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The quantum vacuum constitutes a fascinating medium of study, in particular since near-future laser facilities will be able to probe the nonlinear nature of this vacuum. There has been a large number of proposed tests of the low-energy, high intensity regime of quantum electrodynamics (QED) where the nonlinear aspects of the electromagnetic vacuum come into play, and we will here give a short description of some of these. Such studies can shed light, not only on the validity of QED, but also on certain aspects of nonperturbative effects, and thus also give insights for quantum field theories in general. [ABSTRACT FROM AUTHOR]

The purpose of the study was to analyse the generalisability and geographic transportability of survival estimates produced by commonly used prognostic factors. We compared the influence of tumour size, histologic grade, axillary nodal status, oestrogen and progesterone receptor contents, age at diagnosis and two prognostication schemes (the Nottingham Prognostic Index and St. Gallen criteria) in two nationwide cohorts of patients diagnosed with breast cancer in 1991-2, the FinProg (n=2923, Finland) and the SEER series (n=43,249, the United States (US)). Eight-year estimates of breast cancer-specific (84% versus 80%), relative (86% versus 83%), and overall (70% versus 69%) survival were slightly more favourable in the SEER than in the FinProg series, respectively. Despite differences in demographic variables and the frequency of use of adjuvant therapies and mammography screening between the series, the prognostic factors examined produced close to overlapping survival curves with similar shapes. The results suggest that quantitative survival estimates based on frequently used prognostic factors and prognostication schemes are generalisable and transportable between large, unselected cohorts of breast cancer patients. [ABSTRACT FROM AUTHOR]

The clinical utility of CA 15-3, polypeptide specific antigen (TPS), tissue polypeptide antigen (TPA), human chorionic gonadotropin (hCGbeta) and tumour-associated trypsin inhibitor (TATI) as indicators of chemotherapy response was assessed in advanced breast cancer. Serum was prospectively collected in one center before treatment (after the first course of chemotherapy) and at response evaluation from 57 patients taking part in a multicentre randomized trial comparing docetaxel with sequential methotrexate and 5-fluorouracil in the treatment of advanced breast cancer. The pretreatment levels of the serum markers were not predictors of the later response to treatment. Changes in the TPS level showed the strongest association with clinical response after the first course of chemotherapy and CA 15-3 at the best response evaluation. However, distinct mismatches occurred with every marker. The most problematic error was an increase in marker levels in patients with clinical responses, which might have caused interruption of therapy. This occurred in 8% and 17% of patients after the first course of chemotherapy and in 4% and 17% of patients at the best response evaluation with CA 15-3 and TPS, respectively. Moreover, after the first course of chemotherapy only 39% and 33% of the patients with progressive disease could be identified on the basis of increasing levels of CA 15-3 and TPS. respectively. Later, at clinical disease progression, TPA and TPS were found to be better indicators of disease progression than CA 15-3. In conclusion, changes in CA 15-3 or TPS levels usually correlate with clinical response, but owing to distinct discordances, they should not be used as sole indicators of response to chemotherapy in advanced breast cancer. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Possible pro-carcinogenic association of endotoxin non lung cancer among Shanghai women textile workers" in the 2014 issue is presented.

The article focuses on the applications of virtual microscopy in the field of medical sciences. Virtual microscopy has a high potential for various tasks in pathology education, in clinical meeting activity, and in quality control. Applications requiring multiple copies of microscope slides are ideally suited to virtual microscopy. Inter-laboratory comparisons of histopathological diagnoses have been conducted by preparing replicate sets of microscope glass slides and distributing them to the participating pathologists. Virtual microscopy allows each participant to view exactly the same tissue section, thus facilitating quality control programmes, even at a nationwide or an international scale.

Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study. [ABSTRACT FROM PUBLISHER]

Introduction: Previous studies of breast cancer have shown that patients whose tumors are detected by mammography screening have a more favorable survival. Little is known, however, about the long-term prognostic impact of screen detection. The purpose of the current study was to compare breast cancer-specific long-term survival of patients whose tumors were detected in mammography screening compared with those whose tumors were detected by other methods.Methods: Breast cancer patients diagnosed within five specified geographical areas in Finland in 1991 and 1992 were identified (N = 2,936). Detailed clinical, treatment and outcome data, as well as tissue samples, were collected. Women with in situ carcinoma, distant metastases at the time of primary diagnosis and women who were not treated surgically were excluded. The main analyses were performed after excluding patients with other malignancy or contralateral breast cancer, followed by sensitivity analyses with different exclusion criteria. Median follow-up time was 15.4 years. Univariate and multivariate analyses of breast cancer-specific survival were performed.Results: Of patients included in the main analyses (n = 1,884), 22% (n = 408) of cancers were screen-detected and 78% (n = 1,476) were detected by other methods. Breast cancer-specific 15-year survival was 86% for patients with screen-detected cancer and 66% for patients diagnosed using other methods (P < 0.0001, HR = 2.91). Similar differences in survival were observed in women at screening age (50 to 69 years), as well as in clinically important subgroups, such as patients with small tumors (≤ 1 cm in diameter) and without nodal involvement (N0). Women with breast cancer diagnosed on the basis of screening mammography had a more favorable prognosis than those diagnosed outside screening programs, following adjustments according to patient age, tumor size, axillary lymph node status, histological grade and hormone receptor status. Significant differences in the risk of having future contralateral breast cancer according to method of detection were not observed.Conclusions: Breast cancer detected by mammography screening is an independent prognostic factor in breast cancer and is associated with a more favorable survival rate as well as in long-term follow-up. [ABSTRACT FROM AUTHOR]

A correction to the article "Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study," that was published in the previous issue is presented.

A response by L. Laurenti to a letter to the editor about his article "Efficacy and safety of low-dose alemtuzumab as treatment of autoimmune hemolytic anemia in pretreated B-cell chronic lymphocytic leukemia" is presented.

An uncertainty quantification analysis is performed to further investigate the nature of the “two-stage” wear process of the paper-based friction lining in a wet clutch. In this approach, the results of a computerized wear prediction model are examined through sensitivity analysis and a model validation that utilizes the Monte Carlo (MC) method. Extensive computational results that take into account the uncertainty and variability in the input data are presented to gain insight into the evolution of temperature and wear during the engagement process. [ABSTRACT FROM AUTHOR]

A methodology for prediction of wear in the friction lining of a wet clutch subjected to repeated engagement cycles is presented. The wear mechanism is related to both thermal degradation and mechanical effects. The temperature history is obtained by performing a thermohydrodynamic (THD) analysis of the entire engagement process including engagement, soaking, dwelling and stabilization periods. The predictions of the model are in accordance to the experimentally observed “two-stage” wear rate phenomenon recently reported in the literature. [ABSTRACT FROM AUTHOR]

The Internet provides a unique opportunity for scientists to be in direct contact with the public in order to promote citizens' scientific literacy. Recently, Internet users have started to spend most of their online time on social networking sites (SNS). Knowledge of how these SNSs work as an arena for interaction, as well as for the development of scientific literacy, is important to guide scientists' activities online, and to be able to understand how people develop knowledge of science. This was evaluated by scrutinizing the Facebook page of the Monterey Bay Aquarium Research Institute and the consequences for users' ocean literacy. We investigated which practices could increase the number of users reached by a Facebook story. We also found that Facebook pages do not offer the appropriate social context to foster participation since it has only a few of the features of an arena where such practices could develop. [ABSTRACT FROM AUTHOR]

The majority of mortality associated with cancer is due to formation of metastases from the primary tumor. Adhesion mediated by different integrin heterodimers has an important role during cell migration and invasion. Protein interactions with the β1-integrin cytoplasmic tail are known to influence integrin affinity for extracellular ligands, but regulating binding partners for the α-subunit cytoplasmic tails have remained elusive. In this study, we show that mammary-derived growth inhibitor (MDGI) (also known as FABP-3 or H-FABP) binds directly to the cytoplasmic tail of integrin α-subunits and its expression inhibits integrin activity. In breast cancer cell lines, MDGI expression correlates with suppression of the active conformation of integrins. This results in reduced integrin adhesion to type I collagen and fibronectin and inhibition of cell migration and invasion. In tissue microarray of 1331 breast cancer patients, patients with MDGI-positive tumors had more favorable 10-year distant disease-free survival compared with patients with MDGI-negative tumors. Our data indicate that MDGI is a novel interacting partner for integrin α-subunits, and its expression modulates integrin activity and suppresses cell invasion in breast cancer patients. Retained MDGI expression is associated with favorable prognosis. [ABSTRACT FROM AUTHOR]

