Analysis of ergonomics problems contact-centers

The analysis of the ergonomic problems of the contact center. It allocates main factors of influence on man- operator

Development of a validated patient-reported symptom metric for pediatric Eosinophilic Esophagitis: qualitative methods

<p>Abstract</p> <p>Background</p> <p>Previous attempts to measure symptoms in pediatric Eosinophilic Esophagitis (EoE) have not fully included patients and parents in the item development process. We sought to identify and validate key patient self-reported and parent proxy-reported outcomes (PROs) specific to EoE.</p> <p>Methods</p> <p>We developed methodology for focus and cognitive interviews based on the Food and Drug Administration (FDA) guidelines for PROs, the validated generic PedsQL™ guidelines, and the consolidated criteria for reporting qualitative research (COREQ). Both child (ages 8-12 and 13-18) and parent-proxy (ages 2-4, 5-7, 8-12, and 13-18) interviews were conducted.</p> <p>Results</p> <p>We conducted 75 interviews to construct the new instrument. Items were identified and developed from individual focus interviews, followed by cognitive interviews for face and content validation. Initial domains of symptom frequency and severity were developed, and open-ended questions were used to generate specific items during the focus interviews. Once developed, the instrument construct, instructions, timeframe, scoring, and specific items were systematically reviewed with a separate group of patients and their parents during the cognitive interviews.</p> <p>Conclusions</p> <p>To capture the full impact of pediatric EoE, both histologic findings and PROs need to be included as equally important outcome measures. We have developed the face and content validated Pediatric Eosinophilic Esophagitis Symptom Score (PEESS™ v2.0). The PEESS™ v2.0 metric is now undergoing multisite national field testing as the next iterative instrument development phase.</p

Development of the Pediatric Quality of Life Inventory™ Eosinophilic Esophagitis Module items: qualitative methods

Abstract Background Currently there is no disease-specific outcome measure to assess the health-related quality of life (HRQOL) of pediatric patients with Eosinophilic Esophagitis (EoE). Therefore, the objective of this qualitative study was to further develop and finalize the items and support the content validity for the new Pediatric Quality of Life Inventory™ (PedsQL™) Eosinophilic Esophagitis Module. Methods Multiphase qualitative methodology was utilized in the development of the PedsQL™ EoE Module conceptual model. Focus interview transcripts of pediatric patients with EoE and their parents and expert review were previously used to develop the initial items and domains for the PedsQL™ EoE Module. In the current investigation, utilizing the respondent debriefing methodology, cognitive interviewing was conducted individually with pediatric patients with EoE and their parents on each newly developed item. Results Information from a total of 86 participants was obtained in combination from the previous investigation and the current study. From the previous 42 focus interviews, items were developed around the domain themes of symptoms, difficulties with eating food, treatment adherence, worry about symptoms and illness, feelings of being different than family and peers, and problems discussing EoE with others. In the current study’s cognitive interviewing phase, a separate cohort of 44 participants systematically reviewed and provided feedback on each item. Items were added, modified or deleted based on this feedback. Items were finalized after this feedback from patients and parents. Conclusions Using well-established qualitative methods, the content validity of the new PedsQL™ Eosinophilic Esophagitis Module items was supported in the current investigation. In the next iterative instrument development phase, the PedsQL™ Eosinophilic Esophagitis Module is now undergoing multisite national field testing.</p

A study of variable hydration states in topotecan hydrochloride

Abstract Topotecan hydrochloride, a pharmaceutical compound developed as a treatment for cancer, exhibits variable hydration states in a crystalline solid form chosen for manufacturing. This variability requires additional controls for successful development, and presents a characterization and detection challenge for analytical methods. In this study, overall water content was determined by Karl Fischer titration and thermogravimetric analysis (TGA) on topotecan HCl equilibrated at different relative humidity levels. These results, when combined with information obtained from dynamic water vapor sorption and differential scanning calorimetry (DSC), indicate that this form of topotecan HCl contains 3 mol of water integral to the crystalline structure and up to two additional moles of water depending on the relative humidity. Powder X-ray diffraction experiments did not detect significant differences in topotecan HCl samples equilibrated at trihydrate and pentahydrate states, and showed that the crystal lattice dimensions are not affected unless the form is dried below the trihydrate state. This behavior is typical of crystal structures with channels that can accommodate additional loosely bound water. To study the role of the loosely bound water in the crystal structure in more detail, solid-state 13 C and 15 N nuclear magnetic resonance (NMR) were used to examine the differences between the hydration states. Both the trihydrate and pentahydrate states yielded similar solid-state NMR spectra, consistent with the lack of change in the crystal lattice. However, minor but readily detectable differences in the 13 C spectra are observed with changes in water content. Interpretation of this data suggests that the loosely bound channel water is hydrogen-bonding to specific portions of the topotecan parent molecule. Topotecan HCl trihydrate was hydrated with D 2 O vapor to confirm the nature and location of the channel water using 13 C and 2 H solid-state NMR. Despite the detectable association of the channel water with hydrogen bonding sites on the topotecan molecule, 2 H quadrupolar echo experiments indicate that the channel water is highly mobile at room temperature and at −60 • C

Synthesis of 5-Fluoro- and 5-Hydroxymethanoprolines via Lithiation of <i>N</i>-BOC-methanopyrrolidines. Constrained C^γ-Exo and C^γ-Endo Flp and Hyp Conformer Mimics

Proline derivatives with a C^γ-exo pucker typically display a high amide bond trans/cis (<i>K</i>_T/C) ratio. This pucker enhances n→π* overlap of the amide oxygen and ester carbonyl carbon, which favors a trans amide bond. If there were no difference in n→π* interaction between the ring puckers, then the correlation between ring pucker and <i>K</i>_T/C might be broken. To explore this possibility, proline conformations were constrained using a methylene bridge. We synthesized discrete gauche and anti 5-fluoro- and 5-hydroxy-<i>N</i>-acetylmethanoproline methyl esters from 3-syn and 3-anti fluoro- and hydroxymethanopyrrolidines using directed α-metalation to introduce the α-ester group. NBO calculations reveal minimal n→π* orbital interactions, so contributions from other forces might be of greater importance in determining <i>K</i>_T/C for the methanoprolines. Consistent with this hypothesis, greater trans amide preferences were found in CDCl₃ for anti isomers en-MetFlp and en-MetHyp (72–78% trans) than for the syn stereoisomers ex-MetFlp and ex-MetHyp (54–67% trans). These, and other, <i>K</i>_T/C results that we report here indicate how substituents on proline analogues can affect amide preferences by pathways other than ring puckering and n→π* overlap and suggest that caution should be exercised in assigning enhanced pyrrolidine C^γ-exo ring puckering based solely on enhanced trans amide preference