Plasmonic‐enhanced NIR‐II downconversion fluorescence beyond 1500 nm from core–shell–shell lanthanide nanoparticles

This paper reports on the light amplification of NaGdF4:Yb,Er,Ce@NaGdF4:Yb,Nd@NaGdF4 core–shell–shell downconversion nanoparticles (CSS‐DCNPs) in the near‐infrared second biological window (NIR‐II: 1000–1700 nm) by plasmonic nanostructures. Through a precisely controlled plasmonic metallic nanostructure, fluorescence from Yb3+ induced 1000 nm emission, Nd3+ induced 1060 nm emission, and Er3+ induced 1527 nm emission are enhanced 1.6‐fold, 1.7‐fold, and 2.2‐fold, respectively, under an 808 nm laser excitation for the CSS‐DCNPs coupled with a gold hole‐cap nanoarray (Au‐HCNA), while the Er3+ induced 1527 nm emission under a 980 nm laser excitation is enhanced up to 6‐fold. To gain insight into the enhancement mechanism, the plasmonic modulation of Er3+ induced NIR‐II emission at 1550 nm under 980 nm excitation is studied by FDTD simulation and lifetime measurements, showing the observed fluorescence enhancement can be attributed to a combination of enhanced excitation and an increased radiative decay rate

The impact of the Trauma Triage App on pre-hospital trauma triage: design and protocol of the stepped-wedge, cluster-randomized TESLA trial

Abstract Background Field triage of trauma patients is crucial to get the right patient to the right hospital within a particular time frame. Minimization of undertriage, overtriage, and interhospital transfer rates could substantially reduce mortality rates, life-long disabilities, and costs. Identification of patients in need of specialized trauma care is predominantly based on the judgment of Emergency Medical Services professionals and a pre-hospital triage protocol. The Trauma Triage App is a smartphone application that includes a prediction model to aid Emergency Medical Services professionals in the identification of patients in need of specialized trauma care. The aim of this trial is to assess the impact of this new digital approach to field triage on the primary endpoint undertriage. Methods The Trauma triage using Supervised Learning Algorithms (TESLA) trial is a stepped-wedge cluster-randomized controlled trial with eight clusters defined as Emergency Medical Services regions. These clusters are an integral part of five inclusive trauma regions. Injured patients, evaluated on-scene by an Emergency Medical Services professional, suspected of moderate to severe injuries, will be assessed for eligibility. This unidirectional crossover trial will start with a baseline period in which the default pre-hospital triage protocol is used, after which all clusters gradually implement the Trauma Triage App as an add-on to the existing triage protocol. The primary endpoint is undertriage on patient and cluster level and is defined as the transportation of a severely injured patient (Injury Severity Score ≥ 16) to a lower-level trauma center. Secondary endpoints include overtriage, hospital resource use, and a cost-utility analysis. Discussion The TESLA trial will assess the impact of the Trauma Triage App in clinical practice. This novel approach to field triage will give new and previously undiscovered insights into several isolated components of the diagnostic strategy to get the right trauma patient to the right hospital. The stepped-wedge design allows for within and between cluster comparisons. Trial registration Netherlands Trial Register, NTR7243. Registered 30 May 2018, https://www.trialregister.nl/trial/7038

In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome

Global quieting of high-frequency seismic noise due to COVID-19 pandemic lockdown measures

Human activity causes vibrations that propagate into the ground as high-frequency seismic waves. Measures to mitigate the COVID-19 pandemic caused widespread changes in human activity, leading to a months-long reduction in seismic noise of up to 50%. The 2020 seismic noise quiet period is the longest and most prominent global anthropogenic seismic noise reduction on record. While the reduction is strongest at surface seismometers in populated areas, this seismic quiescence extends for many kilometers radially and hundreds of meters in depth. This provides an opportunity to detect subtle signals from subsurface seismic sources that would have been concealed in noisier times and to benchmark sources of anthropogenic noise. A strong correlation between seismic noise and independent measurements of human mobility suggests that seismology provides an absolute, real-time estimate of population dynamics

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

Success or failure of critical steps in community case management of malaria with rapid diagnostic tests: a systematic review

Background: Malaria still causes high morbidity and mortality around the world, mainly in sub-Saharan Africa. Community case management of malaria (CCMm) by community health workers (CHWs) is one of the strategies to combat the disease by increasing access to malaria treatment. Currently, the World Health Organization recommends to treat only confirmed malaria cases, rather than to give presumptive treatment. Objectives. This systematic review aims to provide a comprehensive overview of the success or failure of critical steps in CCMm with rapid diagnostic tests (RDTs). Methods. The databases of Medline, Embase, the Cochrane Library, the library of the \u27Malaria in Pregnancy\u27 consortium, and Web of Science were used to find studies on CCMm with RDTs in SSA. Studies were selected according to inclusion and exclusion criteria, subsequently risk of bias was assessed and data extracted. Results: 27 articles were included. CHWs were able to correctly perform RDTs, although specificity levels were variable. CHWs showed high adherence to test results, but in some studies a substantial group of RDT negatives received treatment. High risk of bias was found for morbidity and mortality studies, therefore, effects on morbidity and mortality could not be estimated. Uptake and acceptance by the community was high, however negative-tested patients did not always follow up referral advice. Drug or RDT stock-outs and limited information on CHW motivation are bottlenecks for sustainable implementation. RDT-based CCMm was found to be cost effective for the correct treatment of malaria in areas with low to medium malaria prevalence, but study designs were not optimal. Discussion. Trained CHWs can deliver high quality care for malaria using RDTs. However, lower RDT specificity could lead to missed diagnoses of non-malarial causes of fever. Other threats for CCMm are non-adherence to negative test results and low referral completion. Integrated CCM may solve some of these issues. Unfortunately, morbidity and mortality are not adequately investigated. More information is needed about influencing sociocultural aspects, CHW motivation and stock supply. Conclusion: CCMm is generally well executed by CHWs, but there are several barriers for its success. Integrated CCM may overcome some of these barriers

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake