Sampling methods for activation correlation graphs to predict neural network generalization using topological data analysis

Treballs finals del Màster de Fonaments de Ciència de Dades, Facultat de matemàtiques, Universitat de Barcelona. Curs: 2022-2023. Tutor: Sergio Escalera Guerrero i Rubén Ballester Bautista[en] The performance of a deep neural network (DNN) is dependent on its ability to generalize. This ability is often expressed in the difference in accuracy on a training and test set, or the generalization gap. Recent research has seen the use of topological data analysis to estimate this performance gap without the use of a test set. Here, persistent homology measures are derived from a weighted graph of neuron activation correlations (functional network graph). The resulting persistence diagram is vectorized by a number of statistical summaries and correlated with the generalization gap. However, the computational complexity of persistent homology calculations hinders the application to DNNs with a larger number of activations. Methods are needed to sample these activations without losing predictive power. This work assesses the effect of different sampling strategies on the resulting persistence diagrams and their summaries. These include (non-)stratified random sampling, three methods based on notions of neuron importance similar to those used in pruning, and one using $k$-means++. In line with previous research some of these strategies provide models for predicting the generalization gap with high accuracy. The investigations provide insight and open up new lines of research into the structure of the functional network activation graph

Outcome assessment in epilepsy: available rating scales for adults and methodological issues pertaining to the development of scales for childhood epilepsy.

During the past decade, several scales have been developed to improve the assessment of outcome in epilepsy. These scales were developed for adults and their reliability, validity and usefulness have been established. However, there is also a need for alternative measures of outcome in childhood epilepsy, especially a measure of seizure severity (SS) and measures pertaining to quality of life (QoL). Four of these adult scales are reviewed and compared to examine their applicability in childhood epilepsy. Two important methodological differences between them are discussed: (a) patient self-report vs. physician-based scales and (b) generic vs. disease-specific instruments. QoL in epilepsy is briefly reviewed. Severity of seizures and severity of side-effects are relatively neglected areas of importance to QoL in epilepsy. The existing instruments for adults are not appropriate for children in their present form. Some specific methodological issues, which are relevant for the development of scales for children with epilepsy, are subsequently discussed. New scales pertaining to physical and psychosocial aspects of QoL in childhood epilepsy are being developed. In the near future, data on their reliability, validity and usefulness will become available. A combination of scales focusing on specific aspects of QoL, including SS and severity of adverse effects, and more traditional clinical data may provide a more complete assessment of outcome in childhood epilepsy

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Patients’ use of information about medicine side effects in relation to experiences of suspected adverse drug reactions

Background Adverse drug reactions (ADRs) are common, and information about medicines is increasingly widely available to the public. However, relatively little work has explored how people use medicines information to help them assess symptoms that may be suspected ADRs. Objective Our objective was to determine how patients use patient information leaflets (PILs) or other medicines information sources and whether information use differs depending on experiences of suspected ADRs. Method This was a cross-sectional survey conducted in six National Health Service (NHS) hospitals in North West England involving medical in-patients taking at least two regular medicines prior to admission. The survey was administered via a questionnaire and covered use of the PIL and other medicines information sources, perceived knowledge about medicines risks/ADRs, experiences of suspected ADRs, plus demographic information. Results Of the 1,218 respondents to the survey, 18.8 % never read the PIL, whilst 6.5 % only do so if something unexpected happens. Educational level was related to perceived knowledge about medicines risks, but not to reading the PIL or seeking further information about medicines risks. Over half the respondents (56.0 %) never sought more information about possible side effects of medicines. A total of 57.2 % claimed they had experienced a suspected ADR. Of these 85.9 % were either very sure or fairly sure this was a reaction to a medicine. Over half of those experiencing a suspected ADR (53.8 %) had read the PIL, of whom 36.2 % did so before the suspected ADR occurred, the remainder afterwards. Reading the PIL helped 84.8 % of these respondents to decide they had experienced an ADR. Educational level, general knowledge of medicines risks and number of regular medicines used all increased the likelihood of experiencing an ADR. Conclusion More patients should be encouraged to read the PIL supplied with medicines. The results support the view that most patients feel knowledgeable about medicines risks and suspected ADRs and value information about side effects, but that reading about side effects in PILs or other medicines information sources does not lead to experiences of suspected ADRs

Visual hypersensitivity in patients treated with anti-calcitonin gene–related peptide (receptor) monoclonal antibodies

Objective: To evaluate the effect of treatment with anti-calcitonin gene–related peptide (CGRP; receptor) antibodies on visual hypersensitivity in patients with migraine. Background: Increased visual sensitivity can be present both during and outside migraine attacks. CGRP has been demonstrated to play a key role in light-aversive behavior. Methods: In this prospective follow-up study, patients treated for migraine with erenumab (n = 105) or fremanezumab (n = 100) in the Leiden Headache Center were invited to complete a questionnaire on visual sensitivity (the Leiden Visual Sensitivity Scale [L-VISS]), pertaining to both their ictal and interictal state, before starting treatment (T0) and 3 months after treatment initiation (T1). Using a daily e-diary, treatment effectiveness was assessed in weeks 9–12 compared to a 4-week pre-treatment baseline period. L-VISS scores were compared between T0 and T1. Subsequently, the association between the reduction in L-VISS scores and the reduction in monthly migraine days (MMD) was investigated. Results: At 3 months, the visual hypersensitivity decreased, with a decrease in mean ± standard deviation (SD) ictal L-VISS (from 20.1 ± 7.7 to 19.2 ± 8.1, p = 0.042) and a decrease in mean ± SD interictal L-VISS (from 11.8 ± 6.6 to 11.1 ± 7.0, p = 0.050). We found a positive association between the reduction in MMD and the decrease in interictal L-VISS (β = 0.2, p = 0.010) and the reduction in ictal L-VISS (β = 0.3, p = 0.001). Conclusion: A decrease in visual hypersensitivity in patients with migraine after treatment with anti-CGRP (receptor) antibodies is positively associated with clinical response on migraine.</p

Validity of health insurance data to identify people with epilepsy

BACKGROUND: Large administrative databases may prove useful to assess epilepsy-related comorbidity and mortality. Despite their increased use, their validity as data source in epilepsy is yet under-ascertained. METHODS: Achmea is a large Dutch health insurance company covering about 25% of the population. We performed a retrospective cohort study using data from the Achmea Health Insurance Database (AHID) over the period 2006-2009. To assess the validity of epilepsy codes in the AHID, we randomly invited 1000 individuals (age 18-75 years insured by Achmea), attending an epilepsy centre or a district hospital during 2006-2009, to participate. Informed consent was provided and 293 were eligible for inclusion. We compared the diagnostic codes for epilepsy in AHID with the diagnosis in their case-notes (reference standard). As additional measure of validity, we compared prevalence of epilepsy codes in AHID (based on anonymized data of all 26.297 subjects with this code in AHID) with epilepsy prevalence rates in the general Dutch population to estimate an age-specific standardized prevalence ratio. RESULTS: We identified 293 participants with an epilepsy code in AHID. The majority (278) of them had a definite or possible diagnosis of epilepsy in the case-notes; i.e. a positive predictive value of 0.95 (95% CI 0.92-0.97). The overall prevalence of epilepsy codes in the AHID was slightly higher than the putative prevalence in the general Dutch population (7.4/1.000 vs. 6.8/1.000) with a Standardized Prevalence Ratio of 1.08 (95% CI: 1.08-1.09). CONCLUSIONS: Our findings demonstrate the validity of AHID data for a diagnosis of epilepsy and confirm previous work on using administrative data for epilepsy research

A prospective study of adverse drug reactions to antiepileptic drugs in children

Objectives To prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour. Setting A single centre prospective observational study. Participants Children (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit. Primary and secondary outcomes Primary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes. Results 180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR. Conclusions Behavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children