Xanthine oxidoreductase (XOR) is a key enzyme in degradation of DNA and RNA, and has previously been shown to be decreased in aggressive breast and gastric cancer. In this study, XOR expression was assessed in tissue microarray specimens of 478 patients with colorectal cancer and related to clinical parameters. In addition, we performed in vitro studies of XOR activity, protein and mRNA in colon cancer cells (Caco-2). Results from the tissue expression analyses show that XOR was decreased in 62% and undetectable in 22% of the tumours as compared to normal tissue. Loss of XOR was associated with poor grade of differentiation (p=0.006) and advanced Dukes stage (p=0.03). In multivariate survival analysis, XOR was a prognostic factor (p=0.008), independent of Dukes stage, histological grade, age and tumour location. The in vitro analyses show that XOR is not measurable in undifferentiated Caco-2 cells, but appears and increases with differentiation. We conclude that XOR expression is associated with histological grade of differentiation and extent of disease in colorectal cancer, and it provides significant prognostic information independently of established factors. [ABSTRACT FROM AUTHOR]

Abstract: Array CGH (comparative genomic hybridization) screening of large patient cohorts with mental retardation and/or multiple congenital anomalies (MR/MCA) has led to the identification of a number of new microdeletion and microduplication syndromes. Recently, a recurrent copy number variant (CNV) at chromosome 16p11.2 was reported to occur in up to 1% of autistic patients in three large autism studies. In the screening of 4284 patients with MR/MCA with various array platforms, we detected 22 individuals (14 index patients and 8 family members) with deletions in 16p11.2, which are genomically identical to those identified in the autism studies. Though some patients shared a facial resemblance and a tendency to overweight, there was no evidence for a recognizable phenotype. Autism was not the presenting feature in our series. The assembled evidence indicates that recurrent 16p11.2 deletions are associated with variable clinical outcome, most likely arising from haploinsufficiency of one or more genes. The phenotypical spectrum ranges from MR and/or MCA, autism, learning and speech problems, to a normal phenotype. [Copyright &y& Elsevier]

Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59–69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor ‘first dose’ reactions. All 5 patients responded with a 2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4–7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2–12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.Leukemia (2007) 21, 511–514. doi:10.1038/sj.leu.2404512; published online 11 January 2007 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Alemtuzumab as First-Line Therapy for B-Cell Chronic Lymphocytic Leukemia: Long-Term Follow-Up of Clinical Effects, Infectious Complications and Risk of Richter Transformation," in the October 19, 2006 issue.

B cell chronic lymphocytic leukemia (B-CLL) is a chronic leukemia manifested by increased numbers of B cells in circulation. The slow, smouldering nature of the disease in a significant proportion of the cases makes it an ideal target for immunotherapy. Dendritic cell (DC)-based immunotherapy is emerging as an exciting modality with significant clinical potential. In this study, three strategies for delivering antigens to DC, namely apoptotic bodies (Apo-DC), tumor lysates, and tumor RNA were studied in an autologous setting. In all six CLL patients, Apo-DC induced higher HLA-restricted, T cell responses than DC pulsed with tumor lysate or RNA. Real-time PCR confirmed higher expression of genes for IL-2 and IFN-?in T cells stimulated with Apo-DC. Concurrently, no IL-10 and low IL-4 responses indicated that the immune response was primarily of the Th1 type. Enzyme-linked immunospot assay revealed high IFN-?secretion by T cells when Apo-DC was used to stimulate autologous T cells in all patients. Our data suggest that cellular vaccines with DC loaded with apoptotic bodies may be a suitable approach for immunotherapy of B-CLL.Leukemia (2004) 18, 1810-1815. doi:10.1038/sj.leu.2403517 Published online 23 September 2004 [ABSTRACT FROM AUTHOR]

DNA copy number changes were studied by comparative genomic hybridization (CGH) on bone marrow samples obtained from 72 patients with childhood acute lymphoblastic leukemia (ALL) at diagnosis. The patients had been admitted to the Helsinki University Central Hospital (Finland) between 1982 and 1997. CGH showed DNA copy number changes in 45 patients (62.5%) with a mean of 4.6 aberrations per patient (range, 1 to 22). The results of CGH and chromosome banding analysis were generally concordant, but CGH facilitated specific karyotyping in 34 cases. DNA copy number gains were more frequent than losses (gains:losses, 6:1). Gains of DNA sequences affected almost exclusively whole chromosomes and were most commonly observed in chromosomes 21 (25%), 18 (22.2%), X (19.4%), 10 (19.4%) and 17 (19.4%). The most common partial gain was 1q31-q32 (8.3%). The most common gains of chromosomes 21, 18, X, 10, 17, 14, 4, 6 and 8 appeared concurrently. High-level amplifications of small chromosome regions were sporadic, detected only in two patients (2.8%). Chromosome 21 was involved in both cases. The most common losses were 9p22-pter (12.5%) and 12p13-pter (11.1%). No statistically significant association between the CGH findings and the diagnostic white blood cell count was observed. [ABSTRACT FROM AUTHOR]