Measurement of the 2νββ decay half-life of 150Nd and a search for 0νββ decay processes with the full exposure from the NEMO-3 detector

We present results from a search for neutrinoless double-β (0νββ) decay using 36.6 g of the isotope 150Nd with data corresponding to a live time of 5.25 y recorded with the NEMO-3 detector. We construct a complete background model for this isotope, including a measurement of the two-neutrino double-β decay half-life of T2ν 1=2 ¼ ½9.34 0.22ðstatÞ þ0.62 −0.60 ðsystÞ × 1018 y for the ground state transition, which represents the most precise result to date for this isotope. We perform a multivariate analysis to search for 0νββ decays in order to improve the sensitivity and, in the case of observation, disentangle the possible underlying decay mechanisms. As no evidence for 0νββ decay is observed, we derive lower limits on half-lives for several mechanisms involving physics beyond the standard model. The observed lower limit, assuming light Majorana neutrino exchange mediates the decay, is T0ν 1=2 > 2.0 × 1022 y at the 90% C.L., corresponding to an upper limit on the effective neutrino mass of hmνi < 1.6–5.3 eV

Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study

Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3&nbsp;days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3&nbsp;days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60\u20131.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14\u20131.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Heparin-binding protein (HBP): an early marker of respiratory failure after trauma?

Background Trauma and its complications contribute to morbidity and mortality in the general population. Trauma victims are susceptible to acute respiratory distress syndrome (ARDS) and sepsis. Polymorphonuclear leucocytes (PMNs) are activated after trauma and there is substantial evidence of their involvement in the development of ARDS. Activated PMNs release heparin-binding protein (HBP), a granule protein previously shown to be involved in acute inflammatory reactions. We hypothesised that there is an increase in plasma HBP content after trauma and that the increased levels are related to the severity of the trauma or later development of severe sepsis and organ failure (ARDS). Methods and Material We investigated HBP in plasma samples within 36h from trauma in 47 patients admitted to a level one trauma centre with a mean injury severity score (ISS) of 26 (2134). ISS, admission sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded at admission. ARDS and presence of severe sepsis were determined daily during intensive care. Results We found no correlation between individual maximal plasma HBP levels at admission and ISS, admission SOFA or APACHE II. We found, however, a correlation between HBP levels and development of ARDS (P=0.026, n=47), but not to severe sepsis. Conclusion HBP is a potential biomarker candidate for early detection of ARDS development after trauma. Further research is required to confirm a casual relationship between plasma HBP and the development of ARDS

Heparin-binding protein (HBP/CAP37) - a link to endothelin-1 in endotoxemia-induced pulmonary oedema?

BackgroundVascular leakage and oedema formation are key components in sepsis. In septic patients, plasma levels of the vasoconstrictive and pro-inflammatory peptide endothelin-1 (ET-1) correlate with mortality. During sepsis, neutrophils release heparin-binding protein (HBP) known to increase vascular permeability and to be a promising biomarker of human sepsis. As disruption of ET-signalling in endotoxemia attenuates formation of oedema, we hypothesized that this effect could be related to decreased levels of HBP. To investigate this, we studied the effects of ET-receptor antagonism on plasma HBP and oedema formation in a porcine model of sepsis. In addition, to further characterize a potential endothelin/HBP interaction, we investigated the effects of graded ET-receptor agonist infusions. MethodsSixteen anesthetized pigs were subjected to 5h of endotoxemia and were randomized to receive either the ET-receptor antagonist tezosentan or vehicle after 2h. Haemodynamics, gas-exchange and lung water were monitored. In separate experiments, plasma HBP was measured in eight non-endotoxemic animals exposed to graded infusion of ET-1 or sarafotoxin 6c. ResultsEndotoxemia increased plasma ET-1, plasma HBP, and extravascular lung water. Tezosentan-treatment markedly attenuated plasma HBP and extravascular lung water, and these parameters correlated significantly. Tezosentan decreased pulmonary vascular resistance and increased respiratory compliance. In non-endotoxemic pigs graded ET-1 and sarafotoxin 6c infusions caused a dose-dependent increase in plasma HBP. ConclusionsET-receptor antagonism reduces porcine endotoxin-induced pulmonary oedema and plasma levels of the oedema-promoting protein HBP. Moreover, direct ET-receptor stimulation distinctively increases plasma HBP. Together, these results suggest a novel mechanism by which ET-1 contributes to formation of oedema during experimental sepsis

Heparin-binding protein as a biomarker of post-injury sepsis in trauma patients

Background: Heparin-binding protein (HBP) is a neutrophil-derived protein advocated as a biomarker in sepsis. We evaluated plasma HBP as a predictor of post-injury sepsis in trauma patients. Methods: Ninety-seven trauma patients were studied during the first week of intensive care. Injury-related data were collected and clinical parameters registered daily. Plasma HBP was sampled on day 1, 3 and 5 after trauma and evaluated for associations with injury-related parameters and sepsis. The predictive properties of HBP were compared to C-reactive protein (CRP) and white blood cell count (WBC). Results: Median Injury Severity Score was 33, one-third of the trauma patients received massive transfusion and a quarter was in shock on arrival. Overall 30-day mortality was 8%. Plasma HBP was significantly higher in severely injured patients and associated with shock on arrival, massive transfusions and organ failure. Septic patients had higher levels of HBP only on day 5. When evaluated for prediction of onset of sepsis during the two following days after plasma sampling by receiver operating characteristic (ROC) analyses, areas under the curves were non-significant for all time points. Similar patterns were seen for CRP and WBC. Conclusion: In trauma patients, HBP levels are related to severity of injury and organ dysfunction. Heparin-binding protein was weakly associated with sepsis and only at the later stage of the observation period of 1 week. Moreover, HBP showed poor discriminatory properties as an early biomarker of post-injury sepsis. Trauma-induced inflammation during the post-injury phase may blunt the sepsis-predictive performance of HBP