The Alaska experience

The management responsibilities of the Alaska Department of Natural Resources are summarized and the establishment of a geoprocessor system is described. Specific capabilities were defined based on surveys of potential users and pre-existing systems. The procurement process, the initially purchased equipment, and system upgrading are described. Cost, installation and maintenance, site location, training, and staffing of the system are examined

Duration of patients’ visits to the hospital emergency department

Background Length of stay is an important indicator of quality of care in Emergency Departments (ED). This study explores the duration of patients’ visits to the ED for which they are treated and released (T&R). Methods Retrospective data analysis and multivariate regression analysis were conducted to investigate the duration of T&R ED visits. Duration for each visit was computed by taking the difference between admission and discharge times. The Healthcare Cost and Utilization Project (HCUP) State Emergency Department Databases (SEDD) for 2008 were used in the analysis. Results The mean duration of T&R ED visit was 195.7 minutes. The average duration of ED visits increased from 8 a.m. until noon, then decreased until midnight at which we observed an approximately 70-minute spike in average duration. We found a substantial difference in mean duration of ED visits (over 90 minutes) between Mondays and other weekdays during the transition time from the evening of the day before to the early morning hours. Black / African American patients had a 21.4-minute longer mean duration of visits compared to white patients. The mean duration of visits at teaching hospitals was substantially longer than at non-teaching hospitals (243.8 versus 175.6 minutes). Hospitals with large bed size were associated with longer duration of visits (222.2 minutes) when compared to hospitals with small bed size (172.4 minutes) or those with medium bed size (166.5 minutes). The risk-adjusted results show that mean duration of visits on Mondays are longer by about 4 and 9 percents when compared to mean duration of visits on non-Monday workdays and weekends, respectively. Conclusions The duration of T&R ED visits varied significantly by admission hour, day of the week, patient volume, patient characteristics, hospital characteristics and area characteristics

Stereochemical studies on protonated bridgehead amines. ^1H NMR determination of cis and trans B-C ring-fused structures for salts of hexahydropyrrolo [2,1-a] isoquinolines and related C ring homologs. Capture of unstable ring-fused structures in the solid state

Acid-addition salts of tricyclic isoquinolines 2a/b, 3a/b, 4a-4c, 5, 6a/b, 7, 8a/b, 9a/b, and 17a/b were studied by high-field ^1H NMR in CDCl_3 solution. Cis (e.g., 14 and 15 in Figure 1) and trans (e.g., 13)B-C ring-fused structures were identified by using the vicinal ^3J(CH-NH) coupling constants, which demonstrate a Karplus-like behavior. In some cases, we initially observed a trans form, which converted to a cis A form by N H proton exchange. For 4c.HBr, the exchange process was slowed by addition of trifluoroacetic acid. In many cases, cis A and cis B structures were preferred in solution. The pendant phenyl group exerted a strong influence on the preferred solution structure. Observation of the initial, unstable trans-fused structures was related to their capture in the solid state and release intact on dissolution. X-ray diffraction was performed on the HBr salts of 2a (B-C cis), 2b (B-C cis), and 4c (B-C trans). The result for 4c.HBr confirmed the connection between the initial trans form in solution and the solid state. For 17b.HCI two conformers, associated with hindered rotation about the bond connecting the 2,6-disubstituted phenyl group to the tricyclic array, were detected at ambient probe temperature; however, rotamers were not observed for either of the two forms (trans and cis A) of 17a.HBr. Two conformers were also found for 16b.HBr. Temperature-dependent behavior was recorded in the ^1H NMR spectra of 17b.HBr and 16b.HBr; the activation free energy for interconversion of conformers was estimated to be in the vicinity of 17 kcal/mol for the former and 14-15 kcal/mol for the latter. The ^1H NMR spectrum of butaclamol hydrochloride (20.HC1), a potent neuroleptic agent, in Me_2SO-d_6 revealed two species in a ratio of 81:19, which were assigned as trans and cis A forms, respectively. ^1H NMR data for various free bases are also presented and discussed. Empirical force field calculations on three model hydrocarbons are discussed from a perspective of finding an explanation for the configurational/conformational behavior of the bridgehead ammonium salts. Diverse literature examples of structures for protonated bridgehead amines are also discussed. A tentative rationale is suggested for the preference of cis A forms in some protonated tetrahydroisoquinoline derivatives

