Implementation of a prehospital whole blood program: Lessons learned.

Early blood administration by Emergency Medical Services (EMS) to patients suffering from hemorrhagic shock improves outcomes. Prehospital blood programs represent an invaluable resuscitation capability that directly addresses hemorrhagic shock and mitigates subsequent multiple organ dysfunction syndrome. Prehospital blood programs must be thoughtfully planned, have multiple safeguards, ensure adequate training and credentialing processes, and be responsible stewards of blood resources. According to the 2022 best practices model by Yazer et al, the four key pillars of a successful prehospital program include the following: (1) the rationale for the use and a description of blood products that can be transfused in the prehospital setting, (2) storage of blood products outside the hospital blood bank and how to move them to the patient in the prehospital setting, (3) prehospital transfusion criteria and administration personnel, and (4) documentation of prehospital transfusion and handover to the hospital team.  This concepts paper describes our operational experience using these four pillars to make Maryland's inaugural prehospital ground-based low-titer O-positive whole blood program successful. These lessons learned may inform other EMS systems as they establish prehospital blood programs to help improve outcomes and enhance mass casualty response.

Exudates from Miscanthus x giganteus change the response of a root-associated Pseudomonas putida strain towards heavy metals.

The composition of root exudates is modulated by several environmental factors, and it remains unclear how that affects beneficial rhizosphere or inoculated microorganisms under heavy metal (HM) contamination. Therefore, we evaluated the transcriptional response of Pseudomonas putida E36 (a Miscanthus x giganteus isolate with plant growth promotion-related properties) to Cd, Pb and Zn in an in vitro study implementing root exudates from M. x giganteus. To collect root exudates and analyse their composition plants were grown in a pot experiment under HM and control conditions. Our results indicated higher exudation rate for plants challenged with HM. Further, out of 29 organic acids identified and quantified in the root exudates, 8 of them were significantly influenced by HM (e.g., salicylic and terephthalic acid). The transcriptional response of P. putida E36 was significantly affected by the HM addition to the growth medium, increasing the expression of several efflux pumps and stress response-related functional units. The additional supplementation of the growth medium with root exudates from HM-challenged plants resulted in a downregulation of 29% of the functional units upregulated in P. putida E36 as a result of HM addition to the growth medium. Surprisingly, root exudates + HM downregulated the expression of P. putida E36 functional units related to plant colonization (e.g., chemotaxis, motility, biofilm formation) but upregulated its antibiotic and biocide resistance compared to the control treatment without HM. Our findings suggest that HM-induced changes in root exudation pattern may attract beneficial bacteria that are in turn awarded with organic nutrients, helping them cope with HM stress. However, it might affect the ability of these bacteria to colonize plants growing in HM polluted areas. Those findings may offer an insight for future in vivo studies contributing to improvements in phytoremediation measures.

Dissemination mechanisms of NDM genes in hospitalized patients.

BACKGROUND: NDM-producing Enterobacteriaceae are a major clinical concern worldwide. We characterized NDM-positive pathogens isolated from patients and assessed the dissemination patterns of the bla NDM genes in a hospital setting. METHODS: Eleven NDM-positive Enterobacteriaceae (three Enterobacter hormaechei, six Klebsiella pneumoniae and two Escherichia coli) were isolated from nine patients over a 1 year period. Antimicrobial susceptibility was assessed by MICs. A combination of short- and long-read WGS was used for genome analysis. Clinical treatment history of patients was linked with genetic features of individual isolates to investigate the dissemination patterns of the bla NDM genes and NDM-positive strains. RESULTS: bla NDM in clonal K. pneumoniae were transmitted between two patients. In other instances, an identical IncC plasmid encoding NDM-1 was transmitted between E. coli and K. pneumoniae isolated from the same patient, and an IncX3 plasmid, carrying bla NDM-1 or bla NDM-5, was harboured in non-clonal E. hormaechei. Varying patterns of IS elements were identified as a critical transmission mechanism in association with bla NDM genes. CONCLUSIONS: Multiple transmission patterns were identified in hospitalized patients, including dissemination of clonal bacterial strains carrying resistance genes and horizontal transfer of resistance genes among divergent bacterial strains. Controlling spread of NDM is complex: while attention to standard infection control practices is critically important, this needs to be matched by aggressive efforts to limit unnecessary antimicrobial use, to minimize the selection for and risk of transfer of 'high mobility' resistance genes among Enterobacteriaceae.

Mycobacterium tuberculosis Strains H37ra and H37rv have equivalent minimum inhibitory concentrations to most antituberculosis drugs.

Background: Mycobacterium tuberculosis (Mtb) strains H37Ra and H37Rv are commonly used to study new and re-evaluate old antituberculous agents with respect to their pharmacodynamic effects in vitro. The differences in membrane proteins and, in particular, differences in carrier proteins between Mtb H37Ra and Mtb H37Rv may have an impact on antibiotic potency. The question of whether H37Ra can be used as a reliable surrogate for H37Rv and clinical strains has not been addressed sufficiently. The purpose of this study is to provide a full comparison of susceptibility data of the most common antituberculosis (TB) agents against both Mtb strains. Methods: In addition to a literature review, in vitro checkerboard susceptibility study was conducted comparing the in vitro minimum inhibitory concentration (MIC) of 16 common antituberculous drugs against H37Ra and H37Rv. Heifets-Sanchez TB agar drug susceptibility plates were utilized. Results: Half of the antibiotics demonstrated similar growth inhibition against both strains, while slightly differing MIC values were found for 7 of 16 drugs. With the exception of rifampicin, no marked difference in MIC against H37Ra and H37Rv was observed. Conclusion: While neither the attenuated (H37Ra) nor the virulent strain (H37Rv) is a clinical strain, both strains predicted MICs of clinical isolates equally well, when comparing the current in vitro results to clinical susceptibility data in the literature. H37Ra comes with the benefits of lower experimental costs and less administrative barriers including the requirement of a biosafety Level III environment.

Metabolism of carbamazepine in plant roots and endophytic rhizobacteria isolated from Phragmites australis.

Carbamazepine (CBZ) is a pharmaceutical frequently categorized as a recalcitrant pollutant in the aquatic environment. Endophytic bacteria previously isolated from reed plants have shown the ability to promote growth of their host and to contribute to CBZ metabolism. In this work, a horseradish (Armoracia rusticana) hairy root (HR) culture has been used as a plant model to study the interactions between roots and endophytic bacteria in response to CBZ exposure. HRs could remove up to 5% of the initial CBZ concentration when they were grown in spiked Murashige and Skoog (MS) medium. Higher removal rates were observed when HRs were inoculated with the endophytic bacteria Rhizobium radiobacter (21%) and Diaphorobacter nitroreducens (10%). Transformation products resulting from CBZ degradation were identified using liquid chromatography-ultra high-resolution quadrupole time of flight mass spectrometry (LC-UHR-QTOF-MS). CBZ metabolism could be divided in four pathways. Metabolites involving GSH conjugation and 2,3-dihydroxylation, as well as acridine related compounds are described in plants for the first time. This study presents strong evidence that xenobiotic metabolism and degradation pathways in plants can be modulated by the interaction with their endophytic community. Hence it points to plausible applications for the elimination of recalcitrant compounds such as CBZ from wastewater in CWs.

The price of complexity in financial networks.

Financial institutions form multilayer networks by engaging in contracts with each other and by holding exposures to common assets. As a result, the default probability of one institution depends on the default probability of all of the other institutions in the network. Here, we show how small errors on the knowledge of the network of contracts can lead to large errors in the probability of systemic defaults. From the point of view of financial regulators, our findings show that the complexity of financial networks may decrease the ability to mitigate systemic risk, and thus it may increase the social cost of financial crises.

Acute laryngeal dystonia: a persisting psychiatric emergency.

OBJECTIVE: Acute laryngeal dystonia is one of the most life-threatening medication side effects in psychiatry. It is rare and predominately caused by the use of antipsychotics in at-risk individuals. Within days of a patient's initial presentation, several antipsychotics can be administered for the purposes of acute sedation and ongoing pharmacotherapy. In this case report, we describe a 27-year-old at-risk male, who developed acute laryngeal dystonia in the context of antipsychotic polypharmacy. CONCLUSION: Clinicians should take into account recent sedation and ongoing antipsychotic use in patients at risk of developing acute laryngeal dystonia. Awareness of this condition and prompt treatment with parenteral anticholinergic medication can be lifesaving.

Tracking and forecasting ecosystem interactions in real time.

Evidence shows that species interactions are not constant but change as the ecosystem shifts to new states. Although controlled experiments and model investigations demonstrate how nonlinear interactions can arise in principle, empirical tools to track and predict them in nature are lacking. Here we present a practical method, using available time-series data, to measure and forecast changing interactions in real systems, and identify the underlying mechanisms. The method is illustrated with model data from a marine mesocosm experiment and limnologic field data from Sparkling Lake, WI, USA. From simple to complex, these examples demonstrate the feasibility of quantifying, predicting and understanding state-dependent, nonlinear interactions as they occur in situ and in real time--a requirement for managing resources in a nonlinear, non-equilibrium world.

Metabolism of oxybenzone in a hairy root culture: Perspectives for phytoremediation of a widely used sunscreen agent.

Oxybenzone (OBZ), known as Benzophenone-3, is a commonly used UV filter in sun tans and skin protectants, entering aquatic systems either directly during recreational activities or indirectly through wastewater treatment plants discharge. To study the potential degradation capacity of plants for OBZ in phytotreatment, a well-established hairy root culture (Armoracia rusticana) was treated with OBZ. More than 20% of spiked OBZ (100µM) was eliminated from the medium by hairy roots after 3h of exposure. Two metabolites were identified as oxybenzone-glucoside (OBZ-Glu) and oxybenzone-(6-O-malonyl)-glucoside (OBZ-Mal-Glu) by LC-MS/MS and TOF-MS. Formation of these metabolites was confirmed by enzymatic synthesis, as well as enzymatic and alkaline hydrolysis. Incubation with O-glucosyltransferase (O-GT) extracted from roots formed OBZ-Glu; whereas ß-d-Glucosidase hydrolyzed OBZ-Glu. However, alkaline hydrolysis led to cleavage of OBZ-Mal-Glu and yielded OBZ-Glu. In the hairy root culture, an excretion of OBZ-Glu into the growth medium was observed while the corresponding OBZ-Mal-Glu remained stored in root cells over the incubation time. We propose that metabolism of oxybenzone in plants involves initial conjugation with glucose to form OBZ-Glu followed by malonylation to yield OBZ-Mal-Glu. To our best knowledge this first finding presenting the potential of plants to degrade benzophenone type UV filters by phytoremediation.

Impact of Processing Conditions on Inter-tablet Coating Thickness Variations Measured by Terahertz In-Line Sensing.

A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickness and its inter-tablet variability during the coating process under a number of different process conditions that have been purposefully induced in the production-scale coating process. The changes that were introduced to the coating process include removing the baffles from the coater, adding uncoated tablets to the running process, halting the drum, blockage of spray guns and changes to the spray rate. The terahertz sensor was able to pick up the resulting changes in average coating thickness in the coating drum and we report the impact of these process changes on the resulting coating quality.

Single Step Bi-reforming and Oxidative Bi-reforming of Methane (Natural Gas) with Steam and Carbon Dioxide to Metgas (CO-2H2) for Methanol Synthesis: Self-Sufficient Effective and Exclusive Oxygenation of Methane to Methanol with Oxygen.

Catalysts based on suitable metal oxide supports, such as NiO/MgO and CoO/MgO, were shown to be active for single step bi-reforming, the combined steam and dry reforming of methane or natural gas with H2O and CO2 exclusively to metgas (CO-2H2) for efficient methanol synthesis. Reactions were carried out in a tubular flow reactor under pressures up to 42 bar at 830-910 °C. Using a CH4 to steam to CO2 ratio of ∼3:2:1 in the gas feed, the H2/CO ratio of 2:1 was achieved, which is desired for subsequent methanol synthesis. The needed 2/1 steam/CO2 feed ratio together with the reaction heat for the endothermic bi-reforming can be conveniently obtained by the complete combustion of a quarter part of the overall used methane (natural gas) with oxygen of the air (oxidative bi-reforming). Complete combustion of a part of methane followed by bi-reforming leads to the production of metgas (H2/CO in 2:1 mol ratio) for self-sufficient exclusive methanol synthesis. The long sought after but elusive efficient and selective oxygenation of methane to methanol is thus achieved in an effective and economic way without any oxidation byproduct formation according to CH4 + 1/2O2 → CH3OH.

Amine-free reversible hydrogen storage in formate salts catalyzed by ruthenium pincer complex without pH control or solvent change.

