Developing and validating a comprehensive measure of coordination in patient aligned care teams.

BACKGROUND/OBJECTIVE: Despite numerous extant measures assessing context-specific elements of care coordination, we are unaware of any comprehensive, team-based instrument that measures the requisite mechanisms and conditions required to coordinate successfully. In this study we develop and validate the psychometric properties of the Coordination Practices Survey, a context-agnostic measure of coordination for primary care teams. METHODS: Coordination items were developed based on a systematic literature review; items from previously developed scales were adapted and new items were created as needed; all items were refined after subject matter expert review and feedback. We collected data from Primary Care teams drawn from 1200 Veterans Health Administration (VHA) medical centers and outpatient clinics nationwide. 1645 primary care team members from 512 patient aligned care teams in the Veterans Health Administration completed the survey from 2015 to 2016. Psychometric properties were assessed after data collection using Cronbach's alpha, intraclass correlations and multilevel confirmatory factor analysis to assess the factor structure. RESULTS: Our findings confirmed the psychometric properties of two distinguishable subscales of coordination: (a) Accountability and (b) Common Understanding. The within- and between-team latent structure of each subscale exhibited adequate fit to the data, as well as appropriately high Cronbach's alpha and intraclass correlations. There was insufficient variability in responses to the predictability subscale to properly assess its psychometric properties. CONCLUSION: With context-specific validation, our subscales of accountability and common understanding may be used to assess coordination processes in other contexts for both research and operational applications.

Food insecurity: Comparing odds between working-age veterans and nonveterans with children.

BACKGROUND: Low-income, working-age Veterans with children have risk for food insecurity. Less known is extent to which their risk compares to nonveterans. PURPOSE: To evaluate odds of food insecurity for working-age Veterans with children compared to socioeconomically-matched nonveterans with children. METHOD: We constructed a propensity score-matched cohort using 2011-2014 National Health and Nutrition Examination Survey data. Covariate-adjusted logistic regressions estimated Veterans' odds for overall food insecurity and for each level of severity compared to nonveterans. FINDINGS: We matched 155 Veterans to 310 nonveterans on gender, race/ethnicity, education, income. Models were adjusted for age, marital-status, depression, and listed matched variables. Although Veteran-status had no effect on overall food insecurity (odds ratio = 1.09, 95% confidence interval [0.62,1.93]), Veteran-status increased odds for very low food security (odds ratio = 2.71, 95% confidence interval [1.21, 6.07]). DISCUSSION: Veterans do not have higher odds of food insecurity than non-veterans, but they are more likely to have the more severe very low food security (often associated with hunger) than non-veterans. Investigation of food insecurity's impact on Veteran health/well-being is needed.

Creutzfeldt-Jakob disease and blood transfusion safety.

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case-control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.

What can we learn from COVID-19?: examining the resilience of primary care teams.

Introduction: The COVID-19 pandemic continues to place an unprecedented strain on the US healthcare system, and primary care is no exception. Primary care services have shifted toward a team-based approach for delivering care in the last decade. COVID-19 placed extraordinary stress on primary care teams at the forefront of the pandemic response efforts. The current work applies the science of effective teams to examine the impact of COVID-19-a crisis or adverse event-on primary care team resilience. Methods: Little empirical research has been done testing the theory of team resilience during an extremely adverse crisis event in an applied team setting. Therefore, we conducted an archival study by using large-scale national data from the Veterans Health Administration to understand the characteristics and performance of 7,023 Patient Aligned Care Teams (PACTs) during COVID-19. Results: Our study found that primary care teams maintained performance in the presence of adversity, indicating possible team resilience. Further, team coordination positively predicted team performance (B = 0.53) regardless of the level of adversity a team was experiencing. Discussion: These findings in turn attest to the need to preserve team coordination in the presence of adversity. Results carry implications for creating opportunities for teams to learn and adjust to an adverse event to maintain performance and optimize team-member well-being. Teamwork can act as a protective factor against high levels of workload, burnout, and turnover, and should be studied further for its role in promoting team resilience.

The impact of multidisciplinary team decision-making in locally advanced and recurrent rectal cancer.

INTRODUCTION: Appropriate patient selection within the context of a multidisciplinary team (MDT) is key to good clinical outcomes. The current evidence base for factors that guide the decision-making process in locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) is limited to anatomical factors. METHODS: A registry-based, prospective cohort study was undertaken of patients referred to our specialist MDT between 2015 and 2019. Data were collected on patients and disease characteristics including performance status, Charlson Comorbidity Index, the English Index of Multiple Deprivation quintiles and MDT treatment decision. Curative treatment was defined as neoadjuvant treatment and surgical resection that would achieve a R0 resection, and/or complete treatment of distant metastatic disease. Palliative treatment was defined as non-surgical treatment. RESULTS: In total, 325 patients were identified; 72.7% of patients with LARC and 63.6% of patients with LRRC were offered treatment with curative intent (p = 0.08). Patients with poor performance status (PS > 2; p < 0.001), severe comorbidity (p < 0.001), socio-economic deprivation (p = 0.004), a positive predictive circumferential resection margin (p = 0.005) and metastatic disease (p < 0.001) were associated with palliative treatment. Overall survival in the curative cohort was 49 months (95% confidence interval [CI] 32.4-65.5) compared with 12 months (95% CI 9.1-14.9) in the palliative cohort (p < 0.001). The presence of metastatic disease was identified as a prognostic factor for patients undergoing curative treatment (p = 0.05). The only prognostic factor identified in patients treated palliatively was performance status (p < 0.001). CONCLUSIONS: Our study identifies a number of preoperative, prognostic factors that affect MDT decision-making and overall survival.

An evidence-based, structured, expert approach to selecting essential indicators of primary care quality.

BACKGROUND: The purpose of this article is to illustrate the application of an evidence-based, structured performance measurement methodology to identify, prioritize, and (when appropriate) generate new measures of health care quality, using primary care as a case example. Primary health care is central to the health care system and health of the American public; thus, ensuring high quality is essential. Due to its complexity, ensuring high-quality primary care requires measurement frameworks that can assess the quality of the infrastructure, workforce configurations, and processes available. This paper describes the use of the Productivity Measurement and Enhancement System (ProMES) to compile a targeted set of such measures, prioritized according to their contribution and value to primary care. METHODS: We adapted ProMES to select and rank existing primary care measures according to value to the primary care clinic. Nine subject matter experts (SMEs) consisting of clinicians, hospital leaders and national policymakers participated in facilitated expert elicitation sessions to identify objectives of performance, corresponding measures, and priority rankings. RESULTS: The SMEs identified three fundamental objectives: access, patient-health care team partnerships, and technical quality. The SMEs also selected sixteen performance indicators from the 44 pre-vetted, currently existing measures from three different data sources for primary care. One indicator, Team 2-Day Post Discharge Contact Ratio, was selected as an indicator of both team partnerships and technical quality. Indicators were prioritized according to value using the contingency functions developed by the SMEs. CONCLUSION: Our article provides an actionable guide to applying ProMES, which can be adapted to the needs of various industries, including measure selection and modification from existing data sources, and proposing new measures. Future work should address both logistical considerations (e.g., data capture, common data/programming language) and lingering measurement challenges, such as operationalizating measures to be meaningful and interpretable across health care settings.

Maxillary anterior tooth dimensions and proportions in an Irish young adult population.

This study was undertaken in a young Irish population to determine the dimensions and ratios of the six maxillary anterior teeth. One hundred and nine Irish subjects (age 18-25 inclusive) had irreversible hydrocolloid impressions made of their maxillary dentition poured in type V stone. Clinical crown dimensions were measured with a digital calliper. The stone casts were digitally photographed in a standardised manner enabling calculation of various ratios between the maxillary anterior teeth. Sexual dimorphism existed for various tooth dimensions; most notably canine teeth were in the region of 0·8 mm longer and 0·6 mm wider in males. Central and lateral incisors were found to be 0·5 mm wider in males. It is, therefore, recommended that dimensional tooth guidelines should be given for each of the sexes and not on a population basis. With regard to tooth proportion ratios, no significant differences were found between genders or the left and right sides for any of the measurements or ratios measured. The digitally recorded tooth proportions were similar for both sexes, and the Golden Proportion guidelines could only be applied to the lateral incisor/central incisor widths (0·618). Identified width proportions for the canine/central incisor were 0·58 and for canine/lateral incisor 0·89.

Scrapie infection and endogenous retroviral expression in sheep lymphoid tissues.

Transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative diseases affecting humans and animals. Although many host tissues express PrPC (essential for prion replication), relatively few cell types accumulate significant levels of infectivity, including neurons and other cell types in the nervous system, and follicular dendritic cells in secondary lymphoid organs. This suggests that tissue or cell-specific receptors or cofactors could play a role in controlling differential susceptibility to infection. Endogenous retroviruses (ERV), the remnants of ancient retroviral integration into the host germline, may represent one such cofactor. We examined the effect of scrapie infection on expression of three ovine ERV families (enJSRV/ß1-OERV, γ1-OERV, γ2-OERV) in secondary lymphoid tissues of sheep at different time points following subcutaneous inoculation, using RT-qPCR. These OERVs were constitutively expressed in the prescapular lymph node and spleen of uninfected sheep. However, we were unable to find convincing evidence of specific differential expression of OERV in the same tissues following scrapie infection, in contrast to previous studies of ERV expression in brains of prion-infected mice and macaques. This study is the first to quantify the expression of potentially functional OERV transcripts in sheep lymphoid tissues, opening up interesting questions about the consequences for host immune function.

Improving team coordination in primary-care settings via multifaceted team-based feedback: a non-randomised controlled trial study.

BACKGROUND: Coordination is critical to successful team-based health care. Most clinicians, however, are not trained in effective coordination or teamwork. Audit and feedback (A&F) could improve team coordination, if designed with teams in mind. AIM: The effectiveness of a multifaceted, A&F-plus-debrief intervention was tested to establish whether it improved coordination in primary care teams compared with controls. DESIGN & SETTING: Case-control trial within US Veterans Health Administration medical centres. METHOD: Thirty-four primary care teams selected from four geographically distinct hospitals were compared with 34 administratively matched control teams. Intervention-arm teams received monthly A&F reports about key coordination behaviours and structured debriefings over 7 months. Control teams were followed exclusively via their clinical records. Outcome measures included a coordination composite and its component indicators (appointments starting on time, timely recall scheduling, emergency department utilisation, and electronic patient portal enrolment). Predictors included intervention arm, extent of exposure to intervention, and degree of multiple team membership (MTM). RESULTS: Intervention teams did not significantly improve over control teams, even after adjusting for MTM. Follow-up analyses indicated cross-team variability in intervention fidelity; although all intervention teams received feedback reports, not all teams attended all debriefings. Compared with their respective baselines, teams with high debriefing exposure improved significantly. Teams with high debriefing exposure improved significantly more than teams with low exposure. Low exposure teams significantly increased patient portal enrolment. CONCLUSION: Team-based A&F, including adequate reflection time, can improve coordination; however, the effect is dose dependent. Consistency of debriefing appears more critical than proportion of team members attending a debriefing for ensuring implementation fidelity and effectiveness.

Use of a preclinical test in the control of classical scrapie.

Scrapie control in Great Britain (GB) was originally based on the National Scrapie Plan's Ram Genotyping scheme aimed at reducing the susceptibility of the national flock. The current official strategy to control scrapie in the national flock involves culling susceptible genotypes in individual, known affected flocks (compulsory scrapie flock scheme or CSFS). However, the recent development of preclinical test candidates means that a strategy based on disease detection may now be feasible. Here, a deterministic within-flock model was used to demonstrate that only large flocks with many home-bred ewes are likely to be a significant risk for flock-to-flock transmission of scrapie. For most other flocks, it was found that the CSFS could be replaced by a strategy using a currently available live test without excessive risk to other farmers, even if the proportion of susceptible genotypes in the flock is unusually large. Even for flocks that represent a high risk of harbouring a high prevalence of infection, there would be limited probability of onward transmission if scrapie is detected soon after disease introduction (typically less than 5 years). However, if detection of disease is delayed, the existing CSFS strategy may be the most appropriate control measure in these cases.

Pathogenetical significance of porencephalic lesions associated with intracerebral inoculation of sheep with the bovine spongiform encephalopathy (BSE) agent.

UNLABELLED: Decreased rates of transmission of transmissible spongiform encephalopathies (TSEs) to sheep have been attributed to some polymorphisms of the prion protein (PrP) and to a 'species barrier' on interspecies experiments. In addition, the blood-brain barrier may be a further impediment to TSE neuroinvasion. The intracerebral (I/C) route is generally considered the most efficient for TSE transmission, as it may help to bypass those factors. Therefore, susceptibility of particular species to specific TSE agents is conducted by this route. AIMS: This study characterizes the traumatic brain lesions associated with the I/C injection of the bovine spongiform encephalopathy agent in sheep, assesses the relevance of such lesions in the outcome of clinical disease and provides insight into the mechanisms of PrP(d) conversion and amplification following I/C challenge. METHODS: A total of 27 hemibrains have been macroscopically and immunohistochemically examined to investigate the presence of lesions compatible with the needle track and the PrP(d) distribution, respectively. RESULTS: No residual inoculum was found and the extension and severity of the traumatic brain lesions were unrelated to the clinical outcome. Sheep with PrP(d) accumulation in the brain also showed conspicuous focal aggregates in the porencephalic lesions and in the circumventricular organs. In contrast, sheep without PrP(d) deposits in the brain were also negative in the traumatic lesions. CONCLUSION: Overall, these findings suggest that the efficiency of the I/C route is due to effective absorption and blood recirculation of infection, rather than to primary amplification at the site of injection.

