The immunophenotypic spectrum of primary mediastinal large B‐cell lymphoma reveals prognostic biomarkers associated with outcome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134201/1/ajh24485.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134201/2/ajh24485_am.pd

Primary versus radiation-associated craniofacial osteosarcoma

BACKGROUND. Craniofacial osteosarcoma differs from long bone osteosarcoma in that patients are older, tumors are often low grade, and prognosis is more favorable. Although most are sporadic, some tumors occur in association with prior radiation therapy. The purpose of the current study was to compare clinicopathologic and prognostic features of primary and radiation-associated osteosarcoma. METHODS. The study group consisted of 15 primary and 6 radiation-associated osteosarcomas. Clinical and follow-up data were obtained in every case. Tissue microarrays were immunohistochemically stained for p53, pRB, Ki-67 (MIB-1), and ezrin. DNA was sequenced for TP53 mutations. RESULTS. All radiation-associated osteosarcomas were high grade and half were fibroblastic. In contrast, 47% of primary craniofacial osteosarcomas were high grade and only 1 was fibroblastic. All radiation-associated osteosarcomas recurred, half the patients died of disease, 2 were alive with unresectable tumors, whereas only 1 was alive without disease. In contrast, 80% of patients with primary tumors were alive without disease, 33% had local recurrences, and 13% died of disease. Radiation-associated tumors overexpressed p53 more often (33% vs. 13%), more often had TP53 mutations (33% vs. 8%), had higher proliferative activity (67% vs. 0% showing >50% MIB-1 staining), and expressed ezrin more frequently (83% vs. 40%) than primary tumors. Compared with a control group of 24 high- and 7 low-grade primary extremity osteosarcomas, radiation-associated tumors marked as the high-grade tumors. CONCLUSIONS. Craniofacial radiation-associated osteosarcomas are high-grade tumors that behave more aggressively than most primary craniofacial osteosarcomas. In addition, they demonstrate higher expression rates of adverse prognostic indicators, further highlighting the distinction. Cancer 2006. © 2006 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55776/1/22019_ftp.pd

"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

Sociological and Communication-Theoretical Perspectives on the Commercialization of the Sciences

Both self-organization and organization are important for the further development of the sciences: the two dynamics condition and enable each other. Commercial and public considerations can interact and "interpenetrate" in historical organization; different codes of communication are then "recombined." However, self-organization in the symbolically generalized codes of communication can be expected to operate at the global level. The Triple Helix model allows for both a neo-institutional appreciation in terms of historical networks of university-industry-government relations and a neo-evolutionary interpretation in terms of three functions: (i) novelty production, (i) wealth generation, and (iii) political control. Using this model, one can appreciate both subdynamics. The mutual information in three dimensions enables us to measure the trade-off between organization and self-organization as a possible synergy. The question of optimization between commercial and public interests in the different sciences can thus be made empirical.Comment: Science & Education (forthcoming

Results of combined treatment of anaplastic thyroid carcinoma (ATC)

<p>Abstract</p> <p>Background</p> <p>Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis.</p> <p>Methods</p> <p>We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin.</p> <p>Results</p> <p>Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months.</p> <p>Conclusion</p> <p>Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging.</p

Human skin penetration of a copper tripeptide in vitro as a function of skin layer

We study a set of 28 GRB light-curves detected between 15 December 2002 and 9 June 2003 by the anti-coincidence shield of the spectrometer (SPI) of INTEGRAL. During this period it has detected 50 bursts, that have been confirmed by other instruments, with a time resolution of 50 ms. First, we derive the basic characteristics of the bursts: various duration measures, the count peak flux and the count fluence. Second, a sub-sample of 11 bursts with 12 individual, well-separated pulses is studied. We fit the pulse shape with a model by Kocevski et al. (2003) and find that the pulses are quite self-similar in shape. There is also a weak tendency for the pulses with steep power-law decays to be more asymmetric. Third, the variability of the complex light-curves is studied by analyzing their power-density-spectra (PDS) and their RMS variability.
The averaged PDS, of the whole sample, is a power-law with index of $1.60\pm0.05$ and a break between 1–2 Hz. Fourth, we also discuss the background and noise levels. We found that the background noise has a Gaussian distribution and its power is independent of frequency, i.e., it is white noise. However, it does not follow a Poisson statistic since on average the variance is ~1.6 larger than the mean. We discuss our results in context of the current theoretical picture in which GRBs are created in an anisotropic, highly relativistic outflow from collapsing massive stars. Finally, we note that the exact behaviour of the instrument is not yet known and therefore the above results should be treated as preliminary.

Human skin penetration of a copper tripeptide in vitro as a function of skin layer

Objective and designSkin retention and penetration by copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent.Materials and methodsFlow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. copper tripeptide as permeant was applied on isolated stratum corneum, heat-separated epidermis and dermatomed skin and receptor fluid collected over 48 h in 4 h intervals using inductively coupled plasma mass spectrometry to analyze for copper in tissues and receptor fluid.ResultsThe permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 μg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 97 ± 6.6 μg/cm(2) were retained as depot.ConclusionsCopper as tripeptide was delivered in potentially therapeutically effective amounts for inflammatory disease

Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo

Background: Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA. Methods: Sixty male 3-week-old Dunkin-Hartley guinea pigs were studied. Separate groups of 12 animals were killed at age 4, 12, 20, 28 and 36 weeks, and histological severity of knee OA was evaluated, and cartilage rheological properties were assessed. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Human patients with early and advanced OA and healthy controls were recruited, blood samples were collected, and serum or plasma was prepared. Serum, plasma, and culture medium were analyzed for glycated, oxidized, and nitrated amino acids. Results: Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized, and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p < 0.0001) and instantaneous modulus (r = 0.52–0.56; p < 0.0001), oxidation free adducts correlated positively with OA severity (p < 0.0009–0.0062), and hydroxyproline correlated positively with cartilage thickness (p < 0.0003–0.003). Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro. In clinical translation, plasma glucosepane was increased 38% in early-stage OA (p < 0.05) and sixfold in patients with advanced OA (p < 0.001) compared with healthy controls. Conclusions: These studies further advance the prospective role of glycated, oxidized, and nitrated amino acids as serum biomarkers in diagnostic algorithms for early-stage detection of OA and other arthritic disease. Plasma glucosepane, reported here for the first time to our knowledge, may improve early-stage diagnosis and progression of clinical OA