Beef Cow-calf Vaccine Knowledge Translation and Transfer (KTT) Project: Summary report on producer, veterinarian, and working group surveys regarding vaccine usage and recommendations.

Objective: The overall aim of this project was to create educational materials to support beef veterinarians and cow-calf producers in maximizing appropriate uptake of vaccine use in western Canada. The specific objective of the surveys reported here was to document current vaccine use by producers and vaccination recommendations by veterinarians and other industry stakeholders. Population: Cow-calf producers and veterinarians involved in the western Canadian beef cow-calf sector. Results: Surveys of western Canadian cow-calf producers and veterinarians were conducted in the fall of 2021 regarding current vaccine usage and recommendations, respectively. Uptake of beef cow-calf vaccines deemed "core" vaccines by the American Association of Bovine Practitioners (AABP) varied across cow-calf producers, and recommendations varied across veterinarians responding to the survey. Thirty members of the project working group, consisting of cow-calf producers, veterinarians, academics, and vaccine manufacturers, were also surveyed regarding vaccine recommendations. The recommendations of the working group aligned with AABP recommendations for core and risk-based vaccines. Conclusions: Uptake of core beef vaccines was not complete across the producers surveyed. Therefore, education of beef cow-calf producers regarding the importance of core vaccines is required. Clinical relevance: Findings from these surveys will guide creation of educational materials to promote the use of appropriate beef cow-calf vaccines.

Projet d'application et de transfert des connaissances sur les vaccins (KTT) du Beef Cattle Research Council (BCRC) : rapport sommaire sur les sondages auprès des producteurs, des vétérinaires et des groupes de travail concernant l'utilisation des vaccins et les recommandations. Objectif: L'objectif général de ce projet était de créer du matériel éducatif pour aider les vétérinaires de bovins de boucherie et les éleveurs de vaches-veaux à maximiser l'adoption appropriée de l'utilisation des vaccins dans l'Ouest canadien. L'objectif spécifique des enquêtes rapportées ici était de documenter l'utilisation actuelle des vaccins par les producteurs et les recommandations de vaccination par les vétérinaires et d'autres intervenants de l'industrie. Population: Éleveurs de vaches-veaux et vétérinaires impliqués dans le secteur des vaches-veaux de boucherie de l'Ouest canadien. Résultats: Des sondages auprès des éleveurs de vaches-veaux et des vétérinaires de l'Ouest canadien ont été menés à l'automne 2021 concernant l'utilisation actuelle des vaccins et les recommandations, respectivement. L'adoption des vaccins pour vaches-veaux de boucherie considérés comme des vaccins « de base ¼ par l'American Association of Bovine Practitioners (AABP) variait selon les producteurs de vaches-veaux, et les recommandations variaient selon les vétérinaires répondant à l'enquête. Trente membres du groupe de travail du projet, composé de producteurs de vaches-veaux, de vétérinaires, d'universitaires et de fabricants de vaccins, ont également été interrogés sur les recommandations en matière de vaccins. Les recommandations du groupe de travail sont alignées sur les recommandations de l'AABP pour les vaccins de base et basés sur les risques. Conclusion: L'adoption des vaccins de base pour le bœuf n'était pas complète parmi les producteurs interrogés. Par conséquent, l'éducation des producteurs de vaches-veaux de boucherie concernant l'importance des vaccins de base est nécessaire. Pertinence clinique: Les résultats de ces enquêtes guideront la création de matériel pédagogique pour promouvoir l'utilisation de vaccins appropriés dans les élevages vaches-veaux de boucherie.(Traduit par Dr Serge Messier).

A systematic review and meta-regression of single group, pre-post studies evaluating food safety education and training interventions for food handlers.

