The extent to which weed species vary in their ability to acquire and use different forms of nitrogen (N) (inorganic and organic) has not been investigated but could have important implications for weed survival and weed–crop competition in agroecosystems. We conducted a controlled environment experiment using stable isotopes to determine the uptake and partitioning of organic and inorganic N (amino acids, ammonium, and nitrate) by seven common weed and non-weed species. All species took up inorganic and organic N, including as intact amino acids. Concentrations of 15N derived from both ammonium and amino acids in shoot tissues were higher in large crabgrass [Digitaria sanguinalis (L.) Scop.] and barnyardgrass [Echinochloa crus-galli (L.) P. Beauv] than in common lambsquarters (Chenopodium album L.), redroot pigweed (Amaranthus retroflexus L.), and sorghum-sudangrass [Sorghum bicolor (L.) Moench × Sorghum bicolor (L.) ssp. drummondii (Nees ex Steud.) de Wet & Harlan]. In contrast, the concentration of 15N derived from nitrate was higher in wild mustard (Sinapis arvensis L.) shoots than in wild oat (Avena fatua L.) shoots. Root concentration of 15N derived from ammonium was lower in sorghum-sudangrass compared with other species, except for A. retroflexus and A. fatua, while root concentration of 15N derived from nitrate was lower in A. retroflexus compared with other species, except for C. album and S. arvensis. Discriminant analysis classified species based on their uptake and partitioning of all three labeled N forms. These results suggest that common agricultural weeds can access and use organic N and differentially take up inorganic N forms. Additional research is needed to determine whether species-specific differences in organic and inorganic N uptake influence the intensity of competition for soil N.

Salmonella spp. is a common zoonotic pathogen, causing gastrointestinal infections in people. Pigs and pig meat are a major source of infection. Although farm biosecurity is believed to be important for controlling Salmonella transmission, robust evidence is lacking on which measures are most effective. This study enrolled 250 pig farms across nine European countries. From each farm, 20 pooled faecal samples (or similar information) were collected and analysed for Salmonella presence. Based on the proportion of positive results, farms were categorised as at higher or lower Salmonella risk, and associations with variables from a comprehensive questionnaire investigated. Multivariable analysis indicated that farms were less likely to be in the higher-risk category if they had ‘<400 sows’; used rodent baits close to pig enclosures; isolated stay-behind (sick) pigs; did not answer that the hygiene lock/ anteroom was easy to clean; did not have a full perimeter fence; did apply downtime of at least 3 days between farrowing batches; and had fully slatted flooring in all fattener buildings. A principal components analysis assessed the sources of variation between farms, and correlation between variables. The study results suggest simple control measures that could be prioritised on European pig farms to control Salmonella.

Understanding the distribution and extent of suitable habitats is critical for the conservation of endangered and endemic taxa. Such knowledge is limited for many Central African species, including the rare and globally threatened Grey-necked Picathartes Picathartes oreas, one of only two species in the family Picathartidae endemic to the forests of Central Africa. Despite growing concerns about land-use change resulting in fragmentation and loss of forest cover in the region, neither the extent of suitable habitat nor the potential species’ distribution is well known. We combine 339 (new and historical) occurrence records of Grey-necked Picathartes with environmental variables to model the potential global distribution. We used a Maximum Entropy modelling approach that accounted for sampling bias. Our model suggests that Grey-necked Picathartes distribution is strongly associated with steeper slopes and high levels of forest cover, while bioclimatic, vegetation health, and habitat condition variables were all excluded from the final model. We predicted 17,327 km2 of suitable habitat for the species, of which only 2,490 km2 (14.4%) are within protected areas where conservation designations are strictly enforced. These findings show a smaller global distribution of predicted suitable habitat forthe Grey-necked Picathartes than previously thought. This work provides evidence to inform a revision of the International Union for Conservation of Nature (IUCN) Red List status, and may warrant upgrading the status of the species from “Near Threatened” to “Vulnerable”.

Human infection with antimicrobial-resistant Campylobacter species is an important public health concern due to the potentially increased severity of illness and risk of death. Our objective was to synthesise the knowledge of factors associated with human infections with antimicrobial-resistant strains of Campylobacter. This scoping review followed systematic methods, including a protocol developed a priori. Comprehensive literature searches were developed in consultation with a research librarian and performed in five primary and three grey literature databases. Criteria for inclusion were analytical and English-language publications investigating human infections with an antimicrobial-resistant (macrolides, tetracyclines, fluoroquinolones, and/or quinolones) Campylobacter that reported factors potentially linked with the infection. The primary and secondary screening were completed by two independent reviewers using Distiller SR®. The search identified 8,527 unique articles and included 27 articles in the review. Factors were broadly categorised into animal contact, prior antimicrobial use, participant characteristics, food consumption and handling, travel, underlying health conditions, and water consumption/exposure. Important factors linked to an increased risk of infection with a fluoroquinolone-resistant strain included foreign travel and prior antimicrobial use. Identifying consistent risk factors was challenging due to the heterogeneity of results, inconsistent analysis, and the lack of data in low- and middle-income countries, highlighting the need for future research.

In a survey of infection prevention programs, leaders reported frequent clinical and infection prevention practice modifications to avoid coronavirus disease 2019 (COVID-19) exposure that exceeded national guidance. Future pandemic responses should emphasize balanced approaches to precautions, prioritize educational campaigns to manage safety concerns, and generate an evidence-base that can guide appropriate infection prevention practices.

OBJECTIVES/GOALS: Microtubule poisons, like Taxol, are used to treat triple negative breast cancer (TNBC) and may induce lethal aneuploidy in cancer cells. Patients initially respond, but often develop drug resistance. New targeted drugs that cause aneuploidy may be a valuable approach to therapy. One potential target is the Kinesin 13 MCAK, which limits aneuploidy. METHODS/STUDY POPULATION: TCGA and GSE47561 databases were probed for MCAK expression, and data was stratified by subtype and survival statistics. Knockdown studies were performed to test whether MCAK knockdown sensitizes cells to taxanes for cell proliferation and for induction of aneuploidy. FRET and image-based screens were used to identify MCAK inhibitors from small molecule inhibitor libraries. Inhibitors were then tested for functional effects in multiple cell-based assays and for clonal growth in colony formation assays. RESULTS/ANTICIPATED RESULTS: MCAK expression is upregulated in TNBC and associated with reduced overall survival. Knockdown of MCAK caused a two-to-five-fold reduction of the IC50 for Taxol in cancer cell lines, with no change in normal cell lines. Taxol treatment or MCAK knockdown increased aneuploidy induction, with no additive effect between the two. Our small molecule screen identified three putative MCAK inhibitors, which induced aneuploidy in both taxane-sensitive and taxane-resistant cells. These inhibitors also reduced clonogenic growth, and the most potent inhibitor, C4, caused an approximate five-fold reduction in the IC50 for Taxol in cell proliferation assays. DISCUSSION/SIGNIFICANCE: MCAK can serve as a biomarker of breast cancer prognosis. MCAK knockdown or inhibition sensitizes cancer cells to Taxol without affecting normal cells, making it a potential target in combination therapy. MCAK inhibitors also reduce growth as single agents in taxane resistant lines, giving them potential use as therapies in resistant disease.

In the general population, irritability is associated with later depression. Despite irritability being more prevalent in autistic children, the long-term sequelae are not well explored. We tested whether irritability in early childhood predicted depression symptoms in autistic adolescents, and whether associations could be explained by difficulties in peer relationships and lower educational engagement. Analyses tested the longitudinal associations between early childhood irritability (ages 3–5) and adolescent depression symptoms (age 14) in a prospective inception cohort of autistic children (N = 390), followed from early in development shortly after they received a clinical diagnosis. Mediators were measured in mid-childhood (age 10) by a combination of measures, from which latent factors for peer relationships and educational engagement were estimated. Results showed early childhood irritability was positively associated with adolescent depression symptoms, and this association remained when adjusting for baseline depression. A significant indirect pathway through peer relationships was found, which accounted for around 13% of the association between early childhood irritability and adolescent depression, suggesting peer problems may partially mediate the association between irritability and later depression. No mediation effects were found for education engagement. Results highlight the importance of early screening and intervention for co-occurring irritability and peer problems in young autistic children.

Resistance to beta-lactam antimicrobials caused by extended-spectrum beta-lactamase (ESBL)-producing organisms is a global health concern. The objectives of this study were to (1) summarise the prevalence of potential ESBL-producing Escherichia coli (ESBL-EC) and Salmonella spp. (ESBL-SA) isolates from agrifood and human sources in Canada from 2012 to 2017, and (2) describe the distribution of ESBL genotypes among these isolates. All data were obtained from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). CIPARS analysed samples for the presence of ESBLs through phenotypic classification and identified beta-lactamase genes (blaTEM, blaSHV, blaCTX, blaOXA, blaCMY−2) using polymerase chain reaction (PCR) and whole genome sequencing (WGS). The prevalence of PCR-confirmed ESBL-EC in agrifood samples ranged from 0.5% to 3% across the surveillance years, and was detected most frequently in samples from broiler chicken farms. The overall prevalence of PCR-confirmed ESBL-SA varied between 1% and 4% between 2012 and 2017, and was most frequently detected in clinical isolates from domestic cattle. The TEM-CMY2 gene combination was the most frequently detected genotype for both ESBL-EC and ESBL-SA. The data suggest that the prevalence of ESBL-EC and ESBL-SA in Canada was low (i.e. <5%), but ongoing surveillance is needed to detect emerging or changing trends.

Antimicrobial resistance (AMR) is a complex problem that is a threat to global public health. Consumption of turkey meat may be an important source of foodborne exposure to resistant bacteria; recent outbreaks of multi-drug-resistant Salmonella Reading in Canada and the USA have implicated raw turkey products. To better understand the epidemiology of AMR in farmed turkey production, a scoping review was conducted. The objectives were to identify (1) modifiable factors potentially associated with antimicrobial-resistant Campylobacter, Enterococcus, Escherichia coli and Salmonella enterica along the farm-to-fork pathway in turkeys, and (2) data gaps with respect to factors potentially associated with AMR and Canadian commercial turkey production. A comprehensive search of the peer-reviewed literature was conducted in 2019 and updated in 2021. Thirteen references were included, reporting 36 factors. Antimicrobial use factors and their potential associations with AMR were most frequently reported (n = 15 factors; 42%), followed by biosecurity (n = 11; 31%) and management practices (n = 10; 28%). This review revealed important data gaps; no factors pertaining to S. enterica or to stages other than the farm (e.g. abattoir, retail) were identified, and only one Canadian reference was identified. These findings will inform priorities for future research and surveillance regarding turkeys and AMR.

Resistance to carbapenems in human pathogens is a growing clinical and public health concern. The carbapenems are in an antimicrobial class considered last-resort, they are used to treat human infections caused by multidrug-resistant Enterobacterales, and they are classified by the World Health Organization as ‘High Priority Critically Important Antimicrobials’. The presence of carbapenem-resistant Enterobacterales (CREs) of animal-origin is of concern because targeted studies of Canadian retail seafood revealed the presence of carbapenem resistance in a small number of Enterobacterales isolates. To further investigate this issue, a risk profile was developed examining shrimp and salmon, the two most important seafood commodities consumed by Canadians and Escherichia coli, a member of the Enterobacterales order. Carbapenem-resistant E. coli (CREc) isolates have been identified in shrimp and other seafood products. Although carbapenem use in aquaculture has not been reported, several classes of antimicrobials are utilised globally and co-selection of antimicrobial-resistant microorganisms in an aquaculture setting is also of concern. CREs have been identified in retail seafood purchased in Canada and are currently thought to be uncommon. However, data concerning CRE or CREc occurrence and distribution in seafood are limited, and argue for implementation of ongoing or periodic surveillance.

The dissociative subtype of post-traumatic stress disorder (PTSD-DS) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and is characterised by symptoms of either depersonalisation or derealisation, in addition to a diagnosis of post-traumatic stress disorder (PTSD). This systematic review and meta-analysis sought to estimate the point prevalence of current PTSD-DS, and the extent to which method of assessment, demographic and trauma variables moderate this estimate, across different methods of prevalence estimation. Studies included were identified by searching MEDLINE (EBSCO), PsycInfo, CINAHL, Academic Search Complete and PTSDpubs, yielding 49 studies that met the inclusion criteria (N = 8214 participants). A random-effects meta-analysis estimated the prevalence of PTSD-DS as 38.1% (95% CI 31.5–45.0%) across all samples, 45.5% (95% CI 37.7–53.4%) across all diagnosis-based and clinical cut-off samples, 22.8% (95% CI 14.8–32.0%) across all latent class analysis (LCA) and latent profile analysis (LPA) samples and 48.1% (95% CI 35.0–61.3%) across samples which strictly used the DSM-5 PTSD criteria; all as a proportion of those already with a diagnosis of PTSD. All results were characterised by high levels of heterogeneity, limiting generalisability. Moderator analyses mostly failed to identify sources of heterogeneity. PTSD-DS was more prevalent in children compared to adults, and in diagnosis-based and clinical cut-off samples compared to LCA and LPA samples. Risk of bias was not significantly related to prevalence estimates. The implications of these results are discussed further.

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.

We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.

Of 453 cases, 53% (n = 242) were staff, most aged 25–34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26–64%) than in residents (12%, 95% CI 9–15%).

Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.