Spectroscopic and theoretical studies of UN and UN.

The low-energy electronic states of UN and UN+ have been examined using high-level electronic structure calculations and two-color photoionization techniques. The experimental measurements provided an accurate ionization energy for UN (IE = 50 802 ± 5 cm-1). Spectra for UN+ yielded ro-vibrational constants and established that the ground state has the electronic angular momentum projection Ω = 4. Ab initio calculations were carried out using the spin-orbit state interacting approach with the complete active space second-order perturbation theory method. A series of correlation consistent basis sets were used in conjunction with small-core relativistic pseudopotentials on U to extrapolate to the complete basis set limits. The results for UN correctly obtained an Ω = 3.5 ground state and demonstrated a high density of configurationally related excited states with closely similar ro-vibrational constants. Similar results were obtained for UN+, with reduced complexity owing to the smaller number of outer-shell electrons. The calculated IE for UN was in excellent agreement with the measured value. Improved values for the dissociation energies of UN and UN+, as well as their heats of formation, were obtained using the Feller-Peterson-Dixon composite thermochemistry method, including corrections up through coupled cluster singles, doubles, triples and quadruples. An analysis of the ab initio results from the perspective of the ligand field theory shows that the patterns of electronic states for both UN and UN+ can be understood in terms of the underlying energy level structure of the atomic metal ion.

Eosinophil granule major basic protein 1 deposition in eosinophilic esophagitis correlates with symptoms independent of eosinophil counts.

In patients with eosinophilic esophagitis (EoE), symptoms often do not correlate with peak eosinophil counts (PEC) determined on histopathological examination of biopsy specimens. This may be because eosinophils degranulate during active disease and lose their morphological identity as intact cells and, therefore, are not enumerated on microscopic examination. Eosinophil granule proteins that are released into tissues with degranulation, including major basic protein 1 (eMBP1), likely contribute to disease pathogenesis and, therefore, may correlate with symptoms better than PEC. We sought to determine whether symptoms in patients with EoE more closely relate to eosinophil granule protein deposition than to eosinophil enumeration, especially in patients with fewer than 15 eosinophils per high power field (HPF). Esophageal biopsy specimens from 34 patients diagnosed with EoE were obtained for histopathological examination and for evaluation of eMBP1 staining by indirect immunofluorescence. PEC by histopathology were compared to extracellular eMBP1 grades by immunostaining. PEC and eMBP1 grades also were analyzed for their relationship to symptoms and clinical course. Biopsy specimens from 19 of the 34 patients had fewer than 15 PEC on histopathological examination, and the other 15 patients had 15 or greater PEC. Positive eMBP1 immunostaining was found in all symptomatic patients. EoE symptoms were related to eMBP1 immunostaining grades (p = 0.0001), but not PEC (P = 0.14). Eosinophil granule protein deposition, specifically eMBP1, is increased in esophageal biopsy specimens from symptomatic patients with EoE and may be a marker of disease activity, including patients with EoE who have 'resolved' disease.

RNA sequencing confirms similarities between PPI-responsive oesophageal eosinophilia and eosinophilic oesophagitis.

BACKGROUND: Although current American guidelines distinguish proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE) from eosinophilic oesophagitis (EoE), these entities are broadly similar. While two microarray studies showed that they have similar transcriptomes, more extensive RNA sequencing studies have not been done previously. AIM: To determine whether RNA sequencing identifies genetic markers distinguishing PPI-REE from EoE. METHODS: We retrospectively examined 13 PPI-REE and 14 EoE biopsies, matched for tissue eosinophil content, and 14 normal controls. Patients and controls were not PPI-treated at the time of biopsy. We did RNA sequencing on formalin-fixed, paraffin-embedded tissue, with differential expression confirmation by quantitative polymerase chain reaction (PCR). We validated the use of formalin-fixed, paraffin-embedded vs RNAlater-preserved tissue, and compared our formalin-fixed, paraffin-embedded EoE results to a prior EoE study. RESULTS: By RNA sequencing, no genes were differentially expressed between the EoE and PPI-REE groups at the false discovery rate (FDR) ≤0.01 level. Compared to normal controls, 1996 genes were differentially expressed in the PPI-REE group and 1306 genes in the EoE group. By less stringent criteria, only MAPK8IP2 was differentially expressed between PPI-REE and EoE (FDR = 0.029, 2.2-fold less in EoE than in PPI-REE), with similar results by PCR. KCNJ2, which was differentially expressed in a prior study, was similar in the EoE and PPI-REE groups by both RNA sequencing and real-time PCR. CONCLUSION: Eosinophilic oesophagitis and PPI-REE have comparable transcriptomes, confirming that they are part of the same disease continuum.