BACKGROUND: Food handlers working in retail and food service establishments are a frequent source of foodborne disease outbreaks. Numerous studies have investigated different education and training approaches to improve their safe food handling knowledge, attitudes, and practices. Frequently, these studies use a single group, pre-post design, measuring changes before and after an intervention without a separate control group. OBJECTIVES: We conducted a systematic review of these studies to identify their key characteristics and to evaluate possible predictors of between study heterogeneity in their estimates of intervention effect. METHODS: the review steps included a comprehensive search; relevance screening; article characterization; risk-of-bias assessment; data extraction; and meta-regression on five outcome categories: attitudes and beliefs, knowledge, behaviours, food premise inspection scores, and aerobic plate counts. RESULTS: Among 85 relevant studies identified, the most commonly investigated intervention type was in-person, group-based training courses (81%). Interventions primarily targeted food handlers in educational institutions and restaurants (32% and 31%, respectively). The most frequently measured outcome was food handler knowledge (66%). Studies mostly (89%) covered multiple food safety content areas, primarily targeting personal hygiene (88%) and avoiding cross-contamination (87%). All studies were rated as 'critical' risk of bias given the lack of an independent control group. Significant intervention effects were found for all outcome categories, but substantial heterogeneity was also identified. Studies that informed their intervention from formative research reported larger effect sizes for attitude and belief outcomes, those that based their intervention on a theory of behaviour change reported larger effect sizes for behaviour outcomes, and those published in grey literature sources reported larger effect sizes for behaviour and knowledge outcomes. IMPLICATIONS: The results of this review have identified food safety training and education research gaps and future opportunities.

Effectiveness of Food Handler Training and Education Interventions: A Systematic Review and Meta-Analysis.

Improper food handling among those working in retail and food service settings is a frequent contributor to foodborne illness outbreaks. Food safety training and education interventions are important strategies to improve the behaviors and behavioral precursors (e.g., knowledge and attitudes) of food handlers in these settings. We conducted a comprehensive systematic review to identify, characterize, and synthesize global studies in this area to determine the overall effectiveness of these interventions. The review focused on experimental studies with an independent control group. Review methods included structured search strategy, relevance screening of identified abstracts, characterization of relevant articles, risk of bias assessment, data extraction, meta-analysis of intervention effectiveness for four outcome categories (attitudes, knowledge, behavior, and food premise inspection scores), and a quality of evidence assessment. We identified 18 relevant randomized controlled trials (RCTs) and 29 nonrandomized trials. Among RCTs, 25 (64%) unique outcomes were rated as high risk of bias, primarily owing to concerns about outcome measurement methods, while 45 (98%) nonrandomized trial outcomes were rated as serious risk of bias, primarily because of concerns about confounding bias. High confidence was identified for the effect of training and education interventions to improve food handler knowledge outcomes in eight RCT studies (standardized mean difference = 0.92; 95% confidence interval: 0.03, 1.81; I2 = 86%). For all other outcomes, no significant effect was identified. In contrast, nonrandomized trials identified a statistically significant positive intervention effect for all outcome types, but confidence in these findings was very low due to possible confounding and other biases. Results indicate that food safety training and education interventions are effective to improve food handler knowledge, but more evidence is needed on strategies to improve behavior change.

Standards in Pupillography.

The number of research groups studying the pupil is increasing, as is the number of publications. Consequently, new standards in pupillography are needed to formalize the methodology including recording conditions, stimulus characteristics, as well as suitable parameters of evaluation. Since the description of intrinsically photosensitive retinal ganglion cells (ipRGCs) there has been an increased interest and broader application of pupillography in ophthalmology as well as other fields including psychology and chronobiology. Color pupillography plays an important role not only in research but also in clinical observational and therapy studies like gene therapy of hereditary retinal degenerations and psychopathology. Stimuli can vary in size, brightness, duration, and wavelength. Stimulus paradigms determine whether rhodopsin-driven rod responses, opsin-driven cone responses, or melanopsin-driven ipRGC responses are primarily elicited. Background illumination, adaptation state, and instruction for the participants will furthermore influence the results. This standard recommends a minimum set of variables to be used for pupillography and specified in the publication methodologies. Initiated at the 32nd International Pupil Colloquium 2017 in Morges, Switzerland, the aim of this manuscript is to outline standards in pupillography based on current knowledge and experience of pupil experts in order to achieve greater comparability of pupillographic studies. Such standards will particularly facilitate the proper application of pupillography by researchers new to the field. First we describe general standards, followed by specific suggestions concerning the demands of different targets of pupil research: the afferent and efferent reflex arc, pharmacology, psychology, sleepiness-related research and animal studies.

Development of Methodology and Study Protocol: Safety and Efficacy of a Single Subretinal Injection of rAAV.hCNGA3 in Patients with CNGA3-Linked Achromatopsia Investigated in an Exploratory Dose-Escalation Trial.

Achromatopsia is an autosomal recessively inherited congenital defect characterized by a lack of cone photoreceptor function, leading to severely impaired vision. In this clinical study, achromatopsia patients were treated with a single subretinal injection of rAAV.hCNGA3 to restore cone function. The focus of this trial was on the safety of the treatment. After surgery, patients were monitored in eight extensive visits during the first year, followed by a 4-year follow-up period with annual visits. For essential complementation of the standard ophthalmological and systemic examinations, disease-specific methods were developed to assess the safety, efficacy, and patient-reported outcomes in this trial.

Interventions to reduce non-typhoidal Salmonella in pigs during transport to slaughter and lairage: Systematic review, meta-analysis, and research synthesis based infection models in support of assessment of effectiveness.

A systematic review of the effectiveness of interventions to reduce Salmonella prevalence or concentration in pork was undertaken. A broad search was conducted in two electronic databases. Each citation was appraised using screening tools designed and tested a priori. Level 1 relevance screening excluded irrelevant citations; level 2 confirmed relevance and categorized. Data were then extracted, and intervention categories were descriptively summarized. Meta-analysis was performed to provide a summary estimate of treatment effect where two or more studies investigated the same intervention in comparable populations. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess the confidence in the estimated summary measures of intervention effect for each data subgroup. Data were also extracted from the control groups of 25 challenge trials captured by the review, to fit logistic regression models of Salmonella infection in pigs, using odds of infection as the outcome measure. The only intervention captured by the review which was significantly associated with reduced risk of Salmonella in field settings, was elimination of lairage, which is not currently feasible commercially. The logistic regression model for fecal Salmonella shedding in pigs with a random intercept for trial yielded the following predictors significantly associated with increased odds of infection: oral challenge route relative to intra-nasal, log increase in challenge dose, and elapsed time post-challenge. Univariable exact logistic regression modeling lymph node contamination post-challenge yielded the following predictors significantly associated with increased odds of Salmonella infection: younger animals relative to older ones; intra-nasal challenge route relative to oral route; and animals sampled within the first 7days post-challenge relative to those sampled at 14 or 21days. We hypothesize that the presence of absence of one or more of these predictors across studies could help to explain the inconsistent and/or non-significant findings reported for some interventions applied at lairage.

Color Pupillography in Dorsal Midbrain Syndrome.

OBJECTIVE: The purpose of this study was to evaluate the pupil response to chromatic stimuli in patients with lesions in the dorsal midbrain and possibly gain new insights into the afferent pupillary pathways. METHODS: Color pupillography was performed in 5 patients with dorsal midbrain syndrome (DMS), and their results were compared with those of 20 healthy control subjects. We used full-field red stimuli (605 nm) that primarily address the rod/cone system and blue stimuli (420 nm) that preferentially activate intrinsically photosensitive retinal ganglion cells (ipRGCs) directly, with a duration of 4 seconds and a stimulus intensity of 28 lx corneal illumination under mesopic conditions. One eye was stimulated, and the consensual pupil response was recorded and analyzed. RESULTS: The pupillary light reflex in patients with DMS was reduced, differed in shape, and showed a prolonged latency time compared to normal subjects. The blue response was less affected than the red response: the mean maximal relative amplitude (M) was 15.8% (SD = 7.8) in patients with DMS compared with 43.0% (SD = 5.5) in normal subjects for red stimulation, and M = 40.8%, SD = 8.4 (DMS) with M = 58.3%, SD = 4.8 (normals) for blue stimulation. The reduction was 63% for red stimulation but only 30% for blue stimulation in patients with DMS. Moreover, there was a preserved postillumination pupil response to blue stimulation in DMS patients. CONCLUSIONS: In DMS, the melanopsin-mediated ipRGC pathway appeared relatively preserved.

Rapid systematic review and meta-analysis of the evidence for effectiveness of primary production interventions to control Salmonella in beef and pork.

Non-typhoidal Salmonella spp. (hereafter referred to as Salmonella) on beef and pork is an important cause of foodborne illness and death globally. A systematic review of the effectiveness of interventions to reduce Salmonella prevalence or concentration in beef and pork was undertaken. A broad search was conducted in Scopus and CAB abstracts. Each citation was appraised using screening tools tested a priori. Level 1 relevance screening excluded irrelevant citations; level 2 confirmed relevance and categorized studies. Data were then extracted, and intervention categories were descriptively summarized. Meta-analysis was performed to provide a summary estimate of treatment effect where two or more studies investigated the same intervention in comparable populations. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used to assess the confidence in the estimated measures of intervention effect for data subgroups.

A Rapid Systematic Review and Meta-Analysis of the Efficacy of Slaughter and Processing Interventions to Control Non-Typhoidal Salmonella in Beef and Pork.

Pork is one of the major food sources of human salmonellosis worldwide, while beef products have been implicated in numerous foodborne outbreaks. As a result, effective interventions to reduce Salmonella contamination during beef and pork processing are of interest to both regulators and industry. We conducted a rapid systematic review and meta-analysis of literature investigating the efficacy of slaughter and processing interventions to control Salmonella in beef and pork. Review steps included: a comprehensive search strategy; relevance screening of abstracts; relevance confirmation of articles; data extraction; risk-of-bias assessment; meta-analysis (where appropriate); and a weight-of-evidence assessment. A total of 191 relevant experimental studies were identified. Two controlled trials indicated that hot water and steam treatments are effective at reducing the prevalence of Salmonella on beef carcasses (relative risk [RR] = 0.11, 95% confidence interval [CI]: 0.02, 0.58), while four trials found that pre-chill organic acid washes are effective at reducing Salmonella on pork carcasses (RR = 0.32, 95% CI: 0.13, 0.78), with high confidence in the estimates of effect. Four quasi-experimental studies found that post-exsanguination chemical washes were effective to reduce the prevalence of Salmonella on cattle hides, with low confidence in the specific estimate of effect; moderate confidence was found for the effect estimates of scalding (RR = 0.20, 95% CI: 0.14, 0.29) and singeing (RR = 0.34, 95% CI: 0.22, 0.52) of pork carcasses. The overall evidence supported enhanced reductions of Salmonella through a multiple-hurdle approach. In conclusion, various slaughter and processing interventions can contribute to reducing Salmonella on beef and pork carcasses, depending on the context of application; an appropriate combination should be selected, validated, and verified by establishment operators within their local conditions.

A systematic review-meta-analysis and meta-regression on the effect of selected competitive exclusion products on Salmonella spp. prevalence and concentration in broiler chickens.

