Regression analysis of ranked segment parameters for optic nerve head classification:a pilot study

Purpose: To determine whether curve-fitting analysis of the ranked segment distributions of topographic optic nerve head (ONH) parameters, derived using the Heidelberg Retina Tomograph (HRT), provide a more effective statistical descriptor to differentiate the normal from the glaucomatous ONH. Methods: The sample comprised of 22 normal control subjects (mean age 66.9 years; S.D. 7.8) and 22 glaucoma patients (mean age 72.1 years; S.D. 6.9) confirmed by reproducible visual field defects on the Humphrey Field Analyser. Three 10°-images of the ONH were obtained using the HRT. The mean topography image was determined and the HRT software was used to calculate the rim volume, rim area to disc area ratio, normalised rim area to disc area ratio and retinal nerve fibre cross-sectional area for each patient at 10°-sectoral intervals. The values were ranked in descending order, and each ranked-segment curve of ordered values was fitted using the least squares method. Results: There was no difference in disc area between the groups. The group mean cup-disc area ratio was significantly lower in the normal group (0.204 ± 0.16) compared with the glaucoma group (0.533 ± 0.083) (p < 0.001). The visual field indices, mean deviation and corrected pattern S.D., were significantly greater (p < 0.001) in the glaucoma group (-9.09 dB ± 3.3 and 7.91 ± 3.4, respectively) compared with the normal group (-0.15 dB ± 0.9 and 0.95 dB ± 0.8, respectively). Univariate linear regression provided the best overall fit to the ranked segment data. The equation parameters of the regression line manually applied to the normalised rim area-disc area and the rim area-disc area ratio data, correctly classified 100% of normal subjects and glaucoma patients. In this study sample, the regression analysis of ranked segment parameters method was more effective than conventional ranked segment analysis, in which glaucoma patients were misclassified in approximately 50% of cases. Further investigation in larger samples will enable the calculation of confidence intervals for normality. These reference standards will then need to be investigated for an independent sample to fully validate the technique. Conclusions: Using a curve-fitting approach to fit ranked segment curves retains information relating to the topographic nature of neural loss. Such methodology appears to overcome some of the deficiencies of conventional ranked segment analysis, and subject to validation in larger scale studies, may potentially be of clinical utility for detecting and monitoring glaucomatous damage. © 2007 The College of Optometrists.

The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment

The transmembrane (TM) domains in P-glycoprotein (P-gp) contain the drug binding sites and undergo conformational changes driven by nucleotide catalysis to effect translocation. However, our understanding of exactly which regions are involved in such events remains unclear. A site-directed labelling approach was used to attach thiol-reactive probes to cysteines introduced into transmembrane segment 6 (TM6) in order to perturb function and infer involvement of specific residues in drug binding and/or interdomain communication. Covalent attachment of coumarin-maleimide at residue 339C within TM6 resulted in impaired ATP hydrolysis by P-gp. The nature of the effect was to reduce the characteristic modulation of basal activity caused by transported substrates, modulators and the potent inhibitor XR9576. Photoaffinity labelling of P-gp with [(3)H]-azidopine indicated that residue 339C does not alter drug binding per se. However, covalent modification of this residue appears to prevent conformational changes that lead to drug stimulation of ATP hydrolysis.

The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein

Structural evidence has demonstrated that P-glycoprotein (P-gp) undergoes considerable conformational changes during catalysis, and these alterations are important in drug interaction. Knowledge of which regions in P-gp undergo conformational alterations will provide vital information to elucidate the locations of drug binding sites and the mechanism of coupling. A number of investigations have implicated transmembrane segment six (TM6) in drug-P-gp interactions, and a cysteine-scanning mutagenesis approach was directed to this segment. Introduction of cysteine residues into TM6 did not disturb basal or drug-stimulated ATPase activity per se. Under basal conditions the hydrophobic probe coumarin maleimide readily labeled all introduced cysteine residues, whereas the hydrophilic fluorescein maleimide only labeled residue Cys-343. The amphiphilic BODIPY-maleimide displayed a more complex labeling profile. The extent of labeling with coumarin maleimide did not vary during the catalytic cycle, whereas fluorescein maleimide labeling of F343C was lost after nucleotide binding or hydrolysis. BODIPY-maleimide labeling was markedly altered during the catalytic cycle and indicated that the adenosine 5'-(beta,gamma-imino)triphosphate-bound and ADP/vanadate-trapped intermediates were conformationally distinct. Our data are reconciled with a recent atomic scale model of P-gp and are consistent with a tilting of TM6 in response to nucleotide binding and ATP hydrolysis.

Measurement of scleral thickness in humans using anterior segment optical coherent tomography

Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to examine meridional variation in anterior scleral thickness (AST) and its association with refractive error, ethnicity and gender. Scleral cross-sections of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7±5.3)) were sampled twice in random order in 8 meridians: [superior (S), inferior (I), nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior-temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-toposterior increments (designated the A-P distance) from the scleral spur (SS) over a 6mm distance. Axial length and refractive error were measured with a Zeiss IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra- And inter-observer variability of AST was assessed for each of the 8 meridians. Mixed repeated measures ANOVAs tested meridional and A-P distance differences in AST with refractive error, gender and ethnicity. Only right eye data were analysed. AST (mean±SD) across all meridians and A-P distances was 725±46μm. Meridian SN was the thinnest (662±57μm) and I the thickest (806 ±60μm). Significant differences were found between all meridians (p<0.001), except S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were found except between SS and 6 mm and between 2 and 4mm. AST measurements at 1mm (682±48 μm) were the thinnest and at 6mm (818±49 μm) the thickest (p<0.001); a significant interaction occurred between meridians and A-P distances (p<0.001). AST was significantly greater (p<0.001) in male subjects but no significant differences were found between refractive error or ethnicity. Significant variations in AST occur with regard to meridian and distance from the SS and may have utility in selecting optimum sites for pharmaceutical or surgical intervention.

Client QoE-oriented segment selection for DASH

A segment selection method controlled by Quality of Experience (QoE) factors for Dynamic Adaptive Streaming over HTTP (DASH) is presented in this paper. Current rate adaption algorithms aim to eliminate buffer underrun events by significantly reducing the code rate when experiencing pauses in replay. In reality, however, viewers may choose to accept a level of buffer underrun in order to achieve an improved level of picture fidelity or to accept the degradation in picture fidelity in order to maintain the service continuity. The proposed rate adaption scheme in our work can maximize the user QoE in terms of both continuity and fidelity (picture quality) in DASH applications. It is shown that using this scheme a high level of quality for streaming services, especially at low packet loss rates, can be achieved. Our scheme can also maintain a best trade-off between continuity-based quality and fidelity-based quality, by determining proper threshold values for the level of quality intended by clients with different quality requirements. In addition, the integration of the rate adaptation mechanism with the scheduling process is investigated in the context of a mobile communication network and related performances are analyzed.

Visitor Center Staff Training: A U.S Assessment

As the first step toward developing benchmarks for travel counselor training, the authors identify the methods and characteristics of existing travel counselor-training programs in the U.S. Responses from 30 out of 50 state tourism agencies indicate that 12 different methods of training are emplyed; however, usage and satisfaction with these various training methods vary.

Visitor At-Destination Search for Travel-Related Services

The phenomenon of at-destination search activity and decision processes utilized by visitors to a location is predominantly an academic unknown. As destinations and organizations increasingly compete for their share of the travel dollar, it is evident that more research need to be done regarding how consumers obtain information once they arrive at a destination. This study examined visitor referral recommendations provided by hotel and non-hotel ''locals" in a moderately-sized community for lodging, food service, and recreational and entertainment venues.

