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It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Environmental impacts of food systems have stimulated research to examine how to create healthy diets that will be more sustainable while meeting nutrient requirements. Increasing compliance with existing food-based dietary guidelines in most jurisdictions could be a first step to improve health and reduce environmental impact. MyPlanetDiet was an all-Ireland 12-week randomised controlled trial designed to inform sustainable healthy dietary guidelines. Healthy adults (n 355) aged 18–64 years with moderate-to-high greenhouse gas emitting (GHGE) diets were recruited from three study sites on the island of Ireland. The aim of this research is to assess the relationship between dietary intakes, diet-related environmental impacts and metabolic health using baseline data collected during the MyPlanetDiet study. Dietary assessments collected using Foodbook24 were used to calculate diet-related GHGE, adherence to healthy eating guidelines (HEG) and healthy eating index (HEI) score. Anthropometrics and metabolic health markers (e.g. lipids, glucose and insulin) were included. Overall HEG adherence was low, with 43 % meeting zero or one HEG food group recommendations. Adherence to 4 + HEG food group targets was associated with 31 % lower diet-related GHGE compared with those with lowest adherence. Higher HEG adherence was associated with lower BMI and waist circumference and higher HEI scores. While our findings suggest HEG adherence is associated with positive health and environmental impacts, substantial behaviour change will be needed to meet existing HEG. Further research is needed to assess response and acceptability to HEG. However, adherence to HEG may be an important first step to reducing the environmental impact of food consumption.
“Improper linear models” (see Dawes, Am. Psychol. 34:571–582, 1979), such as equal weighting, have garnered interest as alternatives to standard regression models. We analyze the general circumstances under which these models perform well by recasting a class of “improper” linear models as “proper” statistical models with a single predictor. We derive the upper bound on the mean squared error of this estimator and demonstrate that it has less variance than ordinary least squares estimates. We examine common choices of the weighting vector used in the literature, e.g., single variable heuristics and equal weighting, and illustrate their performance in various test cases.
OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.
The Recognition Heuristic (Gigerenzer & Goldstein, 1996; Goldstein & Gigerenzer, 2002) makes the counter-intuitive prediction that a decision maker utilizing less information may do as well as, or outperform, an idealized decision maker utilizing more information. We lay a theoretical foundation for the use of single-variable heuristics such as the Recognition Heuristic as an optimal decision strategy within a linear modeling framework. We identify conditions under which over-weighting a single predictor is a mini-max strategy among a class of a priori chosen weights based on decision heuristics with respect to a measure of statistical lack of fit we call “risk”. These strategies, in turn, outperform standard multiple regression as long as the amount of data available is limited. We also show that, under related conditions, weighting only one variable and ignoring all others produces the same risk as ignoring the single variable and weighting all others. This approach has the advantage of generalizing beyond the original environment of the Recognition Heuristic to situations with more than two choice options, binary or continuous representations of recognition, and to other single variable heuristics. We analyze the structure of data used in some prior recognition tasks and find that it matches the sufficient conditions for optimality in our results. Rather than being a poor or adequate substitute for a compensatory model, the Recognition Heuristic closely approximates an optimal strategy when a decision maker has finite data about the world.
To assess the impact of the coronavirus disease 2019 pandemic on head and neck urgent suspected cancer referral pathways in rural areas of Wales.
Method
A retrospective audit was conducted of 2234 head and neck urgent suspected cancer referrals received from January 2019 to November 2020.
Results
The referrals dropped by 35 per cent in 2020 compared to the same period in 2019. The time from general practitioner referral to the first ENT appointment improved during the pandemic (8.0 vs 10.0 days; p < 0.001). Of referrals, 92.1 per cent were seen within a 14-day period in 2020, compared with 79.6 per cent in 2019 (p < 0.001). There were no differences between 2020 and 2019 in terms of: the (confirmed cancer) conversion rate (10.6 per cent vs 9.7 per cent; p = 0.60), general practitioner referral to multidisciplinary team discussion time (35.5 vs 41.5 days; p = 0.40) or general practitioner referral to initiation of treatment time (68.0 vs 78.0 days; p = 0.16).