Due to the intermittent nature of most renewable energy sources, such as solar and wind, energy storage is increasingly required. Since electricity is difficult to store, hydrogen obtained by electrochemical water splitting has been proposed as an energy carrier. However, the handling and transportation of hydrogen in large quantities is in itself a challenge. We therefore present here a method for hydrogen storage based on a CO2 (HCO3 (-) )/H2 and formate equilibrium. This amine-free and efficient reversible system (>90 % yield in both directions) is catalyzed by well-defined and commercially available Ru pincer complexes. The formate dehydrogenation was triggered by simple pressure swing without requiring external pH control or the change of either the solvent or the catalyst. Up to six hydrogenation-dehydrogenation cycles were performed and the catalyst performance remained steady with high selectivity (CO free H2 /CO2 mixture was produced).

Dynamical evidence for causality between galactic cosmic rays and interannual variation in global temperature.

As early as 1959, it was hypothesized that an indirect link between solar activity and climate could be mediated by mechanisms controlling the flux of galactic cosmic rays (CR) [Ney ER (1959) Nature 183:451-452]. Although the connection between CR and climate remains controversial, a significant body of laboratory evidence has emerged at the European Organization for Nuclear Research [Duplissy J, et al. (2010) Atmos Chem Phys 10:1635-1647; Kirkby J, et al. (2011) Nature 476(7361):429-433] and elsewhere [Svensmark H, Pedersen JOP, Marsh ND, Enghoff MB, Uggerhøj UI (2007) Proc R Soc A 463:385-396; Enghoff MB, Pedersen JOP, Uggerhoj UI, Paling SM, Svensmark H (2011) Geophys Res Lett 38:L09805], demonstrating the theoretical mechanism of this link. In this article, we present an analysis based on convergent cross mapping, which uses observational time series data to directly examine the causal link between CR and year-to-year changes in global temperature. Despite a gross correlation, we find no measurable evidence of a causal effect linking CR to the overall 20th-century warming trend. However, on short interannual timescales, we find a significant, although modest, causal effect between CR and short-term, year-to-year variability in global temperature that is consistent with the presence of nonlinearities internal to the system. Thus, although CR do not contribute measurably to the 20th-century global warming trend, they do appear as a nontraditional forcing in the climate system on short interannual timescales.

Is Continuous Flow Superior to Pulsatile Flow in Single Ventricle Mechanical Support? Results from a Large Animal Pilot Study.

Durable mechanical support in situations of physiologic single ventricle has been met with little success so far, particularly in small children. We created an animal model to investigate whether pulsatile or continuous flow would be superior. Three 1 month old sheep (10-16 kg) were instrumented. Via sternotomy and with cardiopulmonary bypass, a large ventricular septal defect and atrial septal defect were created. The left ventricle was cannulated using a Berlin Heart inflow cannula. This was connected sequentially to a continuous flow device (Thoratec HeartMate X, Pleasanton, CA) and to a pulsatile device (Berlin Heart Excor, The Woodlands, TX). Outflow was via a Y-graft to both aorta and pulmonary artery, striving for equal flow to both. Atrial filling pressures were controlled with volume infusions over a wide range. Under comparable loading conditions, significantly higher maximum flow was obtained by HeartMate X than by Excor (4.95 ± 1.27 L/min [range, 3.84-6.34 L/min] for HeartMate X vs. 1.80 ± 0.85 L/min [range, 1.01-2.7 L/min] for Excor; p < 0.05). Judging from this limited animal study, in single ventricle scenarios, continuous flow devices may achieve higher pump flows than pulsatile devices when provided with similar filling pressures. Their clinical use should be investigated. More extensive experimental studies are needed.

Fundamental ecology is fundamental.

The primary reasons for conducting fundamental research are satisfying curiosity, acquiring knowledge, and achieving understanding. Here we develop why we believe it is essential to promote basic ecological research, despite increased impetus for ecologists to conduct and present their research in the light of potential applications. This includes the understanding of our environment, for intellectual, economical, social, and political reasons, and as a major source of innovation. We contend that we should focus less on short-term, objective-driven research and more on creativity and exploratory analyses, quantitatively estimate the benefits of fundamental research for society, and better explain the nature and importance of fundamental ecology to students, politicians, decision makers, and the general public. Our perspective and underlying arguments should also apply to evolutionary biology and to many of the other biological and physical sciences.

A giant molecular spoked wheel.

The modular synthesis of a defined, rigid molecular spoked wheel structure with the sum formula C1878H2682 and a diameter of about 12 nm is described. The attached 96 dodecyl side chains provide the solubility of the 25 260 Da compound in common organic solvents. At the octanoic acid/highly oriented pyrolytic graphite interface, the molecules self-assemble to form an ordered 2D lattice, which is investigated by scanning tunneling microscopy, displaying their structure with submolecular resolution.