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Cognitive skills, such as innovative problem-solving, are hypothesized to aid animals in urban environments. However, the significance of innovation in wild populations, and its expression across individuals and socio-ecological conditions, is poorly understood. To identify how and when innovation arises in urban-dwelling species, we used advanced technologies and new testing and analytical methods to evaluate innovative problem-solving abilities of wild raccoons (Procyon lotor). We deployed multi-compartment puzzle boxes with either one or multiple solution types and identified raccoons using radio frequency identification. Raccoons solved these novel extractive foraging tasks, and their success was influenced by age and exploratory diversity. Successful raccoons always discovered multiple different solution types, highlighting flexible problem-solving. Using a unique, comparative sequence analysis approach, we found that variation in raccoon solving techniques was greater between individuals than within individuals, and this self-similarity intensified during times of competition. Finally, the inclusion of an easier solution in the multi-solution trials enabled previously unsuccessful raccoons to bootstrap their learning and successfully open multiple difficult solutions. Our study suggests that innovative problem-solving is probably influenced by many factors and has provided novel field and analytical methods, as well as new insights on the socio-ecological dynamics of urban populations.

PurposeVideo-electroencephalographic monitoring (VEM) is a core component to the diagnosis and evaluation of epilepsy and dissociative seizures (DS)-also known as functional or psychogenic seizures-but VEM evaluation often occurs later than recommended. To understand why delays occur, we compared how patient-reported clinical factors were associated with time from first seizure to VEM (TVEM) in patients with epilepsy, DS or mixed.MethodsWe acquired data from 1245 consecutive patients with epilepsy, VEM-documented DS or mixed epilepsy and DS. We used multivariate log-normal regression with recursive feature elimination (RFE) to evaluate which of 76 clinical factors interacting with patients' diagnoses were associated with TVEM.ResultsThe mean and median TVEM were 14.6 years and 10 years, respectively (IQR 3-23 years). In the multivariate RFE model, the factors associated with longer TVEM in all patients included unemployment and not student status, more antiseizure medications (current and past), concussion, and ictal behavior suggestive of temporal lobe epilepsy. Average TVEM was shorter for DS than epilepsy, particularly for patients with depression, anxiety, migraines, and eye closure. Average TVEM was longer specifically for patients with DS taking more medications, more seizure types, non-metastatic cancer, and with other psychiatric comorbidities.ConclusionsIn all patients with seizures, trials of numerous antiseizure medications, unemployment and non-student status was associated with longer TVEM. These associations highlight a disconnect between International League Against Epilepsy practice parameters and observed referral patterns in epilepsy. In patients with dissociative seizures, some but not all factors classically associated with DS reduced TVEM.

PurposeWhile certain clinical factors suggest a diagnosis of dissociative seizures (DS), otherwise known as functional or psychogenic nonepileptic seizures (PNES), ictal video-electroencephalography monitoring (VEM) is the gold standard for diagnosis. Diagnostic delays were associated with worse quality of life and more seizures, even after treatment. To understand why diagnoses were delayed, we evaluated which factors were associated with delay to VEM.MethodsUsing data from 341 consecutive patients with VEM-documented dissociative seizures, we used multivariate log-normal regression with recursive feature elimination (RFE) and multiple imputation of some missing data to evaluate which of 76 clinical factors were associated with time from first dissociative seizure to VEM.ResultsThe mean delay to VEM was 8.4 years (median 3 years, IQR 1-10 years). In the RFE multivariate model, the factors associated with longer delay to VEM included more past antiseizure medications (0.19 log-years/medication, standard error (SE) 0.05), more medications for other medical conditions (0.06 log-years/medication, SE 0.03), history of physical abuse (0.75 log-years, SE 0.27), and more seizure types (0.36 log-years/type, SE 0.11). Factors associated with shorter delay included active employment or student status (-1.05 log-years, SE 0.21) and higher seizure frequency (0.14 log-years/log[seizure/month], SE 0.06).ConclusionsPatients with greater medical and seizure complexity had longer delays. Delays in multiple domains of healthcare can be common for victims of physical abuse. Unemployed and non-student patients may have had more barriers to access VEM. These results support earlier referral of complex cases to a comprehensive epilepsy center.

ObjectiveTo develop a Dissociative Seizures Likelihood Score (DSLS), which is a comprehensive, evidence-based tool using information available during the first outpatient visit to identify patients with "probable" dissociative seizures (DS) to allow early triage to more extensive diagnostic assessment.MethodsBased on data from 1616 patients with video-electroencephalography (vEEG) confirmed diagnoses, we compared the clinical history from a single neurology interview of patients in five mutually exclusive groups: epileptic seizures (ES), DS, physiologic nonepileptic seizure-like events (PSLE), mixed DS plus ES, and inconclusive monitoring. We used data-driven methods to determine the diagnostic utility of 76 features from retrospective chart review and applied this model to prospective interviews.ResultsThe DSLS using recursive feature elimination (RFE) correctly identified 77% (95% confidence interval (CI), 74-80%) of prospective patients with either ES or DS, with a sensitivity of 74% and specificity of 84%. This accuracy was not significantly inferior than neurologists' impression (84%, 95% CI: 80-88%) and the kappa between neurologists' and the DSLS was 21% (95% CI: 1-41%). Only 3% of patients with DS were missed by both the fellows and our score (95% CI 0-11%).SignificanceThe evidence-based DSLS establishes one method to reliably identify some patients with probable DS using clinical history. The DSLS supports and does not replace clinical decision making. While not all patients with DS can be identified by clinical history alone, these methods combined with clinical judgement could be used to identify patients who warrant further diagnostic assessment at a comprehensive epilepsy center.

In the era of widespread antiretroviral therapy (ART), consequences of being HIV-exposed is unclear for children, especially in rural communities. A population sample of consecutive births (470/493) in the Eastern Cape of South Africa (SA) were recruited and reassessed at five points over the first 24 months. Maternal and child outcomes between mothers living with and without HIV were assessed using multiple linear and logistic regressions. At birth, 28% of the sample was mothers living with HIV and five additional mothers seroconverted. All mothers living with HIV reported taking ART. The rate of depressed mood and IPV was similar across serostatus. However, mothers living with HIV significantly decreased their alcohol use after learning about their pregnancy and were more likely to exclusively breastfeed when compared to mothers without HIV. Despite maternal HIV status, children had similar growth across the first 24 months of life. Future work is needed to assess if these developmental trajectories will persist.

Alcohol is a major contributor to the global burden of disease. In South Africa, alcohol abuse is hypothesized to correlate with women's HIV status, mental health, and partner relationships over time. All pregnant women in 12 urban, low-income, Cape Town neighborhoods were interviewed at baseline, post-birth, and at 6, 12, 36, and 60 months following delivery with retention rates from 82.5 to 94%. Women were assessed for any alcohol use, problematic drinking, depression, intimate partner violence, and HIV status. Prior to pregnancy discovery and 5 years after giving birth, alcohol use was 25.8 and 24.7%, respectively. Most women decreased their alcohol use during pregnancy. Twenty-one percent reported alcohol use on two or more assessments, and only 15% of the mothers drinking alcohol at 5 years were also drinking at baseline. Mothers with depression had a higher likelihood of drinking alcohol compared to mothers who were not depressed only at baseline and 6 months post-birth. Mothers who experienced IPV had more than twice the likelihood of drinking alcohol compared to non-IPV mothers at all assessments. HIV positive mothers were more likely to drink alcohol compared to mothers without HIV prior to pregnancy discovery and at 5 years post-birth. These longitudinal trends in alcohol use among young women in South Africa represent a large economic, social, and health burden and must be addressed in a comprehensive manner.

Alcohol is a major contributor to the global burden of disease. In South Africa, alcohol abuse is hypothesized to correlate with women's HIV status, mental health, and partner relationships over time. All pregnant women in 12 urban, low-income, Cape Town neighborhoods were interviewed at baseline, post-birth, and at 6, 12, 36, and 60 months following delivery with retention rates from 82.5 to 94%. Women were assessed for any alcohol use, problematic drinking, depression, intimate partner violence, and HIV status. Prior to pregnancy discovery and 5 years after giving birth, alcohol use was 25.8 and 24.7%, respectively. Most women decreased their alcohol use during pregnancy. Twenty-one percent reported alcohol use on two or more assessments, and only 15% of the mothers drinking alcohol at 5 years were also drinking at baseline. Mothers with depression had a higher likelihood of drinking alcohol compared to mothers who were not depressed only at baseline and 6 months post-birth. Mothers who experienced IPV had more than twice the likelihood of drinking alcohol compared to non-IPV mothers at all assessments. HIV positive mothers were more likely to drink alcohol compared to mothers without HIV prior to pregnancy discovery and at 5 years post-birth. These longitudinal trends in alcohol use among young women in South Africa represent a large economic, social, and health burden and must be addressed in a comprehensive manner.

The delivery of high-quality HIV care in rural settings is a global challenge. Despite the successful expansion of antiretroviral therapy (ART) in Africa, viral load (VL) monitoring and ART adherence are poor, especially in rural communities. This article describes a case study of an ART program in the deeply rural Eastern Cape of South Africa. The Zithulele ART Program initiated five innovations over time: (1) establishing district hospital as the logistical hub for all ART care in a rural district, (2) primary care clinic delivery of prepackaged ART and chronic medications for people living with HIV (PLH), (3) establishing central record keeping, (4) incentivizing VL monitoring, and (5) providing hospital-based outpatient care for complex cases. Using a pharmacy database, on-time VL monitoring and viral suppression were evaluated for 882 PLH initiating ART in the Zithulele catchment area in 2013. Among PLH initiating ART, 12.5% (n = 110) were lost to follow-up, 7.7% (n = 68) transferred out of the region, 10.2% (n = 90) left the program and came back at a later date, and 4.0% (n = 35) died. Of the on-treatment population, 82.9% (n = 480/579) had VL testing within 7 months and 92.6% (n = 536/579) by 1 year. Viral suppression was achieved in 85.2% of those tested (n = 457/536), or 78.9% (n = 457/579) overall. The program's VL testing and suppression rates appear about twice as high as national data and data from other rural centers in South Africa, despite fewer resources than other programs. Simple system innovations can ensure high rates of VL testing and suppression, even in rural health facilities.

The delivery of high-quality HIV care in rural settings is a global challenge. Despite the successful expansion of antiretroviral therapy (ART) in Africa, viral load (VL) monitoring and ART adherence are poor, especially in rural communities. This article describes a case study of an ART program in the deeply rural Eastern Cape of South Africa. The Zithulele ART Program initiated five innovations over time: (1) establishing district hospital as the logistical hub for all ART care in a rural district, (2) primary care clinic delivery of prepackaged ART and chronic medications for people living with HIV (PLH), (3) establishing central record keeping, (4) incentivizing VL monitoring, and (5) providing hospital-based outpatient care for complex cases. Using a pharmacy database, on-time VL monitoring and viral suppression were evaluated for 882 PLH initiating ART in the Zithulele catchment area in 2013. Among PLH initiating ART, 12.5% (n = 110) were lost to follow-up, 7.7% (n = 68) transferred out of the region, 10.2% (n = 90) left the program and came back at a later date, and 4.0% (n = 35) died. Of the on-treatment population, 82.9% (n = 480/579) had VL testing within 7 months and 92.6% (n = 536/579) by 1 year. Viral suppression was achieved in 85.2% of those tested (n = 457/536), or 78.9% (n = 457/579) overall. The program's VL testing and suppression rates appear about twice as high as national data and data from other rural centers in South Africa, despite fewer resources than other programs. Simple system innovations can ensure high rates of VL testing and suppression, even in rural health facilities.

OBJECTIVE:Psychogenic nonepileptic seizure (PNES) is a common diagnosis after evaluation of medication resistant or atypical seizures with video-electroencephalographic monitoring (VEM), but usually follows a long delay after the development of seizures, during which patients are treated for epilepsy. Therefore, more readily available diagnostic tools are needed for earlier identification of patients at risk for PNES. A tool based on patient-reported psychosocial history would be especially beneficial because it could be implemented in the outpatient clinic. METHODS:Based on the data from 1375 patients with VEM-confirmed diagnoses, we used logistic regression to compare the frequency of specific patient-reported historical events, demographic information, age of onset, and delay from first seizure until VEM in five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of this information to differentiate PNES only from ES only, we used multivariate piecewise-linear logistic regression trained using retrospective data from chart review and validated based on data from 246 prospective standardized interviews. RESULTS:The prospective area under the curve of our weighted multivariate piecewise-linear by-sex score was 73%, with the threshold that maximized overall retrospective accuracy resulting in a prospective sensitivity of 74% (95% CI: 70-79%) and prospective specificity of 71% (95% CI: 64-82%). The linear model and piecewise linear without an interaction term for sex had very similar performance statistics. In the multivariate piecewise-linear sex-split predictive model, the significant factors positively associated with ES were history of febrile seizures, current employment or active student status, history of traumatic brain injury (TBI), and longer delay from first seizure until VEM. The significant factors as

ObjectiveEarly and accurate diagnosis of patients with psychogenic nonepileptic seizures (PNES) leads to appropriate treatment and improves long-term seizure prognosis. However, this is complicated by the need to record seizures to make a definitive diagnosis. Suspicion for PNES can be raised through knowledge that patients with PNES have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (RoSQs) than patients with epileptic seizures. If the responses on the RoSQ can differentiate PNES from other seizure types, then these forms could be an early screening tool.MethodsOur dataset included all patients admitted from January 2006 to June 2016 for video-electroencephalography at UCLA. RoSQs prior to May 2015 were acquired through retrospective chart review (n=405), whereas RoSQs from subsequent patients were acquired prospectively (n=190). Controlling for sex and number of comorbidities, we used binomial regression to compare the total number of symptoms and the frequency of specific symptoms between five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of RoSQs to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and the number of medical comorbidities.ResultsOn average, patients with PNES or mixed PNES and ES reported more than twice as many symptoms than patients with isolated ES or PSLE (p<0.001). The prospective accuracy to differentiate PNES from ES was not significantly higher than naïve assumption that all patients had ES (76% vs 70%, p>0.1).DiscussionThis analysis of RoSQs confirms that patients with PNES with and without comorbid ES report more symptoms on a population level than patients with epilepsy or PSLE. While these differences help describe the population of patients with PNES, the consisten

ObjectiveEarly and accurate diagnosis of patients with psychogenic nonepileptic seizures (PNES) leads to appropriate treatment and improves long-term seizure prognosis. However, this is complicated by the need to record seizures to make a definitive diagnosis. Suspicion for PNES can be raised through knowledge that patients with PNES have increased somatic sensitivity and report more positive complaints on review-of-systems questionnaires (RoSQs) than patients with epileptic seizures. If the responses on the RoSQ can differentiate PNES from other seizure types, then these forms could be an early screening tool.MethodsOur dataset included all patients admitted from January 2006 to June 2016 for video-electroencephalography at UCLA. RoSQs prior to May 2015 were acquired through retrospective chart review (n=405), whereas RoSQs from subsequent patients were acquired prospectively (n=190). Controlling for sex and number of comorbidities, we used binomial regression to compare the total number of symptoms and the frequency of specific symptoms between five mutually exclusive groups of patients: epileptic seizures (ES), PNES, physiologic nonepileptic seizure-like events (PSLE), mixed PNES plus ES, and inconclusive monitoring. To determine the diagnostic utility of RoSQs to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and the number of medical comorbidities.ResultsOn average, patients with PNES or mixed PNES and ES reported more than twice as many symptoms than patients with isolated ES or PSLE (p<0.001). The prospective accuracy to differentiate PNES from ES was not significantly higher than naïve assumption that all patients had ES (76% vs 70%, p>0.1).DiscussionThis analysis of RoSQs confirms that patients with PNES with and without comorbid ES report more symptoms on a population level than patients with epilepsy or PSLE. While these differences help describe the population of patients with PNES, the consisten

