Joint inversion estimate of regional glacial isostatic adjustment in Antarctica considering a lateral varying Earth structure (ESA STSE Project REGINA)

A major uncertainty in determining the mass balance of the Antarctic ice sheet from measurements of satellite gravimetry, and to a lesser extent satellite altimetry, is the poorly known correction for the ongoing deformation of the solid Earth caused by glacial isostatic adjustment (GIA). Although much progress has been made in consistently modelling the ice-sheet evolution throughout the last glacial cycle, as well as the induced bedrock deformation caused by these load changes, forward models of GIA remain ambiguous due to the lack of observational constraints on the ice sheet's past extent and thickness and mantle rheology beneath the continent. As an alternative to forward modelling GIA, we estimate GIA from multiple space-geodetic observations: GRACE, Envisat/ICESat and GPS. Making use of the different sensitivities of the respective satellite observations to current and past surface mass (ice mass) change and solid Earth processes, we estimate GIA based on viscoelastic response functions to disc load forcing. We calculate and distribute the viscoelastic response functions according to estimates of the variability of lithosphere thickness and mantle viscosity in Antarctica. We compare our GIA estimate with published GIA corrections and evaluate its impact in determining the ice mass balance in Antarctica from GRACE and satellite altimetry. Particular focus is applied to the Amundsen Sea Sector in West Antarctica, where uplift rates of several cm/yr have been measured by GPS. We show that most of this uplift is caused by the rapid viscoelastic response to recent ice-load changes, enabled by the presence of a low-viscosity upper mantle in West Antarctica. This paper presents the second and final contribution summarizing the work carried out within a European Space Agency funded study, REGINA, (www.regina-science.eu)

State-of-the-art in studies of glacial isostatic adjustment for the British Isles: a literature review

Understanding the effects of glacial isostatic adjustment (GIA) of the British Isles is essential for the assessment of past and future sea-level trends. GIA has been extensively examined in the literature, employing different research methods and observational data types. Geological evidence from palaeo-shorelines and undisturbed sedimentary deposits has been used to reconstruct long-term relative sea-level change since the Last Glacial Maximum. This information derived from sea-level index points has been employed to inform empirical isobase models of the uplift in Scotland using trend surface and Gaussian trend surface analysis, as well as to calibrate more theory-driven GIA models that rely on Earth mantle rheology and ice sheet history. Furthermore, current short-term rates of GIA-induced crustal motion during the past few decades have been measured using different geodetic techniques, mainly continuous GPS (CGPS) and absolute gravimetry (AG). AG-measurements are generally employed to increase the accuracy of the CGPS estimates. Synthetic aperture radar interferometry (InSAR) looks promising as a relatively new technique to measure crustal uplift in the northern parts of Great Britain, where the GIA-induced vertical land deformation has its highest rate. This literature review provides an in-depth comparison and discussion of the development of these different research approaches

Harnessing of the Nucleosome Remodeling Deacetylase complex controls lymphocyte development and prevents leukemogenesis

Cell fate decisions depend on the interplay between chromatin regulators and transcription factors. Here we show that activity of the Mi-2β nucleosome remodeling and deacetylase (NuRD) complex was controlled by the Ikaros family of lymphoid-lineage determining proteins. Ikaros, an integral component of the NuRD complex in lymphocytes, tethered this complex to active lymphoid differentiation genes. Loss in Ikaros DNA binding activity caused a local increase in Mi-2β chromatin remodeling and histone deacetylation and suppression of lymphoid gene expression. The NuRD complex also redistributed to transcriptionally poised non-Ikaros gene targets, involved in proliferation and metabolism, inducing their reactivation. Thus, release of NuRD from Ikaros regulation blocks lymphocyte maturation and mediates progression to a leukemic state by engaging functionally opposing epigenetic and genetic networks

Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN):an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial

Background: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. Methods: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 μg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. Findings: Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8–3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference –7·00% [95% CI –12·69 to –1·32]; p=0·016). Interpretation: For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. Funding: British Heart Foundation and Pharmacosmos.</p

Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN):an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial

Background: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. Methods: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 μg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. Findings: Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8–3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference –7·00% [95% CI –12·69 to –1·32]; p=0·016). Interpretation: For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. Funding: British Heart Foundation and Pharmacosmos.</p

Intravenous iron for heart failure, iron deficiency definitions, and clinical response:the IRONMAN trial

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure?METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin &lt; 100 µg/L or transferrin saturation (TSAT) &lt; 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death.RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction &lt; .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT &lt; 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant.CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT &lt; 20% with ferritin &gt; 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.</p

Intravenous iron for heart failure, iron deficiency definitions, and clinical response:the IRONMAN trial

BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure?METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin &lt; 100 µg/L or transferrin saturation (TSAT) &lt; 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death.RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction &lt; .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT &lt; 20%, especially when ferritin was ≥100 µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant.CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT &lt; 20% with ferritin &gt; 100 µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.</p

Effect of an Injury Awareness Education Program on Risk-Taking Behaviors and Injuries in Juvenile Justice Offenders: A Retrospective Cohort Study

Background Risk-taking behavior is a leading cause of injury and death amongst young people. Methodology and Principal Findings This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%–25.8%; number needed to benefit = 4.3, 95%CI 3.9–5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%–2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%–2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05–0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93–0.99) were associated with a lower risk of subsequent traffic or violence-related offences. Significance Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders

Nurses' perceived barriers to the implementation of a Fall Prevention Clinical Practice Guideline in Singapore hospitals

BackgroundTheories of behavior change indicate that an analysis of barriers to change is helpful when trying to influence professional practice. The aim of this study was to assess the perceived barriers to practice change by eliciting nurses\u27 opinions with regard to barriers to, and facilitators of, implementation of a Fall Prevention clinical practice guideline in five acute care hospitals in Singapore.MethodsNurses were surveyed to identify their perceptions regarding barriers to implementation of clinical practice guidelines in their practice setting. The validated questionnaire, \u27Barriers and facilitators assessment instrument\u27, was administered to nurses (n = 1830) working in the medical, surgical, geriatric units, at five acute care hospitals in Singapore.ResultsAn 80.2% response rate was achieved. The greatest barriers to implementation of clinical practice guidelines reported included: knowledge and motivation, availability of support staff, access to facilities, health status of patients, and, education of staff and patients.ConclusionNumerous barriers to the use of the Fall Prevention Clinical Practice Guideline have been identified. This study has laid the foundation for further research into implementation of clinical practice guidelines in Singapore by identifying barriers to change in acute care settings.<br /