Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?

Pedigree analysis showed that a large proportion of Leber hereditary optic neuropathy (LHON) family members who carry a mitochondrial risk variant never lose vision. Mitochondrial haplotype appears to be a major factor influencing the risk of vision loss from LHON. Mitochondrial variants, including m.14484T>C and m.11778G>A, have been added to gene arrays, and thus many patients and research participants are tested for LHON mutations. Analysis of the UK Biobank and Australian cohort studies found more than 1 in 1,000 people in the general population carry either the m.14484T>C or the m.11778G>A LHON variant. None of the subset of carriers examined had visual acuity at 20/200 or worse, suggesting a very low penetrance of LHON. Haplogroup analysis of m.14484T>C carriers showed a high rate of haplogroup U subclades, previously shown to have low penetrance in pedigrees. Penetrance calculations of the general population are lower than pedigree calculations, most likely because of modifier genetic factors. This Matters Arising Response paper addresses the Watson et al. (2022) Matters Arising paper, published concurrently in The American Journal of Human Genetics.

Establishing risk of vision loss in Leber hereditary optic neuropathy.

We conducted an updated epidemiological study of Leber hereditary optic neuropathy (LHON) in Australia by using registry data to establish the risk of vision loss among different LHON mutations, sex, age at onset, and mitochondrial haplogroup. We identified 96 genetically unrelated LHON pedigrees, including 56 unpublished pedigrees, and updated 40 previously known pedigrees, comprising 620 affected individuals and 4,948 asymptomatic carriers. The minimum prevalence of vision loss due to LHON in Australia in 2020 was one in 68,403 individuals. Although our data confirm some well-established features of LHON, the overall risk of vision loss among those with a LHON mutation was lower than reported previously-17.5% for males and 5.4% for females. Our findings confirm that women, older adults, and younger children are also at risk. Furthermore, we observed a higher incidence of vision loss in children of affected mothers as well as in children of unaffected women with at least one affected brother. Finally, we confirmed our previous report showing a generational fall in prevalence of vision loss among Australian men. Higher reported rates of vision loss in males with a LHON mutation are not supported by our work and other epidemiologic studies. Accurate knowledge of risk is essential for genetic counseling of individuals with LHON mutations. This knowledge could also inform the detection and validation of potential biomarkers and has implications for clinical trials of treatments aimed at preventing vision loss in LHON because an overestimated risk may lead to an underpowered study or a false claim of efficacy.

Pregnancy and the eye: What do we need to watch out for? A review.

Pregnancy causes changes in all body systems, including the eye. The eye can undergo physiological and pathological changes in pregnancy. Some changes exacerbate pre-existing eye conditions while other conditions manifest for the first-time during pregnancy. Early recognition and management are essential to prevent sight threatening complications. In addition, some obstetric complications can be associated with ophthalmic signs. Prompt recognition of these eye findings may be life saving for both the mother and the foetus. The aim of this article is to present potential ocular complications in pregnancy and outline the appropriate management to preserve sight and maintain maternal and foetal safety. The safety of the use of common ophthalmological medications will also be discussed.

Global mercury concentrations in biota: their use as a basis for a global biomonitoring framework.

An important provision of the Minamata Convention on Mercury is to monitor and evaluate the effectiveness of the adopted measures and its implementation. Here, we describe for the first time currently available biotic mercury (Hg) data on a global scale to improve the understanding of global efforts to reduce the impact of Hg pollution on people and the environment. Data from the peer-reviewed literature were compiled in the Global Biotic Mercury Synthesis (GBMS) database (>550,000 data points). These data provide a foundation for establishing a biomonitoring framework needed to track Hg concentrations in biota globally. We describe Hg exposure in the taxa identified by the Minamata Convention: fish, sea turtles, birds, and marine mammals. Based on the GBMS database, Hg concentrations are presented at relevant geographic scales for continents and oceanic basins. We identify some effective regional templates for monitoring methylmercury (MeHg) availability in the environment, but overall illustrate that there is a general lack of regional biomonitoring initiatives around the world, especially in Africa, Australia, Indo-Pacific, Middle East, and South Atlantic and Pacific Oceans. Temporal trend data for Hg in biota are generally limited. Ecologically sensitive sites (where biota have above average MeHg tissue concentrations) have been identified throughout the world. Efforts to model and quantify ecosystem sensitivity locally, regionally, and globally could help establish effective and efficient biomonitoring programs. We present a framework for a global Hg biomonitoring network that includes a three-step continental and oceanic approach to integrate existing biomonitoring efforts and prioritize filling regional data gaps linked with key Hg sources. We describe a standardized approach that builds on an evidence-based evaluation to assess the Minamata Convention's progress to reduce the impact of global Hg pollution on people and the environment.

