Climb and flight speeds of shorebirds embarking on an intercontinental flight:Do they achieve the predicted optimal behaviour?

Most Arctic-breeding waders wintering in West Africa cover the first 4000 km of their northward journey in spring by a single flight to western Europe. We examined the extent to which waders economize their night behaviour during departure by comparing climb rates and forward night speeds with predictions based on flight mechanic theory and the relevant morphological measurements made of birds collected on the site. With an optical range finder, we followed 98 wader necks on their departure from Banc d'Arguin in Mauritania, We also measured wind speed and direction at different altitudes by tracking helium-filled balloons and thus were able to deduce airspeeds from groundspeeds of the departing flocks. Of the nine species examined, six showed the predicted negative relationship between climb rate and airspeed, although only one was statistically significant. By normalizing the data, we found a statistically significant negative correlation across all species. Although 17% of the observed climb rates were greater than the predicted theoretical maximum, the average observed climb rate was lower than the predicted optimum and the average observed airspeed was higher. The absolute deviations of climb rates fr om theory may have been because of the existence of pockets of rising and sinking air at the boundary of desert and ocean. That the absolute deviations in average climb rate and airspeed followed the predicted negative relationship is in accordance with the current theory of flight mechanics

A protocol for an international, multicentre pharmacokinetic study for Screening Antifungal Exposure in Intensive Care Units: The SAFE-ICU study

Antifungal agents; Critically ill; DosingAgentes antifúngicos; Enfermo crítico; DosificaciónAgents antifúngics; Malalt crític; DosificacióObjective To describe whether contemporary dosing of antifungal drugs achieves therapeutic exposures in critically ill patients that are associated with optimal outcomes. Adequate antifungal therapy is a key determinant of survival of critically ill patients with fungal infections. Critical illness can alter an antifungal agents’ pharmacokinetics, increasing the risk of inappropriate antifungal exposure that may lead to treatment failure and/or toxicity. Design, setting and participants This international, multicentre, observational pharmacokinetic study will comprise adult critically ill patients prescribed antifungal agents including fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, micafungin, anidulafungin, and amphotericin B for the treatment or prophylaxis of invasive fungal disease. A minimum of 12 patients are targeted for enrolment for each antifungal agent, across 12 countries and 30 intensive care units to perform descriptive pharmacokinetics. Pharmacokinetic sampling will occur during two dosing intervals (occasions): firstly, between days 1 and 3, and secondly, between days 4 and 7 of the antifungal course, collecting three samples per occasion. Patients’ demographic and clinical data will be collected. Main outcome measures The primary endpoint of the study is attainment of pharmacokinetic/pharmacodynamic target exposures that are associated with optimal efficacy. Thirty-day mortality will also be measured. Results and conclusions This study will describe whether contemporary antifungal drug dosing achieves drug exposures associated with optimal outcomes. Data will also be used for the development of antifungal dosing algorithms for critically ill patients. Optimised drug dosing should be considered a priority for improving clinical outcomes for critically ill patients with fungal infections.Funding for this study has been provided by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the Royal Brisbane and Women's Hospital Research Foundation. Gilead Fellowship to Dr FB Sime

Splanchnic metabolism of nutrients and hormones in steers fed alfalfa under conditions of increased absorption of ammonia and L-arginine supply across the portal-drained viscera

Effects of increased ammonia and/or arginine absorption on net splanchnic (portal-drained viscera [PDV] plus liver) metabolism of nonnitrogenous nutrients and hormones in cattle were examined. Six Hereford × Angus steers (501 ± 1 kg BW) prepared with vascular catheters for measurements of net flux across the splanchnic bed were fed a 75% alfalfa:25% (as-fed basis) corn and soybean meal diet (0.523 MJ of ME/[kg BW0.75.d]) every 2 h without (27.0 g of N/kg of DM) and with 20 g of urea/kg of DM (35.7 g of N/kg of DM) in a split-plot design. Net flux measurements were made immediately before and after a 72-h mesenteric vein infusion of L-arginine (15 mmol/h). There were no treatment effects onPDVor hepaticO2 consumption. Dietary urea had no effect on splanchnic metabolism of glucose or L-lactate, but arginine infusion decreased net hepatic removal of L-lactate when urea was fed (P < 0.01). Net PDV appearance of n-butyrate was increased by arginine infusion (P < 0.07), and both dietary urea (P < 0.09) and arginine infusion (P < 0.05) increased net hepatic removal of n-butyrate. Dietary urea also increased total splanchnic acetate output (P < 0.06), tended to increase arterial glucagon concentration (P < 0.11), and decreased arterial ST concentration (P < 0.03). Arginine infusion increased arterial concentration (P < 0.07) and net PDV release (P < 0.10) and tended to increase hepatic removal (P < 0.11) of insulin, as well as arterial concentration (P < 0.01) and total splanchnic output (P < 0.01) of glucagon. Despite changes in splanchnic N metabolism, increased ammonia and arginine absorption had little measurable effect on splanchnic metabolism of glucose and other nonnitrogenous components of splanchnic energy metabolism

Obstetric care models in the Southern Region of Brazil and associated factors

The study sought to identify obstetric care models for low-risk pregnancies in the Southern Region of Brazil and to estimate factors associated with these models and maternal and neonatal outcomes. This is a cross-sectional, hospital-based study using data from the Birth in Brazil survey regarding puerperae and newborns. We identified 2,668 low-risk pregnant women. We carried out an exploratory analysis using the proportion of practices per hospital, among them inducing labor, presence of a companion, cesarean section and skin-to-skin contact, in order to obtain the care models we called Best Practice, Interventionist I and Interventionist II. We then carried out an inferential analysis of the associated characteristics. Results show that access to public or private funding, cultural factors and actions taken by health professional are associated with the care models. Public care had different contexts, one based on public policies and evidence-based practices; and another, that suggests the intentionality of vaginal delivery without considering humanization principles. Private care, on the other hand, is standardized and centered on the medical professional, with higher intervention levels. We conclude there is a predominance of interventionist obstetric care models in the Southern Region of Brazil, a type of care that goes against the best evidence, and that women who receive care in public hospitals have greater chances of benefiting from good practices

Study of electron-irradiated silicon thin films using transient photocurrent spectroscopy

Electron irradiation of silicon thin films creates localised states, which degrade theiropto-electronic properties. We present a series of transient photocurrent spectroscopy (TPC)measurements on electron-irradiated amorphous and microcrystalline silicon films, annealed atprogressively increasing temperatures. This has enabled localised states associated with bothdangling bonds and conduction band tails to be examined over a wide energy range.Trends inthe evolution of the DOS following electron irradiation followed by isochronal annealing stepsindicate reductions in the deep defect density,which correlate with spin density. We also find asteepening of the conduction band tail slope in amorphous silicon on annealing. Both defectdensity and tail slope may be restored close to as-prepared material values. Earlier CPM dataare re-examined, and a similar trend in the valence band tail slope is indicated. Computersimulations predict that following e-irradiation changes in deep defect density primarily controlsolar cell performance, and will tend to obscure effects related to band tails

Optimization of flucloxacillin dosing regimens in critically ill patients using population pharmacokinetic modelling of total and unbound concentrations

Background: Initial appropriate anti-infective therapy is associated with improved outcomes in patients with severe infections. In critically ill patients, altered pharmacokinetic (PK) behaviour is common and known to influence the achievement of PK/pharmacodynamic targets. Objectives: To describe population PK and optimized dosing regimens for flucloxacillin in critically ill patients. Methods: First, we developed a population PK model, estimated between-patient variability (BPV) and identified covariates that could explain BPV through non-linear mixed-effects analysis, using total and unbound concentrations obtained from 35 adult critically ill patients treated with intermittent flucloxacillin. Second, we validated the model using external datasets from two different countries. Finally, frequently prescribed dosing regimens were evaluated using Monte Carlo simulations. Results: A two-compartment model with non-linear protein binding was developed and validated. BPV of the maximum binding capacity decreased from 42.2% to 30.4% and BPV of unbound clearance decreased from 88.1% to 71.6% upon inclusion of serumalbumin concentrations and estimated glomerular filtration rate (eGFR; by CKD-EPI equation), respectively. PTA (target of 100%fT(>MIC)) was 91% for patients with eGFR of 33mL/min and 1 g q6h, 87% for patients with eGFR of 96 mL/min and 2 g q4h and 71% for patients with eGFR of 153 mL/min and 2 g q4h. Conclusions: For patients with high creatinine clearance who are infected with moderately susceptible pathogens, therapeutic drug monitoring is advised since there is a risk of underexposure to flucloxacillin. Due to the non-linear protein binding of flucloxacillin and the high prevalence of hypoalbuminaemia in critically ill patients, dose adjustments should be based on unbound concentrations

Phasevarion Mediated Epigenetic Gene Regulation in Helicobacter pylori

Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M) system, controls expression of a phase-variable regulon of genes (a “phasevarion”), via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates). Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis

Vaccination Targeting a Surface Sialidase of P. acnes: Implication for New Treatment of Acne Vulgaris

BACKGROUND: Acne vulgaris afflicts more than fifty million people in the United State and the severity of this disorder is associated with the immune response to Propionibacterium acnes (P. acnes). Systemic therapies for acne target P. acnes using antibiotics, or target the follicle with retinoids such as isotretinoin. The latter systemic treatment is highly effective but also carries a risk of side effects including immune imbalance, hyperlipidemia, and teratogenicity. Despite substantial research into potential new therapies for this common disease, vaccines against acne vulgaris are not yet available. METHODS AND FINDINGS: Here we create an acne vaccine targeting a cell wall-anchored sialidase of P. acnes. The importance of sialidase to disease pathogenesis is shown by treatment of a human sebocyte cell line with recombinant sialidase that increased susceptibility to P. acnes cytotoxicity and adhesion. Mice immunized with sialidase elicit a detectable antibody; the anti-sialidase serum effectively neutralized the cytotoxicity of P. acnes in vitro and P. acnes-induced interleukin-8 (IL-8) production in human sebocytes. Furthermore, the sialidase-immunized mice provided protective immunity against P. acnes in vivo as this treatment blocked an increase in ear thickness and release of pro-inflammatory macrophage inflammatory protein (MIP-2) cytokine. CONCLUSIONS: Results indicated that acne vaccines open novel therapeutic avenues for acne vulgaris and other P. acnes-associated diseases

Management of cerebral azole-resistant Aspergillus fumigatus infection : a role for intraventricular liposomal-amphotericin B

Objectives: In the pre-azole era, central nervous system (CNS) infections with Aspergillus had a dismal outcome. Survival improved with voriconazole but CNS infections caused by azole-resistant Aspergillus fumigatus preclude its use. Intravenous liposomal-amphotericin B (L-AmB) is the preferred treatment option for azole-resistant CNS infections but has suboptimal brain concentrations. Methods: We describe three patients with biopsy-proven CNS aspergillosis where intraventricular L-AmB was added to systemic therapy. Two patients with azole-resistant aspergillosis and one patient with azole-susceptible CNS aspergillosis were treated with intraventricular L-AmB at a dose of 1 mg weekly. Results: We describe three patients successfully treated with a combination of intravenous and intraventricular L-AmB. All three patients survived but one patient developed serious headaches, most likely not related to this treatment. Conclusions: Intraventricular L-AmB may have a role in the treatment of therapy-refractory CNS aspergillosis when added to systemic therapy. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy

Outpatient parenteral antifungal therapy (OPAT) for invasive fungal infections with intermittent dosing of liposomal amphotericin B

Triazole resistant A. fumigatus has been documented in many parts of the world. In the Netherlands, incidence is now above 10% and results in the need for long-term parenteral therapy with liposomal amphotericin B (LAmB). The long terminal half-life of LAmB suggests that intermittent dosing could be effective, making the application of outpatient antifungal therapy (OPAT) possible. Here, we report our experience with the use of OPAT for Invasive Fungal Infections (IFI). All adult patients treated with LAmB with a 2 or 3 times weekly administration via the outpatient departments in four academic tertiary care centers in the Netherlands and Belgium since January 2010 were included in our analysis. Patient characteristics were collected, as well as information about diagnostics, therapy dose and duration, toxicity, treatment history and outcome of the IFI. In total, 18 patients were included. The most frequently used regimen (67%) was 5 mg/kg 3 times weekly. A partial response to the daily treatment prior to discharge was confirmed by CT-scan in 17 (94%) of patients. A favorable outcome was achieved in 13 (72%) patients. Decrease in renal function occurred in 10 (56%) cases but was reversible in all and was treatment limiting in one patient only. The 100-day mortality and 1-year mortality after initiation of OPAT were 0% and 6%, respectively. In a selected population, and after confirmation of initial response to treatment, our data support the use of OPAT with LAmB for treatment of IFI in an intermittent dosing regimen