Genotype-by-environment interaction of growth traits in rainbow trout (Oncorhynchus mykiss): a continental scale study.

Rainbow trout is a globally important fish species for aquaculture. However, fish for most farms worldwide are produced by only a few breeding companies. Selection based solely on fish performance recorded at a nucleus may lead to lower-than-expected genetic gains in other production environments when genotype-by-environment (G × E) interaction exists. The aim was to quantify the magnitude of G × E interaction of growth traits (tagging weight; BWT, harvest weight; BWH, and growth rate; TGC) measured across 4 environments, located in 3 different continents, by estimating genetic correlations between environments. A total of 100 families, of at least 25 in size, were produced from the mating 58 sires and 100 dams. In total, 13,806 offspring were reared at the nucleus (selection environment) in Washington State (NUC) and in 3 other environments: a recirculating aquaculture system in Freshwater Institute (FI), West Virginia; a high-altitude farm in Peru (PE), and a cold-water farm in Germany (GER). To account for selection bias due to selective mortality, a multitrait multienvironment animal mixed model was applied to analyze the performance data in different environments as different traits. Genetic correlation (rg) of a trait measured in different environments and rg of different traits measured in different environments were estimated. The results show that heterogeneity of additive genetic variances was mainly found for BWH measured in FI and PE. Additive genetic coefficient of variation for BWH in NUC, FI, PE, and GER were 7.63, 8.36, 8.64, and 9.75, respectively. Genetic correlations between the same trait in different environments were low, indicating strong reranking (BWT: rg = 0.15 to 0.37, BWH: rg = 0.19 to 0.48, TGC: rg = 0.31 to 0.36) across environments. The rg between BWT in NUC and BWH in both FI (0.31) and GER (0.36) were positive, which was also found between BWT in NUC and TGC in both FI (0.10) and GER (0.20). However, rg were negative between BWT in NUC and both BWH (-0.06) and TGC (-0.20) in PE. Correction for selection bias resulted in higher additive genetic variances. In conclusion, strong G × E interaction was found for BWT, BWH, and TGC. Accounting for G × E interaction in the breeding program, either by using sib information from testing stations or environment-specific breeding programs, would increase genetic gains for environments that differ significantly from NUC.

Defining desired genetic gains for rainbow trout breeding objective using analytic hierarchy process.

Distributing animals from a single breeding program to a global market may not satisfy all producers, as they may differ in market objectives and farming environments. Analytic hierarchy process (AHP) is used to estimate preferences, which can be aggregated to consensus preference values using weighted goal programming (WGP). The aim of this study was to use an AHP-WGP based approach to derive desired genetic gains for rainbow trout breeding and to study whether breeding trait preferences vary depending on commercial products and farming environments. Two questionnaires were sent out. Questionnaire-A (Q-A) was distributed to 178 farmers from 5 continents and used to collect information on commercial products and farming environments. In this questionnaire, farmers were asked to rank the 6 most important traits for genetic improvement from a list of 13 traits. Questionnaire B (Q-B) was sent to all farmers who responded to Q-A (53 in total). For Q-B, preferences of the 6 traits were obtained using pairwise comparison. Preference intensity was given to quantify (in % of a trait mean; G%) the degree to which 1 trait is preferred over the other. Individual preferences, social preferences, and consensus preferences (Con-P) were estimated using AHP and WGP. Desired gains were constructed by multiplying Con-P by G%. The analysis revealed that the 6 most important traits were thermal growth coefficient (TGC), survival (Surv), feed conversion ratio (FCR), condition factor (CF), fillet percentage (FIL%), and late maturation (LMat). Ranking of traits based on average Con-P values were Surv (0.271), FCR (0.246), TGC (0.246), LMat (0.090), FIL% (0.081), and CF (0.067). Corresponding desired genetic gains (in % of trait mean) were 1.63, 1.87, 1.67, 1.29, 0.06, and 0.33%, respectively. The results from Con-P values show that trait preferences may vary for different types of commercial production or farming environments. This study demonstrated that combination of AHP and WGP can be used to derive desired gains for a breeding program and to quantify differences due to variations market demand or production environment.

Co-morbidities as predictors of mortality in Clostridium difficile infection and derivation of the ARC predictive score.

Clostridium difficile associated diarrhoea (CDAD) has increased significantly in the last 15 years, but predictors of outcome are inadequately understood. This was a cohort study of 2761 patients in North East England between 2002 and 2009, with the end-point of mortality at 30 days. The role of age, gender and co-morbidities was examined by binary logistic regression. Rounded odds ratios were used to develop a predictive score. A predictive score based on age, renal disease and cancer (ARC score) differentiated groups with differing risk of 30-day mortality (risk for score of 0-3 was 9-21%, score of 4-7 was 31-48% and score of 8 was 66%). Co-morbidities were shown to be important predictors of outcome in CDAD, and can be combined with age in the ARC score to assess the likelihood of survival. This requires further validation in other populations, but has important implications for clinical and research practice.

Thirty-day mortality of Clostridium difficile infection in a UK National Health Service Foundation Trust between 2002 and 2008.

Few standardised data are available on mortality rates in patients with Clostridium difficile infection (CDI). The literature often reports 'attributable' mortality or cannot be universally applied. We aimed to investigate the pattern and trends in all-cause mortality in a large unselected cohort of patients affected by CDI. This was done by means of a retrospective cohort study between 2002 and 2008 of all patients with positive stool toxin tests indicating CDI in one National Health Service (NHS) Trust, comprising three general hospitals and seven community hospitals. Vital status of the patients was determined from two sources. In total, 2571 patients with a first episode of CDI were identified (1638 females; median age 82.1 years). Cumulative mortality at 7 days, 14 days, 30 days and 1 year was 13.4%, 20.8%, 32.5% and 58.7%, respectively. There was no significant difference in mortality between sex, year of diagnosis or hospital site. Mortality at 30 days increased incrementally from 3.4% in those aged <40 years to 41% in those >90 years. Mortality rates were significantly higher than reported by previous studies but were remarkably consistent over the time period and between different hospitals within the Trust. Prognosis falls with increasing age, and the age of this cohort may explain the high 30-day absolute mortality. CDI infection is associated with high early mortality. To reduce mortality, new interventions need to be introduced soon after diagnosis. There is a need for standardised outcome data for CDI.

Select Listeria monocytogenes subtypes commonly found in foods carry distinct nonsense mutations in inlA, leading to expression of truncated and secreted internalin A, and are associated with a reduced invasion phenotype for human intestinal epithelial cells.

The surface protein internalin A (InlA) contributes to the invasion of human intestinal epithelial cells by Listeria monocytogenes. Screening of L. monocytogenes strains isolated from human clinical cases (n=46), foods (n=118), and healthy animals (n=58) in the United States revealed mutations in inlA leading to premature stop codons (PMSCs) in L. monocytogenes ribotypes DUP-1052A and DUP-16635A (PMSC mutation type 1), DUP-1025A and DUP-1031A (PMSC mutation type 2), and DUP-1046B and DUP-1062A (PMSC mutation type 3). While all DUP-1046B, DUP-1062A, DUP-16635A, and DUP-1031A isolates (n=76) contained inlA PMSCs, ribotypes DUP-1052A and DUP-1025A (n=72) contained isolates with and without inlA PMSCs. Western immunoblotting showed that all three inlA PMSCs result in the production of truncated and secreted InlA. Searches of the Pathogen Tracker database, which contains subtype and source information for more than 5,000 L. monocytogenes isolates, revealed that the six ribotypes shown to contain isolates with inlA PMSCs were overall more commonly isolated from foods than from human listeriosis cases. L. monocytogenes strains carrying inlA PMSCs also showed significantly (P=0.0004) reduced invasion of Caco-2 cells compared to isolates with homologous 3' inlA sequences without PMSCs. Invasion assays with an isogenic PMSC mutant further supported the observation that inlA PMSCs lead to reduced invasion of Caco-2 cells. Our data show that specific L. monocytogenes subtypes which are common among U.S. food isolates but rare among human listeriosis isolates carry inlA mutations that are associated with, and possibly at least partially responsible for, an attenuated invasion phenotype.

Variation in clinician recommendations for multiple injections during adoption of inactivated polio vaccine.

OBJECTIVES: To describe variation in clinician recommendations for multiple injections during the adoption of inactivated poliovirus vaccine (IPV) in 2 large health maintenance organizations (HMOs), and to test the hypothesis that variation in recommendations would be associated with variation in immunization coverage rates. DESIGN: Cross-sectional study based on a survey of clinician practices 1 year after IPV was recommended and computerized immunization data from these clinicians' patients. STUDY SETTINGS: Two large West Coast HMOs: Kaiser Permanente in Northern California and Group Health Cooperative of Puget Sound. OUTCOME MEASURES: Immunization status of 8-month-olds and 24-month-olds cared for by the clinicians during the study. RESULTS: More clinicians at Group Health (82%), where a central guideline was issued, had adopted the IPV/oral poliovirus vaccine (OPV) sequential schedule than at Kaiser (65%), where no central guideline was issued. Clinicians at both HMOs said that if multiple injections fell due at a visit and they elected to defer some vaccines, they would be most likely to defer the hepatitis B vaccine (HBV) for infants (40%). At Kaiser, IPV users were more likely than OPV users to recommend the first HBV at birth (64% vs 28%) or if they did not, to defer the third HBV to 8 months or later (62% vs 39%). In multivariate analyses, patients whose clinicians used IPV were as likely to be fully immunized at 8 months old as those whose clinicians used all OPV. At Kaiser, where there was variability in the maximum number of injections clinicians recommended at infant visits, providers who routinely recommended 3 or 4 injections at a visit had similar immunization coverage rates as those who recommended 1 or 2. At both HMOs, clinicians who strongly recommended all possible injections at a visit had higher immunization coverage rates at 8 months than those who offered parents the choice of deferring some vaccines to a subsequent visit (at Kaiser, odds ratio [OR]: 1.2; 95% confidence interval [CI]: 1.0-1.5; at Group Health, OR: 1.8; 95% CI: 1.1-2.8). CONCLUSIONS: Neither IPV adoption nor the use of multiple injections at infant visits were associated with reductions in immunization coverage. However, at the HMO without centralized immunization guidelines, IPV adoption was associated with changes in the timing of the first and third HBV. Clinical policymakers should continue to monitor practice variation as future vaccines are added to the infant immunization schedule.

The hidden costs of infant vaccination.

Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1-8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infant's vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of $25 to reduce injections from 4 to 3, $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean costs of $42 in medical utilization and $192 in work-loss among the families who experienced those events (Ns=62 and 35, respectively). When averaged among all 1657 study infants, vaccine-associated symptoms after the index vaccination visit resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct nonmedical costs, yielding total financial costs of $7.70. Parents of infants who had vaccine-associated symptoms said they would have paid a median of $50 to avoid these symptoms. Fever and fussiness were associated in logistic regression analysis with a two-fold increase in the odds of medical utilization, and fever with more than a three-fold increase in work loss. We conclude that multiple injections during a single clinic visit entail psychological costs. The psychological costs of vaccine-associated symptoms, as measured by willingness-to-pay methods, are higher than those resulting from multiple injections. The financial costs of medical utilization and work-loss resulting from common vaccine-associated symptoms are non-negligible and should be incorporated in economic analyses.

A rural-urban comparison of patterns of physician assistant practice.

Access to primary care continues to be a concern in rural areas. The deficit of primary care providers in rural environments has the potential to increase the role of physician assistants (PAs) in the system of rural health care delivery. Little is known about the conditions, sites, and patterns of practice of PAs and their distribution in Pennsylvania, the state with the largest rural population. To learn more about these providers in rural and urban settings and their willingness to practice in underserved areas, the author conducted a census of all PAs who hold a Pennsylvania license. Survey results revealed significant rural-urban differences in socioeconomic, demographic, and practice profile parameters. Providers in rural areas are more likely than urban counterparts to practice primary care in a primary care practice setting; see more patients per week; and are the principal provider of care for a higher percentage of their patients. Experience with managed care is greater for urban PAs. A rural PA is more likely than an urban PA to practice in an underserved area. For both rural and urban PAs who practice primary care, significant differences were noted in their willingness to practice in a rural underserved area, compared to PAs who do not practice primary care.

Nurse practitioners: a comparison of rural-urban practice patterns and willingness to serve in underserved areas.

PURPOSE: To determine nurse practitioners' (NPs) practice patterns and willingness to practice in underserved areas in both rural and urban settings in a largely rural state. DATA SOURCES: A census of all NPs holding a Pennsylvania license and providing addresses in Pennsylvania or one of the contiguous states was conducted in 1996. The ZIP codes of practice sites were matched with 1990 census data. CONCLUSIONS: Nurse practitioners in rural areas are more likely than their urban counterparts to provide primary care in primary care practice settings, they see more patients per week, and they are more likely to be the principal provider of care for a higher percentage of their patients. Experience with managed care contracts is greater for urban NPs as is their willingness to practice in urban underserved areas. Rural NPs were more willing to practice in rural underserved areas than their urban counterparts. IMPLICATIONS FOR PRACTICE: Access to primary care continues to be a concern in rural areas. The increasing market penetration of managed care and the deficit of primary care providers in rural environments may lead to increased opportunities for NPs in the rural health care delivery system.

Obstacle crossing in subjects with stroke.

OBJECTIVE: To study the ability of subjects with stroke to successfully step over an obstacle during ambulation. SETTING: A geriatric rehabilitation unit in a tertiary referral hospital. SUBJECTS: Twenty-four inpatients with stroke (median time poststroke 27 days, interquartile range 21 to 44.5 days) able to walk 10 m unassisted without walking aids; also, 22 healthy subjects. METHOD: Subjects were required to step over obstacles of various heights and widths, ranging from 1cm to 8cm. A fail was scored if the obstacle was contacted by either lower limb or if assistance or upper limb support was required. The choice of leading limb and the presence of visual deficits and neglect were also recorded in the stroke subjects. Subjects were tested on two occasions. RESULTS: Significantly more fails were recorded for stroke subjects, with 13 subjects failing at least once. No preference was shown for leading either with the affected or with the unaffected leg. Stroke subjects showed inconsistent performance over the two testing sessions. CONCLUSION: The ability to negotiate obstacles was compromised and inconsistent in stroke subjects undergoing inpatient rehabilitation. This suggests that gait safety in this population remains threatened.

Clinical outcomes and maternal perceptions of an updated model of perinatal care.

BACKGROUND: Postpartum hospital stays seem likely to remain limited even under new laws which mandate that insurers cover 48-hour hospitalization after uncomplicated delivery. Clinicians, who are increasingly practicing in capitated arrangements, need better information to maximize clinical benefit to mothers and newborns using finite resources. OBJECTIVE AND INTERVENTIONS: This study's aim was to evaluate the clinical outcomes, patient perceptions, and costs of a revised model of perinatal care services. In this model, a new postpartum care center was established for routine follow-up of newborns within 48 hours after hospital discharge, educational efforts were shifted from the postpartum hospitalization to the prenatal period, and lactation consultant hours were increased. DESIGN AND PARTICIPANTS: Controlled, nonrandomized (double cohort) study that compared mothers and newborns with hospital stays of 48 hours or less during the Baseline Care (preintervention) study period (N = 344) with those under the Revised Care (postintervention) study period (N = 456). SETTING: The Hayward, California, medical center of Kaiser Permanente, a nonprofit health maintenance organization. DATA COLLECTION: Telephone interviews were attempted with all mothers 3 weeks after delivery. Data on rehospitalizations, emergency department (ED) and clinic visits, and costs during the first 14 postpartum days were collected from computerized databases and chart review. OUTCOME MEASURES: The combined clinical outcome was defined as any undesirable health event, including rehospitalization, an ED visit, or an urgent clinic visit by either the mother or newborn within the first 14 days postpartum, or breastfeeding discontinuation within the first 21 days postpartum. Maternal satisfaction and costs were also studied. RESULTS: Of 876 attempted interviews, 800 were completed (91%). Analyses were adjusted for age, race, education, parity, breastfeeding experience, and other relevant variables. Among the interviewed mother-newborn pairs, 45% in the Revised Care group experienced the combined clinical outcome, compared with 52% in the Baseline Care group. Newborns in the Revised Care group (29%) were significantly less likely to make urgent clinic visits during the first 14 days of life than those in the Baseline Care group (36%). There were no differences between groups in newborn ED visits or rehospitalizations, maternal clinical outcomes, or breastfeeding continuation. Mothers in the Revised Care group expressed higher satisfaction with the newborn's care, the amount of information they received about newborn care and breastfeeding, and the amount of help they received with breastfeeding. Planned hospital care, planned follow-up visits, and unplanned care costs decreased by $149 per delivery, while the new prenatal class and increased lactation consultant services cost $58 per delivery, for an estimated overall reduction in cost. CONCLUSIONS: We conclude that the revised model of perinatal care in this health maintenance organization medical center improved clinical outcomes and maternal satisfaction for low-risk mothers and newborns without increasing costs.

Outpatient management practices associated with reduced risk of pediatric asthma hospitalization and emergency department visits.

OBJECTIVES: Effective outpatient care is believed to prevent hospitalization and emergency department (ED) visits resulting from childhood asthma. The aim of this study was to suggest priority areas for intervention by identifying outpatient management practices associated with the risk of these adverse outcomes in a large population. METHODS: This case-control study included children aged 0 to 14 years with asthma who were members of a regional health maintenance organization. Cases were children undergoing either a hospitalization or an ED visit for asthma during the study period. Control subjects were children with asthma without a hospitalization or an ED visit during the study period who were matched to patients on age, gender, and number of asthma-related hospitalizations in the past 24 months. Data on provider and parent asthma management practices were collected using chart review, closed-ended telephone interviews with parents, and computerized use databases. Multivariate analyses were conducted using conditional logistic regression models. RESULTS: Data were collected on 508 cases and 990 control subjects. A total of 43% of cases were reported by their parents to have moderately severe or severe asthma, compared with 20% of control subjects. Parents of cases with hospitalization were less likely than control subjects to have a written asthma management plan (44% vs 51%) and to report washing bedsheets in hot water at least twice a month (77% vs 86%). Cases with hospitalization were more likely to have a nebulizer (74% vs 56%). In the final multivariate model, race/ethnicity was not associated with having had either a hospitalization or an ED visit, as was lower socioeconomic status. Having a written asthma management plan [odds ratio (OR): 0.54; 95% confidence interval (CI): 0.30, 0.99] and washing bedsheets in hot water at least twice a month (OR: 0.45; 95% CI: 0.21, 0.94) were associated with reduced odds of hospitalization. Having a written asthma management plan (OR: 0.45; 95% CI: 0.27, 0.76) and starting or increasing medications at the onset of a cold or flu were associated with reduced odds of making an ED visit. CONCLUSIONS: Practices that support early intervention for asthma flare-ups by parents at home, particularly written management plans, are strongly associated with reduced risk of adverse outcomes among children with asthma.

Mosaic partial trisomy 17 due to a ring chromosome identified by fluorescence in situ hybridisation.

We report on a 3-year-old-girl with mosaic partial trisomy 17 due to an additional ring chromosome 17 in 13% of cells analysed. This was identified by fluorescence in situ hybridisation (FISH) using a whole chromosome 17 specific paint as well as probes specific for the Smith-Magenis and Miller-Dieker regions of chromosome 17p. This girl showed mild developmental delay with subtle facial and other minor abnormalities including single palmar creases, generalised joint laxity, and a scoliosis.

An assessment of practice support and continuing medical education needs of rural Pennsylvania family physicians.

Family physicians provide the greatest proportion of care in rural communities. Yet, the number of physicians choosing family practice and rural practice has continued to decline. Undesirable aspects of rural practice, such as professional isolation and a lack of or inadequate resources, are assumed to be associated with this decline. This article reports on the practice support and continuing medical education needs of rural family physicians. A mail survey was conducted in 1993 on a purposive sample of family physicians in 39 of 67 rural-designated or urban Pennsylvania counties with low population densities. The physicians identified needs that included patient education materials and programs, community health promotion, federal regulation updates, technical assistance with computers and business management, database software and a videotape lending library, a drug hotline, and mini-fellowships on clinical skill development. A majority of respondents were willing to participate in clinical educational experiences for students and residents. Some physicians indicated a lack of interest in access to information through telecommunications, e.g., video conference referrals and consultations. Overall, findings revealed that family physicians need and are receptive to a variety of practice support and continuing education programs. A practice support program coupled with policy coordination among public and private organizations is likely to lessen complaints by rural primary care physicians.

The use of early enteral nutrition in abdominal trauma.

Patients who sustain abdominal trauma become hypermetabolic and require aggressive utilization of early enteral nutrition. The purpose of this article is to discuss the physiology of the gut as it relates to the development of septic sequelae and the role of early enteral nutrition in decreasing septic complications based upon the findings of previously published research. The research clearly supports that there are many benefits associated with the initiation of early enteral nutrition in this patient population.

Occlusion edge blur: a cue to relative visual depth.

We studied whether the blur/sharpness of an occlusion boundary between a sharply focused surface and a blurred surface is used as a relative depth cue. Observers judged relative depth in pairs of images that differed only in the blurriness of the common boundary between two adjoining texture regions, one blurred and one sharply focused. Two experiments were conducted; in both, observers consistently used the blur of the boundary as a cue to relative depth. However, the strength of the cue, relative to other cues, varied across observers. The occlusion edge blur cue can resolve the near/far ambiguity inherent in depth-from-focus computations.

Factors influencing retention of rural Pennsylvania family physicians.

BACKGROUND: Rural areas suffer from a lack of primary care physicians. Efforts to retain physicians should focus on modifying or changing attributes of rural practice that are considered by physicians to be undesirable. A practice support outreach program (PSOP) is one initiative expected to enhance retention in rural areas by addressing negative aspects of rural practice. The purpose of this study was to assess factors related to satisfaction and retention of family physicians to develop and implement a PSOP in rural areas of Pennsylvania. METHOD: In 1993 a mail survey was conducted on a convenience sample of 398 family physicians practicing in 39 counties in Pennsylvania. RESULTS: Twenty percent of respondents were considering leaving rural practice. Bivariate analyses indicated that professional isolation, lower reimbursements, and sharing on-call with only 1 other physician were associated with physician's reasons for considering leaving rural practice. A multiple logistic regression revealed that sharing on-call rotation with only 1 other physician and having a solo practice were significant influences in considering leaving rural practice. CONCLUSIONS: Findings suggest support strategies that minimize perceptions of professional isolation and policy efforts that address reimbursement differentials and compliance issues are needed to minimize many complaints of rural family physicians.

Severe microphthalmia, diaphragmatic hernia and Fallot's tetralogy associated with a chromosome 1;15 translocation.

A 9-year-old boy with multiple abnormalities including severe bilateral microphthalmia, diaphragmatic hernia and Fallot's tetralogy is presented. He has also been shown to have an apparently balanced de novo reciprocal translocation, 46,XY,t(1;15)(q41;q21.2), which suggests that one of those breakpoints may be the locus for a gene which is important in morphogenesis.

Could bradykinesia in Parkinson's disease simply be compensation?

Even normal movements can be slow and hesitant. To distinguish between bradykinesia and the simple slow inefficiency sometimes seen in normal movement, we matched the movement durations of 12 patients with Parkinson's disease (PD) and 12 age-matched controls and examined end-point accuracy, number of submovements, force inefficiency, and relative duration of acceleration and deceleration phases of movement. Subjects used an electronic pen which sampled pen-tip position at 200 Hz, and performed a sequence of drawing movements to nine targets (0.5, 1, or 2 cm diameter) upon a WACOM SD420 graphics tablet. Patients could be trained to move at the preferred speed of controls (and vice versa). When moving at the same fast speed as controls, patient's movements were less accurate (increased end-point spread). Even when moving at their own preferred speed, patients' movements were less efficient (more submovements, more zero crossings in acceleration function) than controls moving at the same speed. If bradykinesia simply reflected increased caution and visual guidance, we would expect patients to exhibit prolonged decelerative phases of movement associated with terminal guidance. However, patients consistently required prolonged accelerative phases of movement, suggesting that there was a problem in generating appropriate movement forces to produce the required end-point accuracy. It is hypothesised that bradykinesia is not simply a compensation for defective preparatory processes, but may reflect a defective internal cue in PD which disrupts and impairs the outflow of motor responses.