The effectiveness of various competitive exclusion (CE) products for reducing Salmonella colonization in broiler chickens was evaluated using systematic review-meta-analysis-meta-regression (SR-MA-MR). Relevance screening identified 201 relevant studies that were subjected to methodological assessment. Of these studies, 159 were suitable for data extraction, 66 were presented in a number of MAs and 130 were examined in a meta-regression (MR). Fourteen different CE products were identified, 9 of them commercial products, and the most common route of administration was oral gavage (63.7% of trials). Meta-analyses indicated that a number of CE products reduce Salmonella colonization in broilers, the most effective one being Preempt™ which was formerly known as CF-3. Five study characteristics (publication year, CE type, CE route, sample origin, and Salmonella serovar administered/recovered) and three methodological soundness characteristics (treatment assignment, intervention and laboratory methods description) were retained as statistically significant (p<0.05) in the final MR model. The MR analysis indicated that, undefined CE products outperformed all commercial products, except for: Preempt™ and Broilact(®). Both were considered comparable to the undefined chicken source CE culture products in effectiveness. The administration of CE through spraying the chicks at the hatchery was determined to be just as effective as the oral gavage treatment, and more practical for farmers to administer. The results of this study could be useful in decision-making concerning the on-farm use of CE products in broiler chickens, and as inputs for risk assessments as the industry pushes for more antibiotic-free alternatives. Out of the various interventions to reduce Salmonella colonization in broilers on-farm, CE was the most studied; its inability to be licenced in certain countries and proof of consistent efficacy remains a barrier.

The effectiveness of selected feed and water additives for reducing Salmonella spp. of public health importance in broiler chickens: a systematic review, meta-analysis, and meta-regression approach.

Eating inappropriately prepared poultry meat is a major cause of foodborne salmonellosis. Our objectives were to determine the efficacy of feed and water additives (other than competitive exclusion and antimicrobials) on reducing Salmonella prevalence or concentration in broiler chickens using systematic review-meta-analysis and to explore sources of heterogeneity found in the meta-analysis through meta-regression. Six electronic databases were searched (Current Contents (1999-2009), Agricola (1924-2009), MEDLINE (1860-2009), Scopus (1960-2009), Centre for Agricultural Bioscience (CAB) (1913-2009), and CAB Global Health (1971-2009)), five topic experts were contacted, and the bibliographies of review articles and a topic-relevant textbook were manually searched to identify all relevant research. Study inclusion criteria comprised: English-language primary research investigating the effects of feed and water additives on the Salmonella prevalence or concentration in broiler chickens. Data extraction and study methodological assessment were conducted by two reviewers independently using pretested forms. Seventy challenge studies (n=910 unique treatment-control comparisons), seven controlled studies (n=154), and one quasi-experiment (n=1) met the inclusion criteria. Compared to an assumed control group prevalence of 44 of 1000 broilers, random-effects meta-analysis indicated that the Salmonella cecal colonization in groups with prebiotics (fructooligosaccharide, lactose, whey, dried milk, lactulose, lactosucrose, sucrose, maltose, mannanoligosaccharide) added to feed or water was 15 out of 1000 broilers; with lactose added to feed or water it was 10 out of 1000 broilers; with experimental chlorate product (ECP) added to feed or water it was 21 out of 1000. For ECP the concentration of Salmonella in the ceca was decreased by 0.61 log(10)cfu/g in the treated group compared to the control group. Significant heterogeneity (Cochran's Q-statistic p≤0.10) was observed among studies examining all organic acids (controlled or challenge experiments), butyric acid, formic acid, a formic/propionic acid mixture, fermented liquid feed, and D-mannose. Meta-regressions were conducted to examine the source of heterogeneity among studies. For prevalence outcomes, 36% and 60% of the total variance was within and between studies, respectively. For concentration outcomes, 39% and 33% of the total variance was within and between studies, respectively. Inadequate blinding and randomization was common, and no studies undergoing meta-analysis or meta-regression were conducted on a commercial farm. The strength of evidence of the effect of these additives was very low. Studies conducted under commercial conditions are needed to understand the potential benefit of these interventions for the poultry industry and to improve the strength of evidence of the effectiveness of these additives.

Prevalence of zoonotic bacteria in wild and farmed aquatic species and seafood: a scoping study, systematic review, and meta-analysis of published research.

Increased reliance on seafood has brought to light concerns regarding food safety, but the information to inform risk assessment or surveillance needs is lacking. A scoping study (ScS) was conducted to characterize published research investigating selected zoonotic bacteria and public health topics in various wild and farmed aquatic species and seafood. This was followed by a systematic review (SR) on selected bacteria (Aeromonas spp., generic Escherichia coli, Salmonella spp., and Vibrio spp.) and aquatic species (clams, mussels, oysters, salmon, and shrimp [including prawn]); a meta-analysis (MA) was conducted only at the retail level due to considerable variability among various pathogen/seafood combinations. The ScS revealed the most frequently investigated themes were farm-level prevalence and intervention research for Vibrio spp. and Aeromonas spp. Antimicrobial use (AMU) and the association between AMU and antimicrobial resistance were rarely investigated. The SR indicated a consistent lack of reporting regarding study methodology and results, precluding the use of many studies in and full benefits of MA. MA of Aeromonas, E. coli, and Salmonella prevalence in retail salmon resulted in pooled estimates of 13% (6-27%), 2% (0.1-11%), and 1% (0-5%), respectively. When MA of pathogen/seafood combination resulted in statistically significant heterogeneity (p<0.1), median/range were reported at the region level. The results from our ScS, SR, and MA could be used for better design of future bacteriological surveys of seafood and as inputs for risk assessments or surveillance initiatives in this field.

A systematic review-meta-analysis of chilling interventions and a meta-regression of various processing interventions for Salmonella contamination of chicken.

CONTEXT: The results of individual studies investigating the efficacy of chilling and other processing interventions on Salmonella prevalence or concentration in broiler chicken carcasses are inconsistent or contradictory. OBJECTIVE: Determine efficacy of chilling on reducing Salmonella prevalence or concentration on broiler carcasses using systematic review-meta-analysis, and explore sources of heterogeneity among studies investigating various processing interventions through meta-regression. DATA SOURCES: A comprehensive search included electronic search in six databases, manual search of reference lists of topic-related articles, and consultation with five topic experts to assure that all relevant intervention research was identified. STUDY INCLUSION: Primary intervention research, published in English, encompassing control, challenge, cohort, or before-and-after study designs investigating the efficacy of any chilling or other processing interventions on Salmonella prevalence or concentration in broiler chicken carcasses. RISK OF BIAS ASSESSMENT AND DATA EXTRACTION: Data pertaining to study methodology and reported results, chilling or other processing intervention parameters, populations sampled and outcomes measured were assessed for methodological soundness and extracted by two independent reviewers using pretested checklists. RESULTS: Random-effects meta-analyses of immersion chilling with chlorine (n=9 trials), acetic acid (n=16) and potable water (n=13) trended towards reductions in the odds or log(10)CFU/ml of Salmonella. Significant heterogeneity (P-value≤0.1 and I(2)>25%) precluded the reporting of pooled summary effect estimates. Meta-regression of all processing interventions indicated that serotype, disinfectant type and treatment time and pH were significantly associated with studies reporting reductions in concentration while study design, population sampled, study setting, publication date, intervention and disinfectant type, and treatment pH were significantly associated with studies reporting reductions in prevalence. Methodological and reporting flaws were consistently observed in relevant intervention research as well as a lack of studies conducted under commercial conditions and using Salmonella concentration outcomes. CONCLUSIONS: Chilling may be effective at reducing Salmonella concentration and prevalence, but significant heterogeneity precluded reporting of pooled summary effect estimates for many chilling interventions. Investigations into potential sources of heterogeneity among all processing interventions found that the use of other chemical disinfectants, such as organic acids and surfactants might result in larger reductions in Salmonella contamination than more commonly utilized oxidizing agents like chlorine.

Objective and quantitative analysis of daytime sleepiness in physicians after night duties.

