Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy.

Local blood flow control within the central nervous system (CNS) is critical to proper function and is dependent on coordination between neurons, glia, and blood vessels. Macroglia, such as astrocytes and Müller cells, contribute to this neurovascular unit within the brain and retina, respectively. This study explored the role of microglia, the innate immune cell of the CNS, in retinal vasoregulation, and highlights changes during early diabetes. Structurally, microglia were found to contact retinal capillaries and neuronal synapses. In the brain and retinal explants, the addition of fractalkine, the sole ligand for monocyte receptor Cx3cr1, resulted in capillary constriction at regions of microglial contact. This vascular regulation was dependent on microglial Cx3cr1 involvement, since genetic and pharmacological inhibition of Cx3cr1 abolished fractalkine-induced constriction. Analysis of the microglial transcriptome identified several vasoactive genes, including angiotensinogen, a constituent of the renin-angiotensin system (RAS). Subsequent functional analysis showed that RAS blockade via candesartan abolished microglial-induced capillary constriction. Microglial regulation was explored in a rat streptozotocin (STZ) model of diabetic retinopathy. Retinal blood flow was reduced after 4 wk due to reduced capillary diameter and this was coincident with increased microglial association. Functional assessment showed loss of microglial-capillary response in STZ-treated animals and transcriptome analysis showed evidence of RAS pathway dysregulation in microglia. While candesartan treatment reversed capillary constriction in STZ-treated animals, blood flow remained decreased likely due to dilation of larger vessels. This work shows microglia actively participate in the neurovascular unit, with aberrant microglial-vascular function possibly contributing to the early vascular compromise during diabetic retinopathy.

Social Sensing of Heatwaves.

Heatwaves cause thousands of deaths every year, yet the social impacts of heat are poorly measured. Temperature alone is not sufficient to measure impacts and "heatwaves" are defined differently in different cities/countries. This study used data from the microblogging platform Twitter to detect different scales of response and varying attitudes to heatwaves within the United Kingdom (UK), the United States of America (US) and Australia. At the country scale, the volume of heat-related Twitter activity increased exponentially as temperature increased. The initial social reaction differed between countries, with a larger response to heatwaves elicited from the UK than from Australia, despite the comparatively milder conditions in the UK. Language analysis reveals that the UK user population typically responds with concern for individual wellbeing and discomfort, whereas Australian and US users typically focus on the environmental consequences. At the city scale, differing responses are seen in London, Sydney and New York on governmentally defined heatwave days; sentiment changes predictably in London and New York over a 24-h period, while sentiment is more constant in Sydney. This study shows that social media data can provide robust observations of public response to heat, suggesting that social sensing of heatwaves might be useful for preparedness and mitigation.

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome.

OBJECTIVE: We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial. METHODS: Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM-DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range = 10-34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike-and-wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM-DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. RESULTS: GPFA was captured in eight of 12 patients (total event number across patients = 168, cumulative duration = 358 seconds). Eighty-six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98 milliseconds (interquartile range = 78.5 milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75 milliseconds (interquartile range = 228 milliseconds). One to 0.5 seconds and 0.5-0 seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1-3 Hz) frequency band. For alpha (8-12 Hz) and beta (13-30 Hz) frequencies, PTE was greatest 1-0.5 seconds before GPFA onset. SIGNIFICANCE: Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEG-functional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.

Genetic absence epilepsy: Effective connectivity from piriform cortex to mediodorsal thalamus.

OBJECTIVE: The objective of the study was to quantify effective connectivity from the piriform cortex to mediodorsal thalamus, in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). METHODS: Local field potentials (LFPs) were recorded using microelectrode arrays implanted in the mediodorsal thalamus and piriform cortex, in three urethane anesthetized GAERS and three control rats. Screw electrodes were placed in the primary motor cortex to identify epileptiform discharges. We used transfer entropy to measure effective connectivity from piriform cortex to mediodorsal thalamus prior to and during generalized epileptiform discharges. RESULTS: We observed increased theta band effective connectivity from piriform cortex to mediodorsal thalamus, prior to and during epileptiform discharges in GAERS compared with controls. Increased effective connectivity was also observed in beta and gamma bands from the piriform cortex to mediodorsal thalamus, but only during epileptiform discharges. CONCLUSIONS: This preliminary study suggests that increased effective theta connectivity from the piriform cortex to the mediodorsal thalamus may be a feature of the 'epileptic network' associated with genetic absence epilepsy. Our findings indicate an underlying predisposition of this direct pathway to propagate epileptiform discharges in genetic absence epilepsy.

Multiunit cluster firing patterns of piriform cortex and mediodorsal thalamus in absence epilepsy.

OBJECTIVE: The objective of the study were to investigate patterns of multiunit cluster firing in the piriform cortex (PC) and mediodorsal thalamus (MDT) in a rat model of genetic generalized epilepsy (GGE) with absence seizures and to assess whether these regions contribute to the initiation or spread of generalized epileptiform discharges. METHODS: Multiunit clusters and their corresponding local field potentials (LFPs) were recorded from microelectrode arrays implanted in the PC and MDT in urethane anesthetized Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and nonepileptic control (NEC) rats. Peristimulus time histograms (PSTHs) and cross-correlograms were used to observe transient changes in both the rate of firing and synchrony over time. The phase locking of multiunit clusters to LFP signals (spike-LFP phase locking) was calculated for frequency bands associated with olfactory communication between the two brain regions. RESULTS: There were significant increases in both rate of firing and synchronous activity at the onset of generalized epileptiform discharges in both PC and MDT. Prior to and following these increases in synchronous activity, there were periods of suppression. Significant increases in spike-LFP phase locking were observed within the PC prior to the onset of epileptiform discharges across all spectral bands. There were also significant increases in spike-LFP phase locking within the theta band of the MDT prior to onset. Between the two brain regions, there was a significant decrease in spike-LFP phase locking -0.5 s prior to onset in the theta band which coincided with a significant elevation in spike-LFP phase locking in the gamma band. CONCLUSIONS: Both the PC and MDT are engaged in the absence epilepsy network. Early spike-LFP phase locking between these two brain regions suggests potential involvement in the initiation of seizure activity.

Electrical stimulation of the piriform cortex for the treatment of epilepsy: A review of the supporting evidence.

In this review, we consider how the piriform cortex is engaged in both focal and generalized epilepsy networks and postulate the various neural pathways that can be effectively neuromodulated by stimulation at this site. This highlights the common involvement of the piriform cortex in epilepsy. We address both current and future preclinical studies of deep brain stimulation (DBS) of the piriform cortex, with attention to the critical features of these trials that will enable them to be of greatest utility in informing clinical translation. Although recent DBS trials have utilized thalamic targets, electrical stimulation of the piriform cortex may also be a useful intervention for people with epilepsy. However, more work is required to develop a solid foundation for this approach before considering human trials.

CIDER: Context-sensitive polarity measurement for short-form text.

Researchers commonly perform sentiment analysis on large collections of short texts like tweets, Reddit posts or newspaper headlines that are all focused on a specific topic, theme or event. Usually, general-purpose sentiment analysis methods are used. These perform well on average but miss the variation in meaning that happens across different contexts, for example, the word "active" has a very different intention and valence in the phrase "active lifestyle" versus "active volcano". This work presents a new approach, CIDER (Context Informed Dictionary and sEmantic Reasoner), which performs context-sensitive linguistic analysis, where the valence of sentiment-laden terms is inferred from the whole corpus before being used to score the individual texts. In this paper, we detail the CIDER algorithm and demonstrate that it outperforms state-of-the-art generalist unsupervised sentiment analysis techniques on a large collection of tweets about the weather. CIDER is also applicable to alternative (non-sentiment) linguistic scales. A case study on gender in the UK is presented, with the identification of highly gendered and sentiment-laden days. We have made our implementation of CIDER available as a Python package: https://pypi.org/project/ciderpolarity/.

