Guangzhou Buyers Preference for Premium Hawaiian Grown Product Gift Baskets

Guangzhou buyers' preference for premium Hawaiian grown product gift baskets with conjoint analysis was examined. Relative importance of three gift basket attributes: container type, products origin, and price were examined. Expenditure equivalent index to evaluate how much more each of the gift basket attributes is worth to the buyer was estimated. Main conclusions are: products have to be 'made in Hawaii' to receive the premium price; business buyers are generally less willing to pay a high price; and individual buyers are more willing to pay the higher priced Koa gift basket.Chinese survey data, conjoint analysis, buyer preference, Hawaii gift baskets, Demand and Price Analysis,

Modeling efforts for the Lena delta and Laptev Sea regions

The Lena River is one of the largest rivers in the Arctic and has the largest delta. Given the large territory of the Lena Delta, the direct measurements are by far insufficient, calling for a modeling approach. However, most of the models, which include the Laptev Sea shelf zone, do not resolve the Lena Delta and as a consequence lose information about Lena river stream changes using input data with insufficient quality. In the current work we present the hydrodynamics model for the Lena Delta region and full baroclinic model for the Laptev Sea shelf area. The available hydrological information in the Lena Delta was collected, analyzed and used for the model verification. The developed hydrodynamics model provides the first necessary step for the further modeling efforts in the area. It also gives an input for the larger scale models resolving hydrodynamics of more than twenty main Lena River freshwater channels with switched-on wetting/drying option. Additionally the Lena Plume dynamics in the Lena Delta region of the Laptev Sea are explored by us in simulations performed with the FVCOM (Finite Volume Coastal Ocean Model). The impact of winds and tides on the Lena plume propagation is analysed based on simulations for the summer season of 2008 and also on idealized experiments. For that period, the simulated distributions of temperature and salinity agree well with the observations, including the thick-ness and border position of the buoyant plume. The model simulates the most energetic semi-diurnal and diurnal tidal constituents. The amplitudes and phases of the tidal components at the open boundary were derived from AOTIM5 and TPXO7.1 with corrections. These corrections noticeably improve the agreement of the modelled tidal maps with available tide gauge data

Prolonged exposure to bacterial toxins downregulated expression of toll-like receptors in mesenchymal stromal cell-derived osteoprogenitors

<p>Abstract</p> <p>Background</p> <p>Human mesenchymal stromal cells (MSCs, also known as mesenchymal stem cells) are multipotent cells with potential therapeutic value. Owing to their osteogenic capability, MSCs may be clinically applied for facilitating osseointegration in dental implants or orthopedic repair of bony defect. However, whether wound infection or oral microflora may interfere with the growth and osteogenic differentiation of human MSCs remains unknown. This study investigated whether proliferation and osteogenic differentiation of MSCs would be affected by potent gram-positive and gram-negative derived bacterial toxins commonly found in human settings.</p> <p>Results</p> <p>We selected lipopolysaccharide (LPS) from <it>Escherichia coli </it>and lipoteichoic acid (LTA) from <it>Streptococcus pyogenes </it>as our toxins of choice. Our findings showed both LPS and LTA did not affect MSC proliferation, but prolonged LPS challenge upregulated the osteogenic differentiation of MSCs, as assessed by alkaline phosphatase activity and calcium deposition. Because toll-like receptors (TLRs), in particularly TLR4 and TLR2, are important for the cellular responsiveness to LPS and LTA respectively, we evaluated their expression profiles serially from MSCs to osteoblasts by quantitative PCR. We found that during osteogenic differentiation, MSC-derived osteoprogenitors gradually expressed TLR2 and TLR4 by Day 12. But under prolonged incubation with LPS, MSC-derived osteoprogenitors had reduced TLR2 and TLR4 gene expression. This peculiar response to LPS suggests a possible adaptive mechanism when MSCs are subjected to continuous exposure with bacteria.</p> <p>Conclusion</p> <p>In conclusion, our findings support the potential of using human MSCs as a biological graft, even under a bacterial toxin-rich environment.</p

Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.

RATIONALE: Rifapentine has been investigated at various doses, frequencies, and dosing algorithms but clarity on the optimal dosing approach is lacking. OBJECTIVES: In this individual participant data meta-analysis of rifapentine pharmacokinetics, we characterize rifapentine population pharmacokinetics, including autoinduction, and determine optimal dosing strategies for short-course rifapentine-based regimens for latent tuberculosis infection. METHODS: Rifapentine pharmacokinetic studies were identified though a systematic review of literature. Individual plasma concentrations were pooled, and non-linear mixed effects modeling was performed. A subset of data was reserved for external validation. Simulations were performed under various dosing conditions including current weight-based methods and alternative methods driven by identified covariates. MEASUREMENTS AND MAIN RESULTS: We identified 9 clinical studies with a total of 863 participants with pharmacokinetic data (n=4301 plasma samples). Rifapentine population pharmacokinetics were described successfully with a one-compartment distribution model. Autoinduction of clearance was driven by rifapentine plasma concentration. The maximum effect was a 72% increase in clearance and was reached after 21 days. Drug bioavailability decreased by 27% with HIV infection, decreased by 28% with fasting, and increased by 49% with a high-fat meal. Body weight was not a clinically relevant predictor of clearance. Pharmacokinetic simulations showed that current weight-based dosing leads to lower exposures in low weight individuals, which can be overcome with flat dosing. In HIV-positive patients, 30% higher doses are required to match drug exposure in HIV-negative patients. CONCLUSIONS: Weight-based dosing of rifapentine should be removed from clinical guidelines and higher doses for HIV-positive patients should be considered to provide equivalent efficacy