A novel highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2) can block inflammation- and autoimmune-related pathways.

BACKGROUND: As a member of the Janus kinase (JAK) family, which includes JAK1, JAK2 and JAK3, tyrosine kinase 2 (TYK2) plays an important role in signal transduction and immune system regulation. Moreover, it is also involved in the development of many types of inflammatory and autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE). TYK2 is an attractive therapeutic target, and selective inhibition of TYK2 over other JAK family members is critical for the development of TYK2 small molecule inhibitors. However, targeting the catalytic region of the TYK2 ATP-binding site is a major challenge due to the high structural homology between the catalytic regions of the JAK family proteins. RESULTS: In this study, we developed a novel small molecule inhibitor (QL-1200186) by targeting the pseudokinase regulatory domain (Janus homology 2, JH2) of the TYK2 protein. The binding sites of QL-1200186 were predicted and screened by molecular docking. The inhibitory effects on IFNα, IL-12 and IL-23 signaling were tested in cell lines, human peripheral blood cells and human whole blood. The pharmacokinetic (PK) and pharmacodynamic properties of QL-1200186 were verified in mice. QL-1200186 showed high affinity for TYK2 JH2 and had no apparent selectivity for the TYK2 and JAK homologous kinase domains; these effects were demonstrated using biochemical binding, signaling pathway transduction (JAK1/2/3) and off-target effect assays. More importantly, we revealed that QL-1200186 was functionally comparable and selectivity superior to two clinical-stage TYK2 inhibitors (BMS-986165 and NDI-034858) in vitro. In the PK studies, QL-1200186 exhibited excellent exposure, high bioavailability and low clearance rates in mice. Oral administration of QL-1200186 dose-dependently inhibited interferon-γ (IFNγ) production after interleukin-12 (IL-12) challenge and significantly ameliorated skin lesions in psoriatic mice. CONCLUSION: These findings suggest that QL-1200186 is a highly selective and potent inhibitor of TYK2. QL-1200186 could be an appealing clinical drug candidate for the treatment of psoriasis and other autoimmune diseases. Video Abstract.

Glass Formation in Hybrid Organic-Inorganic Perovskites.

Crystalline materials have governed the development of hybrid organic-inorganic perovskites (HOIPs), giving rise to a variety of fascinating applications such as solar cells and optoelectronic devices. With increasing interest in non-crystalline systems, the glassy state of HOIPs has recently been identified. Here, the basic building blocks of crystalline HOIPs appear to be retained, though their glasses lack long-range periodic order. The emerging family of glasses formed from HOIPs exhibits diverse properties, complementary to their crystalline state. This mini review describes the chemical diversity of both three-dimensional and two-dimensional crystalline HOIPs and demonstrates how glasses are produced from these materials. Specifically, current achievements in melt-quenched glasses formed from HOIPs are highlighted. We conclude with our perspective on the future of this new family of materials.

Patterns in forage fish mercury concentrations across Northeast US estuaries.

Biogeochemical conditions and landscape can have strong influences on mercury bioaccumulation in fish, but these effects across regional scales and between sites with and without point sources of contamination are not well understood. Normal means clustering, a type of unsupervised machine learning, was used to analyze relationships between forage fish (Fundulus heteroclitus and Menidia menidia) mercury (Hg) concentrations and sediment and water column Hg and methylmercury (MeHg) concentrations, ancillary variables, and land classifications within the sub-watershed. The analysis utilized data from 38 sites in 8 estuarine systems in the Northeast US, collected over five years. A large range of mercury concentrations and land use proportions were observed across sites. The cluster correlations indicated that for Fundulus, benthic and pelagic Hg and MeHg concentrations were most related to tissue concentrations, while Menidia Hg was most related to water column MeHg, reflecting differing feeding modes between the species. For both species, dissolved MeHg was most related to tissue concentrations, with sediment Hg concentrations influential at contaminated sites. The models considering only uncontaminated sites showed reduced influence of bulk sediment MeHg for both species, but Fundulus retained sediment drivers at some sites, with dissolved MeHg still highly correlated for both. Dissolved organic carbon (DOC), chlorophyll, land use, and other ancillary variables were of lesser importance in driving bioaccumulation, though DOC was strongly related within some clusters, likely in relation to dissolved Hg. Land use, though not of primary importance, showed relationships opposite to those observed in freshwater, with development positively correlated and forests and agriculture negatively correlated with tissue concentrations across clusters and species. Clusters were composed of sites from geographically distinct systems, indicating the greater importance of small scale drivers of MeHg formation and uptake into the food web over system or region-wide influences.

Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis.

BACKGROUND AND PURPOSE: Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity and a clear, unmet need for an effective therapy. In this work, we evaluated the efficacy of intravenous tissue-type plasminogen activator (IV alteplase) in a prospective cohort study and an updated systematic review and meta-analysis. METHODS: We enrolled consecutive patients with acute central retinal artery occlusion within 48 hours of symptoms onset and with a visual acuity of <20/200 from January 2009 until May 2019. The primary outcomes were safety and functional visual acuity recovery. We compared rates of visual recovery between those treated with alteplase within 4.5 hours of symptom onset to those who did not receive alteplase (including an analysis restricted to untreated patients presenting within the window for treatment). We incorporated these results into an updated systematic review and patient-level meta-analysis. RESULTS: We enrolled 112 patients, of whom 25 (22.3% of the cohort) were treated with IV alteplase. One patient had an asymptomatic intracerebral hemorrhage after IV alteplase treatment. Forty-four percent of alteplase-treated patients had recovery of visual acuity when treated within 4.5 hours versus 13.1% of those not treated with alteplase (P=0.003) and 11.6% of those presenting within 4 hours who did not receive alteplase (P=0.03). Our updated patient-level meta-analysis of 238 patients included 67 patients treated with alteplase within 4.5 hours since time last known well with a recovery rate of 37.3%. This favorably compares with a 17.7% recovery rate in those without treatment. In linear regression, earlier treatment correlated with a higher rate of visual recovery (P=0.01). CONCLUSIONS: This study showed that the administration of intravenous alteplase within 4.5 hours of symptom onset is associated with a higher likelihood of a favorable visual outcome for acute central retinal artery occlusion. Our results strongly support proceeding to a randomized, placebo-controlled clinical trial.

A National-Scale Assessment of Mercury Bioaccumulation in United States National Parks Using Dragonfly Larvae As Biosentinels through a Citizen-Science Framework.

We conducted a national-scale assessment of mercury (Hg) bioaccumulation in aquatic ecosystems, using dragonfly larvae as biosentinels, by developing a citizen-science network to facilitate biological sampling. Implementing a carefully designed sampling methodology for citizen scientists, we developed an effective framework for a landscape-level inquiry that might otherwise be resource limited. We assessed the variation in dragonfly Hg concentrations across >450 sites spanning 100 United States National Park Service units and examined intrinsic and extrinsic factors associated with the variation in Hg concentrations. Mercury concentrations ranged between 10.4 and 1411 ng/g dry weight across sites and varied among habitat types. Dragonfly total Hg (THg) concentrations were up to 1.8-fold higher in lotic habitats than in lentic habitats and 37% higher in waterbodies with abundant wetlands along their margins than those without wetlands. Mercury concentrations in dragonflies differed among families but were correlated (r2 > 0.80) with each other, enabling adjustment to a consistent family to facilitate spatial comparisons among sampling units. Dragonfly THg concentrations were positively correlated with THg concentrations in both fish and amphibians from the same locations, indicating that dragonfly larvae are effective indicators of Hg bioavailability in aquatic food webs. We used these relationships to develop an integrated impairment index of Hg risk to aquatic ecosytems and found that 12% of site-years exceeded high or severe benchmarks of fish, wildlife, or human health risk. Collectively, this continental-scale study demonstrates the utility of dragonfly larvae for estimating the potential mercury risk to fish and wildlife in aquatic ecosystems and provides a framework for engaging citizen science as a component of landscape Hg monitoring programs.

Dragonfly larvae as biosentinels of Hg bioaccumulation in Northeastern and Adirondack lakes: relationships to abiotic factors.

