Sample records for cancers origins consequences

  1. Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer. (United States)

    Ju, Young Seok; Alexandrov, Ludmil B; Gerstung, Moritz; Martincorena, Inigo; Nik-Zainal, Serena; Ramakrishna, Manasa; Davies, Helen R; Papaemmanuil, Elli; Gundem, Gunes; Shlien, Adam; Bolli, Niccolo; Behjati, Sam; Tarpey, Patrick S; Nangalia, Jyoti; Massie, Charles E; Butler, Adam P; Teague, Jon W; Vassiliou, George S; Green, Anthony R; Du, Ming-Qing; Unnikrishnan, Ashwin; Pimanda, John E; Teh, Bin Tean; Munshi, Nikhil; Greaves, Mel; Vyas, Paresh; El-Naggar, Adel K; Santarius, Tom; Collins, V Peter; Grundy, Richard; Taylor, Jack A; Hayes, D Neil; Malkin, David; Foster, Christopher S; Warren, Anne Y; Whitaker, Hayley C; Brewer, Daniel; Eeles, Rosalind; Cooper, Colin; Neal, David; Visakorpi, Tapio; Isaacs, William B; Bova, G Steven; Flanagan, Adrienne M; Futreal, P Andrew; Lynch, Andy G; Chinnery, Patrick F; McDermott, Ultan; Stratton, Michael R; Campbell, Peter J


    Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.

  2. Psychosocial Consequences of Overdiagnostic of Prostate Cancer

    DEFF Research Database (Denmark)

    Nielsen, Sigrid Brisson; Brodersen, John

    Psychosocial Consequences of Overdiagnostic of Prostate Cancer Sigrid Brisson Nielsen & John Brodersen Introduction In Denmark there are approximately 4400 men diagnosed with prostate cancer each year and nearly 1200 men dies of this disease yearly. The incidence of prostate cancer has increased...... for the past twenty years and make up 24 % of all cancer incidents in men. However, the mortality of prostate cancer has not changed in line with this increase. Empirical evidence shows that the increase in incidence of prostate cancer in Denmark without an increase in the mortality is mostly caused...... by opportunistic PSA screening in General Practice. It is recommended that men ≥ 60 year old diagnosed with prostate cancer and a Gleason score ≤ 6 are monitored with active surveillance. This is due to the probability of this type of cancer metastasizing is very small as approximately 90 % of them is assumed...

  3. The origins, determinants, and consequences of human mutations. (United States)

    Shendure, Jay; Akey, Joshua M


    Germline mutations are the principal cause of heritable disease and the ultimate source of evolutionary change. Similarly, somatic mutations are the primary cause of cancer and may contribute to the burden of human disease more broadly than previously appreciated. Here, we review recent insights into the rates, spectrum, and determinants of genomic mutations and how these parameters inform our understanding of both Mendelian and complex human diseases. We also consider models for conceptualizing mutational consequences and outline several key areas for future research, including the development of new technologies to access and quantify the full spectrum of mutations, as well as to better interpret the consequences of mutations with respect to molecular functionality, evolutionary fitness, and disease pathogenicity.

  4. Prostate cancer in men of African origin. (United States)

    McGinley, Kathleen F; Tay, Kae Jack; Moul, Judd W


    Men of African origin are disproportionately affected by prostate cancer: prostate cancer incidence is highest among men of African origin in the USA, prostate cancer mortality is highest among men of African origin in the Caribbean, and tumour stage and grade at diagnosis are highest among men in sub-Saharan Africa. Socioeconomic, educational, cultural, and genetic factors, as well as variations in care delivery and treatment selection, contribute to this cancer disparity. Emerging data on single-nucleotide-polymorphism patterns, epigenetic changes, and variations in fusion-gene products among men of African origin add to the understanding of genetic differences underlying this disease. On the diagnosis of prostate cancer, when all treatment options are available, men of African origin are more likely to choose radiation therapy or to receive no definitive treatment than white men. Among men of African origin undergoing surgery, increased rates of biochemical recurrence have been identified. Understanding differences in the cancer-survivorship experience and quality-of-life outcomes among men of African origin are critical to appropriately counsel patients and improve cultural sensitivity. Efforts to curtail prostate cancer screening will likely affect men of African origin disproportionately and widen the racial disparity of disease.

