Variable aging and storage of dissolved black carbon in the ocean.

During wildfires and fossil fuel combustion, biomass is converted to black carbon (BC) via incomplete combustion. BC enters the ocean by rivers and atmospheric deposition contributing to the marine dissolved organic carbon (DOC) pool. The fate of BC is considered to reside in the marine DOC pool, where the oldest BC 14C ages have been measured (>20,000 14C y), implying long-term storage. DOC is the largest exchangeable pool of organic carbon in the oceans, yet most DOC (>80%) remains molecularly uncharacterized. Here, we report 14C measurements on size-fractionated dissolved BC (DBC) obtained using benzene polycarboxylic acids as molecular tracers to constrain the sources and cycling of DBC and its contributions to refractory DOC (RDOC) in a site in the North Pacific Ocean. Our results reveal that the cycling of DBC is more dynamic and heterogeneous than previously believed though it does not comprise a single, uniformly "old" 14C age. Instead, both semilabile and refractory DBC components are distributed among size fractions of DOC. We report that DBC cycles within DOC as a component of RDOC, exhibiting turnover in the ocean on millennia timescales. DBC within the low-molecular-weight DOC pool is large, environmentally persistent and constitutes the size fraction that is responsible for long-term DBC storage. We speculate that sea surface processes, including bacterial remineralization (via the coupling of photooxidation of surface DBC and bacterial co-metabolism), sorption onto sinking particles and surface photochemical oxidation, modify DBC composition and turnover, ultimately controlling the fate of DBC and RDOC in the ocean.

Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19.

BACKGROUND: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 µg once daily for 14 days or placebo. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28. RESULTS: Of the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, were included in the analysis. There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56). A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups. CONCLUSIONS: Treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.).

Dominant heterocyclic composition of dissolved organic nitrogen in the ocean: A new paradigm for cycling and persistence.

Marine dissolved organic nitrogen (DON) is one of the planet's largest reservoirs of fixed N, which persists even in the N-limited oligotrophic surface ocean. The vast majority of the ocean's total DON reservoir is refractory (RDON), primarily composed of low molecular weight (LMW) compounds in the subsurface and deep sea. However, the composition of this major N pool, as well as the reasons for its accumulation and persistence, are not understood. Past characterization of the analytically more tractable, but quantitatively minor, high molecular weight (HMW) DON fraction revealed a functionally simple amide-dominated composition. While extensive work in the past two decades has revealed enormous complexity and structural diversity in LMW dissolved organic carbon, no efforts have specifically targeted LMW nitrogenous molecules. Here, we report the first coupled isotopic and solid-state NMR structural analysis of LMW DON isolated throughout the water column in two ocean basins. Together these results provide a first view into the composition, potential sources, and cycling of this dominant portion of marine DON. Our data indicate that RDON is dominated by 15N-depleted heterocyclic-N structures, entirely distinct from previously characterized HMW material. This fundamentally new view of marine DON composition suggests an important structural control for RDON accumulation and persistence in the ocean. The mechanisms of production, cycling, and removal of these heterocyclic-N-containing compounds now represents a central challenge in our understanding of the ocean's DON reservoir.

Single Intravenous Dose Dalbavancin Pathway for the Treatment of Acute Bacterial Skin and Skin Structure Infections: Considerations for Emergency Department Implementation and Cost Savings.

BACKGROUND: A pathway for the treatment of acute bacterial skin and skin structure infections (ABSSSI) with a single intravenous (IV) dose of dalbavancin was previously shown to reduce hospital admissions and shorten inpatient length of stay (LOS). OBJECTIVES: To describe pathway implementation at the emergency department (ED) and evaluate cost-effectiveness of a single-dose dalbavancin administered to ED patients who would otherwise be hospitalized to receive usual care with multidose IV antibiotics. METHODS: The dalbavancin pathway was previously implemented at 11 U.S. EDs (doi:10.1111/acem.14258). Patients with ABSSSI, without an unstable comorbidity or infection complication requiring complex management, were treated with a single dose of dalbavancin. At the emergency physicians' discretion, patients were either discharged and received outpatient follow-up or were hospitalized for continued management. A decision analytic cost-effectiveness model was developed from the U.S. healthcare's perspective to evaluate costs associated with the dalbavancin pathway compared with inpatient usual care. Costs (2021 USD) were modeled over a 14-day horizon and included ED visits, drug costs, inpatient stay, and physician visits. One-way and probabilistic sensitivity analyses examined input parameter uncertainty. RESULTS: Driven largely by the per diem inpatient cost and LOS for usual care, the dalbavancin pathway was associated with savings of $5133.20 per patient and $1211.57 per hospitalization day avoided, compared with inpatient usual care. The results remained robust in sensitivity and scenario analyses. CONCLUSION: The new single-dose dalbavancin ED pathway for ABSSSI treatment, which was previously implemented at 11 U.S. EDs, offers robust cost savings compared to inpatient usual care.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. Objective: To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US. Interventions: Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28. Results: Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether ivermectin, with a maximum targeted dose of 600 µg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective: To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Interventions: Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 µg/kg (n = 602) daily, or placebo (n = 604) for 6 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results: Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