Demographic, Behavioral and Perceptual Comparisons of U.S Visitor Experience with Group Package Tours and Free Independent Travel to China

U.S. visitor demand for the China travel experience is anticipated to rise significantly through 2105, causing the Chinese government to employ 100 million service providers over the next six years and raising concern about service delivery and perceptions of the on-site China experience. In an effort to better understand these issues concerning U.S. visitors, this study investigated two specific types of U.S. travelers to China: Group Package Tour (GPT) visitors and Free Independent Travel (FIT) visitors. Results indicated that GPT visitors were more likely to be older and have higher household income than FIT visitors. Four trip-related characteristics of GPT and FIT visitors were found to be significantly different, with GPT visitors showing higher levels of satisfaction with the overall China on-site travel experience.

Molecular characteristics and gene segment usage in IGH gene rearrangements in multiple myeloma.

BACKGROUND AND OBJECTIVES: Analysis of IgH rearrangements in B-cell malignancies has provided clinical researchers with a wide range of information during the last few years. However, only a few studies have contributed to the characterization of these features in multiple myeloma (MM), and they have been focused on the analysis of the expressed IgH allele only. Comparison between the expressed and the non-functional IgH alleles allows further characterizion of the selection processes to which pre-myeloma cells are submitted. DESIGN AND METHODS: We analyzed a cohort of 84 untreated MM patients in order to characterize their functional VDJH and non-functional DJH rearrangements. The pattern of mutations and gene segment usage for both types of rearrangements was analyzed by polymerase chain reaction and sequencing. RESULTS: VH3 and VH1 family members were over- and under-represented, respectively. VH3-30 and VH3-15 segments were the most frequently used, whereas VH4-34 was found only in non-functional or heavily mutated VDJH rearrangements. DH2 and DH3 family members were over-represented in both VDJH and DJH repertoires, while the DH1 family was under-represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2-21 gene segments were found to be over-represented in the functional repertoire while segments commonly used by less mature B-cell malignancies, such as DH6-19 or DH3-3, were under-represented. INTERPRETATION AND CONCLUSIONS: Data reported here help to identify the clonogenic MM cell as a post-germinal center B cell that has undergone selection processes during the germinal center reaction.

Prevalence of biomicroscopic findings in the anterior segment and ocular adnexa among schoolchildren in Natal/Brazil

Objective: To determine the prevalence of ocular findings of the external structures and anterior segment of the eye, detected by biomicroscopic examination in schoolchildren in Natal (RN) - Brazil. Methods: After previous random selection, 1,024 pupils from elementary and secondary public and private schools in the city of Natal were evaluated from March to June 2001. All were submitted to preestablished standard research norms, consisting of identification, demographic information, ophthalmologic biomicroscopic examination, with slit lamp, performed by ophthalmologists from the “Onofre Lopes” University Hospital. Results: Alterations of the conjunctival and palpebral conditions were the most prevalent (10.4% and 6.2% respectively). Follicles (4.2%) and papillae (3.0%) were the frequent conjunctival lesions, while blepharitis (3.5%) and meibomitis (1.1%) were the most detected abnormalities in the eyelids. Upon examining the cornea, iris, lens and anterior vitreous, the most encountered findings were nubecula (0.5%), papillary membrane reliquiae (0.5%), posterior capsula opacity (0.8%) and hyaloid arteria reliquiae (2.0%). Conclusion: The most prevalent findings affecting the external structures of the eye such as eyelids and conjunctiva, consisted of blepharitis followed by follicular reaction of the conjunctiva. The most prevalent abnormalities in the cornea, iris, lens and anterior vitreous were nubecula, papillary membrane reliquiae, posterior capsular opacity and hyaloid arteria reliquiae, in that order

CALS brochure and visitor guide (Center for the Advancement of Laboratory Science)

Located in Coralville in the heart of Iowa’s Creative Corridor, the center for the Advancement of Laboratory Science (CALS) is a public venue intended for use by environmental and public health stakeholders, educational groups, and community businesses and organizations with needs for meeting space. This conference and training facility was established in recognition of a need for a space that unites working professionals, students, educators, community business partners and other community members in a cultivating environment dedicated to environmental and public health stewardship. The CALS is located within the State Hygienic Laboratory at the University of Iowa (SHL) and is comprised of a conference center and training laboratory. The Hygienic Laboratory has a rich history as a national leader in public health education and training and through the CALS. The SHL aims to provide training to the current workforce, recruit the workforce of tomorrow and strengthen community engagement

Improving risk stratification in non-ST-segment elevation myocardial infarction with combined assessment of GRACE and CRUSADE risk scores

BACKGROUND: Risk assessment is fundamental in the management of acute coronary syndromes (ACS), enabling estimation of prognosis. AIMS: To evaluate whether the combined use of GRACE and CRUSADE risk stratification schemes in patients with myocardial infarction outperforms each of the scores individually in terms of mortality and haemorrhagic risk prediction. METHODS: Observational retrospective single-centre cohort study including 566 consecutive patients admitted for non-ST-segment elevation myocardial infarction. The CRUSADE model increased GRACE discriminatory performance in predicting all-cause mortality, ascertained by Cox regression, demonstrating CRUSADE independent and additive predictive value, which was sustained throughout follow-up. The cohort was divided into four different subgroups: G1 (GRACE<141; CRUSADE<41); G2 (GRACE<141; CRUSADE≥41); G3 (GRACE≥141; CRUSADE<41); G4 (GRACE≥141; CRUSADE≥41). RESULTS: Outcomes and variables estimating clinical severity, such as admission Killip-Kimbal class and left ventricular systolic dysfunction, deteriorated progressively throughout the subgroups (G1 to G4). Survival analysis differentiated three risk strata (G1, lowest risk; G2 and G3, intermediate risk; G4, highest risk). The GRACE+CRUSADE model revealed higher prognostic performance (area under the curve [AUC] 0.76) than GRACE alone (AUC 0.70) for mortality prediction, further confirmed by the integrated discrimination improvement index. Moreover, GRACE+CRUSADE combined risk assessment seemed to be valuable in delineating bleeding risk in this setting, identifying G4 as a very high-risk subgroup (hazard ratio 3.5; P<0.001). CONCLUSIONS: Combined risk stratification with GRACE and CRUSADE scores can improve the individual discriminatory power of GRACE and CRUSADE models in the prediction of all-cause mortality and bleeding. This combined assessment is a practical approach that is potentially advantageous in treatment decision-making.

Prevalence of biomicroscopic findings in the anterior segment and ocular adnexa among schoolchildren in Natal/Brazil

Objective: To determine the prevalence of ocular findings of the external structures and anterior segment of the eye, detected by biomicroscopic examination in schoolchildren in Natal (RN) - Brazil. Methods: After previous random selection, 1,024 pupils from elementary and secondary public and private schools in the city of Natal were evaluated from March to June 2001. All were submitted to preestablished standard research norms, consisting of identification, demographic information, ophthalmologic biomicroscopic examination, with slit lamp, performed by ophthalmologists from the “Onofre Lopes” University Hospital. Results: Alterations of the conjunctival and palpebral conditions were the most prevalent (10.4% and 6.2% respectively). Follicles (4.2%) and papillae (3.0%) were the frequent conjunctival lesions, while blepharitis (3.5%) and meibomitis (1.1%) were the most detected abnormalities in the eyelids. Upon examining the cornea, iris, lens and anterior vitreous, the most encountered findings were nubecula (0.5%), papillary membrane reliquiae (0.5%), posterior capsula opacity (0.8%) and hyaloid arteria reliquiae (2.0%). Conclusion: The most prevalent findings affecting the external structures of the eye such as eyelids and conjunctiva, consisted of blepharitis followed by follicular reaction of the conjunctiva. The most prevalent abnormalities in the cornea, iris, lens and anterior vitreous were nubecula, papillary membrane reliquiae, posterior capsular opacity and hyaloid arteria reliquiae, in that order