Reversible Photocontrolled Nanopore Assembly

Self-assembly is a fundamental feature of biological systems, and control of such processes offers fascinating opportunities to regulate function. Fragaceatoxin C (FraC) is a toxin that upon binding to the surface of sphingomyelin-rich cells undergoes a structural metamorphosis, leading to the assembly of nanopores at the cell membrane and causing cell death. In this study we attached photoswitchable azobenzene pendants to various locations near the sphingomyelin binding pocket of FraC with the aim of remote controlling the nanopore assembly using light. We found several constructs in which the affinity of the toxin for biological membranes could be activated or deactivated by irradiation, thus enabling reversible photocontrol of pore formation. Notably, one construct was completely inactive in the thermally adapted state; it however induced full lysis of cultured cancer cells upon light irradiation. Selective irradiation also allowed isolation of individual nanopores in artificial lipid membranes. Photocontrolled FraC might find applications in photopharmacology for cancer therapeutics and has potential to be used for the fabrication of nanopore arrays in nanopore sensing devices, where the reconstitution, with high spatiotemporal precision, of single nanopores must be controlled

Proposal and multicentric validation of a laparoscopic Roux-en-Y gastric bypass surgery ontology.

BACKGROUND Phase and step annotation in surgical videos is a prerequisite for surgical scene understanding and for downstream tasks like intraoperative feedback or assistance. However, most ontologies are applied on small monocentric datasets and lack external validation. To overcome these limitations an ontology for phases and steps of laparoscopic Roux-en-Y gastric bypass (LRYGB) is proposed and validated on a multicentric dataset in terms of inter- and intra-rater reliability (inter-/intra-RR). METHODS The proposed LRYGB ontology consists of 12 phase and 46 step definitions that are hierarchically structured. Two board certified surgeons (raters) with > 10 years of clinical experience applied the proposed ontology on two datasets: (1) StraBypass40 consists of 40 LRYGB videos from Nouvel Hôpital Civil, Strasbourg, France and (2) BernBypass70 consists of 70 LRYGB videos from Inselspital, Bern University Hospital, Bern, Switzerland. To assess inter-RR the two raters' annotations of ten randomly chosen videos from StraBypass40 and BernBypass70 each, were compared. To assess intra-RR ten randomly chosen videos were annotated twice by the same rater and annotations were compared. Inter-RR was calculated using Cohen's kappa. Additionally, for inter- and intra-RR accuracy, precision, recall, F1-score, and application dependent metrics were applied. RESULTS The mean ± SD video duration was 108 ± 33 min and 75 ± 21 min in StraBypass40 and BernBypass70, respectively. The proposed ontology shows an inter-RR of 96.8 ± 2.7% for phases and 85.4 ± 6.0% for steps on StraBypass40 and 94.9 ± 5.8% for phases and 76.1 ± 13.9% for steps on BernBypass70. The overall Cohen's kappa of inter-RR was 95.9 ± 4.3% for phases and 80.8 ± 10.0% for steps. Intra-RR showed an accuracy of 98.4 ± 1.1% for phases and 88.1 ± 8.1% for steps. CONCLUSION The proposed ontology shows an excellent inter- and intra-RR and should therefore be implemented routinely in phase and step annotation of LRYGB

Solution structure of Mannobioses unravelled by means of Raman optical activity

Structural analysis of carbohydrates is a complicated endeavour, due to the complexity and diversity of the samples at hand. Herein, we apply a combined computational and experimental approach, employing molecular dynamics (MD) and density functional theory (DFT) calculations together with NMR and Raman optical activity (ROA) measurements, in the structural study of three mannobiose disaccharides, consisting of two mannoses with varying glycosidic linkages. The disaccharide structures make up the scaffold of high mannose glycans and are therefore important targets for structural analysis. Based on the MD population analysis and NMR, the major conformers of each mannobiose were identified and used as input for DFT analysis. By systematically varying the solvent models used to describe water interacting with the molecules and applying overlap integral analysis to the resulting calculational ROA spectra, we found that a full quantum mechanical/molecular mechanical approach is required for an optimal calculation of the ROA parameters. Subsequent normal mode analysis of the predicted vibrational modes was attempted in order to identify possible marker bands for glycosidic linkages. However, the normal mode vibrations of the mannobioses are completely delocalised, presumably due to conformational flexibility in these compounds, rendering the identification of isolated marker bands unfeasible