Conclusion
Whilst coronavirus disease 2019 reduced the number of overall head and neck urgent suspected cancer referrals, the pathways were generally unchanged, if not slightly improved, in rural Wales.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
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.
Methods:
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:
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.
Conclusions:
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.
We present a detailed analysis of the radio galaxy PKS $2250{-}351$, a giant of 1.2 Mpc projected size, its host galaxy, and its environment. We use radio data from the Murchison Widefield Array, the upgraded Giant Metre-wavelength Radio Telescope, the Australian Square Kilometre Array Pathfinder, and the Australia Telescope Compact Array to model the jet power and age. Optical and IR data come from the Galaxy And Mass Assembly (GAMA) survey and provide information on the host galaxy and environment. GAMA spectroscopy confirms that PKS $2250{-}351$ lies at $z=0.2115$ in the irregular, and likely unrelaxed, cluster Abell 3936. We find its host is a massive, ‘red and dead’ elliptical galaxy with negligible star formation but with a highly obscured active galactic nucleus dominating the mid-IR emission. Assuming it lies on the local M–$\sigma$ relation, it has an Eddington accretion rate of $\lambda_{\rm EDD}\sim 0.014$. We find that the lobe-derived jet power (a time-averaged measure) is an order of magnitude greater than the hotspot-derived jet power (an instantaneous measure). We propose that over the lifetime of the observed radio emission (${\sim} 300\,$Myr), the accretion has switched from an inefficient advection-dominated mode to a thin disc efficient mode, consistent with the decrease in jet power. We also suggest that the asymmetric radio morphology is due to its environment, with the host of PKS $2250{-}351$ lying to the west of the densest concentration of galaxies in Abell 3936.
The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown.
Methods
Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics.
Results
A total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR = 4.825) of developing psychotic disorders, and a reduced risk (HR = 0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P < 0.001).
Conclusions
In the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes.
Significant outcomes
In the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup.
Limitations
While incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.
To document patient characteristics and treatment patterns in a real-world population diagnosed with attention-deficit/hyperactivity disorder (ADHD).
Methods
This was a retrospective chart review of children/adolescents (6–17 years) diagnosed with ADHD in the UK, Germany and Netherlands who initiated stimulant monotherapy (SM), non-stimulant (atomoxetine) monotherapy (NSM) or polypharmacy (SM/NSM ± SM/NSM or other psychotropics) on/after 1-1-2012. To facilitate descriptive comparisons, cohort quotas were imposed: ∼50% SM; ∼25% NSM; ∼25% polypharmacy. Index date was first SM, NSM or polypharmacy treatment on/after 1-1-2012. Patients were required to have ≥ 6 months’ pre-index (baseline) history and ≥ 12 months’ post-index follow-up. Analyses were descriptive.
Results
In total, 497 patients were included (mean [SD] age: 10.8 [2.9] years; 77% male); 65% (SM), 63% (NSM) and 83% (polypharmacy) had at least marked baseline ADHD severity based on Clinical Global Impressions scale (P < 0.05 SM/NSM vs polypharmacy). Ninety percent (SM), 75% (NSM) and 73% (polypharmacy) were pharmacotherapy naïve at index (all P < 0.10); 61% (SM), 65% (NSM) and 72% (polypharmacy) received previous behavioural therapy. In SM patients, methylphenidate was predominant (most frequent brands: Concerta® [29%], Medikinet® [28%]); in polypharmacy patients, methylphenidate plus atomoxetine (22%) or other psychotropic (19%) was most common. Index therapy switch was common, particularly in polypharmacy patients (25%) (P < 0.05 vs SM [14%] and NSM [13%]). Switches were precipitated by poor response in 75% of cases overall.
Conclusions
Polypharmacy patients generally presented a more complicated history (including higher ADHD severity) and treatment pathway versus monotherapy patients. Index therapy switches were commonplace and more frequent in polypharmacy patients, often due to poor response.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
Salmonella prevalence in UK pigs is amongst the highest in Europe, highlighting the need to investigate pig farms which have managed to maintain a low Salmonella seroprevalence. A total of 19 pig farms that had a consistently low (<10%) seroprevalence over 4 years (named Platinum farms) were compared against 38 randomly selected Control farms, chosen to match the same distribution of production types and geographical distribution of the Platinum farms. Each farm was visited and floor faeces and environmental samples were collected. It was shown that Control farms had a significantly higher median percentage of pooled faecal samples positive for Salmonella compared with the Platinum farms (12.1% and 0.4% for pooled faecal samples, respectively) and were more likely to have serovars of public health importance detected (S. Typhimurium/ monophasic variants or S. Enteritidis). Considering the comprehensive on-farm sampling, the identification of farms negative for Salmonella, along with the identification of those that had maintained low prevalence over a long period is important. The risk factor analyses identified pelleted feed, feed deliveries crossing farm perimeter and regular antibiotic use as associated with being a Control farm. Performance data indicated that Platinum farms were performing better for slaughter live weight than Controls. Limited assessments of available pig movement records suggested that the source of pigs was not key to Platinum status, but further study would be needed to confirm this finding. These results emphasise that maintaining very low prevalence on UK farms is achievable.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
Hypothesis
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
Methods
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Results
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Conclusions
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
Ortles mountain (3905 m a.s.l.), South Tyrol, Italy, is the highest mountain of the Eastern European Alps, and its upper glacier, Alto dell’Ortles, presents a unique opportunity to obtain the first paleoenvironmental record from an ice core in this area. To study the suitability of this glacier as a drilling site, in 2009 we performed the first preliminary study of its glaciological characteristics at ˜3830 m a.s.l. The maximum thickness is ˜75 m, and lamination of the exposed ice layers is excellent down to bedrock. Firn and ice lenses were observed in a 10 m shallow core, and the firn/ice transition was below ˜24m. The seasonal chemical signal is clearly preserved only within the uppermost 2008 and 2009 snow/firn. A simple mass-balance model, the incipient ‘smoothing’ of the chemical record, and the observed ice lenses provide evidence that melting, infiltration and refreezing cycles occurred within the firn layers formed before 2008. Nevertheless, the mass balance of the upper part of Alto dell’Ortles was positive (˜800mma_1) during the last few years. We suggest that an environmental history is likely to be well preserved only within the ice layers formed before ˜1980, when summer air temperature was ˜2°C colder than today in this area. Clearly the continued warming trend predicted to occur over the next few decades, and the consequent increase in frequency and/or intensity of infiltration processes, will endanger the preservation of the glacial archive conserved in the deep ice layers of Ortles mountain.
Anecdotal evidence has suggested that outdoor-kept pigs show an improvement to health and productivity after being moved to a new site. This study explores whether Salmonella occurrence reduced and was sustained after moving to a new site. Nine farms were followed for a year in which four sampling visits were completed. The highest detection of Salmonella was from pooled faecal dropping from pigs, run-off/ pooled water, rodents and wild birds. Descriptive summaries showed that the prevalence of both all Salmonella and serovars of public health importance were lower at all visits after the move. Some variability was shown in results from individual farms, but a year after the move, six farms still maintained a lower prevalence. A risk factor model showed that the prevalence at visits 2 and 3 after the move was significantly lower than baseline, after accounting for a number of significant factors that were included in the model. These were sample type and seasonality (included as a priori), presence of coughing in the sampled group and Glasser's disease on the farm, and the use of tent or kennel accommodation. This finding provides important evidence that more frequent site moves may help reduce Salmonella prevalence in outdoor herds.