Search

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

Supercritical fluid chromatography‐mass spectrometry (SFC‐MS) has proved to be a beneficial tool for sample analysis for a wide variety of compounds and, as such, has recently gained the attention of the anti‐doping community. We have tested the applicability of SFC‐MS for routine doping control analysing approximately 3 × 1000 identical anti‐doping samples utilising SFC‐MS instruments from three different vendors: Agilent Technologies, Waters Corporation and Shimadzu Corporation. A 'dilute and inject' approach either without or after hydrolysis of glucuronide metabolites was applied. Most of the compounds included in our study demonstrated excellent chromatography, whereas some showed co‐elution with endogenous interferences requiring MS discrimination. Retention times typically were very stable within batches (%CV ≤ 0.5%), although this appeared to be analyte and column dependent. Chromatographic peak shape was good (symmetrical) and stable over the period of the testing without any change of column. Our results suggest that SFC‐MS is a sensitive, reproducible and robust analytical tool ready to be used in anti‐doping laboratories alongside the currently applied techniques such as gas and liquid chromatography coupled to mass spectrometry. Even if instruments are designed slightly differently, all three setups demonstrated their fitness for the purpose in anti‐doping testing. [ABSTRACT FROM AUTHOR]

BackgroundImmune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration.ObjectiveThe present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology.MethodsA broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age.ResultsAged AD mice displayed severe manifestations of systemic autoimmune/inflammatory dise6ase, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired "cognitive" flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology.ConclusionThe results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD.

Food security and international trade require healthy livestock. A wildlife reservoir can compromise control of livestock disease. When disease is suspected in wildlife, initial questions include whether their behaviour, ecology and proximity to livestock pose a significant risk. Then, what options are there for mitigating risk? If we respond, how should we measure success? Following action, lessons must be learned so that we are more effective during the next disease outbreak. At least 4 discrete populations of feral swine currently exist in England at relatively low densities. In the event of a suspected classical swine fever (CSF) outbreak, investigation zones and control strategies may need to be initiated, and so new models need to be created to fit these English populations. Here, we present an approach to using data collected during scientific research projects and wildlife management exercises to aid decisions on how to resource a program of disease detection and control if CSF was suspected to have broken out in feral swine populations in England. Culling efficiency was estimated through trapping and shooting records. Results were used to create predictive models which determined resources and costs required to carry out an efficient cull within various possible scenarios. Trapping over 26 months at one 427-ha site resulted in the capture of 130 swine at an average of 0.21 swine per trap-night and US$477 per animal. Shooting by two government hunters over 12 months at another site resulted in the culling of 56 swine, equating to 1 swine shot for every 18 hrs 40 mins; total effort was 41 hrs 44 mins with total cost around US$75,628 (US$1,350) per animal. Using simulation models, we estimated the costs of delivering a cull via a combined approach of trapping and shooting to detect CSF at 1% and 5% seroprevelance. Costs ranged widely, depending on scenario, with minimum costs of US$51,404 and $69,029, and maximum costs of US$231,545 and $203,109, respectively. Results suggest that at present it is feasible to deliver a sampling strategy that could detect and potentially resolve the occurrence of CSF in feral swine in England.

The resolution of conflicts between human and wildlife interests often involves lethal control to reduce problem wildlife populations. However, lethal control has always had its limitations, the acceptable methods are becoming fewer, and public opposition is on the increase. Fertility control offers a potential alternative approach that is widely regarded as being inherently more benign. Furthermore, in some circumstances fertility control may have specific advantages over culling. The development of “single-shot” injectable immunocontraceptive vaccines that inhibit the fertility of individual animals for several years is leading to practical applications that exploit this novel technology. Further advances can be expected to lead to the emergence of a new generation of wildlife management tools. A key issue in this process is predicting what the population consequences will be for a particular species, given a specific level of induced infertility. Here, we use population modelling techniques to explore how much fertility control is enough to achieve different levels of population reduction, how long it will take to realise these reductions, and to understand how these effects are shaped by the population biology of the target species. This offers some generic conclusions, with low levels of infertility having little impact on species with high population turnover rates, while modest levels of infertility may yield useful population reductions for species with low intrinsic rates of increase, although such effects take longer to be realised in long-lived species. We also observed that there is potential for optimising the intensity of induced infertility, in terms of the proportion of breeding animals rendered infertile, and the frequency of application; so, for instance, biennial application could be more efficient than annual application for some forms of fertility control in certain species. There is increasing evidence from field studies that the survival of infertile animals is enhanced, probably because they do not incur the costs of reproduction. Our model predicts that this effect will be of limited importance for short-lived species with high intrinsic rates of increase, but it is more likely to compromise population reduction in long-lived species. We suggest that the generic modelling approach can help develop an evidence-based platform for discussing when fertility control can be regarded as a feasible, desirable, and sustainable option to manage problem wildlife.

Cambridge University has been featured in a wide range of studies of the long 18th century, but few have focused exclusively on the dynamics behind its politics. This is surprising since many of the Cambridge University electors were close to leading parliamentarians. The Cambridge University constituency was contested at each of the three successive general elections from 1780 onwards until 1796. Parliamentary contests often brought Cambridge University's political tensions into focus, which is why a detailed analysis of the poll books can demonstrate how different networks within the university behaved and could define the performance of candidates for the constituency. The relationships between the chancellors, vice‐chancellors, high stewards, university officers, college heads, fellows, senate members and members of parliament who collectively made up the leadership are fundamental to understanding the electorate of Cambridge University. These relationships, in terms of friendships, alliances and rivalries, also influenced political and patronage networks within the university. William Pitt the Younger's success in changing the political complexion of Cambridge University is part of the broader realignment in British politics during the final two decades of the 18th century. Under the pressure of these events, Whig unity would come to an end as new divisions between ministerialists and reformers emerged. The experience of Cambridge University can shed light on the national shifts as well as how electioneering was carried out in the university parliamentary constituencies. [ABSTRACT FROM AUTHOR]

We describe three methods of sample preparation for the liquid chromatography coupled with mass spectrometric measurement of insulin‐like growth factor‐I concentration in blood. One method involves trypsin digestion, the second involves intact protein quantification and the third method is a combination of the first two. Step‐by‐step directions are provided for sample collection and handling including transport, storage conditions as well as detailed instructions for preparation for analysis, which can be modified for larger or smaller sample volumes as needed. A fully 15N‐labelled internal standard is used and the merits of a single‐point calibrator are discussed. Example instrumental conditions are presented for both intact and digest methods. [ABSTRACT FROM AUTHOR]

There is increasing demand for benign approaches to the resolution of conflicts between human interests and wildlife. One non-lethal method to reduce the growth and expansion of overabundant wildlife populations is fertility control. Significant progress has been made in recent years on the development of fertility control agents, culminating in the availability of single-dose injectable immunocontraceptive vaccines that inhibit the fertility of individuals for several years. The potential application of such technology is explored here using the European rabbit, gray squirrel, wild boar, and European badger as examples of species that pose problems of damage to agricultural and forestry interests, disease transmission and threats to biodiversity. A simple model is developed that predicts the likely general population consequences of varying levels of infertility for species with differing demographic characteristics. This suggests that low levels of fertility control will have little impact on population size in species with high reproductive rates and high population turnover rates. Modest levels of infertility can significantly reduce the populations of species with relatively low intrinsic rates of increase. However, these reductions may take longer than those arising from high levels of imposed infertility in species with rapid population turnover rates. The modeling approach, as outlined here, could be used to inform future field studies by identifying suitable target species and making predictions about population responses that can be tested empirically. These studies will be necessary to realize the potential of the emerging fertility control technologies in the form of practical wildlife management applications.

TO WHAT DEGREE DO DIGITAL COMMUNICATIONS MEDIA CHALLENGE OR REFLECT VERTICALLY ORGANIZED HIERARCHIES? MANUEL CASTELLS IS one of the most influential and widely cited living sociologists--by our reckoning, using Google [...]

Second-generation anticoagulant rodenticides were introduced to control Norway rats that had become resistant to first-generation compounds. Unfortunately, some rats have become resistant to these as well. The lack of alternative rodenticides with the same attributes of ease of use and relative safety is potentially a serious problem should resistance become so widespread that anticoagulants are no longer effective. However, the second-generation anticoagulants difenacoum and bromadiolone can still be effective provided most rats in a population possess only a low degree of resistance to them. Measures that maximize the uptake of bait, such as using the most palatable formulation, baiting burrows and saturation baiting have to be implemented. The low levels of resistance discovered so far mean that the most potent anticoagulants, such as brodifacoum and flocoumafen, should also control most populations if baits containing either of them are properly applied. These two rodenticides are restricted to indoor use in the United Kingdom and are thus not available to control those rats living outdoors that are highly resistant to all other anticoagulants. Those rats can, however, be controlled with either zinc phosphide or calciferol, preferably after prebaiting. Strategies to manage resistance in the long-term should be implemented before high-degree resistance spreads. One potential tactic is to stop using anticoagulants altogether and allow deleterious pleiotropic effects to reduce the prevalence of resistance in a population. Any attempts to manager resistance are only relevant if the intention is to retain anticoagulant rodenticides, with their undoubted advantages, as the main method of controlling rodent pests.