Patient satisfaction relating to implant treatment by undergraduate and postgraduate dental students--a pilot study.

Recordings of patient satisfaction with provision of dental implant treatment are scarce. This study aimed to evaluate satisfaction amongst patients attending for provision of implant treatment by training undergraduate and postgraduate students at Dublin Dental School and Hospital (DDSH). A questionnaire was formulated and distributed to 100 individuals randomly selected from records of patients who had received implant treatment via student clinics in the previous 5 years. The response rate was 68%. Results showed a high overall level of satisfaction with treatment received.

Impact of team configuration and team stability on primary care quality.

BACKGROUND: The science of effective teams is well documented; far less is known, however, about how specific team configurations may impact primary care team effectiveness. Further, teams experiencing frequent personnel changes (perhaps as a consequence of poor implementation) may have difficulty delivering effective, continuous, well-coordinated care. This study aims to examine the extent to which primary care clinics in the Veterans Health Administration have implemented team configurations consistent with recommendations based on the Patient-Centered Medical Home model and the extent to which adherence to said recommendations, team stability, and role stability impact healthcare quality. Specifically, we expect to find better clinical outcomes in teams that adhere to recommended team configurations, teams whose membership and configuration are more stable over time, and teams whose clinical manager role is more stable over time. METHODS/DESIGN: We will employ a combination of social network analysis and multilevel modeling to conduct a database review of variables extracted from the Veterans Health Administration's Team Assignments Report (TAR) (one of the largest, most diverse existing national samples of primary care teams (nteams > 7000)), as well as other employee and clinical data sources. To ensure the examination of appropriate clinical outcomes, we will enlist a team of subject matter experts to select a concise set of clear, prioritized primary care performance metrics. We will accomplish this using the Productivity Measurement and Enhancement System, an evidence-based methodology for developing and implementing performance measurement. DISCUSSION: We are unaware of other studies of healthcare teams that consider team size, composition, and configuration longitudinally or with sample sizes of this magnitude. Results from this study can inform primary care team implementation policy and practice in both private- and public-sector clinics, such that teams are configured optimally, with adequate staffing, and the right mix of roles within the team. TRIAL REGISTRATION: Not applicable-this study does not involve interventions on human participants.

Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory.

It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

Use of a new immunoassay to measure PrP Sc levels in scrapie-infected sheep brains reveals PrP genotype-specific differences.

The diagnosis of prion diseases, such as scrapie and BSE, has traditionally relied upon the identification of the disease-associated form of the prion protein, PrP(Sc), based on its resistance to digestion by proteinase K (PK). A more recent development is the conformation-dependent immunoassay (CDI), which distinguishes between PrP Sc and normal PrP (PrP C) based on their differing solubility in guanidine hydrochloride rather than resistance or sensitivity to PK. We have developed a CDI-formatted sandwich immunoassay for the measurement of PrP Sc in sheep brain, which discriminates between clinically affected scrapie cases (natural or experimental) and uninfected controls of the same PrP genotype. Using this method, we have shown for the first time that, in sheep, the PrP genotype has a significant influence on the amount of PrP Sc deposited in the brains of animals experimentally infected with scrapie.

A test of the reverberatory activity hypothesis for hippocampal 'place' cells.

One of several tenable hypotheses that can be proposed to explain the complex dynamics of spatially selective hippocampal neural activity postulates that the region of space over which a given cell receives its external input is actually much smaller than the classical 'place field.' According to this notion, the later portions of the field reflect some form of network hysteresis resulting from 'reverberatory' activity within reentrant, synaptically coupled cell assemblies within the hippocampus. This hypothesis predicts that transient, global inhibition, induced after the onset of firing, might truncate the remainder of the place field. To test this hypothesis, principal afferents to the hippocampus were stimulated bilaterally in rats running on a circular track, evoking widespread inhibition throughout the hippocampus, and abolishing all spike activity from simultaneously recorded populations of CA1 pyramidal cells for periods of 150-300 ms. Stimulation at any point within the place field of a given cell suppressed firing only for such brief intervals, followed by an immediate resumption for the remainder of the field. These results suggest that without additional cellular and/or synaptic mechanisms, reverberatory activity alone within the hippocampus does not account for the shape and spatial extent of place fields.

Effect of Structured Touch and Guided Imagery for Pain and Anxiety in Elective Joint Replacement Patients--A Randomized Controlled Trial: M-TIJRP.

CONTEXT: Postoperative management of pain after total joint arthroplasty remains a challenge despite advancements in analgesics. Evidence shows that complementary modalities with mind-body and tactile-based approaches are valid and effective adjuncts to reduce pain and anxiety postoperatively. OBJECTIVE: To investigate the effectiveness of the "M" Technique (M), a registered method of structured touch using a set sequence and number of strokes, and a consistent level of pressure on hands and feet, compared with guided imagery and usual care, for the reduction of pain and anxiety in patients undergoing elective total knee or hip replacement surgery. METHODS: Randomized controlled trial: M-TIJRP (MiTechnique and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a community hospital, 225 male and female patients, aged 38 to 90 years, undergoing elective total hip or knee replacement were randomly assigned to 1 of 3 groups (75 patients in each): M, guided imagery, or usual care. They were blinded to their assignment until the intervention. MAIN OUTCOME MEASURES: Reduction of pain and anxiety postoperatively. Secondary outcomes measured use of pain medication and patient satisfaction. RESULTS: This study yielded positive findings for the management of pain and anxiety in patients undergoing elective joint replacement using M and guided imagery for 18 to 20 minutes compared with usual care. M showed the largest predicted decreases in both pain and anxiety between groups. There was no significant difference in narcotic pain medication use between groups. Patient satisfaction survey ratings were highest for M, followed by guided imagery. CONCLUSION: The benefit of M may be because of the specifically structured sequence of touch by competent caring, trained providers.

LTP induction threshold change in old rats at the perforant path--granule cell synapse.

Old, memory-deficient rats do not show a change in the threshold for long-term potentiation (LTP) induction in hippocampal region CA1. This observation suggests that defective NMDA receptor mechanisms at the Schaffer collateral-CA 1 pyramidal cell synapse cannot explain age-related LTP induction deficits that are observed under some stimulation protocols. The effects of aging on functional electrophysiology are not, however, identical between hippocampal subregions. In fact, at the perforant path-granule cell synapse of rats NMDA receptor-mediated responses are reduced, suggesting a possible change in the threshold for LTP induction at this synapse. This hypothesis was tested in the present experiment. We found that when weak orthodromic stimulation of medial perforant path fibers is paired with intracellular current injection of granule cells, the threshold for LTP induction is elevated in aged, spatial memory-impaired rats compared to middle-aged and young controls. Thus, in addition to there being fewer total medial perforant path synaptic contacts in old rats, greater depolarization and input convergence is required before durable modification of synaptic strength can be induced.

Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors.

The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer's disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer's disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path-granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer's disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.

The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks.

The amino-acid sequence of the PrP protein plays an important role in determining whether sheep are susceptible to scrapie. Although the genetics of scrapie susceptibility are now well understood, there have been few studies of the PrP gene at the population level, especially in commercially farmed sheep. Here we describe the PrP genetic profiles of the breeding stock of four UK sheep flocks, comprising nearly 650 animals in total. Two flocks had been scrapie affected for about eight years and two were scrapie free. Scrapie-resistant PrP genotypes predominated in all flocks but highly susceptible genotypes were present in each case. The distribution of PrP genotypes was similar in the scrapie-affected and scrapie-free flocks. The former, however, showed a slight but significant skew towards more susceptible genotypes despite their previous losses of susceptible sheep. Surprisingly, this skew was apparent in younger, but not older, sheep. We suggest that these patterns may occur if sheep flocks destined to become scrapie affected are predisposed by a genetic profile skewed towards susceptibility. The age structure of the scrapie-affected flocks suggests that the number of losses attributable directly or indirectly to scrapie considerably exceeds that recognized by the farmers, and also that significant losses may occur even in sheep of a moderately susceptible genotype. Similar patterns were not detected in the scrapie-free flocks, indicating that these losses are associated with scrapie infection as well as genotype.