Telemedicine visits in myasthenia gravis: Expert guidance and the Myasthenia Gravis Core Exam (MG-CE).

INTRODUCTION/AIMS: Telemedicine may be particularly well-suited for myasthenia gravis (MG) due to the disorder's need for specialized care, its hallmark fluctuating muscle weakness, and the potential for increased risk of virus exposure among patients with MG during the coronavirus disease 2019 (COVID-19) pandemic during in-person clinical visits. A disease-specific telemedicine physical examination to reflect myasthenic weakness does not currently exist. METHODS: This paper outlines step-by-step guidance on the fundamentals of a telemedicine assessment for MG. The Myasthenia Gravis Core Exam (MG-CE) is introduced as a MG-specific, telemedicine, physical examination, which contains eight components (ptosis, diplopia, facial strength, bulbar strength, dysarthria, single breath count, arm strength, and sit to stand) and takes approximately 10 minutes to complete. RESULTS: Pre-visit preparation, remote ascertainment of patient-reported outcome scales and visit documentation are also addressed. DISCUSSION: Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation.

Hippopotamus are distinct from domestic livestock in their resource subsidies to and effects on aquatic ecosystems.

In many regions of the world, populations of large wildlife have been displaced by livestock, and this may change the functioning of aquatic ecosystems owing to significant differences in the quantity and quality of their dung. We developed a model for estimating loading rates of organic matter (dung) by cattle for comparison with estimated rates for hippopotamus in the Mara River, Kenya. We then conducted a replicated mesocosm experiment to measure ecosystem effects of nutrient and carbon inputs associated with dung from livestock (cattle) versus large wildlife (hippopotamus). Our loading model shows that per capita dung input by cattle is lower than for hippos, but total dung inputs by cattle constitute a significant portion of loading from large herbivores owing to the large numbers of cattle on the landscape. Cattle dung transfers higher amounts of limiting nutrients, major ions and dissolved organic carbon to aquatic ecosystems relative to hippo dung, and gross primary production and microbial biomass were higher in cattle dung treatments than in hippo dung treatments. Our results demonstrate that different forms of animal dung may influence aquatic ecosystems in fundamentally different ways when introduced into aquatic ecosystems as a terrestrially derived resource subsidy.

Annual mass drownings of the Serengeti wildebeest migration influence nutrient cycling and storage in the Mara River.

The annual migration of ∼1.2 million wildebeest (Connochaetes taurinus) through the Serengeti Mara Ecosystem is the largest remaining overland migration in the world. One of the most iconic portions of their migration is crossing of the Mara River, during which thousands drown annually. These mass drownings have been noted, but their frequency, size, and impact on aquatic ecosystems have not been quantified. Here, we estimate the frequency and size of mass drownings in the Mara River and model the fate of carcass nutrients through the river ecosystem. Mass drownings (>100 individuals) occurred in at least 13 of the past 15 y; on average, 6,250 carcasses and 1,100 tons of biomass enter the river each year. Half of a wildebeest carcass dry mass is bone, which takes 7 y to decompose, thus acting as a long-term source of nutrients to the Mara River. Carcass soft tissue decomposes in 2-10 wk, and these nutrients are mineralized by consumers, assimilated by biofilms, transported downstream, or moved back into the terrestrial ecosystem by scavengers. These inputs comprise 34-50% of the assimilated diet of fish when carcasses are present and 7-24% via biofilm on bones after soft tissue decomposition. Our results show a terrestrial animal migration can have large impacts on a river ecosystem, which may influence nutrient cycling and river food webs at decadal time scales. Similar mass drownings may have played an important role in rivers throughout the world when large migratory herds were more common features of the landscape.

Organic matter and nutrient inputs from large wildlife influence ecosystem function in the Mara River, Africa.