Co-occurrence of eosinophilic esophagitis and potential/probable celiac disease in an adult cohort: a possible association with implications for clinical practice.

We describe an adult cohort with eosinophilic esophagitis (EoE) and evidence of celiac disease (CD), propose a change in diagnostic practice to better characterize these conditions, and hypothesize new directions for research. Pediatric studies postulate association between gluten sensitivity and EoE. However, few publications describe the prevalence, detection, or therapeutic and pathophysiologic implications of such association in adults. Retrospective chart review was done on patients diagnosed with EoE from 2009 to 2010 at University of Utah Hospitals and Clinics. Data included sex, age, presentation, duodenal pathology, tissue transglutaminase immunoglobulin A antibody (TTG) positivity, human leukocyte antigen (HLA) type (when indicated), and gross and microscopic Esophagogastroduodenoscopy (EGD) findings. Duodenal biopsy, TTG results, and HLA type were correlated. Endoscopy was repeated after gluten-free diet. Forty-four of 75 patients were followed in EoE specialty clinic with duodenal biopsy and TTG testing per protocol. Six EoE patients had potential or probable CD. No sex or age differences were noted between those with findings of CD and EoE and those with EoE alone. Six patients with findings of CD and EoE followed gluten-free diet. Five underwent repeat endoscopy. Three had resolution of esophageal eosinophilia. Potential or probable CD was commonly found in adults with EoE. Diagnosis of CD may be challenging due to nonspecific symptoms and insufficient duodenal biopsy and serologic testing. Furthermore, gluten-free diet resolved EoE findings in some patients, suggesting possible shared pathophysiology in some cases of EoE and CD. TTG testing and adequate duodenal biopsy may further direct clinical care for EoE patients, and studies are needed to elucidate mechanisms linking EoE and CD.

Endoscopic appearance and location dictate diagnostic yield of biopsies in eosinophilic oesophagitis.

BACKGROUND: Acknowledging that eosinophilic esophagitis (EoE) is a disease with variable involvement throughout the oesophagus, studies have suggested a minimum of five biopsies to diagnose EoE. Although it is accepted that furrows and exudates appear to represent areas of inflammation, no research to date has looked specifically at EoE endoscopic findings to see if eosinophilic infiltrate correlates with specific endoscopic findings. AIM: To evaluate the distribution of eosinophils in EoE and determine whether endoscopic appearances predict the degree of eosinophilia at various locations of the oesophagus. METHODS: We performed a prospective cross sectional study of EoE (treated and untreated) patients to study the distribution of eosinophils according to endoscopic findings. The oesophagus of 10 EoE patients were biopsied up to 32 times in a circumferential manner. The mucosal changes were documented at the site of each biopsy. Histological determination of eosinophil counts and related histopathology of the oesophagus were then correlated with endoscopic findings. Similar biopsy assessments were made in treated (resolved) EoE patients (n = 6) to determine the permanence of specific endoscopic appearances. RESULTS: A total of 16 patients were biopsied (10 EoE, 6 treated EoE). A total of 432 biopsies were obtained in all with 294 biopsies from 10 EoE subjects. Eosinophil density was increased distally in the majority of EoE patients. Biopsies performed in areas of exudates and furrows demonstrated higher eosinophil counts. Lines and normal-appearing oesophagi in EoE subjects were not commonly associated with elevated eosinophil counts (>15 eos/HPF). Rings alone without associated furrows or plaques did not demonstrate elevated eosinophil counts and were seen in resolved EoE (Rx-EoE) as well as in active EoE patients. CONCLUSIONS: Eosinophilic esophagitis remains a variable disease with some patients manifesting extensive disease throughout the oesophagus. Characteristics of furrows and exudates found during endoscopy are associated with higher peak eosinophil counts, requiring fewer biopsies to make a diagnosis. Lines and otherwise normal appearances of the oesophagus suggest a milder mucosal eosinophilia, requiring substantial biopsies to adequately identify fields with diagnostic eosinophil counts.

