Components of the indirect effect in vaccine trials: identification of contagion and infectiousness effects

Vaccination of one person may prevent the infection of another either because (i) the vaccine prevents the first from being infected and from infecting the second or because (ii) even if the first person is infected, the vaccine may render the infection less infectious. We might refer to the first of these mechanisms as a contagion effect and the second as an infectiousness effect. In this paper, for the simple setting of a randomized vaccine trial with households of size two, we use counterfactual theory under interference to provide formal definitions of a contagion effect and an infectiousness effect. Using ideas analogous to mediation analysis, we show that the indirect effect (the effect of one individual\u27s vaccine on another\u27s outcome) can be decomposed into a contagion effect and an infectiousness effect on the risk difference, risk ratio, odds ratio and vaccine efficacy scales. We provide identification assumptions for such contagion and infectiousness effects, and describe a simple statistical techniques to estimate these effects when they are identified. We also give a sensitivity analysis techniques to assess how inferences would change under violations of the identification assumptions. The concepts and results of this paper are illustrated with sample vaccine trial data

Reexamining Por and Para in the Spanish Foreign Language Intermediate Classroom: A Usage-Based, Cognitive Linguistic Approach

The present chapter represents the first stage in the larger investigation; it examines two aspects of applying a usage-based, CL approach to teaching por and para. First, we presented the multiple meanings of the two forms gradually, building learners’ knowledge in a series of scaffolded treatments, throughout the course of an entire semester rather than presenting them all in one concentrated lesson. Second, we presented the multiple meanings of por and para and structured their order of presentation according to a Cognitive Linguistic-inspired analysis, which emphasizes the systematic relationships among the multiple meanings. Such a systematic analysis is consistent with studies in cognitive psychology which have shown that it is easier to retrieve complexes of information if there is a systematic, organizing structure that specifies the relationship among the items, since this structure offers additional routes for accessing information (e.g. Bousfield 1953; Bower et al. 1969; Deese 1959; Lam 2009; Mandler 1967; Tulving 1962). A third area of interest was in examining the efficacy of providing explicit CL explanations of por and para, including discussion of CL concepts, such as the many meanings being represented by a systematically connected polysemy network whose central sense is a spatial relationship between a focus element and a background element, versus an approach which did not explicitly articulate CL concepts and did not explicitly present the multiple meanings as comprising a polysemy network

Concentrating mixtures of neuroactive pharmaceuticals and altered neurotransmitter levels in the brain of fish exposed to a wastewater effluent

Fish can be exposed to a variety of neuroactive pharmaceuticals via the effluent discharges from wastewater treatment plants and concerns have arisen regarding their potential impacts on fish behaviour and ecology. In this study, we investigated the uptake of 14 neuroactive pharmaceuticals from a treated wastewater effluent into blood plasma and brain regions of roach (Rutilus rutilus) after exposure for 15 days. We show that a complex mixture of pharmaceuticals including, 6 selective serotonin reuptake inhibitors, a serotonin-noradrenaline reuptake inhibitor, 3 atypical antipsychotics, 2 tricyclic antidepressants and a benzodiazepine, concentrate in different regions of the brain including the telencephalon, hypothalamus, optic tectum and hindbrain of effluent-exposed fish. Pharmaceuticals, with the exception of nordiazepam, were between 3–40 fold higher in brain compared with blood plasma, showing these neuroactive drugs are readily uptaken, into brain tissues in fish. To assess for the potential for any adverse ecotoxicological effects, the effect ratio was calculated from human therapeutic plasma concentrations (HtPCs) and the measured or predicted fish plasma concentrations of pharmaceuticals. After accounting for a safety factor of 1000, the effect ratios indicated that fluoxetine, norfluoxetine, sertraline, and amitriptyline warrant prioritisation for risk assessment studies. Furthermore, although plasma concentrations of all the pharmaceuticals were between 33 and 5714-fold below HtPCs, alterations in serotonin, glutamate, acetylcholine and tryptophan concentrations were observed in different brain regions of effluent-exposed fish. This study highlights the importance of determining the potential health effects arising from the concentration of complex environmental mixtures in risk assessment studies