Mercury (Hg) is a toxic pollutant, widespread in northeastern US ecosystems. Resource managers' efforts to develop fish consumption advisories for humans and to focus conservation efforts for fish-eating wildlife are hampered by spatial variability. Dragonfly larvae can serve as biosentinels for Hg given that they are widespread in freshwaters, long-lived, exhibit site fidelity, and bioaccumulate relatively high mercury concentrations, mostly as methylmercury (88% ± 11% MeHg in this study). We sampled lake water and dragonfly larvae in 74 northeastern US lakes that are part of the US EPA Long-Term Monitoring Network, including 45 lakes in New York, 43 of which are in the Adirondacks. Aqueous dissolved organic carbon (DOC) and total Hg (THg) were strongly related to MeHg in lake water. Dragonfly larvae total mercury ranged from 0.016-0.918 µg/g, dw across the study area; Adirondack lakes had the minimum and maximum concentrations. Aqueous MeHg and dragonfly THg were similar between the Adirondack and Northeast regions, but a majority of lakes within the highest quartile of dragonfly THg were in the Adirondacks. Using landscape, lake chemistry, and lake morphometry data, we evaluated relationships with MeHg in lake water and THg in dragonfly larvae. Lakewater DOC and lake volume were strong predictors for MeHg in water. Dragonfly THg Bioaccumulation Factors (BAFs, calculated as [dragonfly THg]:[aqueous MeHg]) increased as lake volume increased, suggesting that lake size influences Hg bioaccumulation or biomagnification. BAFs declined with increasing DOC, supporting a potential limiting effect for MeHg bioavailability with higher DOC.

Mercury Levels in Freshwater Fish: Estimating Concentration with Fish Length to Determine Exposures Through Fish Consumption.

Methylmercury (MeHg) is a neurotoxic pollutant that bioaccumulates and biomagnifies in aquatic food webs, impacting the health of piscivorous wildlife and human consumers of predatory fish. While fish mercury levels have been correlated with various biotic and abiotic factors, many studies only measure adults to characterize the health of locally fished populations, omitting information about how local fish bioaccumulate mercury relative to their growth. In this study, we sought to establish length: total mercury (THg) concentration relationships in juvenile and adult fish of four genera (sunfish, yellow perch, white perch, and killifish) across six freshwater pond systems of Nantucket Island to determine safe consumption sizes across species and environmental conditions. A wide length range (2-21 cm) was utilized to develop linear regression models of ln-THg versus fish length. In most cases, different genera within the same pond indicated similar slopes, supporting that all four genera share comparable features of feeding and growth. Comparing individual species across ponds, differences in ln-THg versus fish length were attributable to known environmental Hg-modulators including surface water MeHg levels, pH, and watershed area. Referencing human health and wildlife criteria, our results confirm that numerous Nantucket freshwater ecosystems contain elevated fish THg levels, which could impact the health of not only piscivorous wildlife in all measured ponds but also recreational fishers in at least two measured systems. Future studies should measure THg levels across juvenile and adult fish to detect potential differences in the slope of THg concentration across fish length relevant for local consumption advice.

Dynamics of Cadmium Acclimation in Daphnia pulex: Linking Fitness Costs, Cross-Tolerance, and Hyper-Induction of Metallothionein.

Acclimation increases tolerance to stress in individuals but is assumed to contribute fitness costs when the stressor is absent, though data supporting this widely held claim are sparse. Therefore, using clonal (i.e., genetically identical) cultures of Daphnia pulex, we isolated the contributions of acclimation to the regulation of the metal response gene, metallothionein 1 (MT1), and defined the reproductive benefits and costs of cadmium (Cd)-acclimation. Daphnia pulex were exposed for 50 parthenogenetic generations to environmentally realistic levels (1 µg Cd/L), and tolerance to Cd and other metals assessed during this period via standard toxicity tests. These tests revealed (1) increased tolerance to Cd compared to genetically identical nonacclimated cultures, (2) fitness costs in Cd-acclimated Daphnia when Cd was removed, and (3) cross-tolerance of Cd-acclimated Daphnia to zinc and silver, but not arsenic, thereby defining a functional role for metallothionein. Indeed, Cd-acclimated clones had significantly higher expression of MT1 mRNA than nonacclimated clones, when Cd exposed. Both the enhanced induction of MT1 and tolerant phenotype were rapidly lost when Cd was removed (1-2 generations), which is further evidence of acclimation costs. These findings provide evidence for the widely held view that acclimation is costly and are important for investigating evolutionary principles of genetic assimilation and the survival mechanisms of natural populations that face changing environments.

Factors affecting MeHg bioaccumulation in stream biota: the role of dissolved organic carbon and diet.

The bioaccumulation of the neurotoxin methylmercury (MeHg) in freshwater ecosystems is thought to be mediated by both water chemistry (e.g., dissolved organic carbon [DOC] and dissolved mercury [Hg]) and diet (e.g., trophic position and diet composition). Hg in small streams is of particular interest given their role as a link between terrestrial and aquatic processes. Terrestrial processes determine the quantity and quality of streamwater DOC, which in turn influence the quantity and bioavailability of dissolved MeHg. To better understand the effects of water chemistry and diet on Hg bioaccumulation in stream biota, we measured DOC and dissolved Hg in stream water and mercury concentration in three benthic invertebrate taxa and three fish species across up to 12 tributary streams in a forested watershed in New Hampshire, USA. As expected, dissolved total mercury (THg) and MeHg concentrations increased linearly with DOC. However, mercury concentrations in fish and invertebrates varied non-linearly, with maximum bioaccumulation at intermediate DOC concentrations, which suggests that MeHg bioavailability may be reduced at high levels of DOC. Further, MeHg and THg concentrations in invertebrates and fish, respectively, increased with δ15N (suggesting trophic position) but were not associated with δ13C. These results show that even though MeHg in water is strongly determined by DOC concentrations, mercury bioaccumulation in stream food webs is the result of both MeHg availability in stream water and trophic position.

Toenail mercury Levels are associated with amyotrophic lateral sclerosis risk.

INTRODUCTION: Mercury is a neurotoxic metal that is potentially a risk factor for amyotrophic lateral sclerosis (ALS). Consumption of methylmercury contaminated fish is the primary source of US population exposure to mercury. METHODS: We used inductively coupled plasma mass spectrometry to measure levels of mercury in toenail samples from patients with ALS (n = 46) and from controls (n = 66) as a biomarker of mercury exposure. RESULTS: Patients with ALS had higher toenail mercury levels (odds ratio 2.49, 95% confidence interval 1.18-5.80, P = 0.024) compared with controls, adjusted for age and sex. We also estimated the amount of mercury consumed from finfish and shellfish and found toenail mercury levels elevated overall among patients with ALS and controls in the top quartile for consumption (P = 0.018). DISCUSSION: Biomarker data show that ALS is associated with increased with mercury levels, which were related to estimated methylmercury intake via fish. Replication of these associations in additional populations is warranted. Muscle Nerve, 2018.

Arsenic Reduces Gene Expression Response to Changing Salinity in Killifish.

Toxicogenomic approaches can detect and classify adverse interactions between environmental toxicants and other environmental stressors but require more complex experimental designs and analytical approaches. Here we use novel toxicogenomic techniques to analyze the effect of arsenic exposure in wild killifish populations acclimating to changing salinity. Fish from three populations were acclimated to full strength seawater and transferred to fresh water for 1 or 24 h. Linear models of gene expression in gill tissue identified 31 genes that responded to osmotic shock at 1 h and 178 genes that responded at 24 h. Arsenic exposure (100 µg/L) diminished the responses (reaction norms) of these genes by 22% at 1 h ( p = 1.0 × 10-6) and by 10% at 24 h ( p = 3.0 × 10-10). Arsenic also significantly reduced gene coregulation in gene regulatory networks ( p = 0.002, paired Levene's test), and interactions between arsenic and salinity acclimation were uniformly antagonistic at the biological pathway level ( p < 0.05, binomial test). Arsenic's systematic interference with gene expression reaction norms was validated in a mouse multistressor experiment, demonstrating the ability of these toxicogenomic approaches to identify biologically relevant adverse interactions between environmental toxicants and other environmental stressors.

A Critical Time for Mercury Science to Inform Global Policy.