ObjectiveLow-cost evidence-based tools are needed to facilitate the early identification of patients with possible psychogenic nonepileptic seizures (PNES). Prior to accurate diagnosis, patients with PNES do not receive interventions that address the cause of their seizures and therefore incur high medical costs and disability due to an uncontrolled seizure disorder. Both seizures and comorbidities may contribute to this high cost.MethodsBased on data from 1,365 adult patients with video-electroencephalography-confirmed diagnoses from a single center, we used logistic and Poisson regression to compare the total number of comorbidities, number of medications, and presence of specific comorbidities in five mutually exclusive groups of diagnoses: epileptic seizures (ES) only, PNES only, mixed PNES and ES, physiologic nonepileptic seizurelike events, and inconclusive monitoring. To determine the diagnostic utility of comorbid diagnoses and medication history to differentiate PNES only from ES only, we used multivariate logistic regression, controlling for sex and age, trained using a retrospective database and validated using a prospective database.ResultsOur model differentiated PNES only from ES only with a prospective accuracy of 78% (95% confidence interval =72-84%) and area under the curve of 79%. With a few exceptions, the number of comorbidities and medications was more predictive than a specific comorbidity. Comorbidities associated with PNES were asthma, chronic pain, and migraines (p < 0.01). Comorbidities associated with ES were diabetes mellitus and nonmetastatic neoplasm (p < 0.01). The population-level analysis suggested that patients with mixed PNES and ES may be a population distinct from patients with either condition alone.SignificanceAn accurate patient-reported medical history and medication history can be useful when screening for possible PNES. Our prospectively validated and objective score may assist in the interpretation of the medication

The definitive diagnosis of the type of epilepsy, if it exists, in medication-resistant seizure disorder is based on the efficient combination of clinical information, long-term video-electroencephalography (EEG) and neuroimaging. Diagnoses are reached by a consensus panel that combines these diverse modalities using clinical wisdom and experience. Here we compare two methods of multimodal computer-aided diagnosis, vector concatenation (VC) and conditional dependence (CD), using clinical archive data from 645 patients with medication-resistant seizure disorder, confirmed by video-EEG. CD models the clinical decision process, whereas VC allows for statistical modeling of cross-modality interactions. Due to the nature of clinical data, not all information was available in all patients. To overcome this, we multiply-imputed the missing data. Using a C4.5 decision tree, single modality classifiers achieved 53.1%, 51.5% and 51.1% average accuracy for MRI, clinical information and FDG-PET, respectively, for the discrimination between non-epileptic seizures, temporal lobe epilepsy, other focal epilepsies and generalized-onset epilepsy (vs. chance, p<0.01). Using VC, the average accuracy was significantly lower (39.2%). In contrast, the CD classifier that classified with MRI then clinical information achieved an average accuracy of 58.7% (vs. VC, p<0.01). The decrease in accuracy of VC compared to the MRI classifier illustrates how the addition of more informative features does not improve performance monotonically. The superiority of conditional dependence over vector concatenation suggests that the structure imposed by conditional dependence improved our ability to model the underlying diagnostic trends in the multimodality data.

The definitive diagnosis of the type of epilepsy, if it exists, in medication-resistant seizure disorder is based on the efficient combination of clinical information, long-term video-electroencephalography (EEG) and neuroimaging. Diagnoses are reached by a consensus panel that combines these diverse modalities using clinical wisdom and experience. Here we compare two methods of multimodal computer-aided diagnosis, vector concatenation (VC) and conditional dependence (CD), using clinical archive data from 645 patients with medication-resistant seizure disorder, confirmed by video-EEG. CD models the clinical decision process, whereas VC allows for statistical modeling of cross-modality interactions. Due to the nature of clinical data, not all information was available in all patients. To overcome this, we multiply-imputed the missing data. Using a C4.5 decision tree, single modality classifiers achieved 53.1%, 51.5% and 51.1% average accuracy for MRI, clinical information and FDG-PET, respectively, for the discrimination between non-epileptic seizures, temporal lobe epilepsy, other focal epilepsies and generalized-onset epilepsy (vs. chance, p<0.01). Using VC, the average accuracy was significantly lower (39.2%). In contrast, the CD classifier that classified with MRI then clinical information achieved an average accuracy of 58.7% (vs. VC, p<0.01). The decrease in accuracy of VC compared to the MRI classifier illustrates how the addition of more informative features does not improve performance monotonically. The superiority of conditional dependence over vector concatenation suggests that the structure imposed by conditional dependence improved our ability to model the underlying diagnostic trends in the multimodality data.