The palatability of 12 rodenticide baits, formulated to vary from poorly accepted to well accepted, was measured in laboratory choice tests against Wistar and wild-caught Norway rats. The baits, derived from six bait bases and two active ingredients, difenacoum and bromadiolone, were simultaneously tested in the field against 24 farm infestations (2/formulation) in order to investigate the relationship between palatability and efficacy. Bait acceptance in laboratory tests, with EPA meal as the challenge diet, varied from 7.0 to 50.6% for Wistar rats and 3.7 to 85.1% for wild rats. Changing the challenge diet to a ground-up laboratory animal food significantly increased the apparent palatability of three selected baits to Wistar rats, although the relative palatabilities between the formulations remained the same. Bait acceptance, as measured in the laboratory, was unrelated to the degree of control achieved in farm treatments. The presence or absence of alternative food and whether the baits were placed in containers or applied directly into rat burrows appeared more likely to determine the outcome and overwhelmed any influence due to bait palatability. The combined effect of container- and burrow-baiting reduced the rat populations by an average 96.8% with 16 of the 24 populations tested completely eradicated. The least palatable baits dispensed into burrow entrances controlled rats on all farms, including those with abundant food sources.

Few effective repellents are currently available for the non-lethal management of vertebrate pests. This is perhaps not surprising considering the ad hoc nature of past applications which assumed that the target pest species would have the same attraction/aversion preferences as man. A more rational approach is to identify compounds that have real biological significance for the pest species. Plants have evolved an array of defense chemicals (secondary plant compounds) that inhibit the feeding of vertebrate herbivores, because they are either innately aversive or they generate a conditioned aversion. These compounds are, therefore, ideally suited for use in the reduction of feeding damage to crops, forest plantations and stored food products. Several of these novel plant-derived materials (e.g., cinnamamide) are already undergoing commercial evaluation. This approach facilitates the use of a number of systems to increase a plant's resistance to attack: topical application of the defense compound, systemic stimulation of the plants own resistance mechanisms and genetic enhancement. The two latter systems will enable the utilization of potent repellents that are not commercially viable for topical application and to concentrate their expression in the most palatable and vulnerable tissues. This paper also discusses work undertaken to improve our knowledge of the feeding strategies of target species. A proper understanding of these behaviors is essential before it will finally be possible to predict the field conditions under which a repellent will be effective.

Difenacoum and bromadiolone treatments against Norway rats may fail because: 1) the animals eat little or no bait, 2) reinvasion rapidly offsets any success, or 3) the population contains resistant individuals. By monitoring bait takes and employing independent measures of rat activity such as tracking plates, it is possible to identify, often in the early stages of a treatment, patterns that indicate the contribution of each of these causes to the eventual outcome. If there is no bait take from the majority of bait points visited by rats in the first week then the treatment is unlikely to be successful, no matter how long it continues. Furthermore, treatments carried out on arable farms, where cereals are stored and the environment is relatively undisturbed, are likely to be less successful than those carried out on livestock farms, where alternative food may also be abundant but where the environment is less predictable. Bait takes that persist at the same bait points for longer than 16 days strongly suggest the presence of resistant rats, while immigration may be significantly affecting the treatment if takes recur at more than 30% of points after a period of seven days. Once a given problem has been identified remedial measures can be taken.

Decades after the arrival of the Vietnamese boat people (1979-1981), we reassess their economic integration, along with that of a second wave (1982-1990). We compare current occupational locations and weekly earnings across the two waves and between the Vietnamese and immigrants born in China, Hong Kong, the Philippines, the United Kingdom, and North and West Europe (arriving 1979-1990). Occupational and earnings profiles document that the second Vietnamese wave has done less well than the first. Birthplace differences in demographic characteristics and educational attainments help explain labor market inequalities between the two waves and between the Vietnamese and other groups. Supplemental data for this article is available online at https://doi.org/10.1080/15562948.2021.1957190. [ABSTRACT FROM AUTHOR]

Business education typically embodies traditional organizational values, structures, and processes that focus learning mostly on uniformity and efficiency. In contrast, many First Nation peoples have long used the imagery of a circle as a guiding metaphor for both organizing and educating in ways that respect diversity and align themselves with natural rhythms. Consequently, they educate and work collectively and interdependently, enabling learning to evolve among them and within them. The authors draw on these patterns of insight and position them within a discussion of vital connections among Talking Circle pedagogy, leadership competencies, and the potential to create communities of inclusive learning. (Contains 1 figure and 2 tables.)