Threat management priorities for conserving Antarctic biodiversity.

Antarctic terrestrial biodiversity faces multiple threats, from invasive species to climate change. Yet no large-scale assessments of threat management strategies exist. Applying a structured participatory approach, we demonstrate that existing conservation efforts are insufficient in a changing world, estimating that 65% (at best 37%, at worst 97%) of native terrestrial taxa and land-associated seabirds are likely to decline by 2100 under current trajectories. Emperor penguins are identified as the most vulnerable taxon, followed by other seabirds and dry soil nematodes. We find that implementing 10 key threat management strategies in parallel, at an estimated present-day equivalent annual cost of US$23 million, could benefit up to 84% of Antarctic taxa. Climate change is identified as the most pervasive threat to Antarctic biodiversity and influencing global policy to effectively limit climate change is the most beneficial conservation strategy. However, minimising impacts of human activities and improved planning and management of new infrastructure projects are cost-effective and will help to minimise regional threats. Simultaneous global and regional efforts are critical to secure Antarctic biodiversity for future generations.

Delirium in Pediatric Patients With Respiratory Insufficiency Requiring Noninvasive Ventilation.

Background: Delirium is associated with increased length of stay, duration of mechanical ventilation, in-hospital mortality, and cost. Independent predictors of delirium include age < 2 years, developmental delay, severity of illness, mechanical ventilation, and administration of benzodiazepines and anticholinergic medications. Although patients receiving noninvasive ventilation (NIV) may have been included in prior studies, there are no data specifically focusing on delirium in children receiving NIV. Our primary aim was to investigate the prevalence of delirium in patients on NIV in the pediatric intensive care unit (PICU) and evaluate potentially modifiable risk factors for delirium. Methods: This was a single-center, retrospective study evaluating the prevalence of delirium as established by the Cornell Assessment of Pediatric Delirium (CAPD). We evaluated PICU patients ≤ 18 years old with respiratory insufficiency requiring ≥ 48 h of NIV. Patients receiving invasive mechanical ventilation were excluded from the analysis. Results: There were 202 patients that received ≥ 48 h of NIV during the study period. Of these patients, 43 patients had at least one CAPD score documented while on NIV. There were a total of 143 days on NIV and 137 days with CAPD documentation. The prevalence of delirium, defined as a CAPD score ≥ 9, was 67.4% (29 of 43 patients). Sixty-nine percent of the patients who experienced delirium received benzodiazepines, compared with 14% who did not experience delirium (P = 0.001). Most patients (83.7%) in this cohort received dexmedetomidine. Of patients who received dexmedetomidine and had delirium, 68% received benzodiazepines compared to 25% in the non-delirious group (P = 0.046). Conclusions: Delirium is common in young pediatric patients receiving NIV. As previously shown in the invasive mechanical ventilation population, benzodiazepine exposure continues to be a potentially modifiable risk factor for delirium.

Evolution of surrogate light chain in tetrapods and the relationship between lengths of CDR H3 and VpreB tails.

In the mammalian immune system, the surrogate light chain (SLC) shapes the antibody repertoire during B cell development by serving as a checkpoint for production of functional heavy chains (HC). Structural studies indicate that tail regions of VpreB contact and cover the third complementarity-determining region of the HC (CDR H3). However, some species, particularly bovines, have CDR H3 regions that may not be compatible with this HC-SLC interaction model. With immense structural and genetic diversity in antibody repertoires across species, we evaluated the genetic origins and sequence features of surrogate light chain components. We examined tetrapod genomes for evidence of conserved gene synteny to determine the evolutionary origin of VpreB1, VpreB2, and IGLL1, as well as VpreB3 and pre-T cell receptor alpha (PTCRA) genes. We found the genes for the SLC components (VpreB1, VpreB2, and IGLL1) only in eutherian mammals. However, genes for PTCRA occurred in all amniote groups and genes for VpreB3 occurred in all tetrapod groups, and these genes were highly conserved. Additionally, we found evidence of a new VpreB gene in non-mammalian tetrapods that is similar to the VpreB2 gene of eutherian mammals, suggesting VpreB2 may have appeared earlier in tetrapod evolution and may be a precursor to traditional VpreB2 genes in higher vertebrates. Among eutherian mammals, sequence conservation between VpreB1 and VpreB2 was low for all groups except rabbits and rodents, where VpreB2 was nearly identical to VpreB1 and did not share conserved synteny with VpreB2 of other species. VpreB2 of rabbits and rodents likely represents a duplicated variant of VpreB1 and is distinct from the VpreB2 of other mammals. Thus, rabbits and rodents have two variants of VpreB1 (VpreB1-1 and VpreB1-2) but no VpreB2. Sequence analysis of VpreB tail regions indicated differences in sequence content, charge, and length; where repertoire data was available, we observed a significant relationship between VpreB2 tail length and maximum DH length. We posit that SLC components co-evolved with immunoglobulin HC to accommodate the repertoire - particularly CDR H3 length and structure, and perhaps highly unusual HC (like ultralong HC of cattle) may bypass this developmental checkpoint altogether.

Use and Outcomes of Nasotracheal Intubation Among Patients Requiring Mechanical Ventilation Across U.S. PICUs.

OBJECTIVES: The use and outcomes of nasotracheal intubation in pediatric patients requiring mechanical ventilation have not been quantified. Our goal is to identify prevalence of use, associated factors, and outcomes of nasotracheal versus orotracheal intubation in patients requiring mechanical ventilation. DESIGN: Retrospective cohort study using deidentified data from the Virtual Pediatric Systems database. Data from PICU admissions from January 1, 2015, to December 31, 2016 were analyzed. SETTING: One hundred twenty-one PICUs located within the United States. PATIENTS: PICU admissions requiring an endotracheal tube-either nasotracheal or orotracheal-were included. Those with a tracheostomy tube present at admission were excluded from the study. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Among the 121 PICUs included in the study, 64 PICUs (53%) had zero nasotracheal intubations during the reviewed time period. There were 12,088 endotracheal intubations analyzed, and 680 of them (5.6%) were nasotracheal. Of those patients nasotracheally intubated, most were under 2 years old (88.1%), and 82.2% of them were classified as a cardiac patient. Among these young cardiac patients, the rate of unplanned extubation was 0% in the nasotracheal intubated versus 2.1% in the orotracheal intubated group (p < 0.001) CONCLUSIONS:: Nasotracheal intubation is used in a minority of U.S. PICUs and mainly among young cardiac patients. Nasotracheal intubation is associated with a lower rate of unplanned extubations in this patient population. Future prospective studies analyzing the benefits and complications of nasotracheal versus orotracheal intubation in pediatric patients requiring mechanical ventilation are indicated.

Relative potency of fexofenadine HCl 180 mg, loratadine 10 mg, and placebo using a skin test model of wheal-and-flare suppression.

BACKGROUND: H1-receptor antagonists differ in their ability to produce peripheral H1-blockade. Suppression of histamine-induced flares and wheals is a useful objective test for measuring these differences. OBJECTIVE: To evaluate the relative potency of fexofenadine HCI 180 mg, loratadine 10 mg, and placebo (PBO) in suppressing histamine-induced flares and wheals and compare the onset, duration, and maximum suppression of histamine achieved with each agent. METHODS: Thirty healthy volunteers were enrolled in this randomized, double-blind, single-dose, crossover study. Flares and wheals induced by skin-prick testing with histamine 1.8 mg/mL were measured before treatment, every 20 minutes during the first hour after dosing, and thereafter hourly between 2 and 12 hours and between 23 and 25 hours postdose. RESULTS: Fexofenadine was significantly more effective than loratadine in suppressing the histamine-induced flare response at hours 2 through 7 and 10 through 12 and produced greater flare suppression than did PBO at hours 2 through 25. Onset of flare suppression occurred 2 hours after dosing with fexofenadine and 4 hours after dosing with loratadine. Likewise, fexofenadine was superior to loratadine in suppressing the wheal response from hours 1 through 12 and was more effective than PBO at hours 1 through 12, 24, and 25. Throughout the 25-hour measurement interval, the magnitude of difference in both wheal and flare suppression consistently favored fexofenadine over loratadine. CONCLUSIONS: In a skin test model of wheal-and-flare suppression, fexofenadine showed rapid distribution into the skin compartment with faster onset of action and greater potency vs loratadine.