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In this paper, we describe the system design and capabilities of the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope at the conclusion of its construction project and commencement of science operations. ASKAP is one of the first radio telescopes to deploy phased array feed (PAF) technology on a large scale, giving it an instantaneous field of view that covers $31\,\textrm{deg}^{2}$ at $800\,\textrm{MHz}$. As a two-dimensional array of 36$\times$12 m antennas, with baselines ranging from 22 m to 6 km, ASKAP also has excellent snapshot imaging capability and 10 arcsec resolution. This, combined with 288 MHz of instantaneous bandwidth and a unique third axis of rotation on each antenna, gives ASKAP the capability to create high dynamic range images of large sky areas very quickly. It is an excellent telescope for surveys between 700 and $1800\,\textrm{MHz}$ and is expected to facilitate great advances in our understanding of galaxy formation, cosmology, and radio transients while opening new parameter space for discovery of the unknown.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Methods:
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
Results:
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Conclusions:
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
Subglacial sediments have the potential to reveal information about the controls on glacier flow, changes in ice-sheet history and characterise life in those environments. Retrieving sediments from beneath the ice, through hot water drilled access holes at remote field locations, present many challenges. Motivated by the need to minimise weight, corer diameter and simplify assembly and operation, British Antarctic Survey, in collaboration with UWITEC, developed a simple mechanical percussion corer. At depths over 1000 m however, manual operation of the percussion hammer is compromised by the lack of clear operator feedback at the surface. To address this, we present a new auto-release-recovery percussion hammer mechanism that makes coring operations depth independent and improves hammer efficiency. Using a single rope tether for both the corer and hammer operation, this modified percussion corer is relatively simple to operate, easy to maintain, and has successfully operated at a depth of >2130 m.
Observing fetal development in utero is vital to further the understanding of later-life diseases. Magnetic resonance imaging (MRI) offers a tool for obtaining a wealth of information about fetal growth, development, and programming not previously available using other methods. This review provides an overview of MRI techniques used to investigate the metabolic and cardiovascular consequences of the developmental origins of health and disease (DOHaD) hypothesis. These methods add to the understanding of the developing fetus by examining fetal growth and organ development, adipose tissue and body composition, fetal oximetry, placental microstructure, diffusion, perfusion, flow, and metabolism. MRI assessment of fetal growth, organ development, metabolism, and the amount of fetal adipose tissue could give early indicators of abnormal fetal development. Noninvasive fetal oximetry can accurately measure placental and fetal oxygenation, which improves current knowledge on placental function. Additionally, measuring deficiencies in the placenta’s transport of nutrients and oxygen is critical for optimizing treatment. Overall, the detailed structural and functional information provided by MRI is valuable in guiding future investigations of DOHaD.
Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2–49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2–9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42–49 (95% confidence interval (CI) 52–92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06–1.50, P = 0.010).
The peoples of southern Mesoamerica, including the Classic period Maya, are often claimed to exhibit a distinct type of spatial organization relative to contemporary urban systems. Here, we use the settlement scaling framework and properties of settlements recorded in systematic, full-coverage surveys to examine ways in which southern Mesoamerican settlement systems were both similar to and different from contemporary systems. We find that the population-area relationship in these settlements differs greatly from that reported for other agrarian settlement systems, but that more typical patterns emerge when one considers a site epicenter as the relevant social interaction area, and the population administered from a given center as the relevant interacting population. Our results imply that southern Mesoamerican populations mixed socially at a slower temporal rhythm than is typical of contemporary systems. Residential locations reflected the need to balance energetic and transport costs of farming with lower-frequency costs of commuting to central places. Nevertheless, increasing returns in activities such as civic construction were still realized through lower-frequency social mixing. These findings suggest that the primary difference between low-density urbanism and contemporary urban systems lies in the spatial and temporal rhythms of social mixing.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Observational studies have found associations between smoking and both poorer cognitive ability and lower educational attainment; however, evaluating causality is challenging. We used two complementary methods to explore this.
Methods
We conducted observational analyses of up to 12 004 participants in a cohort study (Study One) and Mendelian randomisation (MR) analyses using summary and cohort data (Study Two). Outcome measures were cognitive ability at age 15 and educational attainment at age 16 (Study One), and educational attainment and fluid intelligence (Study Two).
Results
Study One: heaviness of smoking at age 15 was associated with lower cognitive ability at age 15 and lower educational attainment at age 16. Adjustment for potential confounders partially attenuated findings (e.g. fully adjusted cognitive ability β −0.736, 95% CI −1.238 to −0.233, p = 0.004; fully adjusted educational attainment β −1.254, 95% CI −1.597 to −0.911, p < 0.001). Study Two: MR indicated that both smoking initiation and lifetime smoking predict lower educational attainment (e.g. smoking initiation to educational attainment inverse-variance weighted MR β −0.197, 95% CI −0.223 to −0.171, p = 1.78 × 10−49). Educational attainment results were robust to sensitivity analyses, while analyses of general cognitive ability were less so.
Conclusion
We find some evidence of a causal effect of smoking on lower educational attainment, but not cognitive ability. Triangulation of evidence across observational and MR methods is a strength, but the genetic variants associated with smoking initiation may be pleiotropic, suggesting caution in interpreting these results. The nature of this pleiotropy warrants further study.
Background: Nosocomial central-line–associated bloodstream infections (CLABSIs) are an important cause of morbidity and mortality in hospitalized patients. CLABSI surveillance establishes rates for internal and external comparison, identifies risk factors, and allows assessment of interventions. Objectives: To determine the frequency of CLABSIs among adult patients admitted to intensive care units (ICUs) in CNISP hospitals and evaluate trends over time. Methods: CNISP is a collaborative effort of the Canadian Hospital Epidemiology Committee, the Association of Medical Microbiologists and Infectious Disease Canada and the Public Health Agency of Canada. Since 1995, CNISP has conducted hospital-based sentinel surveillance of healthcare-associated infections. Overall, 55 CNISP hospitals participated in ≥1 year of CLABSI surveillance. Adult ICUs are categorized as mixed ICUs or cardiovascular (CV) surgery ICUs. Data were collected using standardized definitions and collection forms. Line-day denominators for each participating ICU were collected. Negative-binomial regression was used to test for linear trends, with robust standard errors to account for clustering by hospital. We used the Fisher exact test to compare binary variables. Results: Each year, 28–42 adult ICUs participated in surveillance (27–37 mixed, 6–8 CV surgery). In both mixed ICUs and CV-ICUs, rates remained relatively stable between 2011 and 2018 (Fig. 1). In mixed ICUs, CLABSI rates were 1.0 per 1,000 line days in 2011, and 1.0 per 1,000 line days in 2018 (test for linear trend, P = .66). In CV-ICUs, CLABSI rates were 1.1 per 1,000 line days in 2011 and 0.8 per 1,000 line days in 2018 (P = .19). Case age and gender distributions were consistent across the surveillance period. The 30-day all-cause mortality rate was 29% in 2011 and in 2018 (annual range, 29%–35%). Between 2011 and 2018, the percentage of isolated microorganisms that were coagulase-negative staphylococci (CONS) decreased from 31% to 18% (P = .004). The percentage of other gram-positive organisms increased from 32% to 37% (P = .34); Bacillus increased from 0% to 4% of isolates and methicillin-susceptible Staphylococcus aureus from 2% to 6%). The gram-negative organisms increased from 21% to 27% (P = .19). Yeast represented 16% in 2011 and 18% in 2018; however, the percentage of yeast that were Candida albicans decreased over time (58% of yeast in 2011 and 30% in 2018; P = .04). Between 2011 and 2018, the most commonly identified species of microorganism in each year were CONS (18% in 2018) and Enterococcus spp (18% in 2018). Conclusions: Ongoing CLABSI surveillance has shown stable rates of CLABSI in adult ICUs from 2011 to 2018. The causative microorganisms have changed, with CONS decreasing from 31% to 18%.
Funding: CNISP is funded by the Public Health Agency of Canada.
Disclosures: Allison McGeer reports funds to her for studies, for which she is the principal investigator, from Pfizer and Merck, as well as consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.
Pollen-mediated gene flow (PMGF) refers to the transfer of genetic information (alleles) from one plant to another compatible plant. With the evolution of herbicide-resistant (HR) weeds, PMGF plays an important role in the transfer of resistance alleles from HR to susceptible weeds; however, little attention is given to this topic. The objective of this work was to review reproductive biology, PMGF studies, and interspecific hybridization, as well as potential for herbicide resistance alleles to transfer in the economically important broadleaf weeds including common lambsquarters, giant ragweed, horseweed, kochia, Palmer amaranth, and waterhemp. The PMGF studies involving these species reveal that transfer of herbicide resistance alleles routinely occurs under field conditions and is influenced by several factors, such as reproductive biology, environment, and production practices. Interspecific hybridization studies within Amaranthus and Ambrosia spp. show that herbicide resistance allele transfer is possible between species of the same genus but at relatively low levels. The widespread occurrence of HR weed populations and high genetic diversity is at least partly due to PMGF, particularly in dioecious species such as Palmer amaranth and waterhemp compared with monoecious species such as common lambsquarters and horseweed. Prolific pollen production in giant ragweed contributes to PMGF. Kochia, a wind-pollinated species can efficiently disseminate herbicide resistance alleles via both PMGF and tumbleweed seed dispersal, resulting in widespread occurrence of multiple HR kochia populations. The findings from this review verify that intra- and interspecific gene flow can occur and, even at a low rate, could contribute to the rapid spread of herbicide resistance alleles. More research is needed to determine the role of PMGF in transferring multiple herbicide resistance alleles at the landscape level.
A new high time resolution observing mode for the Murchison Widefield Array (MWA) is described, enabling full polarimetric observations with up to
$30.72\,$
MHz of bandwidth and a time resolution of
${\sim}$
$0.8\,\upmu$
s. This mode makes use of a polyphase synthesis filter to ‘undo’ the polyphase analysis filter stage of the standard MWA’s Voltage Capture System observing mode. Sources of potential error in the reconstruction of the high time resolution data are identified and quantified, with the
$S/N$
loss induced by the back-to-back system not exceeding
$-0.65\,$
dB for typical noise-dominated samples. The system is further verified by observing three pulsars with known structure on microsecond timescales.
Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for the disorder will contribute to uncovering its neurobiological underpinnings.
Aims
To examine the effect of rare copy number variants (CNVs) associated with schizophrenia on brain cortical anatomy in a sample of unaffected participants from the UK Biobank.
Method
We used regression analyses to compare cortical thickness and surface area (total and across gyri) between 120 unaffected carriers of rare CNVs associated with schizophrenia and 16 670 participants without any pathogenic CNV. A measure of cortical thickness and surface area covariance across gyri was also compared between groups.
Results
Carrier status was associated with reduced surface area (β = −0.020 mm2, P < 0.001) and less robustly with increased cortical thickness (β = 0.015 mm, P = 0.035), and with increased covariance in thickness (carriers z = 0.31 v. non-carriers z = 0.22, P < 0.0005). Associations were mainly present in frontal and parietal areas and driven by a limited number of rare risk alleles included in our analyses (mainly 15q11.2 deletion for surface area and 16p13.11 duplication for thickness covariance).
Conclusions
Results for surface area conformed with previous clinical findings, supporting surface area reductions as an indicator of genetic liability for schizophrenia. Results for cortical thickness, though, argued against its validity as a potential risk marker. Increased structural thickness covariance across gyri also appears related to risk for schizophrenia. The heterogeneity found across the effects of rare risk alleles suggests potential different neurobiological gateways into schizophrenia's phenotype.
Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes.
Method:
Over 200 participants (ages 9–13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes.
Results:
For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (β) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9–10, 11–13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9–10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001.
Conclusion:
These findings suggest that in the 9–10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.
While negative affect reliably predicts binge eating, it is unknown how this association may decrease or ‘de-couple’ during treatment for binge eating disorder (BED), whether such change is greater in treatments targeting emotion regulation, or how such change predicts outcome. This study utilized multi-wave ecological momentary assessment (EMA) to assess changes in the momentary association between negative affect and subsequent binge-eating symptoms during Integrative Cognitive Affective Therapy (ICAT-BED) and Cognitive Behavior Therapy Guided Self-Help (CBTgsh). It was predicted that there would be stronger de-coupling effects in ICAT-BED compared to CBTgsh given the focus on emotion regulation skills in ICAT-BED and that greater de-coupling would predict outcomes.
Methods
Adults with BED were randomized to ICAT-BED or CBTgsh and completed 1-week EMA protocols and the Eating Disorder Examination (EDE) at pre-treatment, end-of-treatment, and 6-month follow-up (final N = 78). De-coupling was operationalized as a change in momentary associations between negative affect and binge-eating symptoms from pre-treatment to end-of-treatment.
Results
There was a significant de-coupling effect at follow-up but not end-of-treatment, and de-coupling did not differ between ICAT-BED and CBTgsh. Less de-coupling was associated with higher end-of-treatment EDE global scores at end-of-treatment and higher binge frequency at follow-up.
Conclusions
Both ICAT-BED and CBTgsh were associated with de-coupling of momentary negative affect and binge-eating symptoms, which in turn relate to cognitive and behavioral treatment outcomes. Future research is warranted to identify differential mechanisms of change across ICAT-BED and CBTgsh. Results also highlight the importance of developing momentary interventions to more effectively de-couple negative affect and binge eating.
Clusters of Salmonella Enteritidis cases were identified by the Minnesota Department of Health using both pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) single nucleotide polymorphism analysis from 1 January 2015 through 31 December 2017. The median turnaround time for obtaining WGS results was 11 days longer than for PFGE (12 vs. 1 day). WGS analysis more than doubled the number of clusters compared to PFGE analysis, but reduced the total number of cases included in clusters by 34%. The median cluster size was two cases for WGS compared to four for PFGE, and the median duration of WGS clusters was 27 days shorter than PFGE clusters. While the percentage of PFGE clusters with a confirmed source (46%) was higher than WGS clusters (32%), a higher percentage of cases in clusters that were confirmed as outbreaks reported the vehicle or exposure of interest for WGS (78%) than PFGE (46%). WGS cluster size was a significant predictor of an outbreak source being confirmed. WGS data have enhanced S. Enteritidis cluster investigations in Minnesota by improving the specificity of cluster case definitions and has become an integral part of the S. Enteritidis surveillance process.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Raw milk cheeses are commonly consumed in France and are also a common source of foodborne outbreaks (FBOs). Both an FBO surveillance system and a laboratory-based surveillance system aim to detect Salmonella outbreaks. In early August 2018, five familial FBOs due to Salmonella spp. were reported to a regional health authority. Investigation identified common exposure to a raw goats' milk cheese, from which Salmonella spp. were also isolated, leading to an international product recall. Three weeks later, on 22 August, a national increase in Salmonella Newport ST118 was detected through laboratory surveillance. Concomitantly isolates from the earlier familial clusters were confirmed as S. Newport ST118. Interviews with a selection of the laboratory-identified cases revealed exposure to the same cheese, including exposure to batches not included in the previous recall, leading to an expansion of the recall. The outbreak affected 153 cases, including six cases in Scotland. S. Newport was detected in the cheese and in the milk of one of the producer's goats. The difference in the two alerts generated by this outbreak highlight the timeliness of the FBO system and the precision of the laboratory-based surveillance system. It is also a reminder of the risks associated with raw milk cheeses.