The study was prematurely discontinued owing to the emergence of adjuvant immunotherapy as standard of care. RESULTS: Of 21 patients enrolled in phase I, 2 patients developed dose-limiting toxicities (DLTs): 1 grade 3 esophagitis with dysphagia (at 40 mg) and 1 grade 3 esophagitis with dehydration (at 80 mg). No DLTs were seen at veliparib dose of 120 mg twice daily, which was selected for the phase II part that enrolled 31 eligible patients. Progression-free survival (PFS) was not different between the 2 arms (P = .20). For the veliparib and placebo arms, response rates were 56% and 69%, PFS at 1 year 47% and 46%, and overall survival at 1 year 89% and 54%, respectively. CONCLUSION: Veliparib with CRT was feasible and well tolerated. Efficacy could not accurately be determined because of early study closure. Nonetheless, there is enthusiasm for the evaluation of PARP inhibitors in lung cancer as predictive biomarkers are being developed and combinations with immunotherapy are attractive