B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA ...and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.
Echinocandins and azoles are widely used in the treatment of candidaemia. Guidelines of the Infectious Diseases Society of America recommend commencing treatment with an echinocandin in candidaemic ...patients with risk factors for Candida glabrata i.e. patients who are elderly, or who have diabetes or malignancy, or those with recent prescription of azoles. We attempted to validate whether age, diabetes and malignancy are associated with C. glabrata candidaemia.
Information in relation to demographics, patient associated risk factors, and laboratory parameters were collected from the casenotes and the laboratory information system. We then analysed the distribution of the risk factors (age, diabetes, and malignancy) in candidaemic patients with C. glabrata and patients with species other than C. glabrata (excluding Candida krusei).
Over a 42-month period (April 2011–September 2017), 124 patients had candidaemia. We analysed data for 119 patients of whom 33 (27.7%) had C. glabrata and the remaining 86 (72.2%) were infected with other species. Sixty-five patients were elderly (age≥65), 40 had some form of malignancy, 34 had diabetes, and 4 patients were prescribed azoles in the 30 days prior to candidaemia (many patients had multiple risk factors). Comparing patients with C. glabrata to patients infected with other species, we found no association with diabetes (39.3% vs. 24.4%, P=0.1), malignancy (36.3 vs. 32.5%, P=0.69), and age (54.5% vs. 54.6%, P=0.99).
Diabetes, malignancy and age are not reliable predictors of candidaemia due to C. glabrata.
Executive Summary Polverini 2017 The Impact of Research on the Future of Dental Education: How Research and Innovation Shape Dental Education and the Dental Profession Slavkin 2017 How Research ...Training Will Shape the Future of Dental, Oral, and Craniofacial Research D’Souza 2017 The Future of Dental Schools in Research Universities and Academic Health Centers McCauley 2017 Oral Health Care in the Future: Expansion of the Scope of Dental Practice to Improve Health Lamster and Myers-Wright 2017 Research and Discovery Science and the Future of Dental Education and Practice Polverini and Krebsbach 2017 The overall goals of the project are to critically assess the current state of oral health professionals’ education and practice in the United States; identify important trends that will shape the future of dental education and practice over the coming 25 years; develop practical strategies for restructuring dental education to address long-range challenges, including those related to finances, research, diversity, and access disparities; and prepare a long-term strategic plan for implementing the changes needed in dental education. The project also aims to identify sustainable economic models that will provide dental schools with necessary resources to meet their interrelated missions of education, research, and service; recommend ways to strengthen the science-based clinical education programs of dental students and residents; and develop plans for closer integration of dental schools with other academic health center units so as to produce more effective and efficient education, research, and clinical programs. Women scientists remain underrepresented in leadership positions in dental education and research. ...there is a dearth of underrepresented minority scientists in biomedical research at all levels of the research workforce. While dental schools should continue to aggressively compete for funding from NIDCR, their research portfolio should also expand to other NIH institutes, other federal agencies (e.g., National Science Foundation, Department of Veterans Affairs, Department of Defense), foundations, and industry.
Helper T (Th) cell differentiation is highly regulated by cytokines but initiated by mitogens. By examining gene expression in discrete generations of dividing cells, we have delineated the ...relationship between proliferation and differentiation. Initial expression of IL-2 is cell cycle-independent, whereas effector cytokine expression is cell cycle-dependent. IFNγ expression increases in frequency with successive cell cycles, while IL-4 expression requires three cell divisions. Cell cycle progression and cytokine signaling act in concert to relieve epigenetic repression and can be supplanted by agents that hyperacetylate histones and demethylate DNA. Terminally differentiated cells exhibit stable epigenetic modification and cell cycle-independent gene expression. These data reveal a novel mechanism governing Th cell fate that initially integrates proliferative and differentiative signals and subsequently maintains stability of the differentiated state.