Comparison of frozen and RNALater solid tissue storage methods for use in RNA expression microarrays

BACKGROUND: Primary human tissues are an invaluable widely used tool for discovery of gene expression patterns which characterize disease states. Tissue processing methods remain unstandardized, leading to unanswered concerns of how to best store collected tissues and maintain reproducibility between laboratories. We subdivided uterine myometrial tissue specimens and stored split aliquots using the most common tissue processing methods (fresh, frozen, RNALater) before comparing quantitative RNA expression profiles on the Affymetrix U133 human expression array. Split samples and inclusion of duplicates within each processing group allowed us to undertake a formal genome-wide analysis comparing the magnitude of result variation contributed by sample source (different patients), processing protocol (fresh vs. frozen vs. 24 or 72 hours RNALater), and random background (duplicates). The dataset was randomly permuted to define a baseline pattern of ANOVA test statistic values against which the observed results could be interpreted. RESULTS: 14,639 of 22,283 genes were expressed in at least one sample. Patient subjects provided the greatest sources of variation in the mixed model ANOVA, with replicates and processing method the least. The magnitude of variation conferred by processing method (24 hours RNALater vs 72 hours RNALater vs. fresh vs frozen) was similar to the variability seen within replicates. Subset analysis of the test statistic according to gene functional class showed that the frequency of "outlier" ANOVA results within each functional class is overall no greater than expected by chance. CONCLUSIONS: Ambient storage of tissues for 24 or 72 hours in RNALater did not contribute any systematic shift in quantitative RNA expression results relative to the alternatives of fresh or frozen tissue. This nontoxic preservative enables decentralized tissue collection for expression array analysis without a requirement for specialized equipment

Endometrial Tumor Classification by Histomorphology and Biomarkers in the Nurses’ Health Study

Objective: Endometrial cancers have historically been classified by histomorphologic appearance, which is subject to interobserver disagreement. As molecular and biomarker testing has become increasingly available, the prognostic significance and accuracy of histomorphologic diagnoses have been questioned. To address these issues for a large, prospective cohort study, we provide the results of a centralized pathology review and biomarker analysis of all incidental endometrial carcinomas occurring between 1976 and 2012 in the Nurses' Health Study. Methods: Routine histology of all (n = 360) cases was reviewed for histomorphologic diagnosis. Cases were subsequently planted in a tissue microarray to explore expression of a variety of biomarkers (e.g., ER, PR, p53, PTEN, PAX2, AMACR, HNF1β, Napsin A, p16, PAX8, and GATA3). Results: Histologic subtypes included endometrioid (87.2%), serous (5.6%), carcinosarcoma (3.9%), clear cell (1.7%), and mixed type (1.7%). Biomarker results within histologic subtypes were consistent with existing literature: abnormal p53 was frequent in serous cases (74%), and HNF1β (67%), Napsin A (67%), and AMACR (83%) expression was frequent in clear cell carcinomas. Our dataset also allowed for examination of biomarker expression across non-preselected histologies. The results demonstrated that (1) HNF1β was not specific for clear cell carcinoma, (2) TP53 mutations occurred across many histologies, and (3) GATA3 was expressed across multiple histotypes, with 75% of positive cases demonstrating high-grade features. Conclusions: Our findings establish the subtypes of endometrial cancer occurring in the Nurses' Health Study, corroborate the sensitivity of certain well-established biomarkers, and call into question previously identified associations between certain biomarkers (e.g., HNF1B) and particular histotypes

Physical Electronics

Contains reports on three research projects

Microwave and Physical Electronics

Contains reports on seven research projects