Charge Transfer and Built-in Electric Fields between a Crystalline Oxide and Silicon.

We report charge transfer and built-in electric fields across the epitaxial SrNb_{x}Ti_{1-x}O_{3-δ}/Si(001) interface. Electrical transport measurements indicate the formation of a hole gas in the Si and the presence of built-in fields. Hard x-ray photoelectron measurements reveal pronounced asymmetries in core-level spectra that arise from these built-in fields. Theoretical analysis of core-level spectra enables built-in fields and the resulting band bending to be spatially mapped across the heterojunction. The demonstration of tunable charge transfer, built-in fields, and the spatial mapping of the latter, lays the groundwork for the development of electrically coupled, functional heterojunctions.

Engineered Unique Elastic Modes at a BaTiO_{3}/(2×1)-Ge(001) Interface.

The strong interaction at an interface between a substrate and thin film leads to epitaxy and provides a means of inducing structural changes in the epitaxial film. These induced material phases often exhibit technologically relevant electronic, magnetic, and functional properties. The 2×1 surface of a Ge(001) substrate applies a unique type of epitaxial constraint on thin films of the perovskite oxide BaTiO_{3} where a change in bonding and symmetry at the interface leads to a non-bulk-like crystal structure of the BaTiO_{3}. While the complex crystal structure is predicted using first-principles theory, it is further shown that the details of the structure are a consequence of hidden phases found in the bulk elastic response of the BaTiO_{3} induced by the symmetry of forces exerted by the germanium substrate.

Comparison of empirical continuous positive airway pressure (CPAP) treatment versus initial portable sleep monitoring followed by CPAP treatment for patients with suspected obstructive sleep apnoea.

BACKGROUND: Polysomnography is labour-intensive for diagnosing obstructive sleep apnoea (OSA). We compared two algorithms for initiating continuous positive airway pressure (CPAP) treatment for patients with suspected OSA. METHODS: Symptomatic OSA patients were randomised into either algorithm I or II. Algorithm I consisted of an empirical CPAP trial whereas algorithm II utilised an Apnea Risk Evaluation System, a wireless device applied on the forehead, for establishing a diagnosis before a CPAP trial for 3 weeks. Primary outcome was success of CPAP trial, defined as CPAP usage > 4 h/night and willingness to continue CPAP. Subjective usefulness of CPAP, accuracy of Apnea Risk Evaluation System versus polysomnography and CPAP adherence at 6 months were secondary end-points. RESULTS: Altogether 138 patients in algorithm I and 110 patients in algorithm II completed the CPAP trial. There were no significant differences between these algorithms with respect to the primary end-point. The sensitivity and specificity of algorithm I versus II as a diagnostic test for OSA were 0.3, 0.8 versus 0.31, 1.00 respectively. In predicting CPAP adherence at 6 months, the likelihood ratio positive for algorithms I and II was 2.7 and 5.27 respectively. The mean (SE) time taken from the first consultation to the end of CPAP trial in algorithm I and algorithm II was 60 (2) and 98 (5) days, respectively, P < 0.01. CONCLUSION: An ambulatory approach with portable sleep monitoring for diagnosing OSA before a CPAP trial can identify more patients who would adhere to CPAP at 6 months than empirical CPAP treatment alone.

Multifocal electroretinography changes in patients on ethambutol therapy.

PURPOSE: To evaluate the multifocal electroretinography (mfERG) changes in patients on ethambutol therapy. METHODS: A cross-sectional observational study of 17 visually asymptomatic patients receiving antituberculosis therapy with ethambutol. Patients underwent complete ophthalmic examination and mfERG recordings. The first-order mfERG N1 and P1 response amplitudes and implicit times of six concentric rings were analysed and compared with 17 normal age-similar controls. Correlation analyses were performed between the patients' mfERG parameters with parameters of ethambutol usage (daily dose of ethambutol per body weight, duration of ethambutol therapy, cumulative dose of ethambutol, and cumulative dose of ethambutol per body weight). RESULTS: The mean duration of ethambutol therapy was 3.6 months (range: 2-9 months) and the mean daily dose per body weight was 13.2 mg/kg/day. Analysis of response amplitude measures showed no significant difference in the mfERG N1 and P1 response amplitudes between the ethambutol and control groups at all ring eccentricities (P>0.05). For implicit times, there were significant delays in the mfERG P1 implicit times of rings 4-6 in the ethambutol group compared with controls (P=0.012 to P=0.041). Correlation analyses showed no significant correlation between the mfERG and ethambutol parameters (P>0.05). CONCLUSIONS: The mfERG findings suggested that visually asymptomatic patients receiving ethambutol therapy might have localized mild electrophysiological changes involving the peripheral macula. These changes might be related to localized alteration of metabolism or physiological changes associated with ethambutol therapy.