In Flanders Fields: John McCrae as Physician, Poet, Soldier.

John McCrae (1872-1918) was a Canadian physician, poet, and soldier who fought and died in the First World War. He penned perhaps his most memorable and lasting poem, "In Flanders Fields," shortly after the death of a comrade at the Second Battle of Ypres in 1915. The poem gained almost instant popularity, being used for recruiting efforts and victory bond sales throughout the remainder of the war, and solidified forever the symbol of the poppy as a memorial token for the service members who had perished. His death towards the end of the war, like that of so many others in the perilous years between 1914 and 1918, cut short the trajectory of what had already amounted to a brilliant career. As a close friend of such titans of medicine as William Osler and Harvey Cushing, as well as acquainted with the likes of Rudyard Kipling, it is not difficult to imagine the impact that his passing had upon the future of medicine and literature.

Carbonaceous vs. total biochemical oxygen demand as a basis for WRRF design and performance monitoring.

The standard 5-day biochemical oxygen demand (BOD5 ) measurement of water quality is used widely as a design parameter for water resource recovery facilities (WRRFs). This measure usually includes a component of nitrogenous oxygen demand (NOD) that can cause oversizing of biological processes and under-evaluation of process capacity. Carbonaceous BOD (CBOD5 ) more closely represents oxygen demand associated with biodegradation of organic constituents of a wastewater than does BOD5 and therefore should be used as a basis for sizing aerobic treatment processes. Nitrogenous oxygen demand or reduced nitrogen content should be used as a loading and process performance parameter for nitrogen removal processes. PRACTITIONER POINTS: Oxygen demand for aerobic biodegradation reactions typically is divided into two major categories-carbonaceous biochemical oxygen demand (CBOD) and nitrogenous oxygen demand (NOD). Use of BOD5 as a design parameter and CBOD5 as an effluent water quality parameter distorts the true performance and loading rate capacity of a treatment plant. Carbonaceous BOD (CBOD5 ) more closely represents oxygen demand associated with biodegradation of organic constituents of a wastewater than does BOD5 and therefore should be used as a basis for sizing and evaluating the performance of aerobic treatment processes. Nitrogenous oxygen demand or reduced nitrogen content should be used as a loading and process performance parameter for nitrogen removal processes.

Comparing the mutagenicity of toxaphene after aging in anoxic soils and accumulating in fish.

A test program was conducted to evaluate the mutagenicity of toxaphene residuals extracted from aged soils and from fish collected in creeks near a toxaphene-contaminated site. The ultimate objective was to determine if the residual toxaphene congeners were more or less mutagenic than those in technical-grade toxaphene. The study showed that the mutagenicity of the bioaccumulated toxaphene congeners in fish, expressed as colony revertants per microg of residual toxaphene, was no greater than that of technical-grade toxaphene. The mutagenic impact of the toxaphene residuals in aged soil statistically was less than that for technical-grade toxaphene. Two specific congeners, a hexachlorobornane (labeled Hx-Sd) and a heptachlorobornane (labeled Hp-Sd), were found to accumulate over time in both soil and fish extracts, but did not show increased mutagenic impacts relative to that produced by technical-grade toxaphene.

Anatomical imaging of the piriform cortex in epilepsy.

The piriform cortex is a distinct brain region that plays a key role in the sense of smell. The piriform cortex is the major part of primary olfactory cortex and has broad connections that extend beyond the olfactory regions into limbic and fronto-temporal cortical networks. Numerous studies have described these anatomical connections via microscopic imaging and tracer studies. More recently, macroscopic anatomical imaging studies have demonstrated changes in the piriform cortex in humans with focal epilepsy as well as in animal models, suggesting this brain region can play a critical role in epileptogenesis. This review examines the imaging methods and techniques that have been most informative, leading to our current understanding of the anatomy and subdivsions of the piriform cortex as well as its connections to other brain structures, and the abnormalities that can be detected in the setting of epilepsy.

Factors affecting oxygen-transfer rates in headspace-gas respirometers.

Satisfactory measures of the biological-oxygen-uptake rate in headspace-gas respirometers can only be achieved if the rate of oxygen transfer from the headspace gas to liquid is greater than the rate of oxygen uptake by microorganisms. In the authors' study, factors potentially affecting oxygen-transfer limitations in headspace-gas respirometers were evaluated quantitatively. Tests were conducted to measure maximum-oxygen-uptake rates by operating a respirometer under various test conditions. Analysis of respirometric data indicated that limiting oxygen-transfer rates were related to mixing intensity, length of magnetic stirring bar, volume of sample, and oxygen content in the headspace gas. A multivariable model was developed to describe the overall contribution of these factors to the limiting oxygen-transfer rate. This model should be useful for estimating maximum-oxygen-transfer rates for essentially all headspace-gas respirometers.

Changes in the biochemical oxygen demand procedure in the 21st edition of Standard Methods for the Examination of Water and Wastewater.

The dilution biochemical oxygen demand (BOD) test has widespread application for design and operation of wastewater treatment processes, evaluating the quality of natural waters, and assessing the effect of wastewater discharges on these waters. While standardization of the BOD-measuring method has become of prime importance in maintaining dependable data acquisition, changes are made as needed in response to questions raised by analysts and to accommodate new applications. The purpose of this article is to describe changes that have been incorporated in the 20th and 21st editions of Standard Methods for the Examination of Water and Wastewater (APHA et al., 1998 and 2004). These changes include changes in text format to clarify the procedural steps, allowance for use of bottle sizes ranging from 60 mL or larger, improvements in quality-control procedures, and improvements in the method of calculating BOD. Other changes include allowance for the use of allylthiourea for nitrification inhibition and broadening the source of seed that can be used for inoculation of BOD samples.

Factors affecting ballasted flocculation reactions.

Ballasted flocculation represents a relatively new technology that shows promise of bringing improvements to the field of water and wastewater treatment. Ballasted flocculation involves the addition of a ballasting agent (high-density microsand, sp gr = 2.65) to a chemically stabilized and coagulated suspension of particulate solids. Tests were conducted to determine the effect of eight independent parameters on the settling velocity of the resulting floc. Measurements showed settling velocities ranging from approximately 100 m/h for 0.5-mm diameter particles to as high as 380 m/h for particles having effective diameters up to 7 mm. Settling velocities for discrete microsand particles and discrete ballasted flocs were found to fit conventional settling theory with reasonable accuracy. The most important factors contributing to the benefits of ballasted flocculation are the large floc sizes that can be maintained, the greater roundness of the floc particles, and a lower shape factor for the ballasted floc, which all contribute to higher settling rates. Higher settling rates allow for substantially smaller sedimentation units and decreased capital costs.

Analyzing the uncorrected error of dilution water demand for the dilution biochemical oxygen demand method.

Dilution water demand (DWD) can cause a positive error when the dilution biochemical oxygen demand (BOD) method is used. Dilution water demand may be attributed to oxidation of organic impurities in the dilution water and nitrification of ammonia added as a nutrient. To minimize the error associated with these sources, the standard BOD method requires that DWD be less than 0.2 mg/L in 5 days and does not allow correction for DWD when calculating test results. This study derives a set of theoretical equations to analyze the uncorrected errors with and without seeding. The authors concluded that DWD can be completely corrected if seeded dilution water is used for the sample dilution. When seeding individual bottles, the uncorrected error approaches 8.3 to approximately 8.8% at a 5-day depletion of 2 mg/L for a typical secondary effluent. Tests without seeding show an almost 1% higher uncorrected error than seeded tests. The analysis also suggests that these errors can be effectively reduced to less than 3% when the 5-day depletion approaches 6 mg/L. even for 5-day biochemical oxygen demand concentrations exceeding I x 10(4) mg/L. Further analysis indicates that, if not inhibited, the ammonium added to dilution water as a nutrient may contribute additional error due to nitrification.