The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world.

Background: Occult bacterial infection is a proposed etiology of low back pain (LBP). However, a causative link between LBP and bacteria remains unconfirmed. Herein, we determined the incidence of occult discitis in patients receiving surgery for LDH. Methods: Study Design: prospective cohort study. Inclusion criteria: consecutive adult patients undergoing discectomy for symptomatic LDH. Exclusion criteria: prior epidural steroid use, prior spinal surgery, and antibiotic use within 2 weeks of surgery. Tissue samples: Four nuclear tissue and ligamentum flavum (control) samples were obtained per patient using stringent aseptic protocol. Samples underwent 16S-PCR and culturing. Results: Eighty-one patients were enrolled (mean age 43.3±13.3 years). All (100%) of tissue samples were negative by 16S PCR and no virulent species were detected. Nuclear and ligament cultures were both negative in 51 (62.9%) cases. Cultures were positive for nuclear tissue only, ligament only, or both in 14.8%, 12.3%, and 9.9% of cases, respectively. Fifteen of 20 (75%) disc positive samples grew a single colony of an indolent species. Conclusions: The findings of this prospective cohort study of consecutive patients receiving surgery for LDH do not support the theory of occult discitis. All samples were 16S-PCR negative, and most cultures were negative or grew a single colony suggestive of contamination.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.

A systematic review and meta-analysis were conducted to determine the efficacy of selective dry-cow antimicrobial therapy compared to blanket therapy (all quarters/all cows). Controlled trials were eligible if any of the following were assessed: incidence of clinical mastitis during the first 30 DIM, frequency of intramammary infection (IMI) at calving, or frequency of IMI during the first 30 DIM. From 3480 identified records, nine trials were data extracted for IMI at calving. There was an insufficient number of trials to conduct meta-analysis for the other outcomes. Risk of IMI at calving in selectively treated cows was higher than blanket therapy (RR = 1.34, 95% CI = 1.13, 1.16), but substantial heterogeneity was present (I2 = 58%). Subgroup analysis showed that, for trials using internal teat sealants, there was no difference in IMI risk at calving between groups, and no heterogeneity was present. For trials not using internal teat sealants, there was an increased risk in cows assigned to a selective dry-cow therapy protocol, compared to blanket treatment, with substantial heterogeneity in this subgroup. However, the small number of trials and heterogeneity in the subgroup without internal teat sealants suggests that the relative risk between treatments may differ from the determined point estimates based on other unmeasured factors.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.

Aspects of neutrophil function are diminished or dysregulated in dairy cows in the weeks just before and after calving, which appears to be an important contributor to the occurrence of retained placenta, mastitis, metritis and endometritis. The timing and mechanisms by which specific elements of neutrophil function are impaired are only partially understood. Oxidative burst capacity is the element of neutrophil function most consistently shown to be impaired in the week after calving, but that observation may partially be biased because oxidative burst has been studied more than other functions. There is sufficient evidence to conclude that the availability of calcium and glucose, and exposure to elevated concentrations of non-esterified fatty acids or β-hydroxybutyrate affect some aspects of neutrophil function. However, these factors have mostly been studied in isolation and their effects are not consistent. Social stressors such as a competitive environment for feeding or lying space should plausibly impair innate immune function, but when studied under controlled conditions such effects have generally not been produced. Similarly, treatment with recombinant bovine granulocyte colony-stimulating factor consistently produces large increases in circulating neutrophil count with modest improvements in function, but this does not consistently reduce the incidence of clinical diseases thought to be importantly attributable to impaired innate immunity. Research is now needed that considers the interactions among known and putative risk factors for impaired neutrophil function in dairy cows in the transition period.

Introduction: Screening for organ and tissue donation is an essential skill for emergency physicians. In 2015, 4564 individuals were on a waiting list for organ transplant and 242 died while waiting. As Canadas donation rates are less than half that of other comparable countries, it is crucial to ensure we are identifying all potential donors. Patients deceased from poisoning are a source that may not be considered for referral as often as those who die from other causes. This study aims to identify if patients dying from poisoning represent an under-referred group and determine what physician characteristics influence referral decisions. Methods: In this cross-sectional unidirectional survey study, physician members of the Canadian Association of Emergency Physicians were invited to participate. Participants were presented with 20 organ donation scenarios that included poisoned and non-poisoned deaths, as well as one ideal scenario for organ or tissue donation used for comparison. Participants were unaware of the objective to explore donation in the context of poisoning deaths. Following the organ donation scenarios, a range of follow-up questions and demographics were included to explore factors influencing the decision to refer or not refer for organ or tissue donation. Results were reported descriptively and associations between physician characteristics and decisions to refer were assessed using odds ratios and 95% confidence intervals. Results: 208/2058 (10.1%) physicians participated. 25% did not refer in scenarios involving a drug overdose (n=71). Specific poisonings commonly triggering the decision to not refer included palliative care medications (n=34, 18%), acetaminophen (n=42, 22%), chemical exposure (n=48, 27%) and organophosphates (n=87, 48%). Factors associated with an increased likelihood to refer potential donors following overdose included previous organ and tissue donation training (OR=2.6), having referred in the past (OR=4.3), available donation support (OR=3.9), greater than 10 years of service (OR=2.1), large urban center (OR=3.8), holding emergency medicine certification (OR=3.6), male gender (OR=2.2, CI), and having indicated a desire to be a donor on government identification (OR=5.8). Conclusion: Scenarios involving drug overdoses were associated with under-referral for organ and tissue donation. As poisoning is not a contraindication for referral, this represents a potential source of donors. By examining characteristics that put clinicians at risk for under-referral of organ or tissue donors, becoming aware of potential biases, improving transplant knowledge bases, and implementing support and training programs for the organ and tissue donation processes, we have the opportunity to improve these rates and reduce morbidity and mortality for Canadians requiring organ or tissue donation.

Background: Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in Capicua (CIC), located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. Methods: Transcriptome profiling of CIC knockout HEK293 cell lines generated using CRISPR was performed using microarray. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence. Transcript and protein changes of CIC targets were tested using RT-qPCR and Western blot following ATXN1L siRNA knockdown. Results: Transcriptomic profiling of CIC knockout cell lines resulted in a list of candidate CIC target genes validated against clinical samples. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction. Derepression of candidate CIC targets at transcript and protein levels was seen upon siRNA knockdown of ATXN1L. Conclusions: The interaction between CIC and ATXN1L is necessary for the repression of CIC target genes, including known oncogenes. Further research into the relationship between CIC and ATXN1L may lead potentially novel avenues of therapeutic approaches for less favorable gliomas.

Somatic mutations in the Capicua (CIC) gene were first identified in Type I low-grade gliomas (LGGs), which are characterized by 1p/19q co-deletions and IDH mutations. They are found at frequencies of ~50-70% in this glioma subtype, and have since been identified in ~40% of stomach adenocarcinomas (STADs) of the microsatellite instability (MSI) subtype; however, the role of these somatic mutations in malignancy has yet to be established. In Drosophila, CIC functions as a transcriptional repressor whose activity is inhibited upon activation of the mitogen-activated protein kinase (MAPK) signalling pathway. Though mammalian CIC appears to retain these functions, only three of its target genes have been established in human cells: ETV1, ETV4, and ETV5 (ETV1/4/5). To further probe CIC’s transcriptional network, we developed CIC knockout cell lines and performed transcriptomic and proteiomic analyses in these and in control cell lines expressing wild type CIC, identifying a total of 582 differentially expressed genes. We also used RNA-seq data from The Cancer Genome Atlas (TCGA) for Type I LGGs and STADs to perform additional differential expression analyses between CIC-deficient and CIC-expressing samples. Though gene-level overlap was limited between the three contexts, we found that CIC appears to regulate the expression of genes involved in cell-cell adhesion, metabolism, and developmental processes in all three contexts. These results shed light on the pathological role of CIC mutations and may help explain why these have been associated with poorer outcome within Type I LGGs.

Much can be learned from terrestrial planets that appear to have had the potential to be habitable, but failed to realize that potential. Mars shows evidence of a once hospitable surface environment. The reasons for its current state, and in particular its thin atmosphere and dry surface, are of great interest for what they can tell us about habitable zone planet outcomes. A main goal of the MAVEN mission is to observe Mars’ atmosphere responses to solar and space weather influences, and in particular atmosphere escape related to space weather ‘storms’ caused by interplanetary coronal mass ejections (ICMEs). Numerical experiments with a data-validated MHD model suggest how the effects of an observed moderately strong ICME compare to what happens during a more extreme event. The results suggest the kinds of solar and space weather conditions that can have evolutionary importance at a planet like Mars.

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0–825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March–October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.

Up to half of dairy cows are affected by at least one of metritis, purulent vaginal discharge, endometritis or cervicitis in the postpartum period. These conditions result from inadequate immune response to bacterial infection (failure to clear pathogenic bacteria from the uterus) or persistent inflammation that impairs rather than enhances reproductive function. The degree of mobilization of fat and how effectively it is used as a metabolic fuel is well recognized as a risk factor for metabolic and infectious disease. Release of non-esterified fatty acids has direct effects on liver and immune function but also produces pro-inflammatory cytokines (tumor necrosis factor α and interleukin-6), which contribute to systemic inflammation and to insulin resistance. Therefore, reproductive tract inflammatory disease may be a function of both local and systemic inflammatory stimuli and regulation as well as regulation of fat metabolism. Better understanding of variables associated with insulin resistance and inflammatory regulation in the liver and adipose tissue may lead to improvement of reproductive tract health. This paper reviews factors that may contribute to postpartum reproductive tract inflammatory diseases in dairy cows and their inter-relationships, impacts and treatment.

Extended abstract of a paper presented at Microscopy and Microanalysis 2005 in Honolulu, Hawaii, USA, July 31--August 4, 2005

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.