The ‘Archpro Carnuntum’ Project – Integrated Archaeological Interpretation of Combined Prospection Data, Carnuntum (Austria) = Az „Archpro Carnuntum” projekt – kombinált kutatási adatok integrált régészeti értelmezése, Carnuntum (Ausztria)

The potential of large-scale, non-invasive prospection methods has been widely recognized in archaeology in recent years. Their outstanding possibilities for the exploration of urban centres have been realised early on and applied at selected sites. The ‘ArchPro Carnuntum’ project stands out for its extensive investigation of a Roman provincial capital by the combined application of a wide variety of survey methods (aerial archaeology, magnetometry, ground penetrating radar, extensive field survey) resulting in detailed information on the ancient infrastructure of the Roman metropolis. Within the project, it was not only possible to discover new settlement areas, but in some cases even to deduce their former purpose. As a result, the military administrative centre, newly built residential areas, and temporary military camps could be detected in the archaeological landscape of Carnuntum. This paper presents an overview of the results of this internationally unique prospection project. Az elmúlt évek során széles körben felismerték a régészet tudományterületén alkalmazható nagyszabású, nem invazív jellegű kutatási módszerekben rejlő potenciált. A módszer települési központok feltárásának területén alkalmazható lehetőségei már korán valósággá váltak, és alkalmazásra kerültek a kiválasztott helyszíneken. Az „ArchPro Carnuntum” projekt a római provinciális főváros átfogó vizsgálatával a legkülönfélébb felmérési módszerek (légi régészet, magnetometria, földradar, kiterjedt terepi felmérés) együttes alkalmazásával kiemelkedik ezek közül, és részletes információval szolgál a római város antik infrastruktúrájával kapcsolatban. A projekt során nem kizárólag új települési területek felfedezésére nyílt mód, hanem egyes esetekben következtetni lehetett a területek egykori funkciójára is. Mindezek eredményeként a carnuntumi régészeti területen kimutathatóvá vált a katonai igazgatási központ, valamint az új építésű lakónegyedek és az ideiglenes katonai táborhelyek is. Jelen tanulmány ezen nemzetközi szinten is egyedülálló kutatási projekt eredményeiről nyújt áttekintést

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Beyond "flat-earth" maps of the third sector: enhancing our understanding of the contribution of "below-radar" organisations

This paper summarises a fuller report on research commissioned by the Northern Rock Foundation’s Third Sector Trends Study (TSTS) to assess the scale and distribution of ‘below-the-radar’ (BTR) organisations. The specific aim of this study was to provide a picture of the local third sector in North East England and Cumbria which went beyond organisations appearing on lists provided by regulatory bodies such as the Charity Commission. Many organisations do not appear on such ‘radars’, with the result that research risks producing what one commentator described as ‘flat earth maps’ of the third secto

The influence of disability, socioeconomic status & regionality on higher education access & participation

Little is known about the cumulative impact of disability, low socioeconomic status and regionality on students in Australia and the barriers, levers and influences that impact their higher education decisions making. The overarching objectives of the program of research were to determine the factors that influence the decisions of people from low SES background with a disability from regional and remote areas to attend university and to provide strategies that might be effective in reducing barriers to higher education among young people with a disability

Immune reconstitution in children following chemotherapy for acute leukemia

Abstract Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long‐term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18‐month following treatment, with 30‐39 patients analyzed at each time point. Total lymphocytes were reduced during maintenance chemotherapy and remained low 18 months following treatment completion. CD4 T cells remained significantly reduced 18 months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B‐cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B cells, particularly nonclass‐switched memory B cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B‐cell numbers recover rapidly, disruption of memory/naïve balance persists and T‐cell compartment persist at 18 months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization

Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia

Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimens on immunity, and thus infectious susceptibility and response to immunisation. Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimen<br/