Disruption of the prostaglandin metabolome and characterization of the pharmaceutical exposome in fish exposed to wastewater treatment works effluent as revealed by nanoflow-nanospray mass spectrometry-based metabolomics

Fish can be exposed to a complex mixture of chemical contaminants, including pharmaceuticals, present in discharges of wastewater treatment works (WwTWs) effluents. There is little information on the effects of effluent exposure on fish metabolism, especially the small molecule signaling compounds which are the biological target of many pharmaceuticals. We applied a newly developed sensitive nanoflow-nanospray mass spectrometry nontargeted profiling technique to identify changes in the exposome and metabolome of roach (Rutilus rutilus) exposed to a final WwTWs effluent for 15 days. Effluent exposure resulted in widespread reduction (between 50% and 90%) in prostaglandin (PG) profiles in fish tissues and plasma with disruptions also in tryptophan/serotonin, bile acid and lipid metabolism. Metabolite disruptions were not explained by altered expression of genes associated with the PG or tryptophan metabolism. Of the 31 pharmaceutical metabolites that were detected in the effluent exposome of fish, 6 were nonsteroidal anti-inflammatory drugs but with plasma concentrations too low to disrupt PG biosynthesis. PGs, bile acids, and tryptophan metabolites are important mediators regulating a diverse array of physiological systems in fish and the identity of wastewater contaminants disrupting their metabolism warrants further investigation on their exposure effects on fish health

A Synthesis of Human-related Avian Mortality in Canada

Many human activities in Canada kill wild birds, yet the relative magnitude of mortality from different sources and the consequent effects on bird populations have not been systematically evaluated. We synthesize recent estimates of avian mortality in Canada from a range of industrial and other human activities, to provide context for the estimates from individual sources presented in this special feature. We assessed the geographic, seasonal, and taxonomic variation in the magnitude of national-scale mortality and in population-level effects on species or groups across Canada, by combining these estimates into a stochastic model of stage-specific mortality. The range of estimates of avian mortality from each source covers several orders of magnitude, and, numerically, landbirds were the most affected group. In total, we estimate that approximately 269 million birds and 2 million nests are destroyed annually in Canada, the equivalent of over 186 million breeding individuals. Combined, cat predation and collisions with windows, vehicles, and transmission lines caused > 95% of all mortality; the highest industrial causes of mortality were the electrical power and agriculture sectors. Other mortality sources such as fisheries bycatch can have important local or species-specific impacts, but are relatively small at a national scale. Mortality rates differed across species and families within major bird groups, highlighting that mortality is not simply proportional to abundance. We also found that mortality is not evenly spread across the country; the largest mortality sources are coincident with human population distribution, while industrial sources are concentrated in southern Ontario, Alberta, and southwestern British Columbia. Many species are therefore likely to be vulnerable to cumulative effects of multiple human-related impacts. This assessment also confirms the high uncertainty in estimating human-related avian mortality in terms of species involved, potential for population-level effects, and the cumulative effects of mortality across the landscape. Effort is still required to improve these estimates, and to guide conservation efforts to minimize direct mortality caused by human activities on Canada's wild bird populations. As avian mortality represents only a portion of the overall impact to avifauna, indirect effects such as habitat fragmentation and alteration, site avoidance, disturbance, and related issues must also be carefully considered

Synthesis and Characterization of a Family of Air-Stable Ferrocene- and Ruthenocene-Containing Primary, Secondary, and Tertiary Phosphines

The synthesis and characterization of a family of air-stable primary, secondary, and tertiary phosphines containing all possible combinations of ethylferrocene and ethylruthenocene substituents are reported. Each phosphine was characterized by 1H, 13C, and 31P NMR spectroscopy, IR and UV-vis absorption spectroscopy, mass spectrometry, and elemental analysis. With the exception of primary ethylruthenocene phosphine 8a, all of the title compounds have been studied by single crystal X-ray crystallography. Ferrocene-containing phosphines showed maximum absorption at wavelengths of ca. 440 nm and qualitatively reversible oxidation waves in their cyclic voltammograms with intensities scaling to the number of ferrocene units present. The average metal-cyclopentadienyl centroid distances observed for ferrocene-containing phosphines were shorter than those of ruthenocene-containing phosphines, which also had maximum absorption wavelengths of ca. 320 nm and underwent irreversible electrochemical oxidation. Phosphines containing both ethylferrocene and ethylruthenocene substituents displayed properties consistent with the presence of both metallocene types