  5. Origins, Consequences, and Management of Countertransference: A Case Study (United States)

    Rosenberger, Eric W.; Hayes, Jeffrey A.


    Insight into the construct of countertransference may be gained by studying the relationships among its constituents. Toward that end, a single therapy dyad was analyzed for 13 sessions. Client verbalizations predicted to trigger countertransference reactions were studied in relation to their possible consequences, and the potential mitigating…

  6. Pathogenesis and consequences of uniparental disomy in cancer. (United States)

    Makishima, Hideki; Maciejewski, Jaroslaw P


    The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can be found in specific cancer types and probably contribute to clonal outgrowth owing to various mechanisms. In this review we explore the types, topography, genesis, pathophysiological consequences, and clinical implications of uniparental disomy.

  7. Psychologic consequences of breast cancer on partner and family. (United States)

    Northouse, L L; Cracchiolo-Caraway, A; Appel, C P


    Breast cancer can have psychologic consequences not only for patients but also for the entire family system. Research indicates a major impact on the husband, the marital relationship, the children, and family roles and responsibilities. Greater attention needs to be given to the family members to ensure that they get the support they need, and to enable them to maintain their supportive roles with the patient.

  8. Hypotheses of cancer weakening and origin. (United States)

    Chan, John Cheung Yuen


    modified organisms from ancient eukaryotic genes (GMOE). The GMOE group lives in hypoxic environments and metabolizes glucose by fermentation. GMOEs represent advanced cancer, which proliferate aggressively and are resistant to DNA damage. It has been demonstrated that as an ERV becomes more prevalent in a mammalian genome, the possibility that the mammal will develop cancer increases. The hypothesis also states that most cancers have their origins in GMOV by the incorporation of viral genes from junk genes. As the cancer progresses, further subgroups of cancer GMOs will develop. If the cancer advances even further, the GMOE could eventually develop prior to late-stage cancer. Because the genes of ancient eukaryotes have enhanced innate immunity, GMOE will eventually prevail over the weaker GMOV during cancer subgroup competition. Hence, cancer development is mainly determined by genes in the mammalian genome. An inherent weakness of cancer cells is their dependence on glucose and iron. Furthermore, they cannot tolerate physical disturbance. Ancient gene GMOs can be treated with a combination of mechanical vibration using glucose-coated magnetic nanoparticles and strengthening of the immune system. Herein, I suggest trials for verifying this hypothesis.

  9. Cells of Origin of Epithelial Ovarian Cancers (United States)


    AWARD NUMBER: W81XWH-14-1-0280 TITLE: Cells of Origin of Epithelial Ovarian Cancers PRINCIPAL INVESTIGATOR: Zhe Li, PhD CONTRACTING...Xie, Zhe Li 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...Lined Inclusion Cysts or Teratomas. PLoS ONE 8, e65067. Sherman-Baust, C.A., Kuhn, E., Valle, B.L., Shih Ie, M., Kurman, R.J., Wang , T.L., Amano, T

  10. Keeping the Faith : Origins of Confidence in Charitable Organizations and its Consequences for Philanthropy

    NARCIS (Netherlands)

    Bekkers, René


    Origins and consequences of charitable confidence are investigated with the Giving in the Netherlands Panel Survey 2002-2004 (n=1,246). Charitable confidence is higher among the higher educated, children of volunteers, younger age groups, those with more faith in people, those who are aware of stand

  11. Luminal cells are favored as the cell of origin for prostate cancer (United States)

    Wang, Zhu A.; Toivanen, Roxanne; Bergren, Sarah K.; Chambon, Pierre; Shen, Michael M.


    The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we use a novel lineage-tracing strategy to assess the cell of origin in a diverse range of mouse models, including Nkx3.1+/–; Pten+/–, Pten+/–, Hi-Myc, and TRAMP mice, as well as a hormonal carcinogenesis model. Our results show that luminal cells are consistently the observed cell of origin for each model in situ; however, explanted basal cells from these mice can generate tumors in grafts. Consequently, we propose that luminal cells are favored as cells of origin in many contexts, whereas basal cells only give rise to tumors after differentiation into luminal cells. PMID:25176651

  12. The political use of the cancer metaphor: negative consequences for the public and the cancer community. (United States)

