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Previous studies demonstrated that polyclonal antibodies against foot-and-mouth disease virus (FMDV) generated by vaccination can mediate immune functions not only through virus neutralization but also through promoting virus uptake by macrophages and dendritic cells that are otherwise resistant to FMDV infection. This causes abortive infections resulting in activation, enhanced antigen presentation but also cell death. Here we report the use of RAW264.7 cells representing a murine macrophage cells line to characterize opsonizing functions of a collection of monoclonal antibodies (mAbs) against FMDV O and A serotypes. We demonstrate that all neutralizing immunoglobulin G isotype mAbs are able to opsonize FMDV resulting in increased cell death of RAW264.7 cells. In contrast, neutralizing IgM antibodies did not possess this activity. Opsonization was observed with broader reactivity within the serotype when compared to neutralization. Importantly, the anti-O serotype D9 mAb reacting with the continuous epitope within the G-H loop of VP1 that contains the RGD binding site of FMDV, opsonized several FMDV serotypes despite its restricted neutralizing activity within the O serotype. Furthermore, by generating RAW264.7 cells expressing bovine CD32, an easy-to-use cell-based assay system to test for bovine antibody-dependent enhanced infection of FMDV was generated and tested with a collection of sera. The data indicate that opsonizing titers correlated better with vaccine dose when compared to neutralizing titers. On the other hand, neutralization and opsonization titers were similar predictive of protection. We conclude that low avidity interactions are sufficient to mediate Fcγ receptor-mediated immune functions that could contribute to protective immune responses against FMDV.

When a target stimulus occurs in the presence of distracters, decisions are less accurate. But how exactly do distracters affect choices? Here, we explored this question using measurement of human behaviour, psychophysical reverse correlation and computational modelling. We contrasted two models: one in which targets and distracters had independent influence on choices (independent model) and one in which distracters modulated choices in a way that depended on their similarity to the target (interaction model). Across three experiments, participants were asked to make fine orientation judgments about the tilt of a target grating presented adjacent to an irrelevant distracter. We found strong evidence for the interaction model, in that decisions were more sensitive when target and distracter were consistent relative to when they were inconsistent. This consistency bias occurred in the frame of reference of the decision, that is, it operated on decision values rather than on sensory signals, and surprisingly, it was independent of spatial attention. A normalization framework, where target features are normalized by the expectation and variability of the local context, successfully captures the observed pattern of results.

African Swine Fever virus (ASFV) is a large double-enveloped DNA virus of the Asfarviridae family that causes a lethal hemorrhagic disease in domestic pigs and wild boars. Since 2007, a highly virulent genotype II strain has emerged and spread in Europe and South-East Asia, where millions of animals succumbed to the disease. Field- and laboratory-attenuated strains of ASFV cause highly variable clinical disease severity and survival, and mechanisms remain unclear. We hypothesized that the immunological and hygienic status of pigs is a determinant of ASF disease course. Here we compared the immunological profile at baseline and in response to ASFV infection in specific pathogen-free (SPF) and farm-raised Large White domestic pigs. At steady state, SPF pigs showed lower white blood cell counts and a lower basal inflammatory and antiviral transcriptomic profile compared to farm pigs, associated with profound differences in gut microbiome composition. After inoculation with a highly virulent ASFV genotype II strain (Armenia 2008), severe clinical signs, viremia and pro-inflammatory cytokines appeared sooner in SPF pigs, indicating a reduced capacity to control early virus replication. In contrast, during infection with an attenuated field isolate (Estonia 2014), SPF pigs presented a milder and shorter clinical disease with full recovery, whereas farm pigs presented severe protracted disease with 50% lethality. Interestingly, farm pigs showed higher production of inflammatory cytokines, whereas SPF pigs produced more anti-inflammatory IL-1ra early after infection and presented a stronger expansion of leukocytes in the recovery phase. Altogether, our data indicate that the hygiene-dependent innate immune status has a double-edge sword impact on immune responses in ASF pathogenesis. While the higher baseline innate immune activity helps the host in reducing initial virus replication, it promotes immunopathological cytokine responses, and delays lymphocyte proliferation after infection with an attenuated strain. Such effects should be considered for live vaccine development and vigilance.

Objectives The Ministry of Justice’s pioneering data linking programme Data First, funded by Administrative Data Research UK, links administrative datasets across the justice system and with other government departments to enable research providing critical new insights on justice system users, their pathways, and outcomes across a range of public services. Approach The first two datasets shared under the Data First project are magistrates’ courts and Crown Court data which have been deidentified, deduplicated and linked to provide a joined-up picture of criminal court defendant and case journeys. Accredited researchers can access this data using the ONS Secure Research Service to conduct research. Administrative Data Research UK has funded four Research Fellows to conduct analysis using this linked data. Additionally, analysts within the Ministry of Justice Data First team have published a research report showcasing the potential of the linked criminal courts data. The presentation will primarily focus on this work. Results The Data First criminal courts datasets have enabled, for the first time, the extent and nature of repeat users to be explored at scale for research. In March 2022, the Ministry of Justice published exploratory analysis of returning defendants and the potential of linked criminal courts data. The key findings of this report will be covered in the presentation. The research demonstrates more than half of defendants returned to the courts within the data period, but this was highest for specific offence groups, including theft, robbery and drug offences. Locality-based analysis on Crown Court defendants highlights important insights on the backgrounds of justice system users, showing an over-representation of defendants residing in the most deprived areas in England and Wales compared to the general population. Conclusion The presentation will demonstrate how linked administrative data available through the ground-breaking Data First programme can be effectively used for research. This insight improves our understanding of individuals in the justice system as well as providing a rich resource to develop the evidence base for government policy and practice.

Abstract Mycoplasma hyopneumoniae (M. hyopneumoniae) is one of the primary agents involved in the porcine respiratory disease complex, economically one of the most important diseases in pigs worldwide. The pathogen adheres to the ciliated epithelium of the trachea, bronchi, and bronchioles, causes damage to the mucosal clearance system, modulates the immune system and renders the animal more susceptible to other respiratory infections. The pathogenesis is very complex and not yet fully understood. Cell-mediated and likely also mucosal humoral responses are considered important for protection, although infected animals are not able to rapidly clear the pathogen from the respiratory tract. Vaccination is frequently practiced worldwide to control M. hyopneumoniae infections and the associated performance losses, animal welfare issues, and treatment costs. Commercial vaccines are mostly bacterins that are administered intramuscularly. However, the commercial vaccines provide only partial protection, they do not prevent infection and have a limited effect on transmission. Therefore, there is a need for novel vaccines that confer a better protection. The present paper gives a short overview of the pathogenesis and immune responses following M. hyopneumoniae infection, outlines the major limitations of the commercial vaccines and reviews the different experimental M. hyopneumoniae vaccines that have been developed and tested in mice and pigs. Most experimental subunit, DNA and vector vaccines are based on the P97 adhesin or other factors that are important for pathogen survival and pathogenesis. Other studies focused on bacterins combined with novel adjuvants. Very few efforts have been directed towards the development of attenuated vaccines, although such vaccines may have great potential. As cell-mediated and likely also humoral mucosal responses are important for protection, new vaccines should aim to target these arms of the immune response. The selection of proper antigens, administration route and type of adjuvant and carrier molecule is essential for success. Also practical aspects, such as cost of the vaccine, ease of production, transport and administration, and possible combination with vaccines against other porcine pathogens, are important. Possible avenues for further research to develop better vaccines and to achieve a more sustainable control of M. hyopneumoniae infections are discussed.

Similar to human monocytes, bovine monocytes can be split into CD14highCD16- classical, CD14highCD16high intermediate and CD14-/dimCD16high nonclassical monocytes (cM, intM, and ncM, respectively). Here, we present an in-depth analysis of their steady-state bulk- and single-cell transcriptomes, highlighting both pronounced functional specializations and transcriptomic relatedness. Bulk gene transcription indicates pro-inflammatory and antibacterial roles of cM, while ncM and intM appear to be specialized in regulatory/anti-inflammatory functions and tissue repair, as well as antiviral responses and T-cell immunomodulation. Notably, intM stood out by high expression of several genes associated with antigen presentation. Anti-inflammatory and antiviral functions of ncM are further supported by dominant oxidative phosphorylation and selective strong responses to TLR7/8 ligands, respectively. Moreover, single-cell RNA-seq revealed previously unappreciated heterogeneity within cM and proposes intM as a transient differentiation intermediate between cM and ncM.

Abstract Background The benefits of pimobendan in the treatment of congestive heart failure (CHF) in cats with hypertrophic cardiomyopathy (HCM) have not been evaluated prospectively. Hypothesis/Objectives To investigate the effects of pimobendan in cats with HCM and recent CHF and to identify possible endpoints for a pivotal study. We hypothesized that pimobendan would be well‐tolerated and associated with improved outcome. Animals Eighty‐three cats with HCM and recently controlled CHF: 30 with and 53 without left ventricular outflow tract obstruction. Methods Prospective randomized placebo‐controlled double‐blind multicenter nonpivotal field study. Cats received either pimobendan (0.30 mg/kg q12h, n = 43), placebo (n = 39), or no medication (n = 1) together with furosemide (

Ben Harvey et al. use the gradient provided by a natural CO2 seep off Shikine Island, Japan and lab microcosm experiments to determine how ocean acidification promotes turf algal habitat conditions that create stabilizing feedback loops and hysteresis capable of locking turf systems in place. These results further our understanding of feedback loops initiated by ocean acidification, and can assist in the management of coastal habitats.

Dear readers, The year 2024 marks the hundredth year of publication of Italica. To celebrate this occasion and to illustrate the richness, reach, and influence of our journal, we will [...]

American entrepreneur, television producer, media owner, and philanthropist, Ted Turner, once described Rupert Murdoch as "the most dangerous man in the world" (Beahm, 1). This is not an unusual judgement. But it is also one which may contribute to sustaining the Murdoch "brand," his notoriety, and appeal to supporters. This article examines the deep origins of Murdoch's cynical worldview, and the source of an ambition that drove him from ownership of a small provincial Australian newspaper to global media mogul. What compelled the need to disseminate often dangerously divisive views on as large a stage as possible, while purporting to be acting in the interests of society's disenfranchised? The purpose of the article is to critically, but disinterestedly, question the credibility of judgement, and so challenge the basis of his public influence. The article's approach is gendered and historical. It examines the values modelled by his grandfather, Patrick, and transmitted to his father, Keith. It looks at the less direct, yet significant modelling of his boarding school headmaster, the institution that acted in loco parentis from age 10 to 18. It looks at the boyhood version of Rupert Murdoch and finds a direct, undeviating line of sight between the adolescent and the adult. Without access to the same eloquent and intimate relationship shared by Patrick and Keith, Rupert created for himself in adolescence a persona which not only distorted but inverted the altruism cherished by his male predecessors. [ABSTRACT FROM AUTHOR]

Simple Summary: Thrips are among the most damaging insect pests affecting greenhouse horticulture crops. Research on biological control of these pests has focused on the dominant species, western flower thrips (WFT). However, a second species, onion thrips (OT), has become more prevalent in greenhouse ornamentals in Ontario, and biocontrol strategies for WFT do not control OT sufficiently to prevent crop losses. Although thrips' natural enemies have been tested against OT alone, there are few studies examining how effective they are for OT compared to WFT. We conducted several laboratory trials examining the relative efficacy of several natural enemies typically used in thrips biocontrol, including predators, parasitic nematodes, and a fungal-based biopesticide. All of the natural enemies tested were at least as effective at killing OT as they were for WFT in the laboratory, indicating that they all have the potential to manage both species equally well. Possible explanations why this potential is not realized in commercial greenhouse operations are explored. Thrips biocontrol research in greenhouse crops has focused primarily on western flower thrips (WFT; Frankliniella occidentalis). However, recent outbreaks of onion thrips (OT; Thrips tabaci) in Ontario, Canada, demonstrate that biocontrol-based IPM programs for WFT do not control OT sufficiently to prevent crop losses. A lack of comparative studies makes it difficult to determine which program components for WFT are failing for OT. We conducted several laboratory trials examining the extent to which commercial biocontrol products kill OT compared to WFT. These included phytoseiid mites (Amblyseius swirskii, Neoseiulus cucumeris, Amblydromalus limonicus, Iphiseius degenerans), a large generalist predator (Orius insidiosus), an entomopathogenic fungus (Beauveria bassiana strain GHA), and entomopathogenic nematodes (Steinernema feltiae, S. carpocapsae, Heterorhabditis bacteriophora). In no-choice trials, A. swirskii and O. insidiosus consumed more OT than WFT (first instars and adults, respectively). In choice trials, A. swirskii, N. cucumeris, and O. insidiosus consumed more OT than WFT. Steinernema feltiae caused higher mortality in OT than WFT. There was no difference in mortality between thrips species exposed to other biocontrol agents. This suggests available tools have the potential to manage OT as well as WFT. Possible explanations why this potential is not realized in commercial settings are explored. [ABSTRACT FROM AUTHOR]

Abstract Background Lack of sustainable access to clean drinking water continues to be an issue of paramount global importance, leading to millions of preventable deaths annually. Best practices for providing sustainable access to clean drinking water, however, remain unclear. Widespread installation of low-cost, in-home, point of use water filtration systems is a promising strategy. Methods We conducted a prospective, randomized, controlled trial whereby 16 villages were selected and randomly assigned to one of four treatment arms based on the installation location of Sawyer® PointONE™ filters (filter in both home and school; filter in home only; filter in school only; control group). Water samples and self-reported information on diarrhea were collected at multiple times throughout the study. Results Self-reported household prevalence of diarrhea decreased from 25.6 to 9.76% from installation to follow-up (at least 7 days, and up to 200 days post-filter installation). These declines were also observed in diarrhea with economic or educational consequences (diarrhea which led to medical treatment and/or missing school or work) with baseline prevalence of 9.64% declining to 1.57%. Decreases in diarrhea prevalence were observed across age groups. There was no evidence of a loss of efficacy of filters up to 200 days post-filter installation. Installation of filters in schools was not associated with decreases in diarrhea prevalence in school-aged children or family members. Unfiltered water samples both at schools and homes contained potential waterborne bacterial pathogens, dissolved heavy metals and metals associated with particulates. All dissolved metals were detected at levels below World Health Organization action guidelines. Conclusions This controlled trial provides strong evidence of the effectiveness of point-of-use, hollow fiber membrane filters at reducing diarrhea from bacterial sources up to 200 days post-installation when installed in homes. No statistically significant reduction in diarrhea was found when filters were installed in schools. Further research is needed in order to explore filter efficacy and utilization after 200 days post-installation. Trial registration ClinicalTrials.gov, NCT03972618 . Registered 3 June 2019—retrospectively registered.

The clinical course of chronic lymphocytic leukaemia (CLL) is variable and difficult to predict. Here, the authors conduct a genome wide association study meta-analysis for time to first treatment in CLL patients and report two loci associating with progressive disease.

Abstract Introduction Vaginal dilation is often indicated as an intervention for the management of radiation therapy‐induced vaginal adhesions and stenosis (RTVAS). However, limited research exists underpinning this intervention and diversity in patient recommendations internationally are reported. In the absence of New Zealand (NZ) national guidelines regarding the management of RTVAS, a survey of NZ radiation therapy departments was conducted to gain an overview of current practice. Methods A two‐section online survey was developed to capture RTVAS education and management overview across NZ. Section one focused on departmental resourcing and section two on local standard practice regarding vaginal dilator usage. One RTVAS education representative from each department was invited to complete the survey. Results Eight of nine NZ departments completed the survey. Consistent treatment indications were identified for RTVAS patient education with the involvement of diverse staffing groups at various time‐points throughout the treatment process. Protocols for RTVAS management existed in each RT department with staff commonly trained by informal peer observation. Dilator usage was recommended regardless of patient sexual activity. Agreement was shown regarding the recommended start time of dilator usage and frequency. The recommended duration of dilator use post‐treatment varied from 6 months to greater than 36 months. Conclusions This work illustrates both concordance and diversity in practice and contributes to the limited body of literature available. Further research is warranted to explore patterns of practice between departmental protocols and individual practitioners in further detail.

Abstract Understudied, coinfections are more frequent in pig farms than single infections. In pigs, the term “Porcine Respiratory Disease Complex” (PRDC) is often used to describe coinfections involving viruses such as swine Influenza A Virus (swIAV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and Porcine CircoVirus type 2 (PCV2) as well as bacteria like Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae and Bordetella bronchiseptica. The clinical outcome of the various coinfection or superinfection situations is usually assessed in the studies while in most of cases there is no clear elucidation of the fine mechanisms shaping the complex interactions occurring between microorganisms. In this comprehensive review, we aimed at identifying the studies dealing with coinfections or superinfections in the pig respiratory tract and at presenting the interactions between pathogens and, when possible, the mechanisms controlling them. Coinfections and superinfections involving viruses and bacteria were considered while research articles including protozoan and fungi were excluded. We discuss the main limitations complicating the interpretation of coinfection/superinfection studies, and the high potential perspectives in this fascinating research field, which is expecting to gain more and more interest in the next years for the obvious benefit of animal health.

Abstract New vaccine formulations that include novel strains of Mycoplasma hyopneumoniae and innovative adjuvants designed to induce cellular immunity could improve vaccine efficacy against this pathogen. The aim of this experimental study was to assess the efficacy of three experimental bacterin formulations based on M. hyopneumoniae field strain F7.2C which were able to induce cellular immunity. The formulations included a cationic liposome formulation with the Mincle receptor ligand trehalose 6,6-dibehenate (Lipo_DDA:TDB), a squalene-in-water emulsion with Toll-like receptor (TLR) ligands targeting TLR1/2, TLR7/8 and TLR9 (SWE_TLR), and a poly(lactic-co-glycolic acid) micro-particle formulation with the same TLR ligands (PLGA_TLR). Four groups of 12 M. hyopneumoniae-free piglets were primo- (day (D) 0; 39 days of age) and booster vaccinated (D14) intramuscularly with either one of the three experimental bacterin formulations or PBS. The pigs were endotracheally inoculated with a highly and low virulent M. hyopneumoniae strain on D28 and D29, respectively, and euthanized on D56. The main efficacy parameters were: respiratory disease score (RDS; daily), macroscopic lung lesion score (D56) and log copies M. hyopneumoniae DNA determined with qPCR on bronchoalveolar lavage (BAL) fluid (D42, D56). All formulations were able to reduce clinical symptoms, lung lesions and the M. hyopneumoniae DNA load in the lung, with formulation SWE_TLR being the most effective (RDSD28–D56 −61.90%, macroscopic lung lesions −88.38%, M. hyopneumoniae DNA load in BAL fluid (D42) −67.28%). Further experiments raised under field conditions are needed to confirm these results and to assess the effect of the vaccines on performance parameters.

This study was initiated to better understand the nature of innate immune responses and the relatively weak and delayed immune response against porcine reproductive and respiratory syndrome virus (PRRSV). Following modified live virus (MLV) vaccination or infection with two PRRSV-2 strains, we analyzed the transcriptome of peripheral blood mononuclear cells collected before and at three and seven days after vaccination or infection. We used blood transcriptional modules (BTMs)-based gene set enrichment analyses. BTMs related to innate immune processes were upregulated by PRRSV-2 strains but downregulated by MLV. In contrast, BTMs related to adaptive immune responses, in particular T cells and cell cycle, were downregulated by PRRSV-2 but upregulated by MLV. In addition, we found differences between the PRRSV strains. Only the more virulent strain induced a strong platelet activation, dendritic cell activation, interferon type I and plasma cell responses. We also calculated the correlations of BTM with the neutralizing antibody and the T-cell responses. Early downregulation (day 0–3) of dendritic cell and B-cell BTM correlated to both CD4 and CD8 T-cell responses. Furthermore, a late (day 3–7) upregulation of interferon type I modules strongly correlated to helper and regulatory T-cell responses, while inflammatory BTM upregulation correlated more to CD8 T-cell responses. BTM related to T cells had positive correlations at three days but negative associations at seven days post-infection. Taken together, this work contributes to resolve the complexity of the innate and adaptive immune responses against PRRSV and indicates a fundamentally different immune response to the less immunogenic MLV compared to field strains which induced robust adaptive immune responses. The identified correlates of T-cell responses will facilitate a rational approach to improve the immunogenicity of MLV.

Biofilms harbour a wealth of microbial diversity and fulfil key functions in coastal marine ecosystems. Elevated carbon dioxide (CO2) conditions affect the structure and function of biofilm communities, yet the ecological patterns that underpin these effects remain unknown. We used high-throughput sequencing of the 16S and 18S rRNA genes to investigate the effect of elevated CO2 on the early successional stages of prokaryotic and eukaryotic biofilms at a CO2 seep system off Shikine Island, Japan. Elevated CO2 profoundly affected biofilm community composition throughout the early stages of succession, leading to greater compositional homogeneity between replicates and the proliferation of the potentially harmful algae Prymnesium sp. and Biddulphia biddulphiana. Species turnover was the main driver of differences between communities in reference and high CO2 conditions, rather than differences in richness or evenness. Our study indicates that species turnover is the primary ecological pattern that underpins the effect of elevated CO2 on both prokaryotic and eukaryotic components of biofilm communities, indicating that elevated CO2 conditions represent a distinct niche selecting for a distinct cohort of organisms without the loss of species richness.