Acute pain pathways: protocol for a prospective cohort study.

INTRODUCTION: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses. METHODS AND ANALYSIS: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients' patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids. ETHICS AND DISSEMINATION: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT04509115.

Physical mixing in coastal waters controls and decouples nitrification via biomass dilution.

Nitrification is a central process of the aquatic nitrogen cycle that controls the supply of nitrate used in other key processes, such as phytoplankton growth and denitrification. Through time series observation and modeling of a seasonally stratified, eutrophic coastal basin, we demonstrate that physical dilution of nitrifying microorganisms by water column mixing can delay and decouple nitrification. The findings are based on a 4-y, weekly time series in the subsurface water of Bedford Basin, Nova Scotia, Canada, that included measurement of functional (amoA) and phylogenetic (16S rRNA) marker genes. In years with colder winters, more intense winter mixing resulted in strong dilution of resident nitrifiers in subsurface water, delaying nitrification for weeks to months despite availability of ammonium and oxygen. Delayed regrowth of nitrifiers also led to transient accumulation of nitrite (3 to 8 µmol · kgsw-1) due to decoupling of ammonia and nitrite oxidation. Nitrite accumulation was enhanced by ammonia-oxidizing bacteria (Nitrosomonadaceae) with fast enzyme kinetics, which temporarily outcompeted the ammonia-oxidizing archaea (Nitrosopumilus) that dominated under more stable conditions. The study reveals how physical mixing can drive seasonal and interannual variations in nitrification through control of microbial biomass and diversity. Variable, mixing-induced effects on functionally specialized microbial communities are likely relevant to biogeochemical transformation rates in other seasonally stratified water columns. The detailed study reveals a complex mechanism through which weather and climate variability impacts nitrogen speciation, with implications for coastal ecosystem productivity. It also emphasizes the value of high-frequency, multiparameter time series for identifying complex controls of biogeochemical processes in aquatic systems.

Evaluation of a novel handheld point-of-care ultrasound device in an African emergency department.

BACKGROUND: Many point-of-care ultrasound devices are now "pocket-sized" or handheld, allowing easy transport during travel and facilitating use in crowded spaces or in austere low-resource settings. Concerns remain about their durability, image quality, and clinical utility in those environments. METHOD: Five emergency physicians with training in point-of-care ultrasound employed the Butterfly iQ, a novel handheld ultrasound device, in routine clinical care in a busy, high-acuity African emergency department over a period of 10 weeks. We retrospectively evaluated the performance of the Butterfly iQ from the perspectives of both the clinicians using the device and expert ultrasound faculty reviewing the images. RESULTS: We found advantages of the Butterfly iQ in a high-acuity African emergency department include its use of a single probe for multiple functions, small size, ease of transport, relatively low cost, and good image quality in most functions. Disadvantages include large probe footprint, lower, though still adequate, cardiac imaging quality, frequent overheating, and reliance on internet-based cloud storage, but these were surmountable. We also report a wide variety of patient presentations, pathology, and procedures to which the device was used. CONCLUSION: We conclude the Butterfly iQ is an effective, though imperfect, point-of-care ultrasound device in a low-resource emergency setting. We will continue to employ the device in clinical emergency care and teaching in this setting.

COVID-19: A review of therapeutics under investigation.

The COVID-19 outbreak has disrupted global health care networks and caused thousands of deaths and an international economic downturn. Multiple drugs are being used on patients with COVID-19 based on theoretical and in vitro therapeutic targets. Several of these therapies have been studied, but many have limited evidence behind their use, and clinical trials to evaluate their efficacy are either ongoing or have not yet begun. This review summarizes the existing evidence for medications currently under investigation for treatment of COVID-19, including remdesivir, chloroquine/hydroxychlorquine, convalescent plasma, lopinavir/ritonavir, IL-6 inhibitors, corticosteroids, and angiotensin-converting enzyme inhibitors.

An adapted emergency department triage algorithm for the COVID-19 pandemic.

The novel coronavirus disease 2019 (COVID-19) pandemic, with its public health implications, high case fatality rate, and strain on hospital resources, will continue to challenge clinicians and researchers alike for months to come. Accurate triage of patients during the pandemic will assign patients to the appropriate level of care, provide the best care for the maximum number of patients, rationally limit personal protective equipment (PPE) usage, and mitigate nosocomial exposures. The authors describe an adapted COVID-19 pandemic triage algorithm for emergency departments (EDs) guided by the best available evidence and responses to prior pandemics, with recommendations for clinician PPE use for each level of encounter in the setting of an ongoing PPE shortage. Our algorithm adheres to Centers for Disease Control and Prevention guidelines and supports discharge of patients with mild symptoms coupled with explicit and strict return precautions and infection control education.

Geomicrobiology of the carbon, nitrogen and sulphur cycles in Powell Lake: a permanently stratified water column containing ancient seawater.