    Meisenberg, Barry R; Meisenberg, Samuel W


    There has been an increase in the use of cancer as a political metaphor, most recently to describe the threat of international terrorism. The powerful cancer metaphor implies a particular political problem is serious, progressive and deadly. As such to use a cancer metaphor prepares the public for a set of serious, intense and prolonged actions. While politically useful for a governmental to communicate policy, there are negative consequences to the use of the cancer metaphor. It perpetuates among the public and patients old stereotypes of cancer prognosis and therapies that oncologists have tried to combat through education. These education efforts are designed to help patients avoid overly aggressive treatments, surveillance, monitoring and surgeries. It is hard to successfully educate the general public and patients when they continuously receive alternative messages from political leaders who use the cancer metaphor for a different purpose. Professional cancer educators and clinicians should be aware of this trend and redouble efforts to educate that the political metaphor is for politics only and misleading in the public health and clinical arenas.

  13. Psychosocial consequences for children of a parent with cancer : A pilot study

    NARCIS (Netherlands)

    Huizinga, GA; van der Graaf, WTA; Visser, A; Dijkstra, JS; Hoekstra-Weebers, JEHM


    When cancer is diagnosed in a parent, this may also have consequences for the children. The purpose of this pilot study was to gain more insight into the psychosocial consequences for children of a parent with cancer, from the perspective of both the children and their parents. For this study, 14 fa

  14. Cancer Risk in Astronauts: A Constellation of Uncommon Consequences (United States)

    Milder, Caitlin M.; Elgart, S. Robin; Chappell, Lori; Charvat, Jaqueline M.; Van Baalen, Mary; Huff, Janice L.; Semones, Edward J.


    Excess cancers resulting from external radiation exposures have been noted since the early 1950s, when a rise in leukemia rates was first reported in young atomic bomb survivors [1]. Further studies in atomic bomb survivors, cancer patients treated with radiotherapy, and nuclear power plant workers have confirmed that radiation exposure increases the risk of not only leukemia, but also a wide array of solid cancers [2,3]. NASA has long been aware of this risk and limits astronauts' risk of exposure-induced death (REID) from cancer by specifying permissible mission durations (PMD) for astronauts on an individual basis. While cancer is present among astronauts, current data does not suggest any excess of known radiation-induced cancers relative to a comparable population of U.S. adults; however, very uncommon cancers have been diagnosed in astronauts including nasopharyngeal cancer, lymphoma of the brain, and acral myxoinflammatory fibroblastic sarcoma. In order to study cancer risk in astronauts, a number of obstacles must be overcome. Firstly, several factors make the astronaut cohort considerably different from the cohorts that have previously been studied for effects resulting from radiation exposure. The high rate of accidents and the much healthier lifestyle of astronauts compared to the U.S. population make finding a suitable comparison population a problematic task. Space radiation differs substantially from terrestrial radiation exposures studied in the past; therefore, analyses of galactic cosmic radiation (GCR) in animal models must be conducted and correctly applied to the human experience. Secondly, a large enough population of exposed astronauts must exist in order to obtain the data necessary to see any potential statistically significant differences between the astronauts and the control population. Thirdly, confounders and effect modifiers, such as smoking, diet, and other space stressors, must be correctly identified and controlled for in those

  15. Exploring depressive personality traits in youth: origins, correlates, and developmental consequences. (United States)

    Rudolph, Karen D; Klein, Daniel N


    Research suggests that depressive personality (DP) disorder may represent a persistent, trait-based form of depression that lies along an affective spectrum ranging from personality traits to diagnosable clinical disorders. A significant gap in this area of research concerns the development of DP and its applicability to youth. The present research explored the construct of DP traits in youth. Specifically, this study examined the reliability, stability, and validity of the construct, potential origins of DP traits, and the developmental consequences of DP traits. A sample of 143 youth (mean age = 12.37 years, SD = 1.26) and their caregivers completed semistructured interviews and questionnaires on two occasions, separated by a 12-month interval. The measure of DP traits was reliable and moderately stable over time. Providing evidence of construct validity, DP traits were associated with a network of constructs, including a negative self-focus, high-negative and low-positive emotionality, and heightened stress reactivity. Moreover, several potential origins of DP traits were identified, including a history of family adversity, maternal DP traits, and maternal depression. Consistent with hypotheses regarding their developmental significance, DP traits predicted the generation of stress and the emergence of depression (but not nondepressive psychopathology) during the pubertal transition. Finally, depression predicted subsequent DP traits, suggesting a reciprocal process whereby DP traits heighten risk for depression, which then exacerbates these traits. These findings support the construct of DP traits in youth, and suggest that these traits may be a useful addition to developmental models of risk for youth depression.

