Solar Mikheyev-Smirnov-Wolfenstein Effect with Three Generations of Neutrinos

Under the assumption that the density variation of the electrons can be approximated by an exponential function, the solar Mikheyev-Smirnov-Wolfenstein effect is treated for three generations of neutrinos. The generalized hypergeometric functions that result from the exact solution of this problem are studied in detail, and a method for their numerical evaluation is presented. This analysis plays a central role in the determination of neutrino masses, not only the differences of their squares, under the assumption of universal quark-lepton mixing.Comment: 22 pages, LaTeX, including 2 figure

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Palaeoproterozoic magnesite: lithological and isotopic evidence for playa/sabkha environments

Magnesite forms a series of 1- to 15-m-thick beds within the approximate to2.0 Ga (Palaeoproterozoic) Tulomozerskaya Formation, NW Fennoscandian Shield, Russia. Drillcore material together with natural exposures reveal that the 680-m-thick formation is composed of a stromatolite-dolomite-'red bed' sequence formed in a complex combination of shallow-marine and non-marine, evaporitic environments. Dolomite-collapse breccia, stromatolitic and micritic dolostones and sparry allochemical dolostones are the principal rocks hosting the magnesite beds. All dolomite lithologies are marked by delta C-13 values from +7.1 parts per thousand to +11.6 parts per thousand (V-PDB) and delta O-18 ranging from 17.4 parts per thousand to 26.3 parts per thousand (V-SMOW). Magnesite occurs in different forms: finely laminated micritic; stromatolitic magnesite; and structureless micritic, crystalline and coarsely crystalline magnesite. All varieties exhibit anomalously high delta C-13 values ranging from +9.0 parts per thousand to +11.6 parts per thousand and delta O-18 values of 20.0-25.7 parts per thousand. Laminated and structureless micritic magnesite forms as a secondary phase replacing dolomite during early diagenesis, and replaced dolomite before the major phase of burial. Crystalline and coarsely crystalline magnesite replacing micritic magnesite formed late in the diagenetic/metamorphic history. Magnesite apparently precipitated from sea water-derived brine, diluted by meteoric fluids. Magnesitization was accomplished under evaporitic conditions (sabkha to playa lake environment) proposed to be similar to the Coorong or Lake Walyungup coastal playa magnesite. Magnesite and host dolostones formed in evaporative and partly restricted environments; consequently, extremely high delta C-13 values reflect a combined contribution from both global and local carbon reservoirs. A C- 13-rich global carbon reservoir (delta C-13 at around +5 parts per thousand) is related to the perturbation of the carbon cycle at 2.0 Ga, whereas the local enhancement in C-13 (up to +12 parts per thousand) is associated with evaporative and restricted environments with high bioproductivity

Pulsational Mapping of Calcium Across the Surface of a White Dwarf

We constrain the distribution of calcium across the surface of the white dwarf star G29-38 by combining time series spectroscopy from Gemini-North with global time series photometry from the Whole Earth Telescope. G29-38 is actively accreting metals from a known debris disk. Since the metals sink significantly faster than they mix across the surface, any inhomogeneity in the accretion process will appear as an inhomogeneity of the metals on the surface of the star. We measure the flux amplitudes and the calcium equivalent width amplitudes for two large pulsations excited on G29-38 in 2008. The ratio of these amplitudes best fits a model for polar accretion of calcium and rules out equatorial accretion.Comment: Accepted to the Astrophysical Journal. 16 pages, 10 figures

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

"Open Innovation" and "Triple Helix" Models of Innovation: Can Synergy in Innovation Systems Be Measured?

The model of "Open Innovations" (OI) can be compared with the "Triple Helix of University-Industry-Government Relations" (TH) as attempts to find surplus value in bringing industrial innovation closer to public R&D. Whereas the firm is central in the model of OI, the TH adds multi-centeredness: in addition to firms, universities and (e.g., regional) governments can take leading roles in innovation eco-systems. In addition to the (transversal) technology transfer at each moment of time, one can focus on the dynamics in the feedback loops. Under specifiable conditions, feedback loops can be turned into feedforward ones that drive innovation eco-systems towards self-organization and the auto-catalytic generation of new options. The generation of options can be more important than historical realizations ("best practices") for the longer-term viability of knowledge-based innovation systems. A system without sufficient options, for example, is locked-in. The generation of redundancy -- the Triple Helix indicator -- can be used as a measure of unrealized but technologically feasible options given a historical configuration. Different coordination mechanisms (markets, policies, knowledge) provide different perspectives on the same information and thus generate redundancy. Increased redundancy not only stimulates innovation in an eco-system by reducing the prevailing uncertainty; it also enhances the synergy in and innovativeness of an innovation system.Comment: Journal of Open Innovations: Technology, Market and Complexity, 2(1) (2016) 1-12; doi:10.1186/s40852-016-0039-

"Meaning" as a sociological concept: A review of the modeling, mapping, and simulation of the communication of knowledge and meaning

The development of discursive knowledge presumes the communication of meaning as analytically different from the communication of information. Knowledge can then be considered as a meaning which makes a difference. Whereas the communication of information is studied in the information sciences and scientometrics, the communication of meaning has been central to Luhmann's attempts to make the theory of autopoiesis relevant for sociology. Analytical techniques such as semantic maps and the simulation of anticipatory systems enable us to operationalize the distinctions which Luhmann proposed as relevant to the elaboration of Husserl's "horizons of meaning" in empirical research: interactions among communications, the organization of meaning in instantiations, and the self-organization of interhuman communication in terms of symbolically generalized media such as truth, love, and power. Horizons of meaning, however, remain uncertain orders of expectations, and one should caution against reification from the meta-biological perspective of systems theory

B-cell-specific checkpoint molecules that regulate anti-tumour immunity.

The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth

The Cost-Effectiveness of Improving Diabetes Care in U.S. Federally Qualified Community Health Centers

Objective. To estimate the incremental cost-effectiveness of improving diabetes care with the Health Disparities Collaborative (HDC), a national collaborative quality improvement (QI) program conducted in community health centers (HCs). Data Sources/Study Settings. Data regarding the impact of the Diabetes HDC program came from a serial cross-sectional follow-up study (1998, 2000, 2002) of the program in 17 Midwestern HCs. Data inputs for the simulation model of diabetes came from the latest clinical trials and epidemiological studies. Study Design. We conducted a societal cost-effectiveness analysis, incorporating data from QI program evaluation into a Monte Carlo simulation model of diabetes. Data Collections/Extraction Methods. Data on diabetes care processes and risk factor levels were extracted from medical charts of randomly selected patients. Principal Findings. From 1998 to 2002, multiple processes of care (e.g., glycosylated hemoglobin testing [HbA1C] [71 -\u3e 92 percent] and ACE inhibitor prescribing [33 -\u3e 55 percent]) and risk factor levels (e.g., 1998 mean HbA1C 8.53 percent, mean difference 0.45 percent [95 percent confidence intervals -0.72, -0.17]) improved significantly. With these improvements, the HDC was estimated to reduce the lifetime incidence of blindness (17 -\u3e 15 percent), end-stage renal disease (18 -\u3e 15 percent), and coronary artery disease (28 -\u3e 24 percent). The average improvement in quality-adjusted life year (QALY) was 0.35 and the incremental cost-effectiveness ratio was $33,386/QALY. Conclusions. During the first 4 years of the HDC, multiple improvements in diabetes care were observed. If these improvements are maintained or enhanced over the lifetime of patients, the HDC program will be cost-effective for society based on traditionally accepted thresholds