In this trailblazing book, leading educational expert David Shaffer examines how particular video and computer games can help teach kids to think like doctors, lawyers, engineers, urban planners, ...journalists and other professionals. Based on more than a decade of research in technology, game science, and education, this book revolutionizes how we think about education in the digital age. (DIPF/Orig.).
In this 12‐month, multicenter, randomized, open‐label, noninferiority study, de novo renal transplant recipients (RTxRs) were randomized (1:1) to receive everolimus plus low‐dose tacrolimus ...(EVR+LTac) or mycophenolate mofetil plus standard‐dose Tac (MMF+STac) with induction therapy (basiliximab or rabbit anti‐thymocyte globulin). Noninferiority of composite efficacy failure rate (treated biopsy‐proven acute rejection tBPAR/graft loss/death/loss to follow‐up) in EVR+LTac versus MMF+STac was missed by 1.4%, considering the noninferiority margin of 10% (24.6% vs. 20.4%; 4.2% −3.0, 11.4). Incidence of tBPAR (19.1% vs. 11.2%; p < 0.05) was significantly higher, while graft loss (1.3% vs. 3.9%; p < 0.05) and composite of graft loss/death/lost to follow‐up (6.1% vs. 10.5%, p = 0.05) were significantly lower in EVR+LTac versus MMF+STac groups, respectively. Mean estimated glomerular filtration rate was similar between EVR+LTac and MMF+STac groups (63.1 22.0 vs. 63.1 19.5 mL/min/1.73 m2) and safety was comparable. In conclusion, EVR+LTac missed noninferiority versus MMF+STac based on the 10% noninferiority margin. Further studies evaluating optimal immunosuppression for improved efficacy will guide appropriate dosing and target levels of EVR and LTac in RTxRs.
This 12‐month, multicenter, randomized, open‐label study in de novo renal transplant recipients reports statistically better graft survival, similar renal function, and comparable safety, despite missing the noninferiority margin of composite efficacy failure rate, with an everolimus plus low‐dose tacrolimus regimen versus mycophenolate mofetil plus standard dose tacrolimus.
Objective
To identify which patient characteristics and treatments are associated with hearing improvement in patients with pediatric sudden sensorineural hearing loss (SSNHL).
Methods
PubMed, Web of ...Science, Cochrane Library, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for articles published before February 5, 2019, and references of relevant articles were screened. Original English‐language case series and cohort studies were included if they addressed SSNHL in patients <20 years of age. Study characteristics, patient demographics, symptoms, treatments, and hearing outcomes were extracted. The primary outcome was hearing improvement.
Results
Thirteen studies were included, totaling 605 patients (670 ears). Hearing did not improve in 46.7% of ears (95% confidence interval CI: 34.4% to 59.0%). Imaging (computed tomography and/or magnetic resonance imaging) results were described in three studies, and 24.2% of ears (95% CI: 7.7% to 40.6%) had abnormal findings. The most common serological finding was cytomegalovirus immunoglobulin (Ig)G or IgM (34.3% of ears tested, 95% CI: −2.9% to 71.6%). Unilateral hearing loss (odds ratio OR:3.85, P < .001), tinnitus (OR: 2.20, P = .003), age >12 years (OR: 2.11, P = .002), and ascending audiogram (OR: 3.66, P = .005), but not systemic or intratympanic steroids, were associated with increased odds of partial or complete improvement. In contrast, profound hearing loss (OR: 0.29, P < .001) and treatment delay of >6 days (OR: 0.27, P < .001) were associated with decreased odds of improvement.
Conclusions
Despite treatment, half of patients had no improvement in hearing. Prognostic factors associated with hearing improvement were generally consistent with those established in the adult population. Further research with consistent definitions for hearing improvement is needed to improve the understanding and treatment of pediatric SSNHL.
Level of Evidence
Laryngoscope, 131:425–434, 2021
After decades of de-prioritizing shareholders’ economic interests and low corporate profitability, Japan introduced the JPX-Nikkei400 in 2014. The index highlighted the country’s “best-run” companies ...by annually selecting the 400 most profitable of its large and liquid firms. We find that managers competed for inclusion in the index by significantly increasing return on equity (ROE), and they did so at least in part due to their reputational or status concerns. The ROE increase was predominantly driven by improvements in margins, which were in turn partially driven by cutting research and development (R&D) intensity. Our findings suggest that indexes can affect managerial behavior through reputational or status incentives.
Effective strategies to guide cell alignment and the deposition of an oriented extracellular matrix are critical for the development of anisotropic engineered tissues suitable for the repair of ...ligament defects. Electrospinning is a promising means to create meshes that can align adherent cells, but the effect of fiber mesh architecture on differentiation has not been examined closely. Therefore, the goal of this study was to determine the effect of fiber diameter and the degree of fiber alignment on mesenchymal progenitor cell morphology, proliferation, and ligament gene expression. Specifically, a poly(ester urethane)urea elastomer was electrospun onto rigid supports under conditions designed to independently vary the mean fiber diameter (from 0.28 to 2.3 microm) and the degree of fiber alignment. Bone marrow stromal cells--seeded onto supported meshes--adhered to and proliferated on all surfaces. Cells assumed a more spindle-shaped morphology with increasing fiber diameter and degree of fiber alignment, and oriented parallel to fibers on aligned meshes. Expression of the ligament markers collagen 1alpha1, decorin, and tenomodulin appeared to be sensitive to fiber diameter and greatest on the smallest fibers. Concurrently, expression of the transcription factor scleraxis appeared to decrease with increasing fiber alignment. These results suggest that the formation of a ligament-like tissue on electrospun scaffolds is enhanced when the scaffolds consist of aligned submicron fibers.
Additively manufactured precipitation hardened (PH) martensitic grade stainless steels display wide variations in their heat treatment response and mechanical properties. Much of this variability can ...be attributed to the selection of the atomizing gas and the resulting variations in powder composition. Differences in nitrogen compositions present in argon and nitrogen atomized powders led to the formation of a wide range of retained austenite levels between 0 and 81 vol% and significant differences in mechanical properties in as-deposited and aged 17-4 PH grade stainless steels. Material fabricated using argon atomized powder contained little to no retained austenite and displayed mechanical properties in the peak-aged condition similar to those in wrought alloys (1359 ± 59 MPa ultimate tensile strength and 10.1 ± 0.8% elongation to failure). On the other hand, materials fabricated with nitrogen atomized powder displayed between 20% and 81% retained austenite, leading to discontinuous yielding driven by the strain-induced transformation of the retained austenite to martensite. Even with the presence of this discontinuous yielding, the materials fabricated using the nitrogen atomized powders consistently displayed strengths 300 MPa higher in the as-deposited, 200 MPa higher in the peak-aged, and 500 MPa higher in the over-aged conditions than materials fabricated using the argon atomized powders. By directly comparing the local strains and microstructures in nitrogen atomized materials, a 011γ//001α relationship in line with the Bain transformation process was present between the retained austenite and transformed martensite across the as-deposited and aged conditions.
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This paper tackles a railcar fleet sizing optimization problem in the chemical industry. In some sectors of the chemical industry, railcars are used not only as a means of transportation but also as ...storage space; thus, it is necessary to consider inventory in the determination of the optimal fleet size. Because of the long lifespans of railcars, this problem is formulated as a long-term capacity expansion problem considering various economic factors. A mixed-integer programming approach to modeling and solving this problem is proposed and a substantial improvement is demonstrated, compared to existing rule-based methods.
The Consortium for Mouse Cell Line Authentication was formed to validate Short Tandem Repeat (STR) markers for intraspecies identification of mouse cell lines. The STR profiling method is a multiplex ...polymerase chain reaction (PCR) assay comprised of primers targeting 19 mouse STR markers and two human STR markers (for interspecies contamination screening). The goals of the Consortium were to perform an interlaboratory study to-(1) validate the mouse STR markers to uniquely identify mouse cell lines (intraspecies identification), (2) to provide a public database of mouse cell lines with the National Institute of Standards and Technology (NIST)-validated mouse STR profiles, and (3) to publish the results of the interlaboratory study. The interlaboratory study was an international effort that consisted of 12 participating laboratories representing institutions from academia, industry, biological resource centers, and government. The study was based on 50 of the most commonly used mouse cell lines obtained from the American Type Culture Collection (ATCC). Of the 50 mouse cell lines, 18 had unique STR profiles that were 100% concordant (match) among all Consortium laboratory members, and the remaining 32 cell lines had discordance that was resolved readily and led to improvement of the assay. The discordance was due to low signal and interpretation issues involving artifacts and genotyping errors. Although the total number of discordant STR profiles was relatively high in this study, the percent of labs agreeing on allele calls among the discordant samples was above 92%. The STR profiles, including electropherogram images, for NIST-validated mouse cell lines will be published on the NCBI BioSample Database (https://www.ncbi.nlm.nih.gov/biosample/). Overall, the interlaboratory study showed that the multiplex PCR method using 18 of the 19 mouse STR markers is capable of discriminating at the intraspecies level between mouse cell lines. Further studies are ongoing to refine the assay including (1) development of an allelic ladder for improving the accuracy of allele calling and (2) integration of stutter filters to identify true stutter.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cocaine is a highly addictive psychostimulant drug of abuse that constitutes an ongoing public health threat. Emerging research is revealing that numerous peripheral effects of this drug may serve as ...conditioned stimuli for its central reinforcing properties. The gut microbiota is emerging as one of these peripheral sources of input to cocaine reward. The primary objective of the present study was to determine how cocaine HCl and methylenedioxypyrovalerone, both of which powerfully activate central reward pathways, alter the gut microbiota. Cocaine methiodide, a quaternary derivative of cocaine that does not enter the brain, was included to assess peripheral influences on the gut microbiota. Both cocaine congeners caused significant and similar alterations of the gut microbiota after a 10-day course of treatment. Contrary to expectations, the effects of cocaine HCl and MDPV on the gut microbiota were most dissimilar. Functional predictions of metabolic alterations caused by the treatment drugs reaffirmed that the cocaine congeners were similar whereas MDPV was most dissimilar from the other two drugs and controls. It appears that the monoamine transporters in the gut mediate the effects of the treatment drugs. The effects of the cocaine congeners and MDPV on the gut microbiome may form the basis of interoceptive cues that can influence their abuse properties.
Herein we report the first example of the catalytic aerobic partial oxidation of allyl ether to its acrylate ester derivative. Many partial oxidations often need an expensive oxidant such as ...peroxides or other species to drive such reactions. In addition, selective generation of esters using porous catalysts has been elusive. This reaction is catalyzed by a Li ion promoted mesoporous manganese oxide (meso-Mn
O
) under mild conditions with no precious metals, a reusable heterogeneous catalyst, and easy isolation. This process is very attractive for the oxidation of allyl ethers. We report on the catalytic activity, selectivity, and scope of the reaction. In the best cases presented, almost complete conversion of allyl ether with near complete chemo-selectivity towards acrylate ester derivatives is observed. Based on results from controlled experiments, we propose a possible reaction mechanism for the case in which N-hydroxyphthalimide (NHPI) is used in combination with trichloroacetonitrile (CCl
CN).
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