Faculty Bibliography

Reports an error in the original article by Ana C. Krieger et al (Journal of Sleep Research, 2004[Dec], Vol 13[4], 407-441.) The manufacturer of the Oxford Sleep Resistance Test, OSLER was inadvertently omitted. The manufacturer is: Stowood Scientific Instruments, Oxford, UK. (The following abstract of this article originally appeared in record 2004-21174-013). The objectives were to evaluate the correlation between sleep onset as defined by the Oxford sleep resistance (OSLER) test and by simultaneous electroencephalography (EEG) and to determine the correlation between sleep latencies measured by the OSLER test and maintenance of wakefulness test (MWT) performed on the same day. This was a prospective, cross-sectional study carried out in a tertiary-care university-based sleep laboratory. Participants were 11 consecutive subjects presenting to the sleep center with clinical indications for nocturnal polysomnography and MWT. The interventions included MWT and OSLER test. Mean sleep latencies for the OSLER and MWT in each subject were closely correlated (ICC = 0.94, [Intra-class correlation] P < 0.05). Sleep latency by OSLER and simultaneous measurement of EEG also had excellent agreement (ICC = 0.91) with a bias of -0.97 min. The OSLER test is a practical and reliable tool for evaluating daytime sleepiness when compared with the MWT. No obvious systematic adaptation was seen during sequential OSLER test performance. Given its portability and minimal technical requirements, the OSLER test may be useful for largescale applications in the evaluation of daytime wakefulness and vigilance.

STUDY OBJECTIVES: Evaluate the utility of overnight monitoring limited to nasal cannula airflow and oximetry in the diagnosis of obstructive sleep apnea-hypopnea syndrome (OSAHS). DESIGN: Prospective randomized study, blinded analysis. SETTING: Sleep disorder center, academic institution. PARTICIPANTS: 56 patients with suspected OSAHS, 10 normal volunteers. MEASUREMENTS AND RESULTS: In-laboratory full nocturnal polysomnography (NPSG) and unattended ambulatory study with monitoring of only airflow and oximetry performed in randomized order. Obstructive respiratory events were scored on the full NPSG while visualizing all signals and then rescored on the full NPSG and on the ambulatory study while visualizing only airflow and oximetry signals. Respiratory disturbance indexes (RDI) for the limited studies (RDIFlowNPSG and RDIFlowAmbulatory) were calculated as the sum of the apneas and hypopneas (defined using airflow amplitude and O2 desaturation) divided by the valid flow-signal time. The reference RDIFullNPSG was calculated from the sum of the apneas and hypopneas (defined using flow amplitude, O2 desaturation and electroencephalographic arousal) identified on the full NPSG divided by the total sleep time. RDIFullNPSG was greater than RDIFlowNPSG (bias = 5.6 events per hour) and RDIFlowAmbulatory (bias = 10.9 events per hour), but the differences were mainly in subjects with an RDI > 40 events per hour. The diagnostic sensitivity and specificity for the diagnosis of OSAHS using a cutoff of 18 events per hour were 96% and 93% using the flow signal from the NPSG and 88% and 92% using the flow signal from the ambulatory study performed on a separate night. CONCLUSIONS: In subjects with OSAHS, analysis of the flow signal from a nasal cannula can provide an RDI similar to that obtained in a full NPSG.

Replicating adenoviral vectors are capable of multiplying up to a thousandfold in the target cell, a property that might prove to be of tremendous potential for cancer therapy. However, restricting viral replication and toxicity to cancer cells is essential to optimize safety. It has been proposed that modifications of the E1a protein that impair binding to Rb or p300 will prevent S-phase induction in normal cells, resulting in selective viral replication in tumor cells. However, it remains uncertain which of the several possible E1a modifications would be most effective at protecting normal cells without compromising the oncolytic effect of the vector. In this study, we have expressed several E1a-deletion mutants at high levels using the CMV promoter and tested them for their ability to facilitate S-phase induction, viral replication, and cytotoxicity in both normal and cancer cells. Deletion of the Rb-binding domain within E1a only slightly decreased the ability of the virus to induce S phase in growth-arrested cells. The effect of this deletion on viral replication and cytotoxicity was variable. There was reduced cytotoxicity in normal bronchial epithelial cells; however, in some normal cell types there was equal viral replication and cytotoxicity compared with wild type. Deletions in both the N-terminus and the Rb-binding domain were required to block S-phase induction effectively in growth-arrested normal cells; in addition, this virus demonstrated reduced viral replication and cytotoxicity in normal cells. An equally favorable replication and cytotoxicity profile was induced by a virus expressing E1a that is incapable of binding to the transcriptional adapter motif (TRAM) of p300. All viruses were equally cytotoxic to cancer cells compared with wild-type virus. In conclusion, deletion of the Rb-binding site alone within E1a may not be the most efficacious means of targeting viral replication and toxicity. However, deletion within the N-terminus in conjunction with a deletion within the Rb-binding domain, or deletion of the p300-TRAM binding domain, induces a more favorable cytotoxicity profile.

The objectives were to evaluate the correlation between sleep onset as defined by the Oxford sleep resistance (OSLER) test and by simultaneous electroencephalography (EEG) and to determine the correlation between sleep latencies measured by the OSLER test and maintenance of wakefulness test (MWT) performed on the same day. This was a prospective, cross-sectional study carried out in a tertiary-care university-based sleep laboratory. Participants were 11 consecutive subjects presenting to the sleep center with clinical indications for nocturnal polysomnography and MWT. The interventions included MWT and OSLER test. Mean sleep latencies for the OSLER and MWT in each subject were closely correlated (ICC = 0.94, [Intra-class correlation]P < 0.05). Sleep latency by OSLER and simultaneous measurement of EEG also had excellent agreement (ICC = 0.91) with a bias of -0.97 min. The OSLER test is a practical and reliable tool for evaluating daytime sleepiness when compared with the MWT. No obvious systematic adaptation was seen during sequential OSLER test performance. Given its portability and minimal technical requirements, the OSLER test may be useful for large-scale applications in the evaluation of daytime wakefulness and vigilance.

Bowhead whales, Balaena mysticetus, migrate west during fall approximately 10-75 km off the north coast of Alaska, passing the petroleum developments around Prudhoe Bay. Oil production operations on an artificial island 5 km offshore create sounds heard by some whales. As part of an effort to assess whether migrating whales deflect farther offshore at times with high industrial noise, an acoustical approach was selected for localizing calling whales. The technique incorporated DIFAR (directional frequency and recording) sonobuoy techniques. An array of 11 DASARs (directional autonomous seafloor acoustic recorders) was built and installed with unit-to-unit separation of 5 km. When two or more DASARs detected the same call, the whale location was determined from the bearing intersections. This article describes the acoustic methods used to determine the locations of the calling bowhead whales and shows the types and precision of the data acquired. Calibration transmissions at GPS-measured times and locations provided measures of the individual DASAR clock drift and directional orientation. The standard error of the bearing measurements at distances of 3-4 km was approximately 1.35 degrees after corrections for gain imbalance in the two directional sensors. During 23 days in 2002, 10,587 bowhead calls were detected and 8383 were localized

Longitudinal modelling of lung function in Duchenne's muscular dystrophy is complicated by a mixture of both growth and decline in lung function within each subject, an unknown point of separation between these phases and significant heterogeneity between individual trajectories. Linear mixed effects models can be used, assuming a single changepoint for all cases; however, this assumption may be incorrect. The paper describes an extension of linear mixed effects modelling in which random changepoints are integrated into the model as parameters and estimated by using a stochastic EM algorithm. We find that use of this 'mixture modelling' approach improves the fit significantly