A theoretical spectroscopic study of HeI and HeBr.

Highly accurate potential energy functions for the HeI and HeBr molecules have been calculated using an ab initio treatment that included basis set extrapolation to the complete basis set, as well as spin-orbit coupling in the ground 2sigma+ and first 2pi excited doublet states. The rovibronic bound state energies and resonance lifetimes were also evaluated by a Prony analysis of the autocorrelation function of the evolving wave packet.

Molecular structure, spectroscopy and matrix photochemistry of fluorocarbonyl iodide, FC(O)I.

The molecular structure of FC(O)I has been determined by gas electron diffraction. High-level ab initio methods, including coupled-cluster and the new correlation-consistent basis sets for fourth row elements, have been used to calculate the structure of FC(O)I. A comprehensive vibrational spectroscopic study (both IR and Raman) complemented by high-level calculations has also been performed. Furthermore, UV, mass, and NMR spectra have been recorded for FC(O)I. The matrix photochemistry of FC(O)I has been studied with a low-pressure mercury lamp and with a high-pressure xenon lamp in combination with interference and cut-off filters. UV photolysis revealed the formation of the OC. IF and OC.FI complexes and further photolysis of these complexes at lambda>320 nm resulted in a re-formation of FC(O)I. The structural conformation of the complexes has been characterized by comparing shifts in their CO and IF vibrational modes with respect to those of the free species. The structures, vibrational properties, and stability of the complexes were analyzed with the aid of coupled-cluster ab initio calculations.

Identification of human serum interferants in the recombinant P-selectin glycoprotein ligand-1 clinical ELISA using MALDI MS and RP-HPLC.

A colorimetric enzyme-linked immunosorbent assay (ELISA) was developed to detect circulating levels of rPSGL to permit pharmacokinetic analysis of clinical samples. The ELISA is an asymmetric sandwich utilizing a monoclonal antibody pair. Initial validation studies indicated that 57% of normal individuals scored above the limit of detection of the assay. Specificity experiments indicated that the signal was not due to circulating endogenous P-selectin glycoprotein ligand-1 (PSGL-1). Using matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and sampling within the individual microplate wells, the interferant was detected in the vicinity of 6.6 kDa in lipemic and normal human sera, but not delipidized sera. These results were consistent with the ELISA data where 97.5% of known lipemic, 57% of normal, and 0% of delipidized sera scored above detectable limits in the ELISA. Preparative isolations of the 6.6 kDa species were performed using reversed-phase high performance liquid chromatography (RP-HPLC) with UV and MS detection. Edman N-terminal sequencing identified the 6.6 kDa unknown as Apolipoprotein C-I. Additional apolipoproteins were found by MALDI and RP-HPLC. Digestion of sera with liposome lipase and extraction of sera with anti-apolipoprotein C-I, C-II, and C-III antibody beads significantly reduced the ELISA interference. These experiments combined with the MALDI detection of phosphatidylcholine-type lipids from NHS eluate suggested that lipoprotein particles or remnants were causing the interference. A method combining Triton-X 100 with sonication was developed to overcome this interference without altering rPSGL recovery in the ELISA.

Electric-field-induced second-harmonic generation in GaN devices.

Electric-field-induced second-harmonic generation is used to detect electric fields in a GaN UV Schottky photodiode and in a GaN light-emitting diode. The second-harmonic signal is measured as a function of bias voltage and incident laser power. This technique is sensitive to small applied voltages and can be used to track electronic waveforms. The photocurrent generated by this technique is found to be less than 100 pA when the fundamental and second-harmonic frequencies are both below the device bandgap.

High-sensitivity detection of CH radicals in flames by use of a diode-laser-based near-ultraviolet light source.

CH radical distributions in ethylene-air and methane-air diffusion flames are mapped by wavelength-modulation absorption spectroscopy (WMS). Tunable, wavelength-modulated 426-nm light is generated by frequency doubling of a modulated 852-nm distributed Bragg reflector diode laser. Absorbances of 5 x 10(-5) are measured with second-harmonic (2f) WMS with a signal-to-noise ratio of 3:1 in a 3-Hz measurement bandwidth. The feasibility of simultaneous line-of-sight absorption and spatially resolved laser-induced-fluorescence detection with a single excitation beam is also demonstrated. This near-UV source is suitable for microgravity drop-tower experiments and other applications in which compact, rugged, energy-efficient instrumentation is required.

Strategies to improve diabetes care delivery.

Although the primary care office is an important location for integrating new advances in the treatment of diabetes, the current delivery of preventive primary care for patients with diabetes falls short of clinical recommendations. Barriers within the existing health care system, practice structure, and physician and patient support services are among the most commonly cited obstacles to initiating better preventive care. As public health groups demand greater accountability from the medical system, regulatory efforts focus more scrutiny on systems, clinic practices, and even individual physician practices. Although improving care delivery effectively and efficiently is difficult, strategies to exist that can increase the likelihood of improving patient outcomes. Successful diabetes initiatives are often characterized by the consensual adoption of an evidence-based treatment plan. Effective physician-oriented interventions include the use of reminder systems, local opinion leaders, and academic detailing. In addition, several national diabetes initiatives are likely to influence primary care practice. New measures of accountability will be widely used to determine the quality of primary diabetes care delivery.

Measuring substance abuse program treatment orientations: the Drug and Alcohol Program Treatment Inventory.

Assessment of therapeutic orientation is a significant problem in substance abuse program evaluation. This study reports the initial results of a new approach to measuring treatment orientation through a self-report survey that focuses on distinctive features of substance abuse treatment orientations. The Drug and Alcohol Program Treatment Inventory (DAPTI) assesses treatment goals and activities specific to eight orientations: AA/12 Step, Therapeutic Community, Cognitive-Behavioral, Insight/Psychodynamic, Rehabilitation, Dual Diagnosis, Medical and Marital/Family Systems. We present findings from a nationwide assessment of 327 Veterans Administration (VA) Substance Abuse treatment programs that demonstrate promising subscale internal consistency, discriminant validity, and concurrent validity. In addition, the DAPTI distinguishes between programs with independently verified orientations and between inpatient, extended care, outpatient, and methadone maintenance programs. The DAPTI may be helpful in systematically assessing differences in treatment orientations between different types of programs, such as inpatient, community residential, and outpatient care.

Comparison of home glucose monitoring with the oral glucose tolerance test to detect gestational glucose intolerance.

BACKGROUND: Recent evidence suggests that infant morbidity is increased among women who have abnormal prenatal glucose screening tests but who do not have gestational diabetes mellitus (GDM). These women fall into a diagnostic gray zone and historically have not been treated. METHODS: Forty-eight pregnant women with abnormal oral glucose challenge test results performed self-monitored blood glucose (SMBG) testing seven times per day for 1 week before undergoing a diagnostic 100-g oral glucose tolerance test (OGTT). At delivery, perinatal complications and birthweights were recorded. Results of SMBG tests for women with normal OGTTs were correlated with infant birthweights. RESULTS: Thirteen infants (37%) were found to be large for gestational age (LGA). Significant correlation was found between increasing birthweight and increasing average fasting SMBG values (P < .001), increasing percentage of SMBG values above 120 mg/dL (6.7 mmol/L) (P < .01), and increasing average SMBG values (P < .016). CONCLUSIONS: Maternal home glucose values at 28 weeks correlate with the risk of LGA infant births among women in the diagnostic gray zone. Women with average fasting SMBG values > 95 mg/dL (5.3 mmol/L) are at increased risk for giving birth to LGA infants and may be more likely to exhibit complications usually associated with GDM.