Ganoderma lucidum polysaccharides can induce human monocytic leukemia cells into dendritic cells with immuno-stimulatory function

<p>Abstract</p> <p>Background</p> <p>Previous studies demonstrated <it>Ganoderma lucidum </it>polysaccharides (GL-PS), a form of bioactive β-glucan can stimulate the maturation of monocyte-derived dendritic cells (DC). The question of how leukemic cells especially in monocytic lineage respond to GL-PS stimuli remains unclear.</p> <p>Results</p> <p>In this study, we used <it>in vitro</it> culture model with leukemic monocytic cell-lines THP-1 and U937 as monocytic effectors cells for proliferation responses and DCs induction. We treated the THP-1 and U937 cells with purified GL-PS (100 μg/mL) or GL-PS with GM-CSF/IL-4. GL-PS alone induced proliferative response on both THP-1 and U937 cells but only THP-1 transformed into typical DC morphology when stimulated with GL-PS plus GM-CSF/IL-4. The transformed THP-1 DCs had significant increase expression of HLA-DR, CD40, CD80 and CD86 though not as high as the extent of normal monocyte-derived DCs. They had similar antigen-uptake ability as the normal monocyte-derived DCs positive control. However, their potency in inducing allogeneic T cell proliferation was also less than that of normal monocyte-derived DCs.</p> <p>Conclusion</p> <p>Our findings suggested that GL-PS could induce selected monocytic leukemic cell differentiation into DCs with immuno-stimulatory function. The possible clinical impact of using this commonly used medicinal mushroom in patients with monocytic leukemia (AML-M4 and M5) deserved further investigation.</p

CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity

Amplification of the C19MC oncogenic miRNA cluster and high LIN28 expression has been linked to a distinctly aggressive group of cerebral CNS-PNETs (group 1 CNS-PNETs) arising in young children. In this study, we sought to evaluate the diagnostic specificity of C19MC and LIN28, and the clinical and biological spectra of C19MC amplified and/or LIN28+ CNS-PNETs. We interrogated 450 pediatric brain tumors using FISH and IHC analyses and demonstrate that C19MC alteration is restricted to a sub-group of CNS-PNETs with high LIN28 expression; however, LIN28 immunopositivity was not exclusive to CNS-PNETs but was also detected in a proportion of other malignant pediatric brain tumors including rhabdoid brain tumors and malignant gliomas. C19MC amplified/LIN28+ group 1 CNS-PNETs arose predominantly in children <4 years old; a majority arose in the cerebrum but 24 % (13/54) of tumors had extra-cerebral origins. Notably, group 1 CNS-PNETs encompassed several histologic classes including embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma, ependymoblastoma and CNS-PNETs with variable differentiation. Strikingly, gene expression and methylation profiling analyses revealed a common molecular signature enriched for primitive neural features, high LIN28/LIN28B and DNMT3B expression for all group 1 CNS-PNETs regardless of location or tumor histology. Our collective findings suggest that current known histologic categories of CNS-PNETs which include ETANTRs, medulloepitheliomas, ependymoblastomas in various CNS locations, comprise a common molecular and diagnostic entity and identify inhibitors of the LIN28/let7/PI3K/mTOR axis and DNMT3B as promising therapeutics for this distinct histogenetic entity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-014-1291-1) contains supplementary material, which is available to authorized users

Pattern of Relapse and Treatment Response in WNT- Activated Medulloblastoma

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses

Protocol for creating a single, holistic and digitally implementable consensus clinical guideline for multiple multi-morbid conditions

Delivery of future healthcare information systems requires systems to support patients with multi-morbidity. Current approaches to computer interoperable guidelines typically consider only a single clinical guideline for a single condition. There is a need to establish a robust protocolized approach to the development of holistic consensus computer interoperable guidelines in the context of multi-morbidity. The presence of mild cognitive impairment (MCI) and dementia adds an additional challenge to the delivery of effective digital health solutions. CAREPATH proposes an ICT-based solution for the optimization of clinical practice in the treatment and management of multi-morbid older adults with mild cognitive impairment or mild dementia. In this manuscript, we present an evidence-based protocol for the development of a single computer interoperable holistic guideline for a collection of multi-morbid conditions. To the best of our knowledge, this is the first published protocol for the production of a consensus interoperable clinical guideline for people with multi-morbidity, with special focus on older adults with MCI or mild dementia. This addresses a still unmet need for such processes which are expected to play a central role for future integrated healthcare information systems

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio