The epidemiology of epilepsy in rural Tanzania :prevalence, phenotype, risk factors and treatment gap

PhD ThesisIntroduction Epilepsy is especially prevalent in low- and middle-income countries, including those in sub-Saharan Africa (SSA). There are few case-controlled data on epilepsy from SSA, where epilepsy remains largely untreated and highly stigmatized. Aims To determine the prevalence of active epilepsy among adults in a rural population in northern Tanzania. To describe the pattern of disease and quantify the epilepsy treatment gap (ETG) in this population. Methods People with epilepsy (PWE) were identified through door-to-door screening of the adult study population (n=103,026) using a previously validated screening questionnaire. Controls were recruited from the background population. Odds ratios for risk factors and impacts of epilepsy were calculated using logistic regression. The burden of neurocysticercosis (NCC) was assessed using neuro-imaging in cases and serology. The ETG was estimated according to self-reported antiepileptic drug use. Results We identified 291 PWE along with 182 controls. The age-standardised prevalence of active epilepsy was 2.91/1,000. All PWE had convulsive epilepsy, 71.5% being of focal onset. Risk factors for epilepsy were a positive family history (OR 29.0), febrile convulsions in childhood (OR 20.4) and obstetric complications (OR 3.4). Eight cases had NCC; six cases and no controls had antibodies to Taenia solium (p=0.036). PWE were less likely to have completed primary education (OR 0.3) and were more likely to be divorced or separated (OR 7.7). The ETG was 68.4%. Conclusions This is one of the largest community-based studies of epilepsy from SSA to date. The large proportion of focal-onset epilepsy suggests a considerable burden of acquired epilepsy. The high ETG may reflect the stigma experienced by PWE in this population

Digital imaging techniques in otolith data capture, analysis and interpretation

Otoliths or ear-stones are hard, calcium carbonate structures located within the inner ear of bony fishes. Counts of rings and measurements of seasonal growth increments from otoliths are important metrics for assessment and management of fish stocks, and the preparation and microscopic analysis of otoliths forms an essential part of the routine work undertaken by fisheries scientists worldwide. Otolith analysis is a skilled task requiring accuracy and precision, but it is laborious, time-consuming to perform, and represents a significant cost to fisheries management. In the last 2 decades, several attempts to apply ‘computer vision’ (systems that perform high-level tasks and exhibit intelligent behaviour) in otolith analysis have been reported. Although considerable progress has been made and several prototype systems developed, laboratories have been reluctant to adopt image-based computer-assisted age and growth estimation (CAAGE) systems. This paper surveys applications of CAAGE, focusing on their utility for automated ageing using images of otolith macrostructure. A cost-benefit analysis of CAAGE of cod, plaice and anchovy shows that computer vision performs relatively poorly compared with morphometric techniques. However, there is evidence that information from visual features can boost the performance of morphometric CAAGE, and further work is needed to develop effective frameworks for this integrated approach. The cost benefit of these systems might be attractive to smaller laboratories that are already using age-length keys derived from otolith morphometrics for management of smaller artisanal fisheries

Validation of otolith δ18O values as effective natural tags for shelf-scale geolocation of migrating fish

The oxygen isotopic ratio of fish otoliths is increasingly used as a 'natural tag' to assess provenance in migratory species, with the assumption that variations in delta O-18 values closely reflect individual ambient experience of temperature and/or salinity. We employed archival tag data and otoliths collected from a shelf-scale study of the spatial dynamics of North Sea plaice Pleuronectes platessa L., to examine the limits of otolith delta O-18-based geolocation of fish during their annual migrations. Detailed intra-annual otolith delta O-18 measurements for 1997-1999 from individuals of 3 distinct sub-stocks with different spawning locations were compared with delta O-18 values predicted at the monthly, seasonal and annual scales, using predicted sub-stock specific temperatures and salinities over the same years. Spatio-temporal variation in expected delta O-18 values (-0.23 to 2.94%) mainly reflected variation in temperature, and among-zone discrimination potential using otolith delta O-18 varied greatly by temporal scale and by time of year. Measured otolith delta O-18 values (-0.71 to 3.09%) largely mirrored seasonally predicted values, but occasionally fell outside expected delta O-18 ranges. Where mismatches were observed, differences among sub-stocks were consistently greater than predicted, suggesting that in plaice, differential sub-stock growth rates and physiological effects during oxygen fractionation enhance geolocation potential using otolith delta O-18. Comparing intra-annual delta O-18 values over several consecutive years for individuals with contrasted migratory patterns corroborated a high degree of feeding and spawning site fidelity irrespective of the sub-stock. Informed interpretation of otolith delta O-18 values can therefore provide relatively detailed fisheries-relevant data not readily obtained by conventional means

Innovative use of sclerochronology in marine resource management

In recent years, technical and analytical developments in sclerochronology, based on the analysis of accretionary hard tissues, have improved our ability to assess the life histories of a wide range of marine organisms. This Theme Section on the innovative use of sclerochronology was motivated by the cross-disciplinary session ‘Looking backwards to move ahead—how the wider application of new technologies to interpret scale, otolith, statolith and other biomineralised age-registering structures could improve management of natural resources’ convened at the 2016 ICES Annual Science Conference in Riga, Latvia. The contributions to this Theme Section provide examples of applications to improve the assessment and management of populations and habitats, or showcase the potential for sclerochronology to provide a deeper understanding of the interaction between marine life and its environment, including the effects of changing climate

Quantifying physiological influences on otolith microchemistry

Trace element concentrations in fish earstones (‘otoliths’) are widely used to discriminate spatially discrete populations or individuals of marine fish, based on a commonly held assumption that physiological influences on otolith composition are minor, and thus variations in otolith elemental chemistry primarily reflect changes in ambient water chemistry. We carried out a long-term (1-year) experiment, serially sampling seawater, blood plasma and otoliths of mature and immature European plaice (Pleuronectes platessa L.) to test relationships between otolith chemistry and environmental and physiological variables. Seasonal variations in otolith elemental composition did not track seawater concentrations, but instead reflected physiological controls on metal transport and biokinetics, which are likely moderated by ambient temperature. The influence of physiological factors on otolith composition was particularly evident in Sr/Ca ratios, the most widely used elemental marker in applied otolith microchemistry studies. Reproduction also triggered specific variations in otolith and blood plasma metal chemistry, especially Zn/Ca ratios in female fish, which could potentially serve as retrospective spawning indicators. The influence of physiology on the trace metal composition of otoliths may explain the success of microchemical stock discrimination in relatively homogenous marine environments, but could complicate alternative uses for trace element compositions in biominerals of higher organism

Inclusion of jellyfish in 30+ years of Ecopath with Ecosim models

A review of the functional role of jellyfish in Ecopath with Ecosim (EwE) models by Pauly et al. [Pauly, D., Graham, W., Libralato, S., Morissette, L., and Deng Palomares, M. L. 2009. Jellyfish in ecosystems, online databases, and ecosystem models. Hydrobiologia, 616: 67–85.] a decade ago concluded that recreation of jellyfish population dynamics in models required additional ecological research and the careful consideration of their unique biology during model construction. Here, amidst calls for ecosystem-based management and the growing recognition of jellyfishes' role in foodwebs, we investigate how jellyfish are implemented in EwE models and identify areas requiring improvement. Over time, an increasing percentage of models have included jellyfish. Jellyfish were often linked to the wider ecosystem, with many predators and prey included in models. However, ecotrophic efficiency, a measure of the extent to which they are used by higher trophic levels, was frequently set at low values, suggesting that jellyfish are still perceived as under-utilized components of the ecosystem. Moving forward, greater care should be taken to differentiate the functional roles played by ctenophores, cnidarians, and pelagic tunicates. Additionally, when feasible, early life stages should be incorporated as multi-stanza groups to more accurately depict jellyfishes' complex life cycle

Jellyfish on the menu: mtDNA assay reveals scyphozoan predation in the Irish Sea

Localized outbreaks of jellyfish, known as blooms, cause a variety of adverse ecological and economic effects. However, fundamental aspects of their ecology remain unknown. Notably, there is scant information on the role jellyfish occupy in food webs: in many ecosystems, few or no predators are known. To identify jellyfish consumers in the Irish Sea, we conducted a molecular gut content assessment of 50 potential predators using cnidarian-specific mtDNA primers and sequencing. We show that jellyfish predation may be more common than previously acknowledged: uncovering many previously unknown jellyfish predators. A substantial proportion of herring and whiting were found to have consumed jellyfish. Rare ingestion was also detected in a variety of other species. Given the phenology of jellyfish in the region, we suggest that the predation was probably targeting juvenile stages of the jellyfish life cycle

Deciphering c-MYC-regulated genes in two distinct tissues.