Validation of a portable recording device (ApneaLink) for identifying patients with suspected obstructive sleep apnoea syndrome.

BACKGROUND: Polysomnography (PSG) is currently the standard diagnostic procedure for sleep apnoea. This study evaluates the diagnostic accuracy of a portable recording device, ApneaLink (AL; ResMed, Poway, CA, USA) for detection of sleep apnoea in comparisons against PSG. METHODS: The AL device is a three-channel screening tool that measures airflow through a nasal pressure transducer, oximetry and pulse, providing an apnoea-hypopnoea index (AHI) based on recording time. Nocturnal PSG (Alice 4; Healthdyne, Atlanta, GA, USA), with airflow measured by a nasal pressure transducer (ProTech PTAF2; ProTech, Woodinville, WA, USA) and AL recordings were carried out simultaneously in consecutive patients with suspected obstructive sleep apnoea syndrome (OSAS). The PSG recordings were analysed manually by a blinded investigator. The oxygen desaturation index of AL was also compared against the AHI based on PSG. RESULTS: Fifty consecutive subjects with symptoms of OSAS were recruited with mean age of 50 years and body mass index of 27.9 kg/m2. The AHI obtained by the AL device correlated closely to that obtained by PSG (Pearson correlation, r= 0.978, P < 0.001), whereas the correlation between PSG AHI and oxygen desaturation index by AL was also strong (r= 0.895, P < 0.001). Comparison of AHI based on the AL against the PSG demonstrated high sensitivity and specificity at AHI > or =10/h (sensitivity 0.977 and specificity 1.0) and at AHI > or =20/h (sensitivity 0.969 and specificity 1.0). CONCLUSION: The AL portable monitoring device is highly sensitive and specific in quantifying the apnoea-hypopnoea index when compared against hospital based polysomnography in patients with suspected OSAS. The simple device may be useful for screening and diagnostic purpose when access to PSG is limited.

Prevalence and risk factors of airflow obstruction in an elderly Chinese population.

It is common practice to use a forced expiratory volume in one second (FEV(1))/ forced vital capacity (FVC) ratio of <70% as evidence of airflow obstruction. As the FEV(1)/FVC ratio falls with age, the lower limit of normal range (LLN), defined as the bottom 5% in a health reference population, of FEV(1)/FVC ratio has been suggested as a better index to reduce over-diagnosis of chronic obstructive pulmonary disease (COPD), particularly in the elderly. However, there are no large scale studies that focus on the diagnosis of COPD in the elderly based on these definitions. The present prospective epidemiological study involved 1,149 elderly subjects aged > or =60 yrs in the community. Detailed questionnaires, pre- and post-bronchodilator spirometry were performed. In total, 1,008 subjects (mean age 74.2+/-6.4 yrs; 271 males) completed satisfactory spirometry testing. Airflow obstruction was present in 25.9% as defined by the post-bronchodilator FEV(1)/FVC ratio of <70% and in 12.4% defined by the LLN of FEV(1)/FVC ratio. Moderate COPD, at least, was found in 14.0% of patients according to the post-bronchodilator FEV(1)/FVC ratio of <70% and in 8.5% of patients according to LLN of FEV(1)/FVC ratio. In the present elderly Chinese population (mostly females, with low education level and previous exposure to biomass during formative years), the prevalence of chronic obstructive pulmonary disease varied markedly depending on definitions adopted. Further longitudinal studies are needed to determine the precise definition of chronic obstructive pulmonary disease.

Nasal CPAP reduces systemic blood pressure in patients with obstructive sleep apnoea and mild sleepiness.

BACKGROUND: A randomised controlled study was undertaken to examine the effect of nasal continuous positive airway pressure (CPAP) on 24 hour systemic blood pressure (BP) in patients with obstructive sleep apnoea (OSA). METHODS: Patients were fitted with an ambulatory BP measuring device as outpatients during normal activities and recorded for 24 hours before starting therapeutic or subtherapeutic (4 cm H(2)O) CPAP treatment. BP monitoring was repeated before completion of 12 weeks of treatment. The primary end point was the change in 24 hour mean BP. RESULTS: Twenty three of 28 participants in each treatment arm completed the study. There was no significant difference between the two groups in age, body mass index, Epworth Sleepiness Score, apnoea-hypopnoea index, arousal index, and minimum Sao(2). Twenty four patients were hypertensive. The pressure in the therapeutic CPAP group was 10.7 (0.4) cm H(2)O. CPAP usage was 5.1 (0.4) and 2.6 (0.4) hours/night for the therapeutic and subtherapeutic CPAP groups, respectively (p<0.001). After 12 weeks of treatment there were significant differences between the two CPAP groups in mean (SE) changes in 24 hour diastolic BP (-2.4 (1.2) v 1.1 (1.0) mm Hg (95% CI -6.6 to -0.5), p = 0.025); 24 hour mean BP (-2.5 (1.3) v 1.3 (1.1) mm Hg (95% CI -7.2 to -0.2), p = 0.037); sleep time systolic BP (-4.1 (2.1) v 2.2 (1.8) mm Hg (95% CI -11.8 to -0.7), p = 0.028); and sleep time mean BP (-3.6 (1.7) v 1.3 (1.4) mm Hg (95% CI -9.2 to -0.4), p = 0.033). CONCLUSIONS: Compared with subtherapeutic CPAP, 12 weeks of treatment with therapeutic CPAP leads to reductions in 24 hour mean and diastolic BP by 3.8 mm Hg and 3.5 mm Hg, respectively, in mildly sleepy patients with OSA.

Analysis and characterization of an odorant receptor gene cluster in the zebrafish genome.

A 140.7-kb segment of zebrafish genomic DNA known to contain odorant receptor (OR) genes was fully sequenced to characterize more completely the organization of this gene cluster. A total of 20 OR genes were identified in this region. The most highly related genes are grouped in closest proximity to one another and in the same transcriptional orientation, indicating that a series of tandem duplications was responsible for the expansion of the OR gene family in teleost fish. Our analysis also revealed sequences that may be involved in the transcriptional regulation of OR genes within the cluster.

Onset of odorant receptor gene expression during olfactory sensory neuron regeneration.

Individual olfactory sensory neurons are thought to express only one odorant receptor gene from a repertoire of hundreds to thousands of genes. How do these sensory neurons choose just one specific odorant receptor to express during their differentiation? As an initial attempt toward understanding the process of odorant receptor gene regulation, we studied when odorant receptor expression is activated during sensory neuron regeneration. We find that receptor gene expression is activated in postmitotic neurons and can occur in the absence of the olfactory bulb. These results suggest that receptor expression is restricted to the terminal stages of olfactory neuron differentiation, and sensory neurons do not simply inherit the odorant receptor that is already expressed in mitotic precursor cells. Our results also support a model in which odorant receptor gene expression occurs independent of the olfactory bulb.

Formation of precise connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity.

Olfactory neurons expressing the same odorant receptor converge to a small number of glomeruli in the olfactory bulb. In turn, mitral and tufted cells receive and relay this information to higher cortical regions. In other sensory systems, correlated neuronal activity is thought to refine synaptic connections during development. We asked whether the pattern of connections between olfactory sensory axons and mitral cell dendrites is affected when odor-evoked signaling is eliminated in mice lacking functional olfactory cyclic nucleotide-gated (CNG) channels. We demonstrate that olfactory sensory axons converge normally in the CNG channel mutant background. We further show that the pruning of mitral cell dendrites, although slowed during development, is ultimately unperturbed in mutant animals. Thus, the olfactory CNG channel-and by inference correlated neural activity--is not required for generating synaptic specificity in the olfactory bulb.

Functional identification of a goldfish odorant receptor.

The vertebrate olfactory system utilizes odorant receptors to receive and discriminate thousands of different chemical stimuli. An understanding of how these receptors encode information about an odorant's molecular structure requires a characterization of their ligand specificities. We employed an expression cloning strategy to identify a goldfish odorant receptor that is activated by amino acids-potent odorants for fish. Structure-activity analysis indicates that the receptor is preferentially tuned to recognize basic amino acids. The receptor is a member of a multigene family of G protein-coupled receptors, sharing sequence similarities with the calcium sensing, metabotropic glutamate, and V2R class of vomeronasal receptors. The ligand tuning properties of the goldfish amino acid odorant receptor provide information for unraveling the molecular mechanisms underlying olfactory coding.

Atypical glandular cells of undetermined significance (AGUS): cytopathologic features, histopathologic results, and human papillomavirus DNA detection.