  16. The origin, dynamics, and molecular evolution of transmissible cancers

    Directory of Open Access Journals (Sweden)

    Jones EA


    Full Text Available Elizabeth A Jones, Yuanyuan Cheng, Katherine BelovFaculty of Veterinary Science, University of Sydney, NSW, AustraliaAbstract: Three transmissible cancers are known to have emerged naturally in the wild: canine transmissible venereal tumor (CTVT; Tasmanian devil facial tumor disease (DFTD; and a recently discovered leukemia-like cancer in soft-shell clams (Mya arenaria. These cancers have all acquired the ability to pass between individuals. DFTD emerged approximately 20 years ago and has decimated the Tasmanian devil population. CTVT arose over 10,000 years ago in an ancient breed of dog. The clam cancer is believed to have evolved at least 40 years ago. In this manuscript, we review CTVT and DFTD, the two transmissible mammalian cancers, and provide an overview of the leukemia-like cancer of clams. We showcase how genetics and genomics have enhanced our understanding of the unique biology, origins, and evolutionary histories of these rare cancers.Keywords: transmissible cancer, devil facial tumor disease, DFTD, canine transmissible venereal tumor, origin, evolution

  17. [Consequences of tobacco smoking on lung cancer treatments]. (United States)

    Rivera, C; Rivera, S; Fabre, E; Pricopi, C; Le Pimpec-Barthes, F; Riquet, M


    In France, in 2010, tobacco induced 81% of deaths by lung cancer corresponding to about 28,000 deaths. Continued smoking after diagnosis has a significant impact on treatment. In patients with lung cancer, the benefits of smoking cessation are present at any stage of disease. For early stages, smoking cessation decreases postoperative morbidity, reduces the risk of second cancer and improves survival. Previous to surgery, smoking cessation of at least six to eight weeks or as soon as possible is recommended in order to reduce the risk of infectious complications. Tobacco could alter the metabolism of certain chemotherapies and targeted therapies, such as tyrosine kinase inhibitors of the EGF receptor, through an interaction with P450 cytochrome. Toxicity of radiations could be lower in patients with lung cancer who did not quit smoking before treatment. For patients treated by radio-chemotherapy, overall survival seems to be better in former smokers but no difference is observed in terms of recurrence-free survival. For advanced stages, smoking cessation enhances patients' quality of life. Smoking cessation should be considered as full part of lung cancer treatment whatever the stage of disease.

  18. Origins and consequences of hyperosmolar stress in retinal pigmented epithelial cells. (United States)

    Willermain, François; Libert, Sarah; Motulsky, Elie; Salik, Dany; Caspers, Laure; Perret, Jason; Delporte, Christine


    The retinal pigmented epithelium (RPE) is composed of retinal pigmented epithelial cells joined by tight junctions and represents the outer blood-retinal barrier (BRB). The inner BRB is made of endothelial cells joined by tight junctions and glial extensions surrounding all the retinal blood vessels. One of the functions of the RPE is to maintain an osmotic transepithelial gradient created by ionic pumps and channels, avoiding paracellular flux. Under such physiological conditions, transcellular water movement follows the osmotic gradient and flows normally from the retina to the choroid through the RPE. Several diseases, such as diabetic retinopathy, are characterized by the BRB breakdown leading to leakage of solutes, proteins, and fluid from the retina and the choroid. The prevailing hypothesis explaining macular edema formation during diabetic retinopathy incriminates the inner BRB breakdown resulting in increased osmotic pressure leading in turn to massive water accumulation that can affect vision. Under these conditions, it has been hypothesized that RPE is likely to be exposed to hyperosmolar stress at its apical side. This review summarizes the origins and consequences of osmotic stress in the RPE. Ongoing and further research advances will clarify the mechanisms, at the molecular level, involved in the response of the RPE to osmotic stress and delineate potential novel therapeutic targets and tools.

