Potential Benefits on Impairment of Endothelial Function after a High-Fat Meal of 4 Weeks of Flavonoid Supplementation

Studies with foods high in flavonoids have demonstrated improvement in endothelial function. We investigated whether 4 weeks of flavonoid supplementation would prevent an adverse impact on endothelial function of a high-fat meal. Endothelial function was measured by reactive hyperemia peripheral arterial tonometry (RH-PAT). The RH-PAT index was measured both before and 3 h after a high-fat meal, in 23 healthy volunteers. Subjects were randomized in a double-blind, cross-over design to 4 weeks of daily supplementation with OPC-3, or a matching placebo. RH-PAT index before and after the high-fat meal was measured at the beginning and end of each 4-week treatment phase. The high-fat meal caused a decline in endothelial function at baseline in the placebo (-10.71%, P = .006) and flavonoid [-9.97% (P = .077)] groups, and there was no difference in decline between arms (P = .906). The high-fat meal produced a decline after 4 weeks of placebo [-12.37% (P = .005)], but no decline after 4 weeks of flavonoid supplement [-3.16% (P = .663)], and the difference between the two responses was highly significant (P < .0001). Within-group comparisons revealed no difference in endothelial function decline in the placebo arm between baseline and 4 weeks [-10.71% versus -12.37% (P = .758)]. In the flavonoid supplement arm, the difference in endothelial function decline between baseline and 4 weeks was -9.97% versus -3.16%, but did not reach statistical significance (P = .451). These results suggest that the flavonoid supplement used in this study mitigates the impairment of endothelial function caused by a high-fat meal. Whether certain subpopulations derive greater or lesser benefit remains unclear

A hazard and probabilistic safety analysis of a high-level waste transfer process

This paper describes a safety analysis of a transfer process for high-level radioactive and toxic waste. The analysis began with a hazard assessment that used elements of What If, Checklist, Failure Modes and Effects Analysis, and Hazards and Operability Study (HAZOP) techniques to identify and rough-in accident sequences. Based on this preliminary analysis, the most significant accident sequences were developed further using event trees. Quantitative frequency estimates for the accident sequences were based on operational data taken from the historical record of the site where the process is performed. Several modeling challenges were encountered in the course of the study. These included linked initiating and accident progression events, fire propagation modeling, accounting for administrative control violations, and handling mission-phase effects

When should customers control service delivery? Implications for service design

What do a Mongolian stir-fry restaurant and a medical lab providing home testing solutions have in common? They are both innovative services that base their success on customers controlling part of the service delivery. These providers allow service tasks to be performed by the customers as a means of shaping the overall experience and not strictly as a means of "outsourcing" the service. Motivated by such practices, we explore whether and how should providers allocate the control of different tasks of their service to the customers. We model services as multi-step processes with each step affecting customers' experience at other steps. At certain steps the provider may hold an “expert" role and be more capable of performing than the customers, whereas at other steps she holds an “administrative" role and is less capable of performing than the customers. We distinguish between routine services, where the service outcome must conform to standardized specifications, and non-routine services, where the value of the service outcome relies on subjective dimensions. We show that the optimal design is determined by an economically intuitive rule whereby the provider controls the steps based on the marginal benefit she can derive compared to self-service. For routine services, this rule translates to managing “blocks" of steps because the provider benefits from containing the volatility of the experiences across the service even when this implies the provision of service steps with a negative marginal benefit, i.e., steps which she is less capable of performing than the customers. Instead, in non-routine services providers should focus on the value advantage they can ensure through a "core provision" even if this implies forgoing control of steps for which they are more capable of performing than the customers and from which they can derive positive marginal benefit. This implies that in non-routine services the provider exercises more control up to a certain process length; beyond that she delegates more steps to the customers. When customers differ in their abilities to perform the different steps, the provider may offer a service line. Service lines facilitate better segmentation than a single service offering, but their economic benefit exhibits an inverted “U-shaped" relationship with respect to the number of steps that a service comprises. Finally, we find that competition between two providers who differ in their capabilities to perform a service results in service design differentiation where the more capable provider offers a higher-end "focused service" against a lower-end "super-service" offered from the less capable provider

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029

Actinopolyspora algeriensis sp. nov., a novel halophilic actinomycete isolated from a Saharan soil