We intensively reviewed 137 smears initially classified as atypical glandular cells of undetermined significance (AGUS) to refine cytological criteria for evaluating these cases, evaluate histological outcomes, and assess the value of human papillomavirus (HPV) DNA testing in management. Consenting, nonpregnant study participants were identified from a cohort of 46,009 women receiving routine Pap smear screening in a managed care setting. Colposcopy was performed on all women, and at least one histological sample was obtained from each. Review diagnoses were assigned to smears and biopsy specimens by two separate panels of pathologists. DNA testing for cancer-associated HPV types was performed on rinses of cytological samplers after a smear and thin-layer slide had been made. On review, 47 (34%) smears were reclassified as negative, 44 (32%) as AGUS, 30 (22%) as atypical squamous cells of undetermined significance (ASCUS), and 16 (12%) as squamous intraepithelial lesions (SIL). The 19 smears interpreted as high-grade intraepithelial lesions on review included 13 high-grade SIL (HSIL), two HSIL with AGUS, favor neoplastic (endocervical adenocarcinoma in situ [AIS]), and four AGUS, favor neoplastic (AIS). Review histological diagnoses were negative in 105 (77%), squamous or glandular atypia in four (3%), low-grade SIL (LSIL) in nine (7%), HSIL in 12 (9%), AIS in five (4%, including two with concurrent HSIL), and endometrial carcinoma in one (1%). HPV testing identified 11 (92%) of 12 women with histologically confirmed HSIL and all five with AIS (100%). A high-grade intraepithelial lesion or carcinoma is detected in approximately 14% of women with community-based diagnoses of AGUS who are referred for immediate evaluation. Use of refined cytological criteria and HPV DNA testing may permit improved management of women with AGUS.

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.

CONTEXT: A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. DESIGN AND SETTING: Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. PARTICIPANTS: From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. MAIN OUTCOME MEASURES: Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. RESULTS: Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). CONCLUSIONS: For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

Development of the vertebrate main olfactory system.

Olfactory receptor neurons project from the sensory epithelium to stereotyped targets within the olfactory bulb. Recent studies suggest that the generation of this precise spatial map probably involves a hierarchy of guidance events, as receptor neurons integrate information present in the epithelium and bulb to reach their target.

Pathfinding of olfactory neuron axons to stereotyped glomerular targets revealed by dynamic imaging in living zebrafish embryos.

In the vertebrate olfactory system, sensory neurons with common odorant specificities project to specific glomeruli in the olfactory bulb. How do olfactory sensory neurons find their glomerular targets? To address this question, we have visualized the genesis of the peripheral olfactory system in living zebrafish embryos. Dye labelings reveal that a primordial yet stereotyped map of glomeruli is apparent during embryogenesis. By labeling a small number of cells with an ectopically expressed green fluorescent protein reporter, we can observe the dynamic growth behaviors of individual olfactory neuron growth cones as they project to their glomeruli. We find that olfactory axons extend directly to their partner glomeruli, suggesting that these cells' growth cones rely upon pathfinding cues to reach their targets.

Noncoordinate expression of odorant receptor genes tightly linked in the zebrafish genome.

We have characterized the organization and expression of odorant receptor genes clustered within approximately 100 kb of the zebrafish genome. Physical analysis of this genomic region reveals that the receptor genes are tightly linked in tandem arrays. The expression patterns of these genes were evaluated during development as well as in the adult olfactory epithelium. Highly related genes from this array are expressed individually in different olfactory neurons, suggesting that the discriminatory capacity of the vertebrate olfactory system has been maximized by segregating the most similar receptors into distinct cellular pathways. Furthermore, genes from this cluster are activated at different times of development. Together, these results indicate that genomically linked odorant receptor genes are not coordinately regulated.

Comparison of peripheral blood CD34+ concentration, colony-forming units granulocyte-macrophage and mononuclear cells in leukapheresed product for the prediction of peripheral blood CD34+ cell yield harvest.

The aim of this study was to evaluate reliability of parameters which may be used to guide peripheral stem cell harvests in cancer patients prior to myeloablative chemotherapy. Each leukapheresed product was analysed for CD34-positive (CD34+) cell count, mononuclear cell (MNC) count and the number of colony-forming units granulocyte-macrophage (CFU-GM). Each patient's peripheral blood (PB) taken before leukapheresis was analysed for CD34+ concentration. We evaluated whether the CD34+ yield from leukapheresis correlated with any of the three parameters. A total of 119 procedures were performed in 33 patients. The yield of CD34+ cells by leukapheresis correlated weakly but significantly with the peripheral blood CD34+ cell count (R = 0.4 P < 0.05), the MNC cells (R = 0.4, P < 0.05), and CFU-GM (R = 0.4, P < 0.05). When a PB CD34+ count of 50 x 10(6)/L was used as a cut-off value, the accuracy for prediction of adequate leukapheresis (> 1 x 10(6) CD34+ cells/kg) was 78%.