We present the first geomicrobiological characterization of the meromictic water column of Powell Lake (British Columbia, Canada), a former fjord, which has been stably stratified since the last glacial period. Its deepest layers (300-350 m) retain isolated, relict seawater from that period. Fine-scale vertical profiling of the water chemistry and microbial communities allowed subdivision of the water column into distinct geomicrobiological zones. These zones were further characterized by phylogenetic and functional marker genes from amplicon and shotgun metagenome sequencing. Binning of metagenomic reads allowed the linkage of function to specific taxonomic groups. Statistical analyses (analysis of similarities, Bray-Curtis similarity) confirmed that the microbial community structure followed closely the geochemical zonation. Yet, our characterization of the genetic potential relevant to carbon, nitrogen and sulphur cycling of each zone revealed unexpected features, including potential for facultative anaerobic methylotrophy, nitrogen fixation despite high ammonium concentrations and potential micro-aerobic nitrifiers within the chemocline. At the oxic-suboxic interface, facultative anaerobic potential was found in the widespread freshwater lineage acI (Actinobacteria), suggesting intriguing ecophysiological similarities to the marine SAR11. Evolutionary divergent lineages among diverse phyla were identified in the ancient seawater zone and may indicate novel adaptations to this unusual environment.

Quantitative Mid-Infrared Cavity Ringdown Detection of Methyl Iodide for Monitoring Applications.

Methyl iodide is a toxic halocarbon with diverse industrial and agricultural applications, and it is an important ocean-derived trace gas that contributes to the iodine burden of the atmosphere. Quantitative analysis of CH3I is mostly based on gas chromatography coupled with mass spectrometry or electron capture detection (GC-MS/ECD) as of yet, which often limits the ability to conduct in situ high-frequency monitoring studies. This work presents an alternative detection scheme based on mid-infrared continuous wave cavity ringdown spectroscopy (mid-IR cw-CRDS). CH3I was detected at the RR2(15) rovibrational absorption transition at v = 3090.4289 cm-1; part of the corresponding v4 vibration band has been measured with Doppler-limited resolution for the first time. A line strength of S(T = 295 K) = (545 ± 20) cm/mol, corresponding to a line center absorption cross-section σc(p = 0 bar) = (1.60 ± 0.06) × 105 cm2/mol, and pressure-broadening coefficients γp(Ar) = (0.094 ± 0.002) cm-1/bar and γp(N2) = (0.112 ± 0.003) cm-1/bar have been determined. The performance of the detection system has been demonstrated with a tank-purging experiment and has been directly compared with a conventional GC-MS/ECD detection system. Quantitative detection with high reproducibility and continuous sampling is possible with a current noise-equivalent limit of detection of 15 ppb at 20 mbar absorption-cell pressure and 70 s averaging time. This limit of detection is suitable for practical applications in the ppm mixing ratio level range such as workplace monitoring, leak detection, and process studies. Natural environmental abundances are much lower, therefore possibilities for future improvement of the detection limit are discussed.

Doubling of marine dinitrogen-fixation rates based on direct measurements.

Biological dinitrogen fixation provides the largest input of nitrogen to the oceans, therefore exerting important control on the ocean's nitrogen inventory and primary productivity. Nitrogen-isotope data from ocean sediments suggest that the marine-nitrogen inventory has been balanced for the past 3,000 years (ref. 4). Producing a balanced marine-nitrogen budget based on direct measurements has proved difficult, however, with nitrogen loss exceeding the gain from dinitrogen fixation by approximately 200 Tg N yr−1 (refs 5, 6). Here we present data from the Atlantic Ocean and show that the most widely used method of measuring oceanic N2-fixation rates underestimates the contribution of N2-fixing microorganisms (diazotrophs) relative to a newly developed method. Using molecular techniques to quantify the abundance of specific clades of diazotrophs in parallel with rates of 15N2 incorporation into particulate organic matter, we suggest that the difference between N2-fixation rates measured with the established method and those measured with the new method can be related to the composition of the diazotrophic community. Our data show that in areas dominated by Trichodesmium, the established method underestimates N2-fixation rates by an average of 62%. We also find that the newly developed method yields N2-fixation rates more than six times higher than those from the established method when unicellular, symbiotic cyanobacteria and γ-proteobacteria dominate the diazotrophic community. On the basis of average areal rates measured over the Atlantic Ocean, we calculated basin-wide N2-fixation rates of 14 ± 1 Tg N yr−1 and 24 ±1 Tg N yr−1 for the established and new methods, respectively. If our findings can be extrapolated to other ocean basins, this suggests that the global marine N2-fixation rate derived from direct measurements may increase from 103 ± 8 Tg N yr−1 to 177 ± 8 Tg N yr−1, and that the contribution of N2 fixers other than Trichodesmium is much more significant than was previously thought.

Global oceanic production of nitrous oxide.