BACKGROUND: The transcription factor MYC is a critical regulator of diverse cellular processes, including both replication and apoptosis. Differences in MYC-regulated gene expression responsible for such opposing outcomes in vivo remain obscure. To address this we have examined time-dependent changes in global gene expression in two transgenic mouse models in which MYC activation, in either skin suprabasal keratinocytes or pancreatic islet β-cells, promotes tissue expansion or involution, respectively. RESULTS: Consistent with observed phenotypes, expression of cell cycle genes is increased in both models (albeit enriched in β-cells), as are those involved in cell growth and metabolism, while expression of genes involved in cell differentiation is down-regulated. However, in β-cells, which unlike suprabasal keratinocytes undergo prominent apoptosis from 24 hours, there is up-regulation of genes associated with DNA-damage response and intrinsic apoptotic pathways, including Atr, Arf, Bax and Cycs. In striking contrast, this is not the case for suprabasal keratinocytes, where pro-apoptotic genes such as Noxa are down-regulated and key anti-apoptotic pathways (such as Igf1-Akt) and those promoting angiogenesis are up-regulated. Moreover, dramatic up-regulation of steroid hormone-regulated Kallikrein serine protease family members in suprabasal keratinocytes alone could further enhance local Igf1 actions, such as through proteolysis of Igf1 binding proteins. CONCLUSIONS: Activation of MYC causes cell growth, loss of differentiation and cell cycle entry in both β-cells and suprabasal keratinocytes in vivo. Apoptosis, which is confined to β-cells, may involve a combination of a DNA-damage response and downstream activation of pro-apoptotic signalling pathways, including Cdc2a and p19(Arf)/p53, and downstream targets. Conversely, avoidance of apoptosis in suprabasal keratinocytes may result primarily from the activation of key anti-apoptotic signalling pathways, particularly Igf1-Akt, and induction of an angiogenic response, though intrinsic resistance to induction of p19(Arf) by MYC in suprabasal keratinocytes may contribute.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain

<p>Abstract</p> <p>Background</p> <p>The Hox family of homeodomain transcription factors comprises pivotal regulators of cell specification and identity during animal development. However, despite their well-defined roles in the establishment of anteroposterior pattern and considerable research into their mechanism of action, relatively few target genes have been identified in the downstream regulatory network. We have sought to investigate this issue, focussing on the developing hindbrain and the cranial motor neurons that arise from this region. The reiterated anteroposterior compartments of the developing hindbrain (rhombomeres (r)) are normally patterned by the combinatorial action of distinct Hox genes. Alteration in the normal pattern of Hox cues in this region results in a transformation of cellular identity to match the remaining Hox profile, similar to that observed in <it>Drosophila </it>homeotic transformations.</p> <p>Results</p> <p>To define the repertoire of genes regulated in each rhombomere, we have analysed the transcriptome of each rhombomere from wild-type mouse embryos and not those where pattern is perturbed by gain or loss of Hox gene function. Using microarray and bioinformatic methodologies in conjunction with other confirmatory techniques, we report here a detailed and comprehensive set of potential Hox target genes in r2, r3, r4 and r5. We have demonstrated that the data produced are both fully reflective and predictive of rhombomere identity and, thus, may represent some the of Hox targets. These data have been interrogated to generate a list of candidate genes whose function may contribute to the generation of neuronal subtypes characteristic of each rhombomere. Interestingly, the data can also be classified into genetic motifs that are predicted by the specific combinations of Hox genes and other regulators of hindbrain anteroposterior identity. The sets of genes described in each or combinations of rhombomeres span a wide functional range and suggest that the Hox genes, as well as other regulatory inputs, exert their influence across the full spectrum of molecular machinery.</p> <p>Conclusion</p> <p>We have performed a systematic survey of the transcriptional status of individual segments of the developing mouse hindbrain and identified hundreds of previously undescribed genes expressed in this region. The functional range of the potential candidate effectors or upstream modulators of Hox activity suggest multiple unexplored mechanisms. In particular, we present evidence of a potential new retinoic acid signalling system in ventral r4 and propose a model for the refinement of identity in this region. Furthermore, the rhombomeres demonstrate a molecular relationship to each other that is consistent with known observations about neurogenesis in the hindbrain. These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain.</p

How quantitative is metabarcoding: a meta-analytical approach

Metabarcoding has been used in a range of ecological applications such as taxonomic assignment, dietary analysis, and the analysis of environmental DNA. However, after a decade of use in these applications there is little consensus on the extent to which proportions of reads generated corresponds to the original proportions of species in a community. To quantify our current understanding we conducted a structured review and meta‐analysis. The analysis suggests that a weak quantitative relationship may exist between the biomass and sequences produced (slope = 0.52 ±0.34, p<0.01), albeit it with a large degree of uncertainty. None of the tested moderators: sequencing platform type, the number of species used in a trial, or the source of DNA were able to explain the variance. Our current understanding of the factors affecting the quantitative performance of metabarcoding is still limited: additional research is required before metabarcoding can be confidently utilised for quantitative applications. Until then, we advocate the inclusion of mock communities when metabarcoding as this facilitates direct assessment of the quantitative ability of any given study