Animals can be important vectors for the movement of resources across ecosystem boundaries. Animals add resources to ecosystems primarily through egestion, excretion, and carcasses, and the stoichiometry and bioavailability of these inputs likely interact with characteristics of the recipient ecosystem to determine their effects on ecosystem function. We studied the influence of hippopotamus excretion/egestion and wildebeest carcasses, and their interactions with discharge, in the Mara River, Kenya. We measured nutrient dissolution and decomposition rates of wildlife inputs, the influence of inputs on nutrient concentrations and nutrient limitation in the river and the influence of inputs on biofilm growth and function in both experimental streams and along a gradient of inputs in the river. We found that hippopotamus excretion/egestion increases ammonium and coarse particulate organic matter in the river, and wildebeest carcasses increase ammonium, soluble reactive phosphorus, and total phosphorus. Concentrations of dissolved carbon and nutrients in the water column increased along a gradient of wildlife inputs and during low discharge, although concentrations of particulate carbon decreased during low discharge due to deposition on the river bottom. Autotrophs were nitrogen limited and heterotrophs were carbon limited and nitrogen and phosphorus colimited upstream of animal inputs but there was no nutrient limitation downstream of inputs. In experimental streams, hippo and wildebeest inputs together increased biofilm gross primary production (GPP) and respiration (R). These results differed in the river, where low concentrations of hippo inputs increased gross primary production (GPP) and respiration (R) of biofilms, but high concentrations of hippo inputs in conjunction with wildebeest inputs decreased GPP. Our research shows that inputs from large wildlife alleviate nutrient limitation and stimulate ecosystem metabolism in the Mara River and that the extent to which these inputs subsidize the ecosystem is mediated by the quantity and quality of inputs and discharge of the river ecosystem. Thus, animal inputs provide an important ecological subsidy to this river, and animal inputs were likely important in many other rivers prior to the widespread extirpation of large wildlife.

Life history traits and functional processes generate multiple pathways to ecological stability.

Stability contributes to the persistence of ecological communities, yet the interactions among different stabilizing forces are poorly understood. We assembled mesocosms with an algal resource and one to eight different clones of the consumer Daphnia ambigua and tracked algal and Daphnia abundances through time. We then fitted coupled ordinary differential equations (ODEs) to the consumer-resource time series. We show that variation in different components of stability (local stability and the magnitude of population fluctuations) across mesocosms arises through variation in life history traits and the functional processes represented by ODE model parameters. Local stability was enhanced by increased algal growth rate and Daphnia mortality and foraging rate. Population fluctuations were dampened by high Daphnia conversion efficiency and lower interaction strengths, low algal growth rate, high Daphnia death rate, and low Daphnia foraging. These results indicate that (1) stability in consumer-resource systems may arise through the net effect of multiple related stabilizing pathways and (2) different aspects of stability can vary independently and may respond in opposite directions to the same forces.

Ecology under lake ice.

Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer 'growing seasons'. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.

Local adaptation in transgenerational responses to predators.

Environmental signals can induce phenotypic changes that span multiple generations. Along with phenotypic responses that occur during development (i.e. 'within-generation' plasticity), such 'transgenerational plasticity' (TGP) has been documented in a diverse array of taxa spanning many environmental perturbations. New theory predicts that temporal stability is a key driver of the evolution of TGP. We tested this prediction using natural populations of zooplankton from lakes in Connecticut that span a large gradient in the temporal dynamics of predator-induced mortality. We reared more than 120 clones of Daphnia ambigua from nine lakes for multiple generations in the presence/absence of predator cues. We found that temporal variation in mortality selects for within-generation plasticity while consistently strong (or weak) mortality selects for increased TGP. Such results provide us the first evidence for local adaptation in TGP and argue that divergent ecological conditions select for phenotypic responses within and across generations.

Reconciling the role of terrestrial leaves in pond food webs: a whole-ecosystem experiment.

Terrestrial carbon and nutrients can subsidize the detrital pool of freshwater ecosystems; yet, the importance of terrestrial subsidies to lake and pond food webs is uncertain and debated. Terrestrial detritus is expected to have the greatest impact on food webs when water bodies are small and shallow with low levels of incident light. Temporary forested ponds fit this description and are often assumed to have a leaf detritus-based food web, but this has not been quantified. In a whole-ecosystem experiment, we traced the flow of isotopically enriched leaf litter to primary producers and consumers in a small, forested pond. We found that terrestrial leaves provided nutrients to algae, offering an indirect pathway in which leaf litter can enter the food web. Terrestrial leaves were also consumed directly, and larval caddisfly (Limnephilus sp.) shredders likely mobilized leaf nutrients to other consumers, a process overlooked in many previous small-scale experiments that did not incorporate shredders. Unexpectedly, most consumers relied heavily upon algal food pathways despite low light and net heterotrophic conditions. Overall, our study highlights the interconnectedness of algal and leaf litter pathways in small pond food webs, and emphasizes that algal pathways are prevalent and important even in small, shaded ponds with high loads of terrestrial leaf litter.

Impacts of warming revealed by linking resource growth rates with consumer functional responses.

Warming global temperatures are driving changes in species distributions, growth and timing, but much uncertainty remains regarding how climate change will alter species interactions. Consumer-Resource interactions in particular can be strongly impacted by changes to the relative performance of interacting species. While consumers generally gain an advantage over their resources with increasing temperatures, nonlinearities can change this relation near temperature extremes. We use an experimental approach to determine how temperature changes between 5 and 30 °C will alter the growth of the algae Scenedesmus obliquus and the functional responses of the small-bodied Daphnia ambigua and the larger Daphnia pulicaria. The impact of warming generally followed expectations, making both Daphnia species more effective grazers, with the increase in feeding rates outpacing the increases in algal growth rate. At the extremes of our temperature range, however, warming resulted in a decrease in Daphnia grazing effectiveness. Between 25 and 30 °C, both species of Daphnia experienced a precipitous drop in feeding rates, while algal growth rates remained high, increasing the likelihood of algal blooms in warming summer temperatures. Daphnia pulicaria performed significantly better at cold temperatures than D. ambigua, but by 20 °C, there was no significant difference between the two species, and at 25 °C, D. ambigua outperformed D. pulicaria. Warming summer temperatures will favour the smaller D. ambigua, but only over a narrow temperature range, and warming beyond 25 °C could open D. ambigua to invasion from tropical species. By fitting our results to temperature-dependent functions, we develop a temperature- and density-dependent model, which produces a metric of grazing effectiveness, quantifying the grazer density necessary to halt algal growth. This approach should prove useful for tracking the transient dynamics of other density-dependent consumer-resource interactions, such as agricultural pests and biological-control agents.

Intraspecific phenotypic variation among alewife populations drives parallel phenotypic shifts in bluegill.

Evolutionary diversification within consumer species may generate selection on local ecological communities, affecting prey community structure. However, the extent to which this niche construction can propagate across food webs and shape trait variation in competing species is unknown. Here, we tested whether niche construction by different life-history variants of the planktivorous fish alewife (Alosa pseudoharengus) can drive phenotypic divergence and resource use in the competing species bluegill (Lepomis macrochirus). Using a combination of common garden experiments and a comparative field study, we found that bluegill from landlocked alewife lakes grew relatively better when fed small than large zooplankton, had gill rakers better adapted for feeding on small-bodied prey and selected smaller zooplankton compared with bluegill from lakes with anadromous or no alewife. Observed shifts in bluegill foraging traits in lakes with landlocked alewife parallel those in alewife, suggesting interspecific competition leading to parallel phenotypic changes rather than to divergence (which is commonly predicted). Our findings suggest that species may be locally adapted to prey communities structured by different life-history variants of a competing dominant species.

Consumer interaction strength may limit the diversifying effect of intraspecific competition: a test in alewife (Alosa pseudoharengus).

