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Background and Objectives: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy., Methods: The Human Epilepsy Project is a prospective, international, observational study investigating markers of treatment response in newly diagnosed focal epilepsy. Participants were enrolled within 4 months of treatment initiation. Adult participants on levetiracetam, lamotrigine, carbamazepine, or oxcarbazepine monotherapy who completed the AEP and Mini International Neuropsychiatric Interview at enrollment were included. Multivariable generalized linear and penalized logistic regression models assessed differences in total and itemized marginal AEP scores and dichotomized responses ("never/rarely" vs "sometimes/always")., Results: A total of 225 adults initiated on levetiracetam (n = 132, 59%), lamotrigine (n = 55, 24%), carbamazepine (n = 19, 8.4%), or oxcarbazepine (n = 19, 8.4%) were included. There were no significant differences in AEP total scores between ASMs. Patients with depression (adjusted marginal score ratio [aMSR] 1.23, 95% CI 1.09-1.39, p = 0.001) and anxiety (aMSR 1.15, 95% CI 1.04-1.26, p = 0.007) had worse AEP total scores than those without. After adjusting for depression and anxiety, levetiracetam users were >3 times more likely to report feelings of aggression (adjusted odds ratio [aOR] 3.38, 95% CI 1.07-10.7, p = 0.038) and almost half as likely to experience unsteadiness (aOR 0.45, 95% CI 0.21-0.99, p = 0.047) than lamotrigine users. Carbamazepine and oxcarbazepine had the highest rates of discontinuation (42.1%, each), followed by levetiracetam (34.8%) and lamotrigine (16.4%). Levetiracetam users had the highest proportion of discontinuations because of AEs alone (18%), and lamotrigine had the lowest (5%)., Discussion: Systematic screening for AEs in adults with newly diagnosed focal epilepsy on ASM monotherapy showed that those with comorbid psychiatric conditions report greater AEs overall, irrespective of ASM. Levetiracetam was associated with >3-fold risk of psychiatric AEs and half the risk of experiencing unsteadiness than lamotrigine. Levetiracetam had the highest proportion of discontinuations because of AEs alone, while lamotrigine had the lowest.

Objective: This study was undertaken to ascertain the natural history and patterns of antiseizure medication (ASM) use in newly diagnosed focal epilepsy patients who were initially started on monotherapy., Methods: The data were derived from the Human Epilepsy Project. Differences between the durations of the most commonly first prescribed ASM monotherapies were assessed using a Cox proportional hazards model. Subjects were classified into three groups: monotherapy, sequential monotherapy, and polytherapy., Results: A total of 443 patients were included in the analysis, with a median age of 32 years (interquartile range [IQR] = 20-44) and median follow-up time of 3.2 years (IQR = 2.4-4.2); 161 (36.3%) patients remained on monotherapy with their initially prescribed ASM at the time of their last follow-up. The mean (SEM) and median (IQR) duration that patients stayed on monotherapy with their initial ASM was 2.1 (2.0-2.2) and 1.9 (.3-3.5) years, respectively. The most commonly prescribed initial ASM was levetiracetam (254, 57.3%), followed by lamotrigine (77, 17.4%), oxcarbazepine (38, 8.6%), and carbamazepine (24, 5.4%). Among those who did not remain on the initial monotherapy, 167 (59.2%) transitioned to another ASM as monotherapy (sequential monotherapy) and 115 (40.8%) ended up on polytherapy. Patients remained significantly longer on lamotrigine (mean = 2.8 years, median = 3.1 years) compared to levetiracetam (mean = 2.0 years, median = 1.5 years) as a first prescribed medication (hazard ratio = 1.5, 95% confidence interval = 1.0-2.2). As the study progressed, the proportion of patients on lamotrigine, carbamazepine, and oxcarbazepine as well as other sodium channel agents increased from a little more than one third (154, 34.8%) of patients to more than two thirds (303, 68.4%) of patients., Significance: Slightly more than one third of focal epilepsy patients remain on monotherapy with their first prescribed ASM. Approximately three in five patients transition to monotherapy with another ASM, whereas approximately two in five end up on polytherapy. Patients remain on lamotrigine for a longer duration compared to levetiracetam when it is prescribed as the initial monotherapy., (© 2023 International League Against Epilepsy.)

Background and Objectives: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC., Methods: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability., Results: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Formula: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Formula: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds., Discussion: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts., Classification of Evidence: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus., (© 2022 American Academy of Neurology.)

Background and Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns., Methods: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet , to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes., Results: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes, SPaRCNet exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively., Discussion: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs., Classification of Evidence: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists., (© 2023 American Academy of Neurology.)

Background and Objectives: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts., Methods: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ 2 statistics, and logistic regression analyses., Results: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts., Discussion: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence., (© 2022 American Academy of Neurology.)

Purpose of Review: Seizures, including status epilepticus, have been reported in association with acute COVID-19 infection. People with epilepsy (PWE) have suffered from seizure exacerbations during the pandemic. This article reviews the data for clinical and electrographic seizures associated with COVID-19, technical EEG considerations for reducing risk of transmission, and factors contributing to seizure exacerbations in PWE as well as strategies to address this issue., Recent Findings: An increasing number of studies of larger cohorts, accounting for a variety of variables and often utilizing EEG with standardized terminology, are assessing the prevalence of seizures in hospitalized patients with acute COVID-19 infections, and gaining insight into the prevalence of seizures and their effect on outcomes. Additionally, recent studies are evaluating the effect of the pandemic on PWE, barriers faced, and the usefulness of telehealth. Although there is still much to learn regarding COVID-19, current studies help in assessing the risk of seizures, guiding EEG utilization, and optimizing the use of telehealth during the pandemic., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: A phase I feasibility study to determine the accuracy of identifying seizures based on audio recordings., Methods: We systematically generated 166 audio clips of 30 s duration from 83 patients admitted to an epilepsy monitoring unit between 1/2015 and 12/2016, with one clip during a seizure period and one clip during a non-seizure control period for each patient. Five epileptologists performed a blinded review of the audio clips and rated whether a seizure occurred or not, and indicated the confidence level (low or high) of their rating. The accuracy of individual and consensus ratings were calculated., Results: The overall performance of the consensus rating between the five epileptologists showed a positive predictive value (PPV) of 0.91 and a negative predictive value (NPV) of 0.66. The performance improved when confidence was high (PPV of 0.96, NPV of 0.70). The agreement between the epileptologists was moderate with a kappa of 0.584. Hyperkinetic (PPV 0.92, NPV 0.86) and tonic-clonic (PPV and NPV 1.00) seizures were most accurately identified. Seizures with automatisms only and non-motor seizures could not be accurately identified. Specific seizure-related sounds associated with accurate identification included disordered breathing (PPV and NPV 1.00), rhythmic sounds (PPV 0.93, NPV 0.80), and ictal vocalizations (PPV 1.00, NPV 0.97)., Conclusion: This phase I feasibility study shows that epileptologists are able to accurately identify certain seizure types from audio recordings when the seizures produce sounds. This provides guidance for the development of audio-based seizure detection devices and demonstrate which seizure types could potentially be detected., Competing Interests: Declaration of Competing Interest Author DF receives salary support for consulting and clinical trial related activities performed on behalf of The Epilepsy Study Consortium, a non-profit organization. DF receives no personal income for these activities. NYU receives a fixed amount from the Epilepsy Study Consortium towards DF’s salary. Within the past year, The Epilepsy Study Consortium received payments for research services performed by DF from: Adamas, Axcella, Biogen, Crossject, Engage Pharmaceuticals, Eisai, GW Pharmaceuticals, Pfizer, SK Life Science, Takeda, Xenon, and Zynerba. DF has also served as a paid consultant for Eisai. DF has received travel support from Medtronics, Eisai and the Epilepsy Foundation. DF receives research support from the CDC, NINDS, Epilepsy Foundation, Epitel, and Neuropace. DF serves on the scientific advisory board for Receptor Life Sciences. DF holds equity interests in Neuroview Technology and Receptor Life Sciences. Author RSF has done consulting for Medtronic and has stock options in Smart-Watch, Avails Medical, Cerebral Therapeutics, Zeto, Irody, Eysz. Author PD receives research support from the NIH and NeuroPace, Inc. PD has received honoraria for educational materials from NeuroPace, Inc. and travel reimbursement from Medtronic and NeuroPace, Inc. The remaining authors have no conflicts of interest., (Copyright © 2020 British Epilepsy Association. All rights reserved.)

Background: Airway management in the presence of acute cervical spine injury (CSI) is challenging. Because it limits cervical spine motion during tracheal intubation and allows for neurological examination after the procedure, awake fiberoptic bronchoscopy (FOB) has traditionally been recommended. However, with the widespread availability of video laryngoscopy (VL), its use has declined dramatically. Our aim was to describe the frequency of airway management techniques used in patients with CSI at our level I trauma center and report the incidence of neurological injury attributable to airway management., Methods: Adults presenting to the operating room with CSI without a tracheal tube in situ between September 2010 and June 2017 were included. All patients were intubated in the presence of manual-in-line stabilization, a hard cervical collar, or surgical traction. Worsening neurological status was defined as new motor or sensory deficits on postoperative examination., Results: Two hundred fifty-two patients were included, of which 76 (30.2%) had preexisting neurological deficits. VL was the most frequent initial airway management technique used (49.6%). Asleep FOB was commonly performed alone (30.6%) or in conjunction with VL (13.5%). Awake FOB was rarely performed (2.3%), as was direct laryngoscopy (2.8%). All techniques were associated with high first-attempt success rates, and no cases of neurological injury attributable to airway management technique were identified., Conclusions: Among patients with acute CSI at a high-volume academic trauma center, VL was the most commonly used initial intubation technique. Awake FOB and direct laryngoscopy were performed infrequently. No cases of neurological deterioration secondary to airway management occurred with any method. Assuming care is taken to limit neck movement, providers should use the intubation technique with which they have the most comfort and skill.

Background: It is unknown whether postanoxic cortical and subcortical myoclonus are distinct entities with different prognoses., Methods: In this retrospective cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we identified 111 (18%) patients with myoclonus. Basic demographics and clinical characteristics of myoclonus were collected. EEG reports, and, when available, raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded to outcomes. Myoclonus was classified as cortical if there was a preceding, time-locked electrographic correlate and otherwise as subcortical. Outcome at discharge was determined using Cerebral Performance Category., Results: Patients with myoclonus had longer arrests with less favorable characteristics compared to patients without myoclonus. Cortical myoclonus occurred twice as often as subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during hospitalization did not distinguish the two. Rates of electrographic seizures were higher in patients with cortical myoclonus (43%, vs 8% with subcortical). Survival to discharge was worse for patients with myoclonus compared to those without (26% vs 39%, respectively), but did not differ between subcortical and cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus were more likely to be discharged in a comatose state than those with subcortical myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at discharge was equally possible between those with cortical and subcortical myoclonus (12% and 16%, respectively)., Conclusions: Cortical and subcortical myoclonus are seen in every sixth patient with cardiac arrest and cannot be distinguished using clinical criteria. Either condition may have good functional outcomes.

Purpose: To evaluate the success rate of CT-guided bone biopsies in metastatic castration-resistant prostate cancer (mCRPC) and to investigate associated technical, imaging, and clinical parameters affecting diagnostic yields., Materials and Methods: Eighty CT-guided bone biopsy specimens were obtained from 72 men (median age, 68 y; range, 49-89 y) enrolled in a multicenter trial to identify mechanisms of resistance in mCRPC. Successful biopsy was determined by histologic confirmation of tumor cells and successful isolation of RNA for molecular analysis., Results: The overall success rate of CT-guided bone biopsies was 69% (55/80) based on histology and 64% (35/55) based on isolation of molecular material for RNA sequencing. Biopsies performed in lesions with areas of radiolucency had significantly higher diagnostic yields compared with lesions of predominantly dense sclerosis (95% vs 33%; P = .002) and lesions of predominantly subtle sclerosis (95% vs 65%; P = .04). Success rates increased in lesions with density ≤ 475 HU (79% for ≤ 475 HU vs 33% for > 475 HU; P = .001) and in lesions with ill-defined margins (76% for ill-defined margins vs 36% for well-circumscribed margins; P = .005). Alkaline phosphatase was the only clinical parameter to correlate significantly with diagnostic yield (83% for > 110 U/L vs 50% for ≤ 110 U/L; P = .001)., Conclusions: Image-guided bone tumor biopsies can be successfully used to acquire cellular and molecular material for analyses in patients with osteoblastic prostate cancer metastases. Diagnostic yields are significantly increased in lesions with areas of radiolucency, density ≤ 475 HU, ill-defined margins, and interval growth and in patients with alkaline phosphatase > 110 U/L., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L(4)CL). A selective loss of L(4)CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L(4)CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure., Methods and Results: Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L(4)CL and total CL to 90% of non-failing levels (vs. 61-75% in control and lard groups), and attenuated 17-22% decreases in state 3 mitochondrial respiration observed in the control and lard groups (P < 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 ± 2 vs. 29 ± 2%, P < 0.05), while plasma insulin levels were lower (5.4 ± 1.1 vs. 9.1 ± 2.3 ng/mL; P < 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure., Conclusion: Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition.

Cardiolipin (CL) is responsible for modulation of activities of various enzymes involved in oxidative phosphorylation. Although energy production decreases in heart failure (HF), regulation of cardiolipin during HF development is unknown. Enzymes involved in cardiac cardiolipin synthesis and remodeling were studied in spontaneously hypertensive HF (SHHF) rats, explanted hearts from human HF patients, and nonfailing Sprague Dawley (SD) rats. The biosynthetic enzymes cytidinediphosphatediacylglycerol synthetase (CDS), phosphatidylglycerolphosphate synthase (PGPS) and cardiolipin synthase (CLS) were investigated. Mitochondrial CDS activity and CDS-1 mRNA increased in HF whereas CDS-2 mRNA in SHHF and humans, not in SD rats, decreased. PGPS activity, but not mRNA, increased in SHHF. CLS activity and mRNA decreased in SHHF, but mRNA was not significantly altered in humans. Cardiolipin remodeling enzymes, monolysocardiolipin acyltransferase (MLCL AT) and tafazzin, showed variable changes during HF. MLCL AT activity increased in SHHF. Tafazzin mRNA decreased in SHHF and human HF, but not in SD rats. The gene expression of acyl-CoA: lysocardiolipin acyltransferase-1, an endoplasmic reticulum MLCL AT, remained unaltered in SHHF rats. The results provide mechanisms whereby both cardiolipin biosynthesis and remodeling are altered during HF. Increases in CDS-1, PGPS, and MLCL AT suggest compensatory mechanisms during the development of HF. Human and SD data imply that similar trends may occur in human HF, but not during nonpathological aging, consistent with previous cardiolipin studies.

The occurrence of intersex fish is widespread in the rivers of England and Wales. The extent of intersex in fish populations is believed to be strongly linked to their exposure to steroid estrogens. The present study presents, to our knowledge, the first national, catchment-based risk assessment for steroid estrogens in the world. A graphical information system-based model predicted the concentrations of estradiol (E2), estrone, and ethinylestradiol, which were combined and compared with known biological effect levels to predict the risk of endocrine disruption for 10,313 individual river reaches (21,452 km) receiving effluent from more than 2000 sewage treatment plants serving more than 29 million people. The large scale of this assessment underlines the usefulness of computer-based risk assessment methods. Overall, 61% [corrected] of the modeled reaches (all percentages are in terms of the total river length modeled) in England and Wales were predicted to be not at risk from endocrine disruption (mean concentrations, <1 ng/L E2 equivalents). A large range existed in the percentage of river reaches at risk in the various regions, from 5% in Wales to 67% in the Thames catchment. Important factors influencing this proportion are the population density, particularly their location, and the available dilution. A very small proportion of reaches (approximately 1-3%) were predicted to be at high risk (>10 ng/L E2 equivalents). Many of these high-risk reaches, however, were ditches, which were composed almost entirely of sewage effluent. The model could be applied equally well to any other chemical of concern emanating from the human population that would be impractical to assess by measurement.

A model of auditory thalamic organization is presented incorporating cellular laminae, oriented dendritic arbors and tectothalamic axons as a basis for the tonotopic map at this level of the central auditory system. The heart of this model is the laminar organization of neuronal somata in the ventral division of the medial geniculate body (MGV) of the rabbit, visible in routine Nissl stains. Microelectrode studies have demonstrated a step-wise ascending progression of best frequencies perpendicular to the cell layers. The dendritic arbors of MGV neurons are aligned parallel to the cellular laminae and dendritic tree width along the frequency axis corresponds closely with the frequency steps seen in microelectrode studies. In the laminated subdivision, tectothalamic axons terminate in the form of bands closely aligned with the laminae and dendritic arbors of thalamic relay neurons. The bands of tectothalamic axons extend in the anterior-posterior (A-P) plane forming a dorsal-ventral series of stacked frequency slabs. In the pars ovoidea region, the homologous spiraling of somata, dendritic fields and tectothalamic axons appear to represent a low-frequency area in this species. At least two types of tectothalamic terminals were found within the bands: large boutons frequently arranged in a glomerular pattern and smaller boutons arising from fine caliber axons. We propose that the rabbit is an ideal model to investigate the structural-functional basis of functional maps in the mammalian auditory forebrain.

Recent EU directives have emphasised the need to understand and limit potential water quality problems within urban river systems. Under certain conditions sediments and contaminants derived from industrial and domestic waste and the urban surface may be expelled into urban rivers via the sewer and drainage system. These discharges may lead to water quality problems within urban catchments. One aspect of water quality is the suspended sediment. This can be directly detrimental to water quality by affecting the habitat for fish and other biota but it is also closely associated with pollutants, such as heavy metals, which may be adsorbed onto the sediments surface. This paper presents a comparative analysis of sediment yields for a small mixed rural/urban catchment, the Bradford Beck in West Yorkshire, over a number of precipitation events. Flow and water quality parameters were monitored at a high temporal resolution at strategic sites within the urban watercourse over a 2-year period. Rainfall was measured at six locations within the catchment. Analysis of discrete rainfall events allowed an understanding of the temporal and spatial variability of sediment transport within the catchment to be developed. The results demonstrated that for individual storms the sediment yields from the urban sub-catchment were generally higher than those from the rural system although the annual yields were comparable. Sediment transport within the urban area, for large events, was dominated by the impact of the Combined Sewer Overflows discharging. Within these events peak suspended sediment concentration, SSC, were generally higher than the rural system. Within smaller events the main sediment source within the urban area was the surface runoff discharging directly to the urban river. Analysis of SSC and discharge relationships illustrated the different sources of sediment for contrasting events. Within the rural system clockwise hysteresis, indicating exhaustion of sediment supply, was noted for larger storms. The high temporal resolution monitoring has enabled a better understanding of sediment dynamics within the Bradford Beck system to be developed. The general conclusions drawn can provide guidance for addressing sediment related water quality issued in other urban systems.

The effects of different wavebands of UV radiation on photosynthesis and the expression and abundance of photosynthetic proteins in oilseed rape (Brassica napus L. cv. Rebel) were investigated. Plants were grown outdoors under natural radiation (52 degrees N, 0 degrees E) supplemented with six wavebands of UV radiation (0.4 Wm(-2)) between 313 nm and 356 nm. A control treatment was centred at 343 nm. Exposure to supplementary UV-A radiation (320-400 nm) had no significant effects, however UV-B radiation, centred at 313 nm, caused a marked reduction in photosynthesis. This decrease was related to a reduction in the initial carboxylation velocity of Rubisco which was further correlated with a large reduction in the expression and abundance of both large and small subunits of Rubisco. These results indicate a molecular mechanism behind UV-B induced reductions in photosynthesis per unit area in plants grown under field conditions.

Information on the magnitude and variability of flow regimes at the river reach scale is a central component of most aspects of water resource and water quality management. However, many decisions are made within catchments for which there are no measured flow data. To meet this challenge, a suite of modelling techniques to assist in the estimation of natural and artificially influenced river-flows at ungauged sites has been developed. This paper summarises these models and how they are incorporated within the GIS framework of the Low Flows 2000 software package. The paper will also describe the implementation of Low Flows 2000 within England and Wales by the Environment Agency, and the use of the system in supporting the implementation of the Environment Agency's Catchment Abstraction Management Strategy. This strategy is focused on the delivery of sustainable abstraction licensing and will contribute to the implementation of the Water Framework Directive within England and Wales.

An outdoor polychromatic response spectrum for the phototropic curvature of the seed pods (siliquas) of oilseed rape (Brassica napus L. cv. Rebel) has been measured. The plants were sown and grown at a location of 52 degrees 12' N and 0 degrees 07' E under natural daylight and ambient environmental conditions with supplementary ultraviolet (UV-B and UV-A) radiation. This radiation had central wavelengths of 313, 319, 324, 339, 348, 356 or 377 nm and was supplied daily for 10 hours at an irradiance of 0.13 W m(-2). An action maximum for phototropic curvature of the siliquas was observed at 319 and 324 nm.

A polychromatic irradiation system for the outdoor exposure of plants or other samples to additional UV and longer-wavelength radiation has been constructed and tested. The system provides a range of wavebands in the ultraviolet-B radiation (280-315 nm) and ultraviolet-A radiation (315-400 nm) spectral regions, and the irradiance is fully adjustable. The performance of the lamp and filter system after over 4000 h of use is described; a brief description of filter degradation after over 30,000 h of use is also presented. Cellulose acetate filters were found to be adequate for some purposes in the UV waveband, but rigid plastic and glass-based filters were superior in terms of stability and the range of spectral combinations available. They also exhibited relatively small changes in transmittance with time. The system is also convenient for the measurement of differential polychromatic action spectra.

The effects of supplementary ultraviolet-A (UV-A) and ultraviolet-B+A (UV-B+A) in the natural environment on the growth and morphology of various ecotypes of Arabidopsis thaliana were investigated. The ecotypes investigated were Columbia (Col-4), Landsberg erecta (Ler-0), Cvi-0, Wassilewskija, Enkheim-D, Aa-0 and Di-1. The mutant hy-4 was also used. Results varied with the radiation treatment, ecotype and parameter measured. Plants subjected to elevated UV-A were both insensitive (all parameters Cvi-0 and Col-4) and sensitive. When responses to UV-A occurred they were mostly inhibitory (all significant responses of Di-1 and Enkheim-D, most parameters of Wassilewskija, and some parameters of hy-4), however, promotive affects were observed for some parameters of Aa-0 and Ler-0. Supplementary UV-B+A inhibited all parameters of Di-1 and Enkheim-D and most parameters of Col-4, Ler-0 and hy-4, but Wassilewskija, Aa-0 and Cvi-0 were mostly insensitive. The magnitude of the UV-B+A response varied with ecotype (compare Di-1 with Ler-0). Some ecotypes were sensitive to UV-A but not UV-B+A (Aa-0), whereas others (Ler-0, Col-4) show the opposite sensitivities. A linear relationship is reported between the degree of UV-B+A inhibition of each ecotype and growth rate. The higher the growth rate the more susceptible the ecotype is to UV-B+A inhibition. This relationship holds for the majority of growth parameters measured.

As part of an ongoing investigation into the effects of long-term UV-B radiation exposure on the growth and morphology of woody perennials, the gas exchange and photosynthesis of five common deciduous tree species were measured. All five tree species had been exposed to UV-B radiation for 5 years, in the field, at an enhancement level equivalent to an 18% ozone depletion. Measurements made during the fifth year of UV-B irradiation recorded reductions in light-saturated photosynthesis, transpiration and water use efficiencies. These changes were accompanied by marked reductions in individual leaf areas, stomatal density, stomatal conductance and carboxylation efficiency. There were no significant changes in the maximum variable fluorescence ratio, the quantum requirement of oxygen evolution, or light-saturated O(2) production. Analysis of the response of net carbon assimilation to changing intercellular CO(2) concentration (A/c(i) response) demonstrated no significant change in stomatal limitation. Reductions in photosynthesis were consistent with decreased carboxylation efficiency. Although all five tree species were similarly affected by UV-B radiation treatment, the magnitude of the responses was species-specific. These findings demonstrate the need for more long-term experimentation and also suggest that changes in water use efficiency may be a significant factor in plants' responses to UV-B radiation.

Polychromatic ultraviolet (UV) action spectra for various growth responses of the dicotyledon Bellis perennis L. (daisy) and the grass Cynosurus cristatus L. (crested dog's-tail) have been measured. The plants were grown in the natural environment and ambient daylight was supplemented with five different UV irradiances centred at eight different wavelengths (313, 318, 320, 322, 339, 348, 356 and 377 nm). Destructive growth analysis was performed on B. perennis and C. cristatus after 300 and 122 days respectively. Dose response curves were created to construct action spectra for individual responses. Different spectral responses were observed in these two plant types. B. perennis exhibited a substantial action maximum at 313 nm for the inhibition of aerial, root and total dry weight; a similar action maximum at 313 nm for the inhibition of leaf expansion was observed. Longer wavelengths were relatively ineffective on these growth parameters, with the exception of a small but statistically significant (P < 0.05) response to 320 nm radiation. By contrast, C. cristatus showed negligible response to 313 nm radiation, for inhibition of aerial, root and total dry weight but substantial responses to longer wavelengths, especially at 339 and 348 nm. These action spectra add weight to suggestions in the literature that UV-A has a role to play in responses in this region of the spectrum. The possible implications of these observations are discussed.

Some responses of various meadow species to enhanced UV-radiation of the natural daylight spectrum are described together with the experimental protocol employed. Growth responses to supplementary UV-B+A are mostly inhibitory when compared to the ambient daylight treatment for Bellis perennis, Cardamine pratensis, Cynosurus critatus and Ranunculus ficaria. However, the response of UV-A treatment compared to that of the UV-B+A varies in significance according to the species and parameter investigated. The pertinence of the ambient and UV-A treatment to data interpretation is discussed. Stomatal conductance of B. perennis was measured throughout the 24 h cycle. Although no significant difference could be found between the stomatal conductance of UV and ambient treated plants during the hours of daylight, at night it was found that the UV-B+A treated plants were unable to achieve the same degree of closure as the ambient treated plants. UV-damage and growth responses could alter the diversity of the meadow ecosystem and these effects could be exacerbated by water loss.

The spectral control of hypocotyl elongation in light-grown Chenopodium rubrum L. seedlings has been studied. The results showed that although the seedlings responded to changes in the quantity of combined red and far-red radiation, they were also very sensitive to changes in the quantity of blue radiation reaching the plant. Altering the proportion of red: far-red radiation in broad waveband white light caused marked differences in hypocotyl extension. Comparison of the responses of green and chlorophyll-free seedlings indicated no qualitative difference in the response to any of the light sources used, although photosynthetically incompetent plants were more sensitive to all wavelengths. Blue light was found to act primarily of a photoreceptor which is different from phytochrome. It is concluded that hypocotyl extension rate in vegetation shade is photoregulated by the quantity of blue light and the proportion of red: far-red radiation. In neutral shade, such as that caused by stones or overlying soil, hypocotyl extension appears to be regulated primarily by the quantity of light in the blue waveband and secondarily by the quantity of light in the red and far-red wavebands.

Detailed action spectra are presented for the inhibition of hypocotyl extension in dark-grown Sinapis alba L. seedlings by continuous (24 h) narrow waveband monochromatic light between 336 nm and 783 nm. The results show four distinct wavebands of major inhibitory action; these are centred in the ultra-violet (λmax=367 nm), blue (λmax=446 nm), red (λmax=653 nm) and far-red (λmax=712 nm) wavebands. Previous irradiation of the plants with red light (which also decreases Ptot) causes decreased inhibitory action by all wavelengths except those responsible for the red light inhibitory response. Pre-irradiation did not alter the wavelength of the action maxima. It is concluded that ultra-violet and blue light act mainly on a photoreceptor which is different from phytochrome.

Relative quantum responsivity curves for inhibition of hypocotyl elongation in Sinapis alba L. seedlings previously grown in white light confirm that a marked "end of day" inhibition response can be induced by a monochromatic light treatment (30 min) at the end of the light period. In dark grown seedlings, however, no growth inhibition can be induced by a 30 min monochromatic light treatment. A prerequisite for an induction response appears to be a pretreatment with continuous light. Far red light is most effective with blue and red light showing a lesser effectiveness. The light pretreatment also shows a marked fluence rate dependency with respect to its ability to allow an induction response to manifest itself. The pretreatment required shows all the characteristics of a classical "HIR" response. The appearance of the effect in plants treated with the herbicide SAN 9789 seems to exclude chlorophyll as being the photoreceptor.

Action spectra for the inhibition by continuous (24-hour) irradiation of hypocotyl growth in 54-hour-old Sinapis alba L. seedlings were measured using seedlings which had had four different pretreatments. These seedlings were either (a) dark-grown with a high total phytochrome level, (b) dark-grown with a low total phytochrome level, (c) light-grown with chlorophyll, or (d) light-grown with no chlorophyll [treated with 4-chloro-5-(methylamino)-2-(alpha,alpha,alpha-trifluoro-m-tolyl)-3(2H) -pyridazinone (San 9789)].The resulting action spectra show that the blue, red, and far-red (716 nm) wavebands are most inhibitory for dark-grown plants with high phytochrome content, whereas hypocotyl growth in dark-grown plants with a low phytochrome content are only slightly inhibited by blue and far-red radiation. In light-grown plants, the effectiveness of blue and far-red light almost disappears. The position of red light effectiveness in chlorophyll-containing plants is shifted to lower wavelengths compared with those containing no chlorophyll.

The influence of far-red (FR; 700-800 nm) radiation on steady-state stomatal conductance and net photosynthesis in P. vulgaris has been studied. Whereas FR radiation alone was relatively ineffective, addition of FR to a background of white light (WL; predominantly 400-700 nm) resulted in increased stomatal conductance. Stomata exhibited a marked diurnal sensitivity to FR. The action maximum for enhancing stomatal conductance was near 714 nm. A combination of FR and infra-red (IR; >800 nm) enhanced net photosynthesis when added to a background of WL. When IR alone was added to WL, there was a net decrease in photosynthesis, indicating that it is the FR waveband which is responsible for the observed photosynthetic effects. Naturally occurring levels of FR radiation (235 μmol·m(-2)·s(-1)) in vegetation-canopy shade enhanced net photosynthetic CO2 gain by 28% when added to a background of 55 μmol·m(-2)·s(-1) WL.

Observations made with primary leaves of Phaseolus vulgaris L. demonstrated that phytochrome modulates light-induced stomatal movement. Removal of the far-red-absorbing form of the pigment (Pfr) with far-red (FR) radiation decreased the time required by the stomata to reach maximal opening following a dark-to-light transition; this effect of FR was fully reversible with red. Removal of Pfr with FR also decreased the time required to reach maximal closure following a light-to-dark transition, and the rate of closure was dependent on the final irradiation treatment before darkness. No evidence was found for phytochrome involvement in determining stomatal aperture under constant conditions of either darkness of light.

Anthocyanin formation in 36h dark grown Sinapis alba L. seedlings and inhibition of hypocotyl elongation in 36h and 54h dark grown and 54h and 7 day light grown seedlings in response to continuous red light could be substituted for by hourly 5 min light pulses where the total fluence over the irradiation period is the same. These pulses are partially (36h) or almost totally (54h and 7 day) reversible by subsequent far-red (RG 9) light pulses. In contrast to 654 nm light, hourly light pulses with 552 nm, 449 nm and 715 nm can at best only partially substitute for continuous irradiation. These data are discussed with respect to the commonly used models for the phytochrome high irradiance response.