Fresh Versus Frozen Engineered Bone–Ligament–Bone Grafts for Sheep Anterior Cruciate Ligament Repair

Surgical intervention is often required to restore knee instability in patients with anterior cruciate ligament (ACL) injury. The most commonly used grafts for ACL reconstruction are tendon autografts or allografts. These current options, however, have shown failure rates requiring revision and continued instability in the long term. The mismatched biomechanical properties of the current tendon grafts compared with native ACL tissue are thought to contribute to these poor outcomes and potential risk of early onset osteoarthritis. As a possible solution to these issues, our laboratory has fabricated tissue-engineered ligament constructs that exhibit structural and functional properties similar to those of native ACL tissue after 6 months implantation. In addition, these tissue-engineered grafts achieve vascular and neural development that exceeds those of patellar tendon grafts. However, the utility of our tissue-engineered grafts is limited by the labor-intensive method required to produce the constructs and the need to use the constructs fresh, directly from the cell culturing system. Ideally, these constructs would be fabricated and stored until needed. Thus, in this study, we investigated the efficacy of freezing our tissue-engineered constructs as a method of preservation before use for ACL reconstruction. We hypothesized that frozen constructs would have similar histological and biomechanical outcomes compared with our fresh model. Our results showed that 6 months postimplantation as an ACL replacement graft, both our tissue-engineered fresh and frozen grafts demonstrated similar mechanical and histological outcomes, indicating that freezing is a suitable method for preserving and storing our graft before ACL reconstruction. The ability to use frozen constructs significantly increases the versatility of our graft technology expanding the clinical utility of our graft.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140250/1/ten.tec.2014.0542.pd

Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Winkler, T. S., van Hengstum, P. J., Donnelly, J. P., Wallace, E. J., Sullivan, R. M., MacDonald, D., & Albury, N. A. Revising evidence of hurricane strikes on Abaco Island (the Bahamas) over the last 700 years. Scientific Reports, 10(1), (2020): 16556, doi:10.1038/s41598-020-73132-x.The northern Bahamas have experienced more frequent intense-hurricane impacts than almost anywhere else in the Atlantic since 1850 CE. In 2019, category 5 (Saffir-Simpson scale) Hurricane Dorian demonstrated the destructive potential of these natural hazards. Problematically, determining whether high hurricane activity levels remained constant through time is difficult given the short observational record (< 170 years). We present a 700-year long, near-annually resolved stratigraphic record of hurricane passage near Thatchpoint Blue Hole (TPBH) on Abaco Island, The Bahamas. Using longer sediment cores (888 cm) and more reliable age-control, this study revises and temporally expands a previous study from TPBH that underestimated the sedimentation rate. TPBH records at least 13 ≥ category 2 hurricanes per century between 1500 to 1670 CE, which exceeds the 9 ≥ category 2 hurricanes per century within 50 km of TPBH since 1850 CE. The eastern United States also experienced frequent hurricanes from 1500 to 1670 CE, but frequency was depressed elsewhere in the Atlantic Ocean. This suggests that spatial heterogeneity in Atlantic hurricane activity since 1850 CE could have persisted throughout the last millennium. This heterogeneity is impacted by climatic and stochastic forcing, but additional high-resolution paleo-hurricane reconstructions are required to assess the mechanisms that impact regional variability.Field support was provided by Jody Albury and the staff of Friends of the Environment in Marsh Harbour, The Bahamas, and technical support was provided was provided by M. Horgan and S. Molodtsov. Funding for this project was provided by NSF Awards OCE-1356509, OCE-1356708, OCE-1854917, OCE-1903616, and ICER-1854980. The open access publishing fees for this article have been covered by the Texas A&M University Open Access to Knowledge Fund (OAKFund), supported by the University Libraries