Intraspecific competition is considered a principal driver of dietary variation, but empirical studies provide mixed support for this mechanism. Here we link comparative and experimental work testing the effects of competition and resource availability on the dietary variation of the alewife (Alosa pseudoharengus). The alewife, a consumer with extreme effects on its resources, was specifically utilized to additionally test the idea that strong interactions between a consumer and its resources can diminish the diversifying effect of competition. First, we compared the short- and long-term diet measures of wild populations across a wide range of densities. Second, in a pair of large-scale field mesocosm experiments, we explored the influence of competition and interaction strength on alewife dietary variation. Results from a whole-lake comparison and field experiments indicated that increasing competition was negatively correlated with population dietary variation. Further, altering the strength of the interaction between the alewife and its prey via prey supplementation eliminated this negative relationship. Collectively, our results suggest that competitive interactions may not drive dietary diversification in the alewife and, potentially, in other highly effective consumers. Our results also indicate that further consideration of the strength of species interactions (and the consumer traits that underlie them) would improve our understanding of the link between intraspecific competition and variation.

Utility of Repetitive Nerve Stimulation in the Diagnosis of Myasthenia Gravis in the Inpatient Setting.

Objectives: Sensitivity and specificity of Repetitive Nerve Stimulation (RNS) is typically reported from outpatient centers, and we hypothesized that these values might not apply to hospitalized patients with higher grades of weakness. RNS may be helpful in rapidly confirming diagnosis of myasthenia gravis (MG) in the inpatient setting, as results from confirmatory antibody testing are often delayed. We sought to characterize the sensitivity and specificity of RNS in the inpatient setting to assist in the early diagnosis of MG. Methods: We performed a retrospective analysis of all adult patients who had inpatient RNS at our center from 2016 to 2021. Inclusion criteria included RNS performed at least at one site and a neurological evaluation which prompted an electrodiagnostic study to evaluate for neuromuscular junction (NMJ) pathology. Descriptive statistics and Fisher exact analysis were performed. Results: Of the 32 identified hospitalized patients, 6 had greater than 10% decrement on slow RNS, confirming NMJ dysfunction. Five were diagnosed with MG, and 1 with Lambert-Eaton myasthenic syndrome. Of the 26 patients with normal RNS, 25 ultimately had alternative causes of weakness. One was later diagnosed as seronegative MG based on clinical improvement with acetylcholinesterase inhibitors. In our inpatient population, the overall sensitivity and specificity of RNS were 83.3% and 96.2% respectively. There was a statistically significant association between a positive RNS and diagnosis of MG (P = .0002). Conclusions: RNS is a highly sensitive and specific test for the diagnosis of MG in an inpatient setting, and these results are likely more rapidly available compared to antibody testing.

Rapid population growth and high management costs have created a narrow window for control of introduced hippos in Colombia.

The introduction of hippos into the wild in Colombia has been marked by their rapid population growth and widespread dispersal on the landscape, high financial costs of management, and conflicting social perspectives on their management and fate. Here we use population projection models to investigate the effectiveness and cost of management options under consideration for controlling introduced hippos. We estimate there are 91 hippos in the middle Magdalena River basin, Colombia, and the hippo population is growing at an estimated rate of 9.6% per year. At this rate, there will be 230 hippos by 2032 and over 1,000 by 2050. Applying the population control methods currently under consideration will cost at least 1-2 million USD to sufficiently decrease hippo population growth to achieve long-term removal, and depending on the management strategy selected, there may still be hippos on the landscape for 50-100 years. Delaying management actions for a single decade will increase minimum costs by a factor of 2.5, and some methods may become infeasible. Our approach illustrates the trade-offs inherent between cost and effort in managing introduced species, as well as the importance of acting quickly, especially when dealing with species with rapid population growth rates and potential for significant ecological and social impacts.

Southern Hemisphere dominates recent decline in global water availability.

Global land water underpins livelihoods, socioeconomic development, and ecosystems. It remains unclear how water availability has changed in recent decades. Using an ensemble of observations, we quantified global land water availability over the past two decades. We show that the Southern Hemisphere has dominated the declining trend in global water availability from 2001 to 2020. The significant decrease occurs mainly in South America, southwestern Africa, and northwestern Australia. In the Northern Hemisphere, the complex regional increasing and decreasing trends cancel each other, resulting in a negligible hemispheric trend. The variability and trend in water availability in the Southern Hemisphere are largely driven by precipitation associated with climate modes, particularly the El Niño-Southern Oscillation. This study highlights their dominant role in controlling global water availability.

Species dynamics alter community diversity-biomass stability relationships.

The relationship between community diversity and biomass variability remains a crucial ecological topic, with positive, negative and neutral diversity-stability relationships reported from empirical studies. Theory highlights the relative importance of Species-Species or Species-Environment interactions in driving diversity-stability patterns. Much previous work is based on an assumption of identical (stable) species-level dynamics. We studied ecosystem models incorporating stable, cyclic and more complex species-level dynamics, with either linear or non-linear density dependence, within a locally stable community framework. Species composition varies with increasing diversity, interacting with the correlation of species' environmental responses to drive either positive or negative diversity-stability patterns, which theory based on communities with only stable species-level dynamics fails to predict. Including different dynamics points to new mechanisms that drive the full range of diversity-biomass stability relationships in empirical systems where a wider range of dynamical behaviours are important.

A cascade of evolutionary change alters consumer-resource dynamics and ecosystem function.

It is becoming increasingly clear that intraspecific evolutionary divergence influences the properties of populations, communities and ecosystems. The different ecological impacts of phenotypes and genotypes may alter selection on many species and promote a cascade of ecological and evolutionary change throughout the food web. Theory predicts that evolutionary interactions across trophic levels may contribute to hypothesized feedbacks between ecology and evolution. However, the importance of 'cascading evolutionary change' in a natural setting is unknown. In lakes in Connecticut, USA, variation in migratory behaviour and feeding morphology of a fish predator, the alewife (Alosa pseudoharengus), drives life-history evolution in a species of zooplankton prey (Daphnia ambigua). Here we evaluated the reciprocal impacts of Daphnia evolution on ecological processes in laboratory mesocosms. We show that life-history evolution in Daphnia facilitates divergence in rates of population growth, which in turn significantly alters consumer-resource dynamics and ecosystem function. These experimental results parallel trends observed in lakes. Such results argue that a cascade of evolutionary change, which has occurred over contemporary timescales, alters community and ecosystem processes.

Recurrent Status Epilepticus in the Setting of Chimeric Antigen Receptor (CAR)-T Cell Therapy.

Axicabtagene ciloleucel (AC) is an FDA-approved anti-CD19 autologous chimeric antigen receptor T-cell (CAR-T) therapy for refractory diffuse large B cell lymphoma (DLBCL). While its efficacy in DLBCL has been promising, neurotoxicity remains a significant concern. We present a case of a 22-year-old woman with chemotherapy-refractory DLBCL who exhibited Grade IV neurotoxicity in the setting of sepsis, after undergoing AC infusion. Despite prophylactic levetiracetam given per guidelines,1,2 she experienced a precipitous mental status decline on post-infusion day 8 (D8) followed by hypoxic respiratory failure in the setting of clinical status epilepticus on D11 and nonconvulsive status epilepticus (NCSE) on D18. While neuroimaging was unremarkable, EEG demonstrated diffuse slowing and 2.5-3 Hz generalized periodic discharges consistent with NCSE. Seizures were initially refractory to lorazepam, increasing doses of levetiracetam, and phenobarbital, requiring a midazolam drip titrated to 50-70% burst suppression for resolution. Methylprednisolone and tocilizumab were used to treat neurotoxicity and cytokine release syndrome, respectively. Empiric antibiotics were used for sepsis. After cessation of sedatives on D19, mental status improved to near baseline. PET/CT just prior to discharge showed a complete response of the DLBCL (Deauville 3). She was discharged on D37 with no further seizure activity. Unfortunately, a 3-month interval PET/CT demonstrated disease progression which continued through salvage pembrolizumab eventually leading to death 1.2 years post-CAR-T infusion. This case illustrates the clinical management challenges of a complex and rare neurotoxic side effect of CAR-T cell therapy, namely NCSE following status epilepticus.

Interpopulation variation in a fish predator drives evolutionary divergence in prey in lakes.

Ecological factors are known to cause evolutionary diversification. Recent work has shown that evolution in strongly interacting predator species has reciprocal impacts on ecosystems. These divergent impacts of predators may alter the selective landscape and cause the evolution of prey. Yet, this link between intraspecific variation and evolution is unexplored. We compared the life history of a species of zooplankton (Daphnia ambigua) from lakes in New England in which the dominant planktivorous predator, the alewife (Alosa pseudoharengus), differs in feeding traits and migratory behaviour. Anadromous alewife (seasonal migrants) exhibit larger gapes, gill-raker spacing and target larger prey than landlocked alewife (year-round freshwater resident). In 'anadromous' lakes, Daphnia are abundant in the spring but extirpated by alewife predation in summer. Daphnia are rare year-round in 'landlocked' lakes. We show that Daphnia from lakes with anadromous alewife grew faster, matured earlier but at the same size and produced more offspring than Daphnia from lakes with landlocked or no alewife across multiple temperature and resource treatments. Our results are inconsistent with a response to size-selective predation but are better explained as an adaptation to colder temperatures and shorter periods of development (countergradient variation) mediated by seasonal alewife predation.

How low can you go? Impacts of a low-flow disturbance on aquatic insect communities.

The natural hydrology of streams and rivers is being extensively modified by human activities. Water diversion, dam construction, and climate change have the potential to increase the frequency and intensity of low-flow events. Flow is a dominant force structuring stream aquatic insect communities, but the impacts of water diversion are poorly understood. Here we report results of an experimental stream flow diversion designed to test how aquatic insect communities respond to a low-flow disturbance. We diverted 40% to 80% of the water in three replicate streams for three summers, leading to summer flow exceedance probabilities of up to 99.9%. Shifts in habitat availability appeared to be a major driver of aquatic insect community responses. Responses also varied by habitat type: total insect density decreased in riffle habitats, but there was no change in pool habitats. Overall, the total biomass of aquatic insects decreased sharply with lowered flow. Collector-filterers, collector-gatherers, and scrapers were especially susceptible, while predatory insects were more resistant. Despite extremely low flow levels, there was no shift in aquatic insect family richness. The experimental water withdrawal did not increase water temperature or decrease water quality, and some wetted habitat was always maintained, which likely prevented more severe impacts on aquatic insect communities.

The meta-gut: community coalescence of animal gut and environmental microbiomes.

All animals carry specialized microbiomes, and their gut microbiota are continuously released into the environment through excretion of waste. Here we propose the meta-gut as a novel conceptual framework that addresses the ability of the gut microbiome released from an animal to function outside the host and alter biogeochemical processes mediated by microbes. We demonstrate this dynamic in the hippopotamus (hippo) and the pools they inhabit. We used natural field gradients and experimental approaches to examine fecal and pool water microbial communities and aquatic biogeochemistry across a range of hippo inputs. Sequencing using 16S RNA methods revealed community coalescence between hippo gut microbiomes and the active microbial communities in hippo pools that received high inputs of hippo feces. The shared microbiome between the hippo gut and the waters into which they excrete constitutes a meta-gut system that could influence the biogeochemistry of recipient ecosystems and provide a reservoir of gut microbiomes that could influence other hosts. We propose that meta-gut dynamics may also occur where other animal species congregate in high densities, particularly in aquatic environments.