Large differences in acclimation capacities towards high-light and high pCO2 between T. hyalina and N. frigida indicate species-specific mechanisms in coping with the two stressors, which may reflect their respective ecological niches. This could potentially alter the balance between sympagic vs. pelagic primary production in a future Arctic. This article is protected by copyright. All rights reserved.Patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein overexpression have very poor prognosis. The cyclin-dependent kinase 7 (CDK7)/super-enhancer inhibitor THZ1 suppresses MYCN gene transcription, reduces neuroblastoma cell proliferation, but does not cause significant cell death. The protein kinase phosphatase 1 nuclear targeting subunit (PNUTS) has recently been shown to interact with c-Myc protein and suppresses c-Myc protein degradation. Here we screened the U.S. Food and Drug Administration-Approved Oncology Drugs Set V from the National Cancer Institute, and identified tyrosine kinase inhibitors (TKIs), including ponatinib and lapatinib, as the Approved Oncology Drugs exerting the best synergistic anticancer effects with THZ1 in MYCN-amplified neuroblastoma cells. Combination therapy with THZ1 and ponatinib or lapatinib synergistically induced neuroblastoma cell apoptosis, while having little effects in normal nonmalignant cells. Differential gene expression analysis identified PNUTS as one of the genes most synergistically reduced by the combination therapy. Reverse transcription polymerase chain reaction and immunoblot analyses confirmed that THZ1 and the TKIs synergistically downregulated PNUTS mRNA and protein expression and reduced N-Myc protein but not N-Myc mRNA expression. In addition, PNUTS knockdown resulted in decreased N-Myc protein but not mRNA expression and decreased MYCN-amplified neuroblastoma cell proliferation and survival. As CDK7 inhibitors are currently under clinical evaluation in patients, our data suggest the addition of the TKI ponatinib or lapatinib in CDK7 inhibitor clinical trials in patients. © 2020 UICC.BACKGROUND Several approaches are used by blood centers when providing minor (non-ABO/D) antigen-negative RBCs to hospitals. Details vary but include providing results on the unit labeling intended for clinical use without retyping or providing results on packing documents or via computer query requiring confirmation. Recent regulatory changes allow labeling with historical minor antigen results, defined as previously performed by the donor center on two different donations with results linked to the donor and confirmed concordant. Here we investigate causes of discrepancies and identify critical process steps. STUDY DESIGN AND METHODS Nine years (2009-2017) of data were reviewed for number, antigen system, and root cause of discrepancies flagged by the computer when retyping donors prior to labeling (internal discrepancies) or reported by the hospital when retested (external discrepancies). https://www.selleckchem.com/products/zasocitinib.html Licensed automated (CcEeK) and tube methods were used. RESULTS Among 300,000 samples phenotyped for CcEe, K, Fya/b , Jka/b , Ss (>3 million antigens), ∼1,389,960 were repeated on 2nd donation with 397 (1/3501) discordant; 205 Fy, 118 Rh, and 74 others. Of ∼682,691 antigen-negative phenotypes provided on unit labeling, ∼37.5% (256,118) were retyped by hospitals with 29 discrepancies (1/8832), primarily Rh variants. CONCLUSION When repeating minor antigen types by serology, discrepancies are primarily associated with weak Fyb , among Caucasian donors, and weak/partial Rh antigens in donors of African ancestry. DNA-based testing avoids these. To label with historical results, accuracy is increased by automated testing with direct computer interface. Testing on two donations with results confirmed to be concordant is not inferior to testing on the current donation. © 2020 AABB.BACKGROUND/OBJECTIVES Recently revised vaccination recommendations for US adults, aged 65 years and older, include both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), with PCV13 now recommended for immunocompetent older people based on shared decision making. The public health impact and cost-effectiveness of this recommendation or of pneumococcal vaccine uptake improvement interventions are unclear. DESIGN Markov decision analysis. SETTING AND PARTICIPANTS Hypothetical 65-year-old general and black population cohorts. INTERVENTION Current pneumococcal vaccination recommendations for US older people, an alternative policy omitting PCV13 in immunocompetent older people, and vaccine uptake improvement programs. RESULTS The current pneumococcal vaccination recommendation was the most effective strategy, but afforded slight public health benefits compared to an alternative (PPSV23 for all older people plus PCV13 for the immunocompromised) and cost grea0 The American Geriatrics Society.OBJECTIVE To examine the association between being a medical doctor (MD) and the risk of incident dementia. DESIGN Cohort study. SETTING Olmsted County, Minnesota. PARTICIPANTS A total of 3460 participants (including 104 MDs), aged 70 years or older, of the population-based Mayo Clinic Study of Aging. MEASUREMENTS Participants were randomly selected from the community and had comprehensive cognitive evaluations at baseline and approximately every 15 months to assess for diagnosis of dementia. For participants who withdrew from the follow-up, dementia diagnosis was also assessed using information available in their medical record. The associations were examined using Cox proportional hazards models, adjusting for sex, education, and apolipoprotein E ε4, using age as the time scale. RESULTS MDs were older (vs "general population"), and most were males (93.3%). MDs without dementia at baseline did not have a significantly different risk for incident dementia (hazard ratio = 1.12; 95% confidence interval = 0.69-1.82; P = .64) compared to the general population. CONCLUSIONS Although the study includes a small number of older, mainly male, MDs, it provides a preliminary insight on cognitive health later in life in MDs, while most previous studies examine the health of younger MDs. Larger longitudinal studies are needed to examine these associations and investigate if associations are modified by sex. © 2020 The American Geriatrics Society.