INTRODUCTION: Work place studies often have the disadvantage of lacking objective data less prone to subject bias. The aim of this study was to contribute objective data to the discussion about safety aspects of night shifts in physicians. For this purpose we applied the Pupillographic Sleepiness Test (PST). METHODS: The PST allows recording and analyses of pupillary sleepiness-related oscillations in darkness for 11 min in the sitting subject. The parameter of evaluation is the Pupillary Unrest Index (PUI; mm/min). For statistical analysis the natural logarithm of this parameter is used (lnPUI). Thirty-four physicians were examined by the PST and subjective scales during the first half of the day. Data taken during a day work period (D) were compared to those taken directly after night duty (N) by a Wilcoxon signed rank test. RESULTS: Night duty caused a mean sleep reduction of 3 h (Difference N-D: median 3 h, minimum 0 h, maximum 7 h, p < 0.001). Time since the last sleep period was about equal in both conditions (Difference N-D: median -0.25 h, min. -4 h, max. 20 h, p = 0.2). The lnPUI was larger after night duty (Difference N-D: median 0.19, min. -0.71, max. 1.29, p = 0.03). The increase of physiologically measured sleepiness correlated significantly with changes in subjective measures (PUI/SSS, Spearman Rho 0.41, p = 0.02; PUI/VAS, Spearman Rho 0.38, p = 0.02). DISCUSSION: Despite a mean sleep duration of 4 h, considerable sleepiness in physicians after nights on duty was found, implying lower safety levels for both patients (if physicians remaining on duty) and physicians while commuting home.

Effect of age on the pupillomotor field.

To differentiate physiologic variation from visual field loss with pupillomotor perimetry, the effect of age on the normal pupillomotor field must be known. Given the absence of reported data, the authors aimed to analyze the effect of age on the pupillomotor field as measured with light stimuli of different properties. Subjects consisted of 23 healthy volunteers aged 20 to 28 years ("younger subjects") and 20 healthy volunteers aged 50 to 67 years ("older subjects"). Within a field of 20 degrees, a sequence of 25 focal light stimuli was performed repeatedly on a monitor. The pupil light reflex (PLR) was recorded to stimuli of different diameter and luminance under mesopic conditions. The mean amplitude of the PLR was calculated for each stimulus location and condition. Increasing stimulus luminance or size caused a larger PLR amplitude and a steeper decline of the PLR amplitude from the center to the periphery of the pupillomotor field. The older subjects had reduced mean PLR amplitude with a less pronounced decrease of PLR amplitude toward the field periphery. For the peripheral locations, the largest PLR amplitude was found in the temporal superior quadrants. There was considerable intra-individual test-retest variation in PLR amplitudes in younger and older subjects. The PLR is markedly reduced in older compared with younger subjects. Older subjects have a relatively less pronounced central peak of sensitivity. There are intra-individual test-retest variations in PLR amplitude and asymmetries in sensitivity within the normal pupillomotor field at any age. These findings must be considered in interpreting the results of pupillomotor perimetry.

Pupil response components: studies in patients with Parinaud's syndrome.

In addition to light flux changes, it is well established that other stimulus attributes such as colour, spatial structure or movement can also cause a transient constriction of the pupil, even when the onset of the stimulus causes a net decrease in light flux level on the retina. Although experimental findings in human subjects with postgeniculate lesions show that the generation of such responses must involve the processing of stimulus attributes in extrastriate areas of the cortex, little is known about the site of integration of cortical signals into the pupillomotor pathway. We have investigated how visual performance and the various components of the pupil response have been affected in subjects with damage to the dorsal midbrain (Parinaud's syndrome). The results show that the probable destruction of the olivary pretectal nucleus and the nucleus of the optic tract has little or no effect on pupil grating or pupil colour responses. The light reflex response, on the other hand, is virtually abolished, with only a small residual component that is similar to the pupil grating response and may not require an afferent projection to the midbrain. These new findings suggest that the site of integration of cortical signals in relation to pupil colour and grating responses and the generation of sleepiness-induced oscillations of the pupil do not rely on the normal functioning of pretectal nuclei that are involved in the light reflex response.