  19. The evolutionary origin of the need to sleep: An inevitable consequence of synaptic neurotransmission?

    Directory of Open Access Journals (Sweden)

    Robert S. Cantor


    Full Text Available It is proposed that the evolutionary origin of the need to sleep is the removal of neurotransmitters (NTs that escape reuptake and accumulate in brain interstitial fluid. Recent work suggests that the activity of ionotropic postsynaptic receptors, rapidly initiated by binding of NTs to extracellular sites, is modulated over longer times by adsorption of these NTs to the lipid bilayers in which the receptors are embedded. This bilayer-mediated mechanism is far less molecularly specific than binding, so bilayer adsorption of NTs that have diffused into synapses for other receptors would modulate their activity as well. Although NTs are recycled by membrane protein reuptake, the process is less than 100% efficient; a fraction escapes the region in which these specific reuptake proteins are localized and eventually diffuses throughout the interstitial fluid. It is estimated that even if only 0.1% of NTs escape reuptake, they would accumulate and adsorb to bilayers in synapses of other receptors sufficiently to affect receptor activity, the harmful consequences of which are avoided by sleep: a period of efficient convective clearance of solutes together with greatly reduced synaptic activity.

  20. Incidental venous thromboembolism in cancer patients: prevalence and consequence

    NARCIS (Netherlands)

    Douma, Renée A.; Kok, Maayke G.M.; Verberne, Lisa M.; Kamphuisen, Pieter W.; Büller, Harry R.


    Introduction: Careful re-evaluation of CT-scans for cancer staging frequently reveals unsuspected venous thromboembolism (VTE) on CT-scans. However, it is unknown how often these findings lead to anticoagulant treatment in daily clinical practice. Methods: Reports from thoracic and/or abdominal CT-s

  1. Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Adam Shlien


    Full Text Available Disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription, coordinated secondary pathway alterations, and increased transcriptional noise. To catalog the rules governing how somatic mutation exerts direct transcriptional effects, we developed an exhaustive pipeline for analyzing RNA sequencing data, which we integrated with whole genomes from 23 breast cancers. Using X-inactivation analyses, we found that cancer cells are more transcriptionally active than intermixed stromal cells. This is especially true in estrogen receptor (ER-negative tumors. Overall, 59% of substitutions were expressed. Nonsense mutations showed lower expression levels than expected, with patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusions, and premature polyadenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data reveals the rules by which transcriptional machinery interprets somatic mutation.

  2. Nutritional consequences of the radiotherapy of head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chencharick, J.D.; Mossman, K.L.


    Nutrition-related complications of radiotherapy were evaluated in 74 head and neck cancer patients. Subjective changes of mouth dryness, taste, dysphagia, appetite, and food preferences were determined by questionnaire before and at weekly intervals during curative radiotherapy. Changes in body weight during therapy were also recorded. In addition, 24-hour dietary histories were taken from eight patients at the beginning and end of treatment. Results of the study indicate that patients were subjectively aware of nutritional problems prior to therapy and that therapy exacerbated these problems. As many as 25% of the patients experienced oral complications such as taste loss and/or dry mouth prior to initiation of radiotherapy. By the end of radiotherapy, over 80% of the patients were aware of oral and nutritional problems. Patients had an average weight loss of 5 kg prior to therapy; this loss of weight did not change during therapy. Diet histories of eight patients indicate significant caloric deficiencies early and late in radiotherapy. The oral and nutritional problems experienced by patients, even prior to therapy, support the idea that nutritional evaluation and maintenance are important not only during therapy, but prior to radiotherapy as well. Nutritional evaluation should be made a routine, integral part of therapy for every cancer patient.

  3. Luminal Cells Are Favored as the Cell of Origin for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Zhu A. Wang


    Full Text Available The identification of cell types of origin for cancer has important implications for tumor stratification and personalized treatment. For prostate cancer, the cell of origin has been intensively studied, but it has remained unclear whether basal or luminal epithelial cells, or both, represent cells of origin under physiological conditions in vivo. Here, we use a novel lineage-tracing strategy to assess the cell of origin in a diverse range of mouse models, including Nkx3.1+/−; Pten+/−, Pten+/−, Hi-Myc, and TRAMP mice, as well as a hormonal carcinogenesis model. Our results show that luminal cells are consistently the observed cell of origin for each model in situ; however, explanted basal cells from these mice can generate tumors in grafts. Consequently, we propose that luminal cells are favored as cells of origin in many contexts, whereas basal cells only give rise to tumors after differentiation into luminal cells.

  4. Mutations and epimutations in the origin of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Peltