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Byline: P. Ferreira, J. Mindel, L. McKnight This paper provides an in-depth analysis of technological and market issues that will impact the development of bandwidth trading markets with liquidity. We provide a very broad definition for a bandwidth trading agreement and we analyse several network topologies in which trading bandwidth would make sense both from a business perspective and a technical perspective. The paper suggests that there is a gap between what the current routing protocols allow carriers to do and what carriers would like to do in order to implement more complex business relationships to trade bandwidth. We provide several examples of such situations. Additionally, we point out two major problems that may hamper the implementation of dynamic and fluid spot markets for bandwidth trading. The first problem is related to the excessive time that disseminating the new routing information generated by an agreement may take. The second problem is associated with the difficulties in performing traffic engineering to balance load across links once carriers become multi-connected, which we believe will be the case for most of them with mature bandwidth trading markets in place. The analysis provided in this paper contributes to understanding the directions in which routing would need to be enhanced in order to establish more attractive bandwidth trading markets. The analysis of market issues addresses the promise of these markets from the perspectives of demand and feasibility. From a public policy perspective, bandwidth trading markets are important because they have the potential to impact the sustainability of competition in the telecommunications sector. Existence and sustainability of market competitors in the service sector is a fundamental tenet of telecommunications policy because competitive markets offer consumers services with better quality that are priced closer to their true costs. This paper shows that there is price volatility in today's bandwidth markets; however not enough to convince market participants to adhere in bulk and thus to build the critical mass needed for the markets to take off. There is a significant amount of education that needs to take place for suppliers and wholesale consumers to become adept at the use of, for example, future contracts for risk management purposes in such markets.

Ingestion of the rat poison N-3-pyridylmethyl-N'-p-nitrophenylurea (PNU) produced ocular toxicity in three humans and in an animal model, the Dutch Belted rabbit. The electroretinogram b wave was especially susceptible to the effects of the rodenticide, and the target tissue appeared to be the retinal pigment epithelium. Injection of PNU itself did not produce ocular toxicity. The poison had to be administered orally. Gentamicin administered orally with PNU prevented the ocular toxicity. Presumably this antibiotic killed those gastrointestinal bacteria responsible for PNU's metabolism into an ocular toxin. L-tryptophan, a known antidote for the lethal effects of PNU, was an antidote for the ocular toxicity when administered orally but not when administered parenterally. [ABSTRACT FROM PUBLISHER]

Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included ( N  = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized β [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P  < 0.001), mandibular width (standardized β [95% CI] = 0.15 [0.10-0.20]; P  < 0.001), and tongue thickness (standardized β [95% CI] = 0.06 [0.02-0.10]; P  = 0.001) and smaller airway width (standardized β [95% CI] = -0.08 [-0.15 to -0.002]; P  = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.

Objective: Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open-label, single-center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment-refractory epilepsy., Methods: Two adult subjects with treatment-refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy., Results: The patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure-free at 12 months, and in the second patient, the frequency reduced from 90-100 seizures per month to 3-6 seizures per month., Significance: This is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment-refractory focal onset epilepsy., (© 2023 International League Against Epilepsy.)

Background: Prediction tools without patient-reported symptoms could facilitate widespread identification of OSA., Research Question: What is the diagnostic performance of OSA prediction tools derived from machine learning using readily available data without patient responses to questionnaires? Also, how do they compare with STOP-BANG, an OSA prediction tool, in clinical and community-based samples?, Study Design and Methods: Logistic regression and machine learning techniques, including artificial neural network (ANN), random forests (RF), and kernel support vector machine, were used to determine the ability of age, sex, BMI, and race to predict OSA status. A retrospective cohort of 17,448 subjects from sleep clinics within the international Sleep Apnea Global Interdisciplinary Consortium (SAGIC) were randomly split into training (n = 10,469) and validation (n = 6,979) sets. Model comparisons were performed by using the area under the receiver-operating curve (AUC). Trained models were compared with the STOP-BANG questionnaire in two prospective testing datasets: an independent clinic-based sample from SAGIC (n = 1,613) and a community-based sample from the Sleep Heart Health Study (n = 5,599)., Results: The AUCs (95% CI) of the machine learning models were significantly higher than logistic regression (0.61 [0.60-0.62]) in both the training and validation datasets (ANN, 0.68 [0.66-0.69]; RF, 0.68 [0.67-0.70]; and kernel support vector machine, 0.66 [0.65-0.67]). In the SAGIC testing sample, the ANN (0.70 [0.68-0.72]) and RF (0.70 [0.68-0.73]) models had AUCs similar to those of the STOP-BANG (0.71 [0.68-0.72]). In the Sleep Heart Health Study testing sample, the ANN (0.72 [0.71-0.74]) had AUCs similar to those of STOP-BANG (0.72 [0.70-0.73])., Interpretation: OSA prediction tools using machine learning without patient-reported symptoms provide better diagnostic performance than logistic regression. In clinical and community-based samples, the symptomless ANN tool has diagnostic performance similar to that of a widely used prediction tool that includes patient symptoms. Machine learning-derived algorithms may have utility for widespread identification of OSA., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Road traffic injuries (RTIs) are a major, global problem. Few studies on RTIs have been conducted in Namibia, despite having one of the highest RTI rates globally. We conducted multinomial logistic regression on national Namibian datasets on RTIs 2012-2014. Being a motorcyclist was associated with the greatest risk of being injured (adjusted Relative Risk Ratio (aRRR) 82.1 (95% CI 47.2-142.9)) or killed (aRRR 202.1 (112.7-362.7)). Risks were also elevated for cyclists (57.3 (23.6-139.5)), pedestrians (15.8 (13.2-18.9), passengers (6.1 (5.2-7.2)), relative to drivers. Among those admitted to hospital, the method of transportation to hospital had the largest association with the risk of dying. To our knowledge this study presents new information on vulnerability of different road users, which can be of use to policymakers to develop specific and targeted interventions to protect the most vulnerable road users.

Background: Anti-NMDA receptor encephalitis (ANRE) is a rare autoimmune neurologic disorder characterized by encephalitis and a constellational of symptoms, including seizures, psychiatric disturbances, autonomic instability, and respiratory insufficiency. It is caused by the anti-NMDA receptor antibody. The most common etiologies for ANRE include malignancy and infection. Ovarian teratoma is the most commonly associated malignancy., Case Description: We describe the first reported case to our knowledge of ovarian teratoma causing ANRE resulting in nonconvulsive status epilepticus (NCSE), which was terminated with vagus nerve stimulation (VNS)., Conclusions: This case report provides a temporal correlation suggesting that VNS significantly altered the natural history of this patient's NCSE-ANRE. As more data are collected, and the VNS treatment modality more liberally used to treat NCSE, especially in the situation of ANRE, stronger layers of evidence will emerge to fill the gaps of understanding beyond this case report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Extreme phenotypes of OSA have not been systematically defined., Research Question: This study developed objective definitions of extreme phenotypes of OSA by using a multivariate approach. The utility of these definitions for identifying characteristics that confer predisposition toward or protection against OSA is shown in a new prospective sample., Study Design and Methods: In a large international sample, race-specific liability scores were calculated from a weighted logistic regression that included age, sex, and BMI. Extreme cases were defined as individuals with an apnea-hypopnea index (AHI) ≥ 30 events/hour but low likelihood of OSA based on age, sex, and BMI (liability scores > 90th percentile). Similarly, extreme controls were individuals with an AHI < 5 events/hour but high likelihood of OSA (liability scores < 10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium, and differences in photography-based craniofacial and intraoral phenotypes were evaluated., Results: This study included retrospective data from 81,338 individuals. A total of 4,168 extreme cases and 1,432 extreme controls were identified by using liability scores. Extreme cases were younger (43.1 ± 14.7 years), overweight (28.6 ± 6.8 kg/m 2 ), and predominantly female (71.1%). Extreme controls were older (53.8 ± 14.1 years), obese (34.0 ± 8.1 kg/m 2 ), and predominantly male (65.8%). These objective definitions identified 29 extreme cases and 87 extreme controls among 1,424 Sleep Apnea Global Interdisciplinary Consortium participants with photography-based phenotyping. Comparisons suggest that a greater cervicomental angle increases risk for OSA in the absence of clinical risk factors, and smaller facial widths are protective in the presence of clinical risk factors., Interpretation: This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic, and physiologic pathways to OSA., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Study Objectives: Obstructive sleep apnea (OSA) is a global health issue and is associated with obesity and oropharyngeal crowding. Global data are limited on the effect of ethnicity and sex on these relationships. We compare associations between the apnea-hypopnea index (AHI) and these risk factors across ethnicities and sexes within sleep clinics., Methods: This is a cross-sectional, multicenter study of patients with OSA from eight sleep centers representing the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Four distinct ethnic groups were analyzed, using a structured questionnaire: Caucasians (Australia, Iceland, Germany, United States), African Americans (United States), Asians (Taiwan), and South Americans (Brazil). Regression analyses and interaction tests were used to assess ethnic and sex differences in relationships between AHI and anthropometric measures (body mass index [BMI], neck circumference, waist circumference) or Mallampati score., Results: Analyses included 1,585 individuals from four ethnic groups: Caucasian (60.6%), African American (17.5%), Asian (13.1%), and South American (8.9%). BMI was most strongly associated with AHI in South Americans (7.8% increase in AHI per 1 kg/m 2 increase in BMI; P < .0001) and most weakly in African Americans (1.9% increase in AHI per 1 kg/m 2 increase in BMI; P = .002). In Caucasians and South Americans, associations were stronger in males than females. Mallampati score differed between ethnicities but did not influence AHI differently across groups., Conclusions: We demonstrate ethnic and sex variations in associations between obesity and OSA. For similar BMI increases, South American patients show greatest AHI increases compared to African Americans. Findings highlight the importance of considering ethnicity and sex in clinical assessments of OSA risk., (© 2019 American Academy of Sleep Medicine.)

Rationale: Several studies have reported that both short and long sleep durations are associated with the metabolic syndrome, but whether a dose-response relationship exists is unclear., Objectives: We performed a metaanalysis to study the magnitude of the association between the different durations of sleep and metabolic syndrome., Methods: We searched in the databases of PubMed, Web of Science, and Ovid (all Journals@Ovid) from inception to October 4, 2014 for cross-sectional studies where an association between metabolic syndrome and sleep duration was analyzed., Measurements and Main Results: Eighteen studies with 75,657 participants were included. Daily sleep duration of 7 to 8 hours was used as the reference group. The odds ratio (OR) of having metabolic syndrome for short (<7 h) sleep was 1.23 (95% CI, 1.11-1.37; P < 0.001; I(2), 71%). The ORs for less than 5 hours, 5 to 6 hours, and 6 to 7 hours of sleep were 1.51 (95% CI, 1.10-2.08; P = 0.01), 1.28 (95% CI, 1.11-1.48; P < 0.001), and 1.16 (95% CI, 1.02-1.31; P = 0.02), respectively. The coefficient of sleep duration on log of ORs was -0.06 ± 0.02 (P = 0.02). The OR for long sleep duration was 1.13 (95% CI, 0.97-1.32; P = 0.10; I(2), 89%)., Conclusions: A dose-response relationship exists between short sleep duration and metabolic syndrome. Those who report a sleep duration of less than 5 hours have a 1.5 higher odds of having metabolic syndrome. Our study does not support the notion that long sleep is associated with metabolic syndrome.

A 37-year-old man with a history of sarcoidosis, hypertension, asthma, depression and prior intravenous drug use presented with complaints of difficulty in finding his way around the house, headache, and blurred vision in both eyes. The symptoms had been increasing in severity over the prior several months. Physical examination showed normal visual acuity, pupil reactions, and fundi but severe, circumferential constriction of the visual fields bilaterally. The visual fields enlarged appropriately on increasing the distance from the patient to the tangent screen. Neuroimaging revealed bilateral, occipital meningeal involvement and parenchymal lesions consistent with sarcoidosis. Treatment with oral corticosteroids produced a mild subjective improvement in the patient's symptoms and stabilized the visual fields, without improving them. This case represents an unusual presentation of presumed neurosarcoidosis involving the visual pathways at the level of the occipital lobes.

Three organizations in the U.S.A. ask health care providers to report adverse effects of drugs in their patients: The Food and Drug Administration; United States Pharmacopoeia; and the National Registry of Drug Induced Ocular Side Effects and Drug Interactions. In a comprehensive Table, the characteristics and procedures of these three organizations are summarized.

A 21-year-old woman with neurofibromatosis type 1 (NF-1) had a unilateral congenital Horner's syndrome with resultant hypopigmentation of the affected iris. Lisch nodules, which are melanocytic hamartomas, were similar in number, size, and pigmentation in both eyes. The present findings suggest that the formation of Lisch nodules is not influenced by the presence or absence of sympathetic innervation of the iris.

E-10-hydroxynortriptyline, a metabolite of nortriptyline with half the norepinephrine re-uptake blocking potency of the parent drug, but only 5% of its anticholinergic effect, was as effective as cocaine in demonstrating ocular sympathetic paresis. In five rabbits with unilateral superior cervical ganglionectomies, bilateral 5% cocaine HCl or E-10-hydroxynortriptyline maleate eye drops increased (P less than 0.001) the mean +/- SE anisocoria at 1 h by 1.84 +/- 0.03 mm or 2.16 +/- 0.33 mm, respectively. A single drop of E-10-hydroxynortriptyline did not alter corneal thickness or endothelial cell count.

In a previous study, pretreatment of rabbit eyes with echothiophate iodide prevented the ocular hypotensive effect of dipivefrin. The present masked study, using inpatient volunteers and nurse-administered drops, investigated whether a similar antagonism of action occurred in human beings. Eight volunteers received 0.25% echothiophate iodide twice a day in both eyes for three weeks. During the second week of therapy, one eye also received 0.25% dipivefrin twice a day and the contralateral eye received 2% epinephrine hydrochloride twice a day. During the third week of therapy, the eyes receiving dipivefrin and epinephrine were reversed. In four volunteers, dipivefrin plus echothiophate produced a significantly greater reduction in intraocular pressure than epinephrine plus echothiophate. As a group the eight eyes treated with dipivefrin plus echothiophate had significantly lower IOPs than the eyes treated with epinephrine plus echothiophate during the second week of therapy. Epinephrine plus echothiophate was never superior to dipivefrin plus echothiophate. Dipivefrin seemed to be effective during combination therapy with echothiophate.

A 20-year-old woman developed severe orthostatic hypotension after attempting suicide by ingesting the rodenticide, Vacor. Oral ergotamine tartrate, 6 mg a day, was useful in treating the orthostatic hypotension. However, a bilateral toxic retinal vasculopathy, consisting of a severe generalized vasoconstriction and mild macular edema, occurred within three weeks. Additional findings were an extinguished electroretinogram and a reduced dark-adaptation retinal sensitivity; because we performed these two tests after instituting ergotamine therapy we do not know whether to attribute their abnormal results to Vacor toxicity, ergotamine toxicity, or a combination of the two.

Topical application of the H2-histamine receptor agonist, dimaprit (S-[4-N,N-dimethylaminopropyl]isothiourea), produced eosinophil chemotaxis into the anterior segment of rabbit eyes only when an H2-antagonist was co-administered. Nordimaprit (S-[4-N,N-dimethylaminoethyl]isothiourea), a structural homologue of dimaprit that lacked activity at histamine receptors, produced eosinophil chemotaxis whether or not an H2-antagonist was co-administered. Onset of eosinophil chemotaxis began after 2 or more days of treatment, and was accompanied by corneal edema, opacification, and ocular inflammation. There was no concurrent eosinophilia in the peripheral blood or in the conjunctiva. The response occurred in pigmented and albino rabbit eyes, and was facilitated by prior co-administration of proparacaine eye drops. Another dimaprit homologue without activity at histamine receptors, homodimaprit (S-[4-N,N-dimethylaminobutyl]isothiourea), did not produce eosinophil chemotaxis when applied topically, nor did the H2-agonists impromidine, histamine, or 4-methylhistamine, whether co-administered with an H2-antagonist or not. It was concluded that dimaprit and nordimaprit produced a selective eosinophil chemotaxis unrelated to H1- and H2-histamine receptor activity. However, the H2-agonist activity of dimaprit appeared to inhibit this response unless neutralized by an H2-antagonist. Topical application of dimaprit with an H2-antagonist or nordimaprit alone may allow large numbers of non-degranulated eosinophils, free of other cell types, to be harvested from the aqueous humor.

Imidazole activates synthesis of acetylcholine by choline acetyltransferase. Pilocarpine hydrochloride, an imidazole derivative, was investigated for its activation effect. In vitro, millimolar concentrations of pilocarpine significantly activated human ciliary body and retinal and rabbit corneal epithelial, iris-ciliary body, and retinal choline acetyltransferases. Concentrations greater than 100mM pilocarpine inhibited acetylcholine synthesis. In vivo, 1% or 4% pilocarpine eyedrops given every 30 minutes for four applications failed to significantly alter rabbit ocular acetylcholine levels. There was a tendency for pilocarpine-treated eyes to have lower levels of acetylcholine. Although pilocarpine altered acetylcholine synthesis by human and rabbit ocular tissues in vitro, this phenomenon could not be demonstrated in rabbits in vivo. However, because tissues of intact rabbit eyes degrade pilocarpine, the possibility remains that this drug can alter acetylcholine synthesis when applied to the intact human eye.

A 32-year old diabetic female had unilateral reduced vision (20/30) in an eye having the ophthalmoscopic appearance of papillophlebitis of the optic nerve head. After an apparently benign course, with recovery, the optic disc became edematous again and a central retinal vein occlusion blinded the eye. Thereafter, an avascular bilobed mass progressively protruded from the optic nerve head. Computerized tomography demonstrated uniform thickening of the optic nerve from the globe through the optic canal. The radiographic appearance was consistent with an optic nerve glioma or meningioma. Spinal fluid, chest x-ray, and serum angiotensin converting enzyme activity were normal. Tuberculin skin test was positive. Optic nerve biopsy demonstrated a noncaseating granuloma and a subsequent Kveim test was positive. Isolated optic nerve sarcoidosis may exist without other systemic manifestations. The appearance on computerized tomography may be similar to that of an optic nerve glioma or meningioma.