To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders.
We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures.
Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes −1.39 to −2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia.
This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups.
To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.
Pilot prospective multicenter surveillance study.
The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.
All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.
In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.
Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).
Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Hydrogen lithography has been used to template phosphine-based surface chemistry to fabricate atomic-scale devices, a process we abbreviate as atomic precision advanced manufacturing (APAM). Here, we use mid-infrared variable angle spectroscopic ellipsometry (IR-VASE) to characterize single-nanometer thickness phosphorus dopant layers (δ-layers) in silicon made using APAM compatible processes. A large Drude response is directly attributable to the δ-layer and can be used for nondestructive monitoring of the condition of the APAM layer when integrating additional processing steps. The carrier density and mobility extracted from our room temperature IR-VASE measurements are consistent with cryogenic magneto-transport measurements, showing that APAM δ-layers function at room temperature. Finally, the permittivity extracted from these measurements shows that the doping in the APAM δ-layers is so large that their low-frequency in-plane response is reminiscent of a silicide. However, there is no indication of a plasma resonance, likely due to reduced dimensionality and/or low scattering lifetime.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.
The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
Major depression is a significant problem for people with a traumatic brain injury (TBI) and its treatment remains difficult. A promising approach to treat depression is Mindfulness-based cognitive therapy (MBCT), a relatively new therapeutic approach rooted in mindfulness based stress-reduction (MBSR) and cognitive behavioral therapy (CBT). We conducted this study to examine the effectiveness of MBCT in reducing depression symptoms among people who have a TBI.
Twenty individuals diagnosed with major depression were recruited from a rehabilitation clinic and completed the 8-week MBCT intervention. Instruments used to measure depression symptoms included: BDI-II, PHQ-9, HADS, SF-36 (Mental Health subscale), and SCL-90 (Depression subscale). They were completed at baseline and post-intervention.
All instruments indicated a statistically significant reduction in depression symptoms post-intervention (p < .05). For example, the total mean score on the BDI-II decreased from 25.2 (9.8) at baseline to 18.2 (11.7) post-intervention (p=.001). Using a PHQ threshold of 10, the proportion of participants with a diagnosis of major depression was reduced by 59% at follow-up (p=.012).
Most participants reported reductions in depression symptoms after the intervention such that many would not meet the criteria for a diagnosis of major depression. This intervention may provide an opportunity to address a debilitating aspect of TBI and could be implemented concurrently with more traditional forms of treatment, possibly enhancing their success. The next step will involve the execution of multi-site, randomized controlled trials to fully demonstrate the value of the intervention.
Traumatic brain injuries (TBI) may lead to persistent depression symptoms. We conducted several pilot studies to examine the efficacy of mindfulness-based interventions to deal with this issue; all showed strong effect sizes. The logical next step was to conduct a randomized controlled trial (RCT).
We sought to determine the efficacy of mindfulness-based cognitive therapy for people with depression symptoms post-TBI (MBCT-TBI).
Using a multi-site RCT design, participants (mean age = 47) were randomized to intervention or control arms. Treatment participants received a group-based, 10-week intervention; control participants waited. Outcome measures, administered pre- and post-intervention, and after three months, included: Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire-9 (PHQ-9), and Symptom Checklist-90-Revised (SCL-90-R). The Philadelphia Mindfulness Scale (PHLMS) captured present moment awareness and acceptance.
BDI-II scores decreased from 25.47 to 18.84 in treatment groups while they stayed relatively stable in control groups (respectively 27.13 to 25.00; p = .029). We did not find statistically significant differences on the PHQ-9 and SCL-90R post- treatment. However, after three months, all scores were statistically significantly lower than at baseline (ps < .01). Increases in mindfulness were associated with decreases in BDI-II scores (r = -.401, p = .025).
MBCT-TBI may alleviate depression symptoms up to three months post-intervention. Greater mindfulness may have contributed to the reduction in depression symptoms although the association does not confirm causality. More work is required to replicate these findings, identify subgroups that may better respond to the intervention, and refine the intervention to maximize its effectiveness.
Given the common view that pre-exercise nutrition/breakfast is important for performance, the present study investigated whether breakfast influences resistance exercise performance via a physiological or psychological effect. Twenty-two resistance-trained, breakfast-consuming men completed three experimental trials, consuming water-only (WAT), or semi-solid breakfasts containing 0 g/kg (PLA) or 1·5 g/kg (CHO) maltodextrin. PLA and CHO meals contained xanthan gum and low-energy flavouring (approximately 122 kJ), and subjects were told both ‘contained energy’. At 2 h post-meal, subjects completed four sets of back squat and bench press to failure at 90 % ten repetition maximum. Blood samples were taken pre-meal, 45 min and 105 min post-meal to measure serum/plasma glucose, insulin, ghrelin, glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations. Subjective hunger/fullness was also measured. Total back squat repetitions were greater in CHO (44 (sd 10) repetitions) and PLA (43 (sd 10) repetitions) than WAT (38 (sd 10) repetitions; P < 0·001). Total bench press repetitions were similar between trials (WAT 37 (sd 7) repetitions; CHO 39 (sd 7) repetitions; PLA 38 (sd 7) repetitions; P = 0·130). Performance was similar between CHO and PLA trials. Hunger was suppressed and fullness increased similarly in PLA and CHO, relative to WAT (P < 0·001). During CHO, plasma glucose was elevated at 45 min (P < 0·05), whilst serum insulin was elevated (P < 0·05) and plasma ghrelin suppressed at 45 and 105 min (P < 0·05). These results suggest that breakfast/pre-exercise nutrition enhances resistance exercise performance via a psychological effect, although a potential mediating role of hunger cannot be discounted.
Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion.
From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP.
All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible.
No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens.
Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.
A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with indistinguishable pulsed-field gel electrophoresis patterns was detected in October 2015. Interviews initially identified nut butters, kale, kombucha, chia seeds and nutrition bars as common exposures. Epidemiologic, environmental and traceback investigations were conducted. Thirteen ill people infected with the outbreak strain were identified in 10 states with illness onset during 18 July–22 November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted seeds have all caused outbreaks previously. Firms producing raw sprouted products, including nut butters, should consider a kill step to reduce the risk of contamination. People at greater risk for foodborne illness may wish to consider avoiding raw products containing raw sprouted ingredients.
The effect of transportation and lairage on the faecal shedding and post-slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4–7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non-STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal–oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves.
Introduction: The ECG diagnosis of acute coronary occlusion (ACO) in the setting of ventricular paced rhythm (VPR) is purported to be impossible. However, VPR has a similar ECG morphology to LBBB. The validated Smith-modified Sgarbossa criteria (MSC) have high sensitivity (Sens) and specificity (Spec) for ACO in LBBB. MSC consist of 1 of the following in 1 lead: concordant ST Elevation (STE) 1 mm, concordant ST depression 1 mm in V1-V3, or ST/S ratio <−0.25 (in leads with 1 mm STE). We hypothesized that the MSC will have higher Sens for diagnosis of ACO in VPR when compared to the original Sgarbossa criteria. We report preliminary findings of the Paced Electrocardiogram Requiring Fast Emergency Coronary Therapy (PERFECT) study Methods: The PERFECT study is a retrospective, multicenter, international investigation of ED patients from 1/2008 - 12/2016 with VPR on the ECG and symptoms suggestive of acute coronary syndrome (e.g. chest pain or shortness of breath). Data from four sites are presented. Acute myocardial infarction (AMI) was defined by the Third Universal Definition of AMI. A blinded cardiologist adjudicated ACO, defined as thrombolysis in myocardial infarction score 0 or 1 on coronary angiography; a pre-defined subgroup of ACO patients with peak cardiac troponin (cTn) >100 times the 99% upper reference limit (URL) of the cTn assay was also analyzed. Another blinded physician measured all ECGs. Statistics were by Mann Whitney U, Chi-square, and McNemars test. Results: The ACO and No-AMI groups consisted of 15 and 79 encounters, respectively. For the ACO and No-AMI groups, median age was 78 [IQR 72-82] vs. 70 [61-75] and 13 (86%) vs. 48 (61%) patients were male. The median peak cTn ratio (cTn/URL) was 260 [33-663] and 0.5 [0-1.3] for ACO vs. no-AMI. The Sens and Spec for the MSC and the original Sgarbossa criteria were 67% (95%CI 39-87) vs. 46% (22-72; p=0.25) and 99% (92-100) vs. 99% (92-100; p=0.5). In pre-defined subgroup analysis of ACO patients with peak cTn >100 times the URL (n=10), the Sens was 90% (54-100) for the MSC vs. 60% (27- 86) for original Sgarbossa criteria (p=0.25). Conclusion: ACO in VPR is an uncommon condition. The MSC showed good Sens for diagnosis of ACO in the presence of VPR, especially among patients with high peak cTn, and Spec was excellent. These methods and results are consistent with studies that have used the MSC to diagnose ACO in LBBB.
Effective methods to increase awareness of preventable infectious diseases are key components of successful control programmes. Rabies is an example of a disease with significant impact, where public awareness is variable. A recent awareness campaign in a rabies endemic region of Azerbaijan provided a unique opportunity to assess the efficacy of such campaigns. A cluster cross-sectional survey concerning rabies was undertaken following the awareness campaign in 600 households in 38 randomly selected towns, in districts covered by the campaign and matched control regions. This survey demonstrated that the relatively simple awareness campaign was effective at improving knowledge of rabies symptoms and vaccination schedules. Crucially, those in the awareness campaign group were also 1·4 times more likely to report that they had vaccinated their pets, an essential component of human rabies prevention. In addition, low knowledge of appropriate post-exposure treatment and animal sources of rabies provide information useful for future public awareness campaigns in the region and other similar areas.
On 27 April 2015, Washington health authorities identified Escherichia coli O157:H7 infections associated with dairy education school field trips held in a barn 20–24 April. Investigation objectives were to determine the magnitude of the outbreak, identify the source of infection, prevent secondary illness transmission and develop recommendations to prevent future outbreaks. Case-finding, hypothesis generating interviews, environmental site visits and a case–control study were conducted. Parents and children were interviewed regarding event activities. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Environmental testing was conducted in the barn; isolates were compared to patient isolates using pulsed-field gel electrophoresis (PFGE). Sixty people were ill, 11 (18%) were hospitalised and six (10%) developed haemolytic uremic syndrome. Ill people ranged in age from <1 year to 47 years (median: 7), and 20 (33%) were female. Twenty-seven case-patients and 88 controls were enrolled in the case–control study. Among first-grade students, handwashing (i.e. soap and water, or hand sanitiser) before lunch was protective (adjusted OR 0.13; 95% CI 0.02–0.88, P = 0.04). Barn samples yielded E. coli O157:H7 with PFGE patterns indistinguishable from patient isolates. This investigation provided epidemiological, laboratory and environmental evidence for a large outbreak of E. coli O157:H7 infections from exposure to a contaminated barn. The investigation highlights the often overlooked risk of infection through exposure to animal environments as well as the importance of handwashing for disease prevention. Increased education and encouragement of infection prevention measures, such as handwashing, can prevent illness.