To evaluate the performance of commercially available seizure detection algorithms in critically ill children.
Diagnostic accuracy comparison between commercially available seizure detection ...algorithms referenced to electroencephalography experts using quantitative electroencephalography trends.
Multispecialty quaternary children's hospital in Canada.
Critically ill children undergoing electroencephalography monitoring.
Continuous raw electroencephalography recordings (n = 19) were analyzed by a neurophysiologist to identify seizures. Those recordings were then converted to quantitative electroencephalography displays (amplitude-integrated electroencephalography and color density spectral array) and evaluated by six independent electroencephalography experts to determine the sensitivity and specificity of the amplitude-integrated electroencephalography and color density spectral array displays for seizure identification in comparison to expert interpretation of raw electroencephalography data. Those evaluations were then compared with four commercial seizure detection algorithms: ICTA-S (Stellate Harmonie Version 7; Natus Medical, San Carlos, CA), NB (Stellate Harmonie Version 7; Natus Medical), Persyst 11 (Persyst Development, Prescott, AZ), and Persyst 13 (Persyst Development) to determine sensitivity and specificity in comparison to amplitude-integrated electroencephalography and color density spectral array.
Of the 379 seizures identified on raw electroencephalography, ICTA-S detected 36.9%, NB detected 92.3%, Persyst 11 detected 75.9%, and Persyst 13 detected 74.4%, whereas electroencephalography experts identified 76.5% of seizures using color density spectral array and 73.7% using amplitude-integrated electroencephalography. Daily false-positive rates averaged across all recordings were 4.7 with ICTA-S, 126.3 with NB, 5.1 with Persyst 11, 15.5 with Persyst 13, 1.7 with color density spectral array, and 1.5 with amplitude-integrated electroencephalography. Both Persyst 11 and Persyst 13 had sensitivity comparable to that of electroencephalography experts using amplitude-integrated electroencephalography and color density spectral array. Although Persyst 13 displayed the highest sensitivity for seizure count and seizure burden detected, Persyst 11 exhibited the best trade-off between sensitivity and false-positive rate among all seizure detection algorithms.
Some commercially available seizure detection algorithms demonstrate performance for seizure detection that is comparable to that of electroencephalography experts using quantitative electroencephalography displays. These algorithms may have utility as early warning systems that prompt review of quantitative electroencephalography or raw electroencephalography tracings, potentially leading to more timely seizure identification in critically ill patients.
Recent work has revealed links between memory, imagination, and problem solving, and suggests that increasing access to detailed memories can lead to improved imagination and problem-solving ...performance. Depression is often associated with overgeneral memory and imagination, along with problem-solving deficits. In this study, we tested the hypothesis that an interview designed to elicit detailed recollections would enhance imagination and problem solving among both depressed and nondepressed participants. In a within-subjects design, participants completed a control interview or an episodic specificity induction prior to completing memory, imagination, and problem-solving tasks. Results revealed that compared to the control interview, the episodic specificity induction fostered increased detail generation in memory and imagination and more relevant steps on the problem-solving task among depressed and nondepressed participants. This study builds on previous work by demonstrating that a brief interview can enhance problem solving among individuals with depression and supports the notion that episodic memory plays a key role in problem solving. It should be noted, however, that the results of the interview are relatively short-lived.
The white shark (Carcharodon carcharias) is a globally distributed top predator. Due to its ecological importance, increasing knowledge through continued research can enhance management measures. One ...such facet of biological knowledge is the identification of shark nursery areas, as protection of these regions is critical to species survival. Presently, there are two known C. carcharias nursery areas in association with the Eastern Australian subpopulation; however, a nursery area associated with the Southern-Western Australian C. carcharias subpopulation has yet to be identified. Herein, we report opportunistic laser photogrammetry, stereo-photogrammetry, and baited remote underwater video systems (BRUVS) data that resulted in the identification of sixteen young-of-the-year (YOY)-juvenile C. carcharias from two separate regions (i.e., Salisbury Island and Daw Island) in South-West Australia. Additionally, anecdotal bycatch data associated with two YOY C. carcharias (i.e., 1.40 and 1.70 m total length) from another location within the Great Australian Bight are reported. While it is premature to conclude that these sites represent discrete or an expansive interconnected nursery area, the sightings success in this study is indicative that future research may want to consider implementing a study during a similar time period (i.e., February–March) while using a similar attractant methodology (i.e., bottom-set BRUVS baited with squid Sepioteuthis australis) to help elucidate the unique life-history characteristics of this C. carcharias subpopulation.