The Diagnostic Accuracy Of Procalcitonin for Urinary Tract Infection in Hospitalized Older Adults: a Prospective Study.

BACKGROUND: The diagnosis of urinary tract infection (UTI) is challenging among hospitalized older adults, particularly among those with altered mental status. OBJECTIVE: To determine the diagnostic accuracy of procalcitonin (PCT) for UTI in hospitalized older adults. DESIGN: We performed a prospective cohort study of older adults (≥65 years old) admitted to a single hospital with evidence of pyuria on urinalysis. PCT was tested on initial blood samples. The reference standard was a clinical definition that included the presence of a positive urine culture and any symptom or sign of infection referable to the genitourinary tract. We also surveyed the treating physicians for their clinical judgment and performed expert adjudication of cases for the determination of UTI. PARTICIPANTS: Two hundred twenty-nine study participants at a major academic medical center. MAIN MEASURES: We calculated the area under the receiver operating characteristic curve (AUC) of PCT for the diagnosis of UTI. KEY RESULTS: In this study cohort, 61 (27%) participants met clinical criteria for UTI. The median age of the overall cohort was 82.6 (IQR 74.9-89.7) years. The AUC of PCT for the diagnosis of UTI was 0.56 (95% CI, 0.46-0.65). A series of sensitivity analyses on UTI definition, which included using a decreased threshold for bacteriuria, the treating physicians' clinical judgment, and independent infectious disease specialist adjudication, confirmed the negative result. CONCLUSIONS: Our findings demonstrate that PCT has limited value in the diagnosis of UTI among hospitalized older adults. Clinicians should be cautious using PCT for the diagnosis of UTI in hospitalized older adults.

Divergent trophic responses of sympatric penguin species to historic anthropogenic exploitation and recent climate change.

The Southern Ocean is in an era of significant change. Historic overharvesting of marine mammals and recent climatic warming have cascading impacts on resource availability and, in turn, ecosystem structure and function. We examined trophic responses of sympatric chinstrap (Pygoscelis antarctica) and gentoo (Pygoscelis papua) penguins to nearly 100 y of shared environmental change in the Antarctic Peninsula region using compound-specific stable isotope analyses of museum specimens. A century ago, gentoo penguins fed almost exclusively on low-trophic level prey, such as krill, during the peak of historic overexploitation of marine mammals, which was hypothesized to have resulted in a krill surplus. In the last 40 y, gentoo penguin trophic position has increased a full level as krill declined in response to recent climate change, increased competition from recovering marine mammal populations, and the development of a commercial krill fishery. A shifting isotopic baseline supporting gentoo penguins suggests a concurrent increase in coastal productivity over this time. In contrast, chinstrap penguins exhibited no change in trophic position, despite variation in krill availability over the past century. The specialized foraging niche of chinstrap penguins likely renders them more sensitive to changes in krill availability, relative to gentoo penguins, as evinced by their declining population trends in the Antarctic Peninsula over the past 40 y. Over the next century, similarly divergent trophic and population responses are likely to occur among Antarctic krill predators if climate change and other anthropogenic impacts continue to favor generalist over specialist species.

Male Youth Ice Hockey Concussion Incidence in a USA Hockey Membership-Adjusted Population: A Peak in 2011 and the Impact of Major Rule Changes.

OBJECTIVE: To investigate the incidence of youth ice hockey-related concussions preceding and following the implementation of new body-checking and head contact rules by USA hockey in 2011. We hypothesized a decrease in concussions after the rule change. DESIGN: Retrospective analysis. SETTING: United States emergency department (ED) data queried in the National Electronic InjurySurveillance System (NEISS). PATIENTS: National Electronic Injury Surveillance System reported male youth (≤18 years) ice hockey concussion cases from January 1, 2002, to December 31, 2016. In total, 848 players were diagnosed with concussion, representing a national estimate of 17 374 cases. INDEPENDENT VARIABLES: Time, specifically years. MAIN OUTCOME MEASURES: Incidences and incidence rates (measured per 10 000 person-years) of male youth ice hockey concussions. Annual trends were analyzed using descriptive and linear or polynomial regression analysis. RESULTS: The national estimate of youth ice hockey-related concussions seen in US emergency departments (EDs) increased significantly from 656 in 2007 to 2042 in 2011 (P < 0.01). During the same period, their respective incidence increased significantly from 21.8 to 66.8 per 10 000, before dropping through 2016 (P < 0.05). After 2011, concussions decreased from 1965 in 2012 to 1292 in 2016 (P = 0.055). The gap in concussion incidence between the 11 to 12 and 13 to 14 divisions widened after 2011 (before 2011: 41 vs 49 per 10 000 person-years [P = 0.80]; after 2011: 45 and 89, respectively [P < 0.01]). CONCLUSIONS: US EDs experienced a significant increase in youth ice hockey concussion visits from 2007 to 2011. After the 2011 rule changes, concussion visits decreased significantly from 2012 to 2016.

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Nanofluid Boiling on Micro/Nano-engineered Surfaces.

This work characterizes the impact of boiling aqueous nanofluids on engineered surfaces designed for boiling enhancement with pure water. Although micro/nano-engineered surfaces have been shown to enhance boiling, these achievements are typically demonstrated using deionized water or other purified fluids. In parallel, particulate-laden fluids, also known as nanofluids, have been shown to enhance boiling as well. In this study, we investigate a variety of engineered surfaces and the boiling degradation due to the addition of SiO2 particles at a fixed concentration of 0.2% by volume but varying sizes from 7 nm to 10 µm. Although the addition of SiO2 particles is shown to moderately improve critical heat flux (CHF) on all the surfaces considered, the heat transfer coefficient (HTC) is seen to deteriorate with the addition of particles of any size. The bare copper surface and a nanostructured surface show particle size-dependent degradation of the HTC due to clogging. Bi-conductive surfaces also show a degradation of the HTC, but it was shown to be independent of the particle size. This work has shown specific and unique degradation mechanisms for each of the surfaces considered including the reduction of nucleation sites and thermal insulation. Additionally, the surfaces tested in this work exhibited a partial-CHF condition occurring with the addition of particles.

Formation and Stability of Thin Condensing Films on Structured Amphiphilic Surfaces.

We present a microamphiphilic surface to promote the formation of a thin, stable liquid film during condensation. The surface consists of a hydrophilic micropillar array with hydrophobic pillar tips and was made using photolithography, deep reactive ion etching, and liftoff. The hydrophobic tips prevent the liquid film from growing thick, thereby keeping the thermal resistance low without the cyclical growth and shedding process of dropwise condensation. The wetting behavior was modeled analytically, and the parameters required for film formation were determined and verified with ESEM experiments. When a surface filled with condensate and lacked a low-pressure zone for the water to leave, a rupture event occurred, and a large Wenzel droplet emerged to flood the surface irreversibly. A number of strategies were found to combat rupture events. Tilting the surface vertically and dipping in a liquid pool gave the condensate a low-pressure region and prevented rupture. Irreversible flooding can also be avoided by ensuring that the emerged droplet was a nonwetting, highly mobile Cassie droplet. Parameters for Cassie-stable amphiphilic surfaces were determined analytically, but the high aspect ratios required prevented the manufacture of these surfaces for this study. Instead a hierarchical design was presented that demonstrated emerged Cassie droplets without challenging the manufacturing limits of the microfabrication procedure. This design avoided Wenzel droplet flooding without the need for a designated low-pressure zone. Additionally, sites for Cassie emergence could be engineered by removing a single pillar from the array at a designated location.

Wicking Enhanced Critical Heat Flux for Highly Wetting Fluids on Structured Surfaces.