A halophilic actinomycete strain designated H19T, was isolated from a Saharan soil in the Bamendil region (Ouargla province, South Algeria) and was characterized taxonomically by using a polyphasic approach. The morphological and chemotaxonomic characteristics of the strain were consistent with those of members of the genus Actinopolyspora, and 16S rRNA gene sequence analysis confirmed that strain H19T was a novel species of the genus Actinopolyspora. DNA–DNA hybridization value between strain H19T and the nearest Actinopolyspora species, A. halophila, was clearly below the 70 % threshold. The genotypic and phenotypic data showed that the organism represents a novel species of the genus Actinopolyspora for which the name Actinopolyspora algeriensis sp. nov. is proposed, with the type strain H19T (= DSM 45476T = CCUG 62415T)

Erasmus Language students in a British University – a case study

Students’ assessment of their academic experience is actively sought by Higher Education institutions, as evidenced in the National Student Survey introduced in 2005. Erasmus students, despite their growing numbers, tend to be excluded from these satisfaction surveys, even though they, too, are primary customers of a University. This study aims to present results from bespoke questionnaires and semi-structured interviews with a sample of Erasmus students studying languages in a British University. These methods allow us insight into the experience of these students and their assessment as a primary customer, with a focus on language learning and teaching, university facilities and student support. It investigates to what extent these factors influence their levels of satisfaction and what costs of adaptation if any, they encounter. Although excellent levels of satisfaction were found, some costs affect their experience. They relate to difficulties in adapting to a learning methodology based on a low number of hours and independent learning and to a guidance and support system seen as too stifling. The results portray this cohort’s British University as a well-equipped and well-meaning but ultimately overbearing institution, which may indicate that minimising costs can eliminate some sources of dissatisfaction

Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline

5-15% of lymphocytes in the peritoneums of normal adult B10.H-2aH- 4bp/Wts (2a4b) mice are CD5+ (Ly-1) B cells that recognize phosphatidyl choline (PtC), a phospholipid component of all mammalian cells. We produced a set of IgM-secreting hybridomas from the peritoneal cells of normal, adult 2a4b mice. We found that this set of hybridomas shows a similarly high frequency of antibodies specific for PtC (21 of 86) that also react with bromelain-treated mouse erythrocytes. Restriction fragment analysis of Ig gene rearrangements and analysis of expressed Ig idiotypes reveal that these cells use a restricted set of variable region genes to generate the PtC-specific antibodies. The Ig genes used by the PtC-specific hybridomas appear to be the same as those found in the PtC-specific Ly-1 B cell lymphomas, CH27 and CH34

Low-Dose Imaging in a New Preclinical Total-Body PET/CT Scanner.

Ionizing radiation constitutes a health risk to imaging scientists and study animals. Both PET and CT produce ionizing radiation. CT doses in pre-clinical in vivo imaging typically range from 50 to 1,000 mGy and biological effects in mice at this dose range have been previously described. [ &lt;sup&gt;18&lt;/sup&gt; F]FDG body doses in mice have been estimated to be in the range of 100 mGy for [ &lt;sup&gt;18&lt;/sup&gt; F]FDG. Yearly, the average whole body doses due to handling of activity by PET technologists are reported to be 3-8 mSv. A preclinical PET/CT system is presented with design features which make it suitable for small animal low-dose imaging. The CT subsystem uses a X-source power that is optimized for small animal imaging. The system design incorporates a spatial beam shaper coupled with a highly sensitive flat-panel detector and very fast acquisition (&lt;10 s) which allows for whole body scans with doses as low as 3 mGy. The mouse total-body PET subsystem uses a detector architecture based on continuous crystals, coupled to SiPM arrays and a readout based in rows and columns. The PET field of view is 150 mm axial and 80 mm transaxial. The high solid-angle coverage of the sample and the use of continuous crystals achieve a sensitivity of 9% (NEMA) that can be leveraged for use of low tracer doses and/or performing rapid scans. The low-dose imaging capabilities of the total-body PET subsystem were tested with NEMA phantoms, in tumor models, a mouse bone metabolism scan and a rat heart dynamic scan. The CT imaging capabilities were tested in mice and in a low contrast phantom. The PET low-dose phantom and animal experiments provide evidence that image quality suitable for preclinical PET studies is achieved. Furthermore, CT image contrast using low dose scan settings was suitable as a reference for PET scans. Total-body mouse PET/CT studies could be completed with total doses of &lt;10 mGy