We use transient time distributions calculated from tracer data together with in situ measurements of nitrous oxide (N(2)O) to estimate the concentration of biologically produced N(2)O and N(2)O production rates in the ocean on a global scale. Our approach to estimate the N(2)O production rates integrates the effects of potentially varying production and decomposition mechanisms along the transport path of a water mass. We estimate that the oceanic N(2)O production is dominated by nitrification with a contribution of only approximately 7 per cent by denitrification. This indicates that previously used approaches have overestimated the contribution by denitrification. Shelf areas may account for only a negligible fraction of the global production; however, estuarine sources and coastal upwelling of N(2)O are not taken into account in our study. The largest amount of subsurface N(2)O is produced in the upper 500 m of the water column. The estimated global annual subsurface N(2)O production ranges from 3.1 ± 0.9 to 3.4 ± 0.9 Tg N yr(-1). This is in agreement with estimates of the global N(2)O emissions to the atmosphere and indicates that a N(2)O source in the mixed layer is unlikely. The potential future development of the oceanic N(2)O source in view of the ongoing changes of the ocean environment (deoxygenation, warming, eutrophication and acidification) is discussed.

Methodological underestimation of oceanic nitrogen fixation rates.

The two commonly applied methods to assess dinitrogen (N(2)) fixation rates are the (15)N(2)-tracer addition and the acetylene reduction assay (ARA). Discrepancies between the two methods as well as inconsistencies between N(2) fixation rates and biomass/growth rates in culture experiments have been attributed to variable excretion of recently fixed N(2). Here we demonstrate that the (15)N(2)-tracer addition method underestimates N(2) fixation rates significantly when the (15)N(2) tracer is introduced as a gas bubble. The injected (15)N(2) gas bubble does not attain equilibrium with the surrounding water leading to a (15)N(2) concentration lower than assumed by the method used to calculate (15)N(2)-fixation rates. The resulting magnitude of underestimation varies with the incubation time, to a lesser extent on the amount of injected gas and is sensitive to the timing of the bubble injection relative to diel N(2) fixation patterns. Here, we propose and test a modified (15)N(2) tracer method based on the addition of (15)N(2)-enriched seawater that provides an instantaneous, constant enrichment and allows more accurate calculation of N(2) fixation rates for both field and laboratory studies. We hypothesise that application of N(2) fixation measurements using this modified method will significantly reduce the apparent imbalances in the oceanic fixed-nitrogen budget.

Tracking the variable North Atlantic sink for atmospheric CO2.

The oceans are a major sink for atmospheric carbon dioxide (CO2). Historically, observations have been too sparse to allow accurate tracking of changes in rates of CO2 uptake over ocean basins, so little is known about how these vary. Here, we show observations indicating substantial variability in the CO2 uptake by the North Atlantic on time scales of a few years. Further, we use measurements from a coordinated network of instrumented commercial ships to define the annual flux into the North Atlantic, for the year 2005, to a precision of about 10%. This approach offers the prospect of accurately monitoring the changing ocean CO2 sink for those ocean basins that are well covered by shipping routes.

An estimate of anthropogenic CO2 inventory from decadal changes in oceanic carbon content.

Increased knowledge of the present global carbon cycle is important for our ability to understand and to predict the future carbon cycle and global climate. Approximately half of the anthropogenic carbon released to the atmosphere from fossil fuel burning is stored in the ocean, although distribution and regional fluxes of the ocean sink are debated. Estimates of anthropogenic carbon (C(ant)) in the oceans remain prone to error arising from (i) a need to estimate preindustrial reference concentrations of carbon for different oceanic regions, and (ii) differing behavior of transient ocean tracers used to infer C(ant). We introduce an empirical approach to estimate C(ant) that circumvents both problems by using measurement of the decadal change of ocean carbon concentrations and the exponential nature of the atmospheric C(ant) increase. In contrast to prior approaches, the results are independent of tracer data but are shown to be qualitatively and quantitatively consistent with tracer-derived estimates. The approach reveals more C(ant) in the deep ocean than prior studies; with possible implications for future carbon uptake and deep ocean carbonate dissolution. Our results suggest that this approachs applied on the unprecedented global data archive provides a means of estimating the C(ant) for large parts of the world's ocean.

The oceanic sink for anthropogenic CO2.

Using inorganic carbon measurements from an international survey effort in the 1990s and a tracer-based separation technique, we estimate a global oceanic anthropogenic carbon dioxide (CO2) sink for the period from 1800 to 1994 of 118 +/- 19 petagrams of carbon. The oceanic sink accounts for approximately 48% of the total fossil-fuel and cement-manufacturing emissions, implying that the terrestrial biosphere was a net source of CO2 to the atmosphere of about 39 +/- 28 petagrams of carbon for this period. The current fraction of total anthropogenic CO2 emissions stored in the ocean appears to be about one-third of the long-term potential.