The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Urodynamic assessment of urinary incontinence

Context : Urodynamic evaluation in the assessment of women complaining of urinary incontinence remains controversial with recent UK National Institute of Health and Clinical Excellence guidance maintaining that it is unnecessary prior to surgery for women with a primarily stress leakage. Other experts contend it should be part of routine preoperative assessment since it establishes a diagnosis, allows more careful patient counseling and predicts surgical outcome. Objectives : To summarize current literature to define the evidence level on which these conflicting opinions are based. Materials and Methods : A systematic literature search was performed and retrieved publications summarized in a narrative evidence review using both original papers and previous reviews. Results : Five hundred and one primary research papers and 65 previous reviews were retrieved. The findings were summarized in a narrative comprising overview, description of methods of bladder and urethral pressure measurement, and a summary of the literature concerning four key questions. Conclusion : The level of evidence was low regarding answering each of the questions posed, preventing firm conclusions. Urodynamic findings do correlate with relevant symptoms and, to some extent, with symptom severity, giving reasonable diagnostic accuracy. There is no reliable evidence that preoperative urodynamic diagnosis improves outcome from surgery for stress incontinence although it is likely to facilitate preoperative discussion. Tests to differentiate sphincter deficiency and urethral hypermobility are not currently recommended due to poor validity and reproducibility. This along with the current use of mid-urethral tapes as the universal primary surgical procedure means differentiation is not a necessity. Preoperative diagnosis of detrusor overactivity does not appear to worsen surgical outcome in women with a primary symptom of stress leakage. Large, well-designed prospective studies are now underway to provide a definitive answer to these questions

Big Rubrics and Weird Genres: The Futility of Using Generic Assessment Tools Across Diverse Instructional Contexts

Interest "all-purpose" assessment of students' writing and/or speaking appeals to many teachers and administrators because it seems simple and efficient, offers a single set of standards that can inform pedagogy, and serves as a benchmark for institutional improvement. This essay argues, however, that such generalized standards are unproductive and theoretically misguided. Drawing on situated approaches to the assessment of writing and speaking, as well as many years of collective experience working with faculty, administrators, and students on communication instruction in highly specific curricular contexts, we demonstrate the advantages of shaping assessment around local conditions, including discipline-based genres and contexts, specific and varied communicative goals, and the embeddedness of communication instruction in particular "ways of knowing" within disciplines and subdisciplines. By sharing analyses of unique genres of writing and speaking at our institutions, and the processes that faculty and administrators have used to create assessment protocols for those genres, we support contextually-based approaches to assessment and argue for the abandonment of generic rubrics

Crisis Management and Security Program (CMS) (Semester Unknown) IPRO 370: Crisis Management and Security Program IPRO 370 Final Report Sp08

The IIT IPRO 370 Crisis Management and Security Program (CMS) is in its fourth stage of development. The current goal is to further develop the capabilities of our web based program that can be used by organizations to assist when determining how well their crisis management plans stand up to different methodologies, assessments, and scenarios during the testing process. Also to start marketing our web site to attract a community of many users to assist in the growth of the CMS program. The initial grant for this project was funded by the Homeland Security Innovation & Entrepreneurship Center. Ms. Irene Rozansky, CEO and founder of R&A Crisis Management Services Inc. will be our sponsor to ensure that we develop a program able to test existing crisis management plans for companies, organizations, and individuals who lack a response ready approach in times of crisis.Deliverable

Crisis Management and Security Program (CMS) (Semester Unknown) IPRO 370: Crisis Management and Security Program IPRO 370 Brochure2 Sp08

The IIT IPRO 370 Crisis Management and Security Program (CMS) is in its fourth stage of development. The current goal is to further develop the capabilities of our web based program that can be used by organizations to assist when determining how well their crisis management plans stand up to different methodologies, assessments, and scenarios during the testing process. Also to start marketing our web site to attract a community of many users to assist in the growth of the CMS program. The initial grant for this project was funded by the Homeland Security Innovation & Entrepreneurship Center. Ms. Irene Rozansky, CEO and founder of R&A Crisis Management Services Inc. will be our sponsor to ensure that we develop a program able to test existing crisis management plans for companies, organizations, and individuals who lack a response ready approach in times of crisis.Deliverable

Crisis Management and Security Program (CMS) (Semester Unknown) IPRO 370

The IIT IPRO 370 Crisis Management and Security Program (CMS) is in its fourth stage of development. The current goal is to further develop the capabilities of our web based program that can be used by organizations to assist when determining how well their crisis management plans stand up to different methodologies, assessments, and scenarios during the testing process. Also to start marketing our web site to attract a community of many users to assist in the growth of the CMS program. The initial grant for this project was funded by the Homeland Security Innovation & Entrepreneurship Center. Ms. Irene Rozansky, CEO and founder of R&A Crisis Management Services Inc. will be our sponsor to ensure that we develop a program able to test existing crisis management plans for companies, organizations, and individuals who lack a response ready approach in times of crisis.Deliverable

Crisis Management and Security Program (CMS) (Semester Unknown) IPRO 370: Crisis Management and Security Program IPRO 370 Final Presentation Sp08

The IIT IPRO 370 Crisis Management and Security Program (CMS) is in its fourth stage of development. The current goal is to further develop the capabilities of our web based program that can be used by organizations to assist when determining how well their crisis management plans stand up to different methodologies, assessments, and scenarios during the testing process. Also to start marketing our web site to attract a community of many users to assist in the growth of the CMS program. The initial grant for this project was funded by the Homeland Security Innovation & Entrepreneurship Center. Ms. Irene Rozansky, CEO and founder of R&A Crisis Management Services Inc. will be our sponsor to ensure that we develop a program able to test existing crisis management plans for companies, organizations, and individuals who lack a response ready approach in times of crisis.Deliverable

Crisis Management and Security Program (CMS) (Semester Unknown) IPRO 370: Crisis Management and Security Program IPRO 370 Ethics Sp08

The IIT IPRO 370 Crisis Management and Security Program (CMS) is in its fourth stage of development. The current goal is to further develop the capabilities of our web based program that can be used by organizations to assist when determining how well their crisis management plans stand up to different methodologies, assessments, and scenarios during the testing process. Also to start marketing our web site to attract a community of many users to assist in the growth of the CMS program. The initial grant for this project was funded by the Homeland Security Innovation & Entrepreneurship Center. Ms. Irene Rozansky, CEO and founder of R&A Crisis Management Services Inc. will be our sponsor to ensure that we develop a program able to test existing crisis management plans for companies, organizations, and individuals who lack a response ready approach in times of crisis.Deliverable