To investigate the role of inner medullary collecting duct (IMCD) urea transporters in the renal concentrating mechanism, we deleted 3 kb of the UT-A urea transporter gene containing a single 140-bp ...exon (exon 10). Deletion of this segment selectively disrupted expression of the two known IMCD isoforms of UT-A, namely UT-A1 and UT-A3, producing UT-A1/3-/- mice. In isolated perfused IMCDs from UT-A1/3-/- mice, there was a complete absence of phloretin-sensitive or vasopressin-stimulated urea transport. On a normal protein intake (20% protein diet), UT-A1/3-/- mice had significantly greater fluid consumption and urine flow and a reduced maximal urinary osmolality relative to wild-type controls. These differences in urinary concentrating capacity were nearly eliminated when urea excretion was decreased by dietary protein restriction (4% by weight), consistent with the 1958 Berliner hypothesis stating that the chief role of IMCD urea transport in the concentrating mechanism is the prevention of urea-induced osmotic diuresis. Analysis of inner medullary tissue after water restriction revealed marked depletion of urea in UT-A1/3-/- mice, confirming the concept that phloretin-sensitive IMCD urea transporters play a central role in medullary urea accumulation. However, there were no significant differences in mean inner medullary Na+ or Cl- concentrations between UT-A1/3-/- mice and wild-type controls, indicating that the processes that concentrate NaCl were intact. Thus, these results do not corroborate the predictions of passive medullary concentrating models stating that NaCl accumulation in the inner medulla depends on rapid vaso-pressin-regulated urea transport across the IMCD epithelium.
Evidence that the phosphoinositide 3-kinase (PI3K) pathway is deregulated in ovarian cancer is largely based on the analysis of surgical specimens sampled at diagnosis and may not reflect the biology ...of advanced ovarian cancer. We aimed to investigate PI3K signaling in cancer cells isolated from patients with advanced ovarian cancer. Ascites samples were analyzed from 88 patients, of whom 61 received further treatment. Cancer cells were immunomagnetically separated from ascites, and the signaling output of the PI3K pathway was studied by quantifying p-AKT, p-p70S6K, and p-GSK3β by ELISA. Relevant oncogenes, such as PIK3CA and AKT, were sequenced by PCR-amplified mass spectroscopy detection methods. In addition, PIK3CA and AKT2 amplifications and PTEN deletions were analyzed by FISH. p-p70S6K levels were significantly higher in cells from 37 of 61 patients who did not respond to subsequent chemotherapy (0.7184 vs. 0.3496; P = 0.0100), and this difference was greater in patients who had not received previous chemotherapy. PIK3CA and AKT mutations were present in 5% and 0% of samples, respectively. Amplification of PIK3CA and AKT2 and deletion of PTEN was seen in 10%, 10%, and 27% of samples, respectively. Mutations of PIK3CA and amplification of PIK3CA/AKT2 or deletion of PTEN did not correlate with levels of p-AKT, p-p70S6K, and p-GSK3β. In patients with advanced ovarian cancer, there is an association between levels of p-p70S6K and response to subsequent chemotherapy. There is no clear evidence that this is driven specifically by PIK3CA or AKT mutations or by amplifications or deletion of PTEN.
To relate early somatosensory evoked potential grades from comatose traumatic brain injury patients to neuropsychological and functional outcome 1 yr later; to determine the day (within the first ...week after traumatic brain injury) that somatosensory evoked potential grade best correlates with outcome; to determine whether somatosensory evoked potential grade improvement in the first week after traumatic brain injury is associated with improved outcome.
Prospective cohort study.
Critical care unit at a university hospital.
Median nerve somatosensory evoked potentials were obtained from 81 comatose patients with traumatic brain injury. Somatosensory evoked potential grades were calculated from results obtained on days 1, 3, and 7 after traumatic brain injury. Glasgow Outcome Scale, Barthel Index, Rivermead Head Injury Follow-up Questionnaire, General Health Questionnaire, Stroop Color-Word Test, Paced Auditory Serial Addition Task, and Symbol-Digit Modalities Test scores were obtained 1 yr after injury.
None.
Somatosensory evoked potential grade on days 1, 3, and 7 related significantly with Glasgow Outcome Scale and Barthel scores (day 3 better than day 1) but did not relate with Rivermead Head Injury Follow-up Questionnaire or General Health Questionnaire scores. Day 3 and day 7 somatosensory evoked potential grades related significantly with Stroop scores. Day 3 somatosensory evoked potential grades related significantly with Symbol-Digit Modalities Test scores. Patients with bilaterally present but abnormal somatosensory evoked potentials, whose somatosensory evoked potential grade improved between days 1 and 3, had marginally better functional outcome than those without somatosensory evoked potential grade improvement.
Day 3 somatosensory evoked potential grade related to information-processing speed, working memory, and the ability to attend to tasks 1 yr after traumatic brain injury. Day 3 somatosensory evoked potential grade had the strongest relationship with functional outcome. Somatosensory evoked potential grades were not related to emotional well-being.
Maintaining a correct balance of N is essential for life. In mammals, the major sources of N in the diet are amino acids and peptides derived from ingested proteins. The immediate endproduct of ...mammalian protein catabolism is ammonia, which is toxic to cells if allowed to accumulate. Therefore, amino acids are broken down in the liver as part of the ornithine-urea cycle, which results in the formation of urea -- a highly soluble, biochemically benign molecule. Mammals cannot break down urea, which is traditionally viewed as a simple waste product passed out in the urine. However, urea from the bloodstream can pass into the gastrointestinal tract, where bacteria expressing urease cleave urea into ammonia and carbon dioxide. The bacteria utilise the ammonia as an N source, producing amino acids and peptides necessary for growth. Interestingly, these microbial products can be reabsorbed back into the host mammalian circulation and used for synthetic processes. This entire process is known as 'urea nitrogen salvaging' (UNS). In this review we present evidence supporting a role for this process in mammals -- including ruminants, non-ruminants and man. We also explore the possible mechanisms involved in UNS, including the role of specialised urea transporters.
Two closely related genes, UT-A (Slc14a2) and UT-B (Slc14a1), encode specialized transporter proteins that modulate the movement of urea across cell membranes. In this article, we report the ...characterization of a cDNA isolated from human colonic mucosa encoding a novel UT-A urea transporter, hUT-A6. The encoded protein is 235 amino acids (aa) in length, making it the smallest UT-A member characterized. On the basis of previous structural predictions, hUT-A6 is structurally unique in that it consists of a single hydrophobic core flanked by hydrophilic NH(2)- and COOH-terminal domains. The transcript encoding hUT-A6 contains a novel 129-bp exon, exon 5a, which, as a result of alternative splicing, introduces a unique 19-aa segment and a stop codon. Functionally, the protein transports urea, and this activity is inhibited by phloretin. Interestingly, despite the lack of a protein kinase A (PKA) consensus site RK(2)-X-ST, transport of urea by hUT-A6 is stimulated by PKA agonists. Deletion of the two PKA consensus sites from murine UT-A3 (mUT-A3) did not affect the stimulatory response of PKA agonists, which, together with the lack of PKA consensus sites in hUT-A6, indicates that regulation of hUT-A6 and mUT-A3 is not mediated through a classic PKA phosphorylation consensus.
The renal UT-A urea transporters UT-A1, UT-A2, and UT-A3 are known to play an important role in the urinary concentrating mechanism. The control of the cellular localization of UT-A transporters is ...therefore vital to overall renal function. In the present study, we have investigated the effect of ubiquitination on UT-A plasma membrane expression in Madin-Darby canine kidney (MDCK) cell lines expressing each of the three renal UT-A transporters. Inhibition of the ubiquitin-proteasome pathway caused an increase in basal transepithelial urea flux across MDCK-rat (r)UT-A1 and MDCK-mouse (m)UT-A2 monolayers (P < 0.01, n = 3, ANOVA) and also increased dimethyl urea-sensitive, arginine vasopressin-stimulated urea flux (P < 0.05, n = 3, ANOVA). Inhibition of the ubiquitin-proteasome pathway also increased basolateral urea flux in MDCK-mUT-A3 monolayers (P < 0.01, n = 4, ANOVA) in a concentration-dependent manner. These increases in urea flux corresponded to a significant increase in UT-A transporter expression in the plasma membrane (P < 0.05, n = 3, ANOVA). Further analysis of the MDCK-mUT-A3 cell line confirmed that vasopressin specifically increased UT-A3 expression in the plasma membrane (P < 0.05, n = 3, ANOVA). However, preliminary data suggested that vasopressin produces this effect through an alternative route to that of the ubiquitin-proteasome pathway. In conclusion, our study suggests that ubiquitination regulates the plasma membrane expression of all three major UT-A urea transporters, but that this is not the mechanism primarily used by vasopressin to produce its physiological effects.
In this study, we engineered a Madin-Darby canine kidney (MDCK) type I cell line to stably express the mouse urea transporter UT-A2. Monolayers of MDCK-mUT-A2 cells had a basal phloretin-inhibitable ...urea permeability of 8.4x10(-6)+/-0.3 cm/s. Treatment of MDCK-mUT-A2 monolayers with AVP led to a rapid dose-dependent increase in trans-monolayer phloretin-inhibitable urea flux. The temporal pattern of response was markedly different from that observed for MDCK cells expressing rat UT-A1. Exposure of MDCK-mUT-A2 cells to either 10 microM forskolin or 250 microM 8-bromo cAMP also increased urea flux rate. Inclusion of the PKA inhibitor H89 (10 microM) had no effect on the forskolin-stimulated increase in urea flux across MDCK-mUT-A2 monolayers. Treatment with either 10 microM CPA or 1 mM ATP also caused an increase in UT-A2-mediated urea flux, although these responses where transient compared with those induced by AVP or elevated cAMP. Taken together, these results show for the first time that UT-A2 is acutely sensitive to AVP, cAMP, or increased intracellular calcium.
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