Prediction of HLA-DQ3.2 beta ligands: evidence of multiple registers in class II binding peptides

Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models. Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2 beta complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2 beta receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2 beta binding and non-binding peptides obtained from biochemical and functional studies. Results: Our model predicts DQ3.2 beta binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve A(ROC) > 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2 beta peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.

Detecting insomnia: comparison of four self-report measures of sleep in a young adult population

The sensitivity and specificity of four self-report measures of disordered sleep - the Sleep Impairment Index (SII), the Sleep Disorders Questionnaire (SDQ), the Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS) and the Sleep-Wake Activity Inventory (SWAI) - were compared in subjects with insomnia and normal sleep. Nineteen young adult subjects met DSM-IV criteria for primary insomnia and another 19 were normal control subjects. Discriminatory characteristics of each measure were assessed using receiver operator characteristic curve analyses. Discriminatory power was maximised for each measure to produce cut-scores applicable for identification of individuals with insomnia. The DBAS, SII and SDQ psychiatric DIMS subscale were found to correlate, and discriminated well between the two groups. The SWAI nocturnal sleep subscale was not found to be an accurate discriminator. The results suggest differences in the measures in their ability to detect insomnia, and offer guidelines as to the optimal use of test scores to identify young adults suspected of insomnia.

Relating body mass index to figural stimuli: population-based normative data for Caucasians

OBJECTIVE: To establish body mass index (BMI) norms for standard figural stimuli using a large Caucasian population-based sample. In addition, we sought to determine the effectiveness of the figural stimuli to identify individuals as obese or thin. DESIGN: All Caucasian twins born in Virginia between 1915 and 1971 were identified by public birth record. In addition, 3347 individual twins responded to a letter published in the newsletter of the American Association of Retired Persons (AARP). All adult twins (aged 18 and over) from both of these sources and their family members were mailed a 16 page 'Health and Lifestyle' questionnaire. SUBJECTS: BMI and silhouette data were available on 16 728 females and 11 366 males ranging in age from 18- 100. MEASUREMENTS: Self-report information on height-weight, current body size, desired body size and a discrepancy score using standard figural stimuli. RESULTS: Gender- and age-specific norms are presented linking BMI to each of the figural stimuli. Additional norms for desired body size and discrepancy scores are also presented. Receiver operating curves (ROC) indicate that the figural stimuli are effective in classifying individuals as obese or thin. CONCLUSIONS: With the establishment of these norms, the silhouettes used in standard body image assessment can now be linked to BMI. Differences were observed between women and men in terms of desired body size and discrepancy scores, with women preferring smaller sizes. The figural stimuli are a robust technique for classifying individuals as obese or thin.

Outcomes of transient evoked otoacoustic emission testing in 6-year-old school children: A comparison with pure tone screening and tympanometry

Objectives: (1) To establish test performance measures for Transient Evoked Otoacoustic Emission testing of 6-year-old children in a school setting; (2) To investigate whether Transient Evoked Otoacoustic Emission testing provides a more accurate and effective alternative to a pure tone screening plus tympanometry protocol. Methods: Pure tone screening, tympanometry and transient evoked otoacoustic emission data were collected from 940 subjects (1880 ears), with a mean age of 6.2 years. Subjects were tested in non-sound-treated rooms within 22 schools. Receiver operating characteristics curves along with specificity, sensitivity, accuracy and efficiency values were determined for a variety of transient evoked otoacoustic emission/pure tone screening/tympanometry comparisons. Results: The Transient Evoked Otoacoustic Emission failure rate for the group was 20.3%. The failure rate for pure tone screening was found to be 8.9%, whilst 18.6% of subjects failed a protocol consisting of combined pure tone screening and tympanometry results. In essence, findings from the comparison of overall Transient Evoked Otoacoustic Emission pass/fail with overall pure tone screening pass/fail suggested that use of a modified Rhode Island Hearing Assessment Project criterion would result in a very high probability that a child with a pass result has normal hearing (true negative). However, the hit rate was only moderate. Selection of a signal-to-noise ratio (SNR) criterion set at greater than or equal to 1 dB appeared to provide the best test performance measures for the range of SNR values investigated. Test performance measures generally declined when tympanometry results were included, with the exception of lower false alarm rates and higher positive predictive values. The exclusion of low frequency data from the Transient Evoked Otoacoustic Emission SNR versus pure tone screening analysis resulted in improved performance measures. Conclusions: The present study poses several implications for the clinical implementation of Transient Evoked Otoacoustic Emission screening for entry level school children. Transient Evoked Otoacoustic Emission pass/fail criteria will require revision. The findings of the current investigation offer support to the possible replacement of pure tone screening with Transient Evoked Otoacoustic Emission testing for 6-year-old children. However, they do not suggest the replacement of the pure tone screening plus tympanometry battery. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Validation of the Edinburgh Postnatal Depression Scale for men, and comparison of item endorsement with their partners

Background: The Edinburgh Postnatal Depression Scale (EPDS) has been validated and used extensively in screening for depression in new mothers, both in English speaking and non-English speaking communities. While some studies have reported the use of the EPDS with Fathers, none have validated it for this group, and thus the appropriate cut-off score for screening for depression or anxiety caseness for this population is not known. Method: Couples were recruited antenatally and interviewed at six weeks postpartum. EPDS scores and distress caseness (depression or anxiety disorders) for 208 fathers and 230 mothers were determined using the Diagnostic Interview Schedule. Results: Analyses of the EPDS for fathers using distress caseness (depression or anxiety disorders) as the criterion shows that a cut-off of 5/6 has optimum receiver operating characteristics. Furthermore acceptable reliability (split-half and internal consistency) and validity (concurrent) coefficients were obtained. For mothers the optimum cut-off screening value to detect distress caseness was 7/8. Item analysis revealed that fathers endorsed seven of the ten items at lower rates to mothers, with the most significant being that referring to crying. Conclusions: The EPDS is a reliable and valid measure of mood in fathers. Screening for depression or anxiety disorders in fathers requires a two point lower cut-off than screening for depression or anxiety in mothers, and we recommend this cut-off to he 5/6. (C) 2001 Elsevier Science B.V. All rights reserved.

Quality of life assessment in the community-dwelling elderly: Validation of the Assessment of Quality of Life (AQoL) Instrument and comparison with the SF-36

Measurement of Health-Related Quality of Life (HRQoL) of the elderly requires instruments with demonstrated sensitivity, reliability, and validity, particularly with the increasing proportion of older people entering the health care system. This article reports the psychometric properties of the 12-item Assessment of Quality of Life (AQoL) instrument in chronically ill community-dwelling elderly people with an 18-month follow-up. Comparator instruments included the SF-36 and the OARS. Construct validity of the AQoL was strong when examined via factor analysis and convergent and divergent validity against other scales. Receiver Operator Characteristic (ROC) curve analyses and relative efficiency estimates indicated the AQoL is sensitive, responsive, and had the strongest predicative validity for nursing home entry. It was also sensitive to economic prediction over the follow-up. Given these robust psychometric properties and the brevity of the scale, AQoL appears to be a suitable instrument for epidemiologic studies where HRQoL and utility data are required from elderly populations. (C) 2003 Elsevier Science Inc. All rights reserved.

Transient evoked otoacoustic emissions in adults: a comparison between two test protocols

This study compares the performance of the Quickscreen and Default protocols of the ILO-96 Otodynamics Analyzer in recording transient evoked otoacoustic emissions (TEOAEs) from adults using clinical decision analysis. Data were collected from 25 males (mean age = 29.0 years, SD = 6.8) and 35 females (mean age = 28.1 years, SD = 9.6). The results showed that the mean signal-to-noise ratios obtained from the Quickscreen were significantly greater than those from the Default protocol at 1,2, and 4 kHz. The comparison of the performance of the two protocols, based on the results using receiver operating characteristics curves, revealed a higher performance of the Quickscreen than the Default protocol at 1 and 4 kHz but not at 2 kHz. In view of the enhanced performance of the Quickscreen over the Default protocol in general, the routine use of the Default protocol for testing adults in audiology clinics should be reconsidered.

What You Get Out of Memory Depends on the Question You Ask

Following study, participants received 2 tests. The 1st was a recognition test; the 2nd was designed to tap recollection. The objective was to examine performance on Test I conditional on Test 2 performance. In Experiment 1, contrary to process dissociation assumptions, exclusion errors better predicted subsequent recollection than did inclusion errors. In Experiments 2 and 3, with alternate questions posed on Test 2, words having high estimates of recollection with one question had high estimates of familiarity with the other question. Results supported the following: (a) the 2-test procedure has considerable potential for elucidating the relationship between recollection and familiarity; (b) there is substantial evidence for dependency between such processes when estimates are obtained using the process dissociation and remember-know procedures; and (c) order of information access appears to depend on the question posed to the memory system.

Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy

OBJECTIVES This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF). BACKGROUND Cardiac resynchronization therapy improves HF symptoms, exercise capacity, and left ventricular (LV) function. Because not all patients respond, preimplantation identification of responders is needed. In the present study, response to CRT was predicted by the presence of LV dyssynchrony assessed by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in patients undergoing CRT was assessed. METHODS Eighty-five patients with end-stage HF, QRS duration >120 ins, and left bundle-branch block were evaluated by tissue Doppler imaging before CRT. At baseline and six months follow-up, New York Heart Association functional class, quality of life and 6-min walking distance, LV volumes, and LV ejection fraction were determined. Events (death, hospitalization for decompensated HF) were obtained during one-year follow-up. RESULTS Responders (74%) and nonresponders (26%) had comparable baseline characteristics, except for a larger dyssynchrony in responders (87 +/- 49 ms vs. 35 +/- 20 ms, p < 0.01). Receiver-operator characteristic curve analysis demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a sensitivity and specificity of 80% to predict clinical improvement and of 92% to predict LV reverse remodeling. Patients with dyssynchrony :65 ms had an excellent prognosis (6% event rate) after CRT as compared with a 50% event rate in patients with dyssynchrony <65 ins (p < 0.001). CONCLUSIONS Patients with LV dyssynchrony greater than or equal to65 ms respond to CRT and have an excellent prognosis after CRT. (C) 2004 by the American College of Cardiology Foundation.

Quantitative myocardial contrast echocardiography for prediction of thrombolysis in myocardial infarction flow in acute myocardial infarction

Clinical evaluation of arterial potency in acute ST-elevation myocardial infarction (STEMI) is unreliable. We sought to identify infarction and predict infarct-related artery potency measured by the Thrombolysis In Myocardial Infarction (TIMI) score with qualitative and quantitative intravenous myocardial contrast echocardiography (MCE). Thirty-four patients with suspected STEMI underwent MCE before emergency angiography and planned angioplasty. MCE was performed with harmonic imaging and variable triggering intervals during intravenous administration of Optison. Myocardial perfusion was quantified offline, fitting an exponential function to contrast intensity at various pulsing intervals. Plateau myocardial contrast intensity (A), rate of rise (beta), and myocardial flow (Q = A x beta) were assessed in 6 segments. Qualitative assessment of perfusion defects was sensitive for the diagnosis of infarction (sensitivity 93%) and did not differ between anterior and inferior infarctions. However, qualitative assessment had only moderate specificity (50%), and perfusion defects were unrelated to TIMI flow. In patients with STEMI, quantitatively derived myocardial blood flow Q (A x beta) was significantly lower in territories subtended by an artery with impaired (TIMI 0 to 2) flow than those territories supplied by a reperfused artery with TIMI 3 flow (10.2 +/- 9.1 vs 44.3 +/- 50.4, p = 0.03). Quantitative flow was also lower in segments with impaired flow in the subtending artery compared with normal patients with TIMI 3 flow (42.8 +/- 36.6, p = 0.006) and all segments with TIMI 3 flow (35.3 +/- 32.9, p = 0.018). An receiver-operator characteristic curve derived cut-off Q value of