Background. Blood and plasma donor screening for hepatitis virus (HBV) DNA, HBV surface antigen (HBsAg), and antibodies to surface (anti-HBs) and core (anti-HBc) antigens allows identification of ...individuals who acquired HBV despite previous HBV vaccination. Methods. Of 14 HBV acute infection donor panels (HBV-DNA-positive/anti-HBc-negative), 6 donors were previously vaccinated (anti-HBs+). We investigated the differences in viral kinetics and immune responses in vaccinated and nonvaccinated individuals. Serial specimens were characterized for HBV DNA and serological markers and 39 cytokines. Results. The rate of viral load increase was blunted, and virus was cleared more rapidly in vaccinated individuals (P = .004). In unvaccinated individuals, induced protein 10 (IP-10), interleukin 10 (IL-10), macrophage inflammatory protein Iβ (MIP-1β), and soluble interleukin 2Rα (sIL-2Rα) levels were commonly elevated at the time of peak viremia. In contrast, vaccinated individuals had earlier peaks in IL-10 and IP-10 responses that occurred at much lower viral loads and coincided with anamnestic anti-hepatitis surface (HBs) responses and clearance of viremia. Conclusion. There is earlier engagement of innate and adaptive immunity in infected subjects with previous vaccination, possibly explaining suppressed viremia in vaccine breakthrough infections. Although breakthrough infections occur in partially protected vaccine recipients, vaccination likely contributes to early control of replication, limiting immune activation and preventing development of clinically significant acute and chronic HBV infection.
Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve ...repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation.
We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death.
Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval CI, 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60).
Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).
Flame structure in wide-distribution ammonium-perchlorate (AP), hydroxyl-terminated-polybutadiene (HTPB) binder, aluminum (Al) composite propellants is studied using 2-D laminates with oxygenated ...binder. Very fine (2-μm) AP (FAP) is used to produce fuel-rich, matrix propellant (oxygenated binder) with a FAP/binder ratio of 75/25. Coarse AP (CAP) is simulated by pressed AP lamina. A flame-structure regime map for the CAP/oxy-fuel matrix interaction flame is generated as a function of oxy-fuel matrix thickness and pressure using high-speed video imaging analysis. The flame structure is found to be similar to that previously described using UV and IR imaging for non-aluminized laminates with split (diffusion) flame structure at high pressures (
P) and low fuel thicknesses (
L) and merged (partially premixed) flame structure for low
P and
L. The CAP/matrix flame regime boundary is shown to be correlated by Peclet number, indicating the relevance of conserved-scalar (Shvab–Zeldovich) theory with simple, global AP/hydrocarbon chemistry to describe the CAP/matrix diffusion-flame stoichiometry. Other findings include a slight stabilizing effect of Al on the 1-D premixed combustion of the marginally stable fuel-rich matrix. Also, when burning in 2-D laminates assisted slightly by the CAP/matrix interaction flame, the 75/25 matrix is found to burn flat (perpendicular to regression direction) even in the split-flame regime, in contrast to lower FAP/binder ratio matrices, which protrude into the gas-phase. Findings such as these are essential for developing a fundamental understanding of and truly predictive simulation capability for combustion of wide-distribution AP propellants, including plateau, mesa and bi-plateau propellants.
The maximum rate at which fish can take up oxygen from their environment to fuel aerobic metabolism is an important feature of their physiology and ecology. Methods to quantify maximum oxygen uptake ...rate (ṀO2), therefore, should reliably and reproducibly estimate the highest possible ṀO2 by an individual or species under a given set of conditions (peak ṀO2). This study determined peak ṀO2 and its repeatability in Gulf killifish, Fundulus grandis, subjected to three methods to elevate metabolism: swimming at increasing water speeds, during recovery after an exhaustive chase, and after ingestion of a large meal. Estimates of peak ṀO2 during swimming and after an exhaustive chase were repeatable across two trials, whereas peak ṀO2 after feeding was not. Peak ṀO2 determined by the three methods was significantly different from one another, being highest during swimming, lowest after an exhaustive chase, and intermediate after feeding. In addition, peak ṀO2 during recovery from an exhaustive chase depended on the length of time of recovery: in nearly 60% of the trials, values within the first hour of the chase were lower than those measured later. A novel and important finding was that an individual's peak ṀO2 was not repeatable when compared across methods. Therefore, the peak ṀO2 estimated for a group of fish, as well as the ranking of individual ṀO2 within that group, depends on the method used to elevate aerobic metabolism.
The Ultra-Low Background Liquid Scintillation Counter developed by Pacific Northwest National Laboratory will expand the application of liquid scintillation counting by enabling lower detection ...limits and smaller sample volumes. By reducing the overall count rate of the background environment approximately 2 orders of magnitude below that of commercially available systems, backgrounds on the order of tens of counts per day over an energy range of ~3–3600keV can be realized. Initial test results of the ULB LSC show promising results for ultra-low background detection with liquid scintillation counting.
•Observed background is within a factor of 2 of the predictions from simulation.•Background achieved is 2 orders of magnitude below commercially available systems.•Backgrounds are in tens of counts per day over an energy range of ~3– 3600keV.•Initial results show promise for ultra-low background detection with the ULB LSC.
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