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PURPOSE: To determine the ability of Saccadic Vector Optokinetic Perimetry (SVOP) to detect and characterise visual field defects in children with brain tumours using eye-tracking technology, as current techniques for assessment of visual fields in young children can be subjective and lack useful detail.METHODS: Case-series study of children receiving treatment and follow-up for brain tumours at the Royal Hospital for Sick Children in Edinburgh from April 2008 to August 2013. Patients underwent SVOP testing and the results were compared with clinically expected visual field patterns determined by a consensus panel after review of clinical findings, neuroimaging, and where possible other forms of visual field assessment.RESULTS: Sixteen patients participated in this study (mean age of 7.2 years; range 2.9-15 years; 7 male, 9 female). Twelve children (75%) successfully performed SVOP testing. SVOP had a sensitivity of 100% and a specificity of 50% (positive predictive value of 80% and negative predictive value of 100%). In the true positive and true negative SVOP results, the characteristics of the SVOP plots showed agreement with the expected visual field. Six patients were able to perform both SVOP and Goldmann perimetry, these demonstrated similar visual fields in every case.CONCLUSION: SVOP is a highly sensitive test that may prove to be extremely useful for assessing the visual field in young children with brain tumours, as it is able to characterise the central 30° of visual field in greater detail than previously possible with older techniques.

Purpose: To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry.Methods: The subjects included children with suspected field defects (n = 10, age 5–15 years), adults with field defects (n = 33, age 39–78 years), healthy children (n = 12, age 6–14 years), and healthy adults (n = 30, age 16–61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient.Results: Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes.Conclusions: SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups.Translational Relevance: SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations.

Purpose To evaluate feasibility, accuracy, and repeatability of suprathreshold Saccadic Vector Optokinetic Perimetry (SVOP) by comparison with Humphrey Field Analyzer (HFA) perimetry. Methods The subjects included children with suspected field defects (n = 10, age 5–15 years), adults with field defects (n = 33, age 39–78 years), healthy children (n = 12, age 6–14 years), and healthy adults (n = 30, age 16–61 years). The test protocol comprised repeat suprathreshold SVOP and HFA testing with the C-40 test pattern. Feasibility was assessed by protocol completeness. Sensitivity, specificity, and accuracy of SVOP was established by comparison with reliable HFA tests in two ways: (1) visual field pattern results (normal/abnormal), and (2) individual test point outcomes (seen/unseen). Repeatability of each test type was assessed using Cohen's kappa coefficient. Results Of subjects, 82% completed a full protocol. Poor reliability of HFA testing in child patients limited the robustness of comparisons in this group. Sensitivity, specificity, and accuracy across all groups when analyzing the visual field pattern results was 90.9%, 88.5%, and 89.0%, respectively, and was 69.1%, 96.9%, and 95.0%, respectively, when analyzing the individual test points. Cohen's kappa coefficient for repeatability of SVOP and HFA was excellent (0.87 and 0.88, respectively) when assessing visual field pattern results, and substantial (0.62 and 0.74, respectively) when assessing test point outcomes. Conclusions SVOP was accurate in this group of adults. Further studies are required to assess SVOP in child patient groups. Translational Relevance SVOP technology is still in its infancy but is used in a number of centers. It will undergo iterative improvements and this study provides a benchmark for future iterations.

International audience; Objectives: Post-traumatic hypopituitarism is well described among adult traumatic brain injury survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. Design: Retrospective exploratory study. Patients: 33 survivors of accidental head injury (27 males). Mean (range) age at study was 13.4y (5.4-21.7y) and median (range) interval since injury, 4.3y (1.4-7.8y). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. Measurements: Early morning urine osmolality and basal hormone evaluation were followed by the GnRH and insulin tolerance (n=25) or glucagon tests (if previous seizures, n=8). Subjects were not primed. Head injury details were extracted from patient records. Results: No subject had short stature (mean height SD score +0.50, range -1.57 to +3.00). Sub-optimal GH responses (Conclusions: No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.

The post journals of certain Hudson's Bay Company forts were examined for evidence that air mass frequencies during the first half of the nineteenth century were markedly different from those of a modern (1955-1959) period. The "partial collective" technique of Bryson was used to determine the modern frequencies and to provide the basis of the conditional probability structure employed to estimate the historic air mass frequencies. There is evidence from each station for which analysis was performed of a greatly increased presence of "Arctic" air, probably as a consequence of a weakened zonal atmospheric circulation and a decrease in the eastward penetration of "Pacific" air.

Epileptic seizures are often un-witnessed and can result in hypoxic brain damage or can be fatal due to injuries, status epilepticus or sudden unexpected death in epilepsy (SUDEP). The first aim of this thesis was to investigate some of the physiological parameters that accompany an epileptic seizure and may be useful in a seizure alarm system. The second aim was to investigate aspects of cardiac dysfunction during clinical and sub-clinical seizures that may be potential contributing factors in SUDEP. Percentage heart rate change and oxygen saturation were studied prospectively during 527 epileptic seizures in 50 patients aged from one-day full term neonate to 60 years with a variety of seizure types (absences, generalised tonic clonic seizures, myoclonic seizures, tonic seizures and focal seizures) and in normal physiological events (e.g. coughing, turning in bed). Higher percentage heart rate change occurred during epileptic seizures (21.8%) than during normal physiological events (16.4%) p

The commonest reproductive disorders of young men (namely low sperm counts, testicular germ cell cancer) may originate in fetal life similar to established disorders (cryptorchidism, hypospadias) that manifest at birth. These disorders are interlinked and may comprise a testicular dysgenesis syndrome (TDS), a concept supported by animal model studies. The latter have identified the likely time-frame within which TDS disorders may be induced, namely within the so-called masculinisation programming window (MPW). During this critical period, sufficient testosterone (androgen) must be produced by the fetal testis to program the male reproductive tract so that it will differentiate and grow normally after the MPW. Impaired androgen production or action within the MPW can result in smaller reproductive organs and their abnormal formation and function (e.g. cryptorchidism, hypospadias). The MPW is thus of fundamental importance in determining normal, or abnormal, male reproductive development and function for later life. There are two big unanswered questions about the MPW. First, what determines its timing? Second, what mechanisms are controlled by androgens specifically within this time-window and not at later time points? Three approaches were undertaken to address the first question experimentally in rats. First, investigation of whether the availability of androgens and or androgen receptors (AR) plays a role in determining the onset or ‘opening’ of the MPW. Second, investigation of whether the expression of AR co-regulators was a factor in determining androgen sensitivity during the MPW. Third, investigation of whether prostaglandins played a role in mediating androgen action in the MPW, as studies in the 1980s had suggested this possibility. To address what mechanisms are controlled by androgens specifically within the MPW, the expression of selected genes in the genital tubercle was investigated before, during and after the MPW in fetuses that had been exposed to treatments that modulated androgen action. Selection of genes was based on microarray studies and data reported in the literature (ie candidate genes). The studies reported in this thesis show that neither availability of androgens nor the AR are important in determining onset of the MPW, and providing exogenous androgens either prior to or during the MPW does not advance or enhance masculinisation. These studies also showed that females may have a slightly different window of susceptibility to androgen action than do males. Key AR co-regulators have been characterized in the male reproductive tract for the first time, two of which (BRG1, CBP) show changes in expression through development of the testis consistent with a role in Sertoli cells. Another AR co-regulator, RWDD1, was found to switch off in the absence of androgen action in the genital tubercle, pointing to a potential role during and/or after the MPW. Studies involving gestational exposure to indomethacin (a compound which inhibits prostaglandin synthesis) during the MPW showed no detectable effect on masculinisation. Finally, evaluation of candidate genes for mediating androgen action in the genital tubercle during the MPW, failed to identify their key involvement, thus they are unlikely to be involved in penis development and disorders such as hypospadias.

Perimetry is essential to identify visual field defects in disorders of the visual pathways. In compliant adults, automated static perimetry (ASP) is the preferred method of visual field assessment. However, children under 10 years have difficulty with the visuo-motor task and constant fixation required. Manual kinetic perimetry is often used for children as it can be adapted to a child’s age. However, it suffers from many of the problems inherent to ASP. In infants perimetry is limited to the “confrontation” technique which can be imprecise and does not generate quantitative data. The lack of reliable ASP in children and quantitative perimetry in infants is a longstanding clinical problem. The aims of this research were to (i) develop, and (ii) clinically evaluate, a technique for ASP in children which utilises “eye tracking”. The first part of this research was concerned with the development of the technique, termed “Saccadic Vector Optokinetic Perimetry” (SVOP). The system comprises a personal computer, display screen, and an X50 eye tracker (Tobii Technology, Sweden). The eye tracker is noncontact and provides data on (i) eye position in 3D space, and (ii) the point of gaze. This allows the screen position of “test stimuli” to be calculated, and eye gaze responses to the “test stimuli” to be assessed in “real time”. A software algorithm was developed to determine if “test stimuli” have been perceived based on the direction, amplitude and latency of a subject’s gaze response. A feasibility study was conducted with 29 subjects comprising 4 groups: (i) healthy adults, (ii) healthy children, (iii) adult patients with visual field defects, and (iv) child patients with visual field defects. Subjects performed SVOP tests which replicated the Humphrey Field Analyser (HFA) C-40 screening test with a stimulus size of Goldmann III and intensity of 14dB. Subjects able to do so also performed equivalent HFA C-40 tests for comparison. In healthy subjects 99.1% of SVOP test points were in agreement with a healthy visual field. In patients with visual field defects, 89.8% of test points were in agreement with HFA equivalent tests. The visual field defects identified using SVOP in the child patients were consistent with their clinical findings. A clinical evaluation of SVOP was undertaken in the second stage of this research with 122 subjects comprising the same four subject groups as in the feasibility trial. An “ideal” test protocol resulted in 8 uniocular visual field tests for each subject comprising 4 SVOP tests and 4 HFA tests. In children where uniocular testing was not tolerable, two binocular SVOP tests were performed. The sensitivity and specificity of the SVOP tests were computed using a direct comparison with reliable HFA tests, and repeatability of SVOP and HFA tests were assessed using Cohen’s kappa coefficient. In child patients unable to provide a reliable HFA test, their clinical history, other clinical findings and the repeatability of their SVOP tests were used to assess the SVOP results. The overall sensitivity and specificity of the SVOP testing was 72.7% and 96.8% respectively. The sensitivity had a greater variation than the specificity amongst the different subject groups. The repeatability of SVOP tests was slightly reduced as compared to the HFA tests across all groups with kappa coefficient’s of 0.65 and 0.74 for SVOP and HFA respectively. In child patients without reliable HFA equivalent tests the SVOP results could commonly be associated with other clinical findings and repeatable testing added to the confidence in the reliability of these cases. The developed SVOP technique performs well with accurate eye tracking data and an attentive child. It has proved extremely useful in identifying and monitoring visual field defects in several child patients who required regular visual field assessment.