The use of micro/nano-scale structures has been shown to enhance critical heat flux (CHF) during pool boiling in recent studies. A correlation between wicking rate and CHF enhancement for structured superhydrophilic surfaces has been reported in prior work of the authors. In that work, a nondimensional correlation was developed and validated using only water as the working fluid. In this study, a highly wetting fluid (FC-72) was used to demonstrate the applicability of this correlation on structured surfaces for nonaqueous liquids. This has been achieved using a simple modification of the experimental procedure for highly wetting fluids. This experimental modification shows no effect on the quantification of the liquid wicking rate. Numerous structured superhydrophilic surfaces have been fabricated and tested, including micro- and nanoscale structures and hierarchical surfaces which showed the highest CHF enhancement (200%). More importantly, this work demonstrates the validity of the nondimensional parameters used in the proposed CHF correlation and its overall applicability to a wide range of nonaqueous liquids.

Increasing subtropical North Pacific Ocean nitrogen fixation since the Little Ice Age.

The North Pacific subtropical gyre (NPSG) plays a major part in the export of carbon and other nutrients to the deep ocean. Primary production in the NPSG has increased in recent decades despite a reduction in nutrient supply to surface waters. It is thought that this apparent paradox can be explained by a shift in plankton community structure from mostly eukaryotes to mostly nitrogen-fixing prokaryotes. It remains uncertain, however, whether the plankton community domain shift can be linked to cyclical climate variability or a long-term global warming trend. Here we analyse records of bulk and amino-acid-specific (15)N/(14)N isotopic ratios (δ(15)N) preserved in the skeletons of long-lived deep-sea proteinaceous corals collected from the Hawaiian archipelago; these isotopic records serve as a proxy for the source of nitrogen-supported export production through time. We find that the recent increase in nitrogen fixation is the continuation of a much larger, centennial-scale trend. After a millennium of relatively minor fluctuation, δ(15)N decreases between 1850 and the present. The total shift in δ(15)N of -2 per mil over this period is comparable to the total change in global mean sedimentary δ(15)N across the Pleistocene-Holocene transition, but it is happening an order of magnitude faster. We use a steady-state model and find that the isotopic mass balance between nitrate and nitrogen fixation implies a 17 to 27 per cent increase in nitrogen fixation over this time period. A comparison with independent records suggests that the increase in nitrogen fixation might be linked to Northern Hemisphere climate change since the end of the Little Ice Age.

Off the Charts: Medical documentation and selective redaction in the age of transparency.

A growing demand for transparency in medicine has the potential to strain the doctor-patient relationship. While information can empower patients, unrestricted patient access to the electronic medical record may have unintended consequences. Medical documentation is often written in language that is inaccessible to people without medical training, and without guidance, patients have no way to interpret the constellation of acronyms, diagnoses, treatments, impressions, and arguments that appear throughout their own chart. Additionally, full transparency may not allow physicians the intellectual or clinical freedom they need to authentically express questions, problematic impressions, and concerns about the patient's clinical and psychosocial issues. This article examines the ethical challenges of transparency in the digital era and suggests that selective redaction may serve as a means to maintain transparency, affirm physician's discretion, and uphold the core values of the doctor-patient relationship amidst disruptive technological change.

A heat vulnerability index to improve urban public health management in San Juan, Puerto Rico.

Increased frequency and length of high heat episodes are leading to more cardiovascular issues and asthmatic responses among the population of San Juan, the capital of the island of Puerto Rico, USA. An urban heat island effect, which leads to foci of higher temperatures in some urban areas, can raise heat-related mortality. The objective of this research is to map the risk of high temperature in particular locations by creating heat maps of the city of San Juan. The heat vulnerability index (HVI) maps were developed using images collected by satellite-based remote sensing combined with census data. Land surface temperature was assessed using images from the Thermal Infrared Sensor flown on Landsat 8. Social determinants (e.g., age, unemployment, education and social isolation, and health insurance coverage) were analyzed by census tract. The data were examined in the context of land cover maps generated using products from the Puerto Rico Terrestrial Gap Analysis Project (USDA Forest Service). All variables were set in order to transform the indicators expressed in different units into indices between 0 and 1, and the HVI was calculated as sum of score. The tract with highest index was considered to be the most vulnerable and the lowest to be the least vulnerable. Five vulnerability classes were mapped (very high, high, moderate, low, and very low). The hottest and the most vulnerable tracts corresponded to highly built areas, including the Luis Munoz International Airport, seaports, parking lots, and high-density residential areas. Several variables contributed to increased vulnerability, including higher rates of the population living alone, disabilities, advanced age, and lack of health insurance coverage. Coolest areas corresponded to vegetated landscapes and urban water bodies. The urban HVI map will be useful to health officers, emergency preparedness personnel, the National Weather Service, and San Juan residents, as it helps to prepare for and to mitigate the potential effects of heat-related illnesses.