Mercury is a global pollutant released into the biosphere by varied human activities including coal combustion, mining, artisanal gold mining, cement production, and chemical production. Once released to air, land and water, the addition of carbon atoms to mercury by bacteria results in the production of methylmercury, the toxic form that bioaccumulates in aquatic and terrestrial food chains resulting in elevated exposure to humans and wildlife. Global recognition of the mercury contamination problem has resulted in the Minamata Convention on Mercury, which came into force in 2017. The treaty aims to protect human health and the environment from human-generated releases of mercury curtailing its movement and transformations in the biosphere. Coincident with the treaty's coming into force, the 13th International Conference of Mercury as a Global Pollutant (ICMGP-13) was held in Providence, Rhode Island USA. At ICMGP-13, cutting edge research was summarized and presented to address questions relating to global and regional sources and cycling of mercury, how that mercury is methylated, the effects of mercury exposure on humans and wildlife, and the science needed for successful implementation of the Minamata Convention. Human activities have the potential to enhance mercury methylation by remobilizing previously released mercury, and increasing methylation efficiency. This synthesis concluded that many of the most important factors influencing the fate and effects of mercury and its more toxic form, methylmercury, stem from environmental changes that are much broader in scope than mercury releases alone. Alterations of mercury cycling, methylmercury bioavailability and trophic transfer due to climate and land use changes remain critical uncertainties in effective implementation of the Minamata Convention. In the face of these uncertainties, important policy and management actions are needed over the short-term to support the control of mercury releases to land, water and air. These include adequate monitoring and communication on risk from exposure to various forms of inorganic mercury as well as methylmercury from fish and rice consumption. Successful management of global and local mercury pollution will require integration of mercury research and policy in a changing world.

Spatial and taxonomic variation of mercury concentration in low trophic level fauna from the Mediterranean Sea.

Studies of mercury (Hg) in the Mediterranean Sea have focused on pollution sources, air-sea mercury exchange, abiotic mercury cycling, and seafood. Much less is known about methylmercury (MeHg) concentrations in the lower food web. Zooplankton and small fish were sampled from the neuston layer at both coastal and open sea stations in the Mediterranean Sea during three cruise campaigns undertaken in the fall of 2011 and the summers of 2012 and 2013. Zooplankton and small fish were sorted by morphospecies, and the most abundant taxa (e.g. euphausiids, isopods, hyperiid amphipods) analyzed for methylmercury (MeHg) concentration. Unfiltered water samples were taken during the 2011 and 2012 cruises and analyzed for MeHg concentration. Multiple taxa suggested elevated MeHg concentrations in the Tyrrhenian and Balearic Seas in comparison with more eastern and western stations in the Mediterranean Sea. Spatial variation in zooplankton MeHg concentration is positively correlated with single time point whole water MeHg concentration for euphausiids and mysids and negatively correlated with maximum chlorophyll a concentration for euphausiids, mysids, and "smelt" fish. Taxonomic variation in MeHg concentration appears driven by taxonomic grouping and feeding mode. Euphausiids, due to their abundance, relative larger size, importance as a food source for other fauna, and observed relationship with surface water MeHg are a good candidate biotic group to evaluate for use in monitoring the bioavailability of MeHg for trophic transfer in the Mediterranean and potentially globally.

Incidence and prevalence of NMOSD in Australia and New Zealand.

OBJECTIVES: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. BACKGROUND: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. METHODS: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. RESULTS: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. CONCLUSIONS: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.

Influence of sample preparation on estuarine macrofauna stable isotope signatures in the context of contaminant bioaccumulation studies.

The ratios of stable isotopes of carbon and nitrogen provide important information on food sources of aquatic organisms and trophic structure of aquatic food webs. For many studies, trophic position and food source are linked to bioaccumulation and trophic transfer of contaminants from prey to predators. In these cases, it is useful to use measurements on whole organisms to make direct comparisons of contaminant bioaccumulation and food web attributes. There is a great deal of variation in methods used for stable isotope analysis, particularly in the selection of tissue type and sample preparation prior to stable isotope analysis. While there have been aquatic studies that examined methodological differences, few have focused on estuarine organisms. In this study, the effects of depuration and tissue dissection on the stable isotope enrichment of common estuarine invertebrates and fish were examined. Homogenized tissues of non-depurated whole organisms were compared to dissected muscle tissue or depurated whole organisms. A 24 h depuration did not change the mean δ15N and δ13C values for most species examined. Additionally, as expected, significant differences in carbon and nitrogen signatures were found when muscle tissues were compared to whole organisms. However, differences were small enough that food source as inferred by δ13C or trophic level as inferred from δ15N would not be inaccurately represented (differences of <1.9‰ for δ13C and <1.2‰ for δ15N). The results of this study suggest that for these common estuarine fish and macroinvertebrates, stable isotopes ratios of samples can be analyzed without depuration in the same way as samples for contaminant analysis, but differences in tissue types must be taken into account when combining data from different sources.