Testing alternative models for the conservation of koalas in fragmented rural-urban landscapes

Predicting the various responses of different species to changes in landscape structure is a formidable challenge to landscape ecology. Based on expert knowledge and landscape ecological theory, we develop five competing a priori models for predicting the presence/absence of the Koala (Phascolarctos cinereus) in Noosa Shire, south-east Queensland (Australia). A priori predictions were nested within three levels of ecological organization: in situ (site level) habitat (< 1 ha), patch level (100 ha) and landscape level (100-1000 ha). To test the models, Koala surveys and habitat surveys (n = 245) were conducted across the habitat mosaic. After taking into account tree species preferences, the patch and landscape context, and the neighbourhood effect of adjacent present sites, we applied logistic regression and hierarchical partitioning analyses to rank the alternative models and the explanatory variables. The strongest support was for a multilevel model, with Koala presence best predicted by the proportion of the landscape occupied by high quality habitat, the neighbourhood effect, the mean nearest neighbour distance between forest patches, the density of forest patches and the density of sealed roads. When tested against independent data (n = 105) using a receiver operator characteristic curve, the multilevel model performed moderately well. The study is consistent with recent assertions that habitat loss is the major driver of population decline, however, landscape configuration and roads have an important effect that needs to be incorporated into Koala conservation strategies.

Investigations into an optimal transmission scheme for a MIMO system operating in a ricain fading environment

This paper describes investigations into an optimal transmission scheme for a multiple input multiple output (MIMO) system operating in a Rician fading environment. The considerations are reduced to determining a covariance matrix of transmitted signals which maximizes the MIMO capacity under the condition that the receiver has perfect knowledge of the channel while the transmitter has the information about selected statistical quantities which are measured at the receiver. An optimal covariance matrix, which requires information of the Rice factor and the signal to noise ratio, is determined. The transmission scheme relying on the choice of the proposed covariance matrix outperforms the other transmission schemes which were reported earlier in the literature. The proposed scheme realizes an upper bound limit for the MIMO capacity under arbitrary Rician fading conditions. ©2005 IEEE

Self-Similarity of Air-Water Flows in Skimming Flows on Stepped Spillways

Skimming flows on stepped spillways are characterised by a significant rate of turbulent dissipation on the chute. Herein an advanced signal processing of traditional conductivity probe signals is developed to provide further details on the turbulent time and length scales. The technique is applied to a 22° stepped chute operating with flow Reynolds numbers between 3.8 and 7.1 E+5. The new correlation analyses yielded a characterisation of large eddies advecting the bubbles. The turbulent length scales were related to the characteristic depth Y90. Some self-similar relationships were observed systematically at both macroscopic and microscopic levels. These included the distributions of void fraction, bubble count rate, interfacial velocity and turbulence level, and turbulence time and length scales. The self-similarity results were significant because they provided a picture general enough to be used to characterise the air-water flow field in prototype spillways.

Key residues characteristic of GATA N-fingers are recognized by FOG

Protein-protein interactions play significant roles in the control of gene expression. These interactions often occur between small, discrete domains within different transcription factors. In particular, zinc fingers, usually regarded as DNA-binding domains, are now also known to be involved in mediating contacts between proteins. We have investigated the interaction between the erythroid transcription factor GATA-1 and its partner, the 9 zinc finger protein, FOG (Friend of GATA). We demonstrate that this interaction represents a genuine finger-finger contact, which is dependent on zinc coordinating residues within each protein. We map the contact domains to the core of the N-terminal zinc finger of GATA-1 and the 6th zinc finger of FOG. Using a scanning substitution strategy we identify key residues within the GATA-1 N-finger which are required for FOG binding. These residues are conserved in the N-fingers of all GATA proteins known to bind FOG, but are not found in the respective C-fingers, This observation may, therefore, account for the particular specificity of FOG for N-fingers, Interestingly, the key N-finger residues are seen to form a contiguous surface, when mapped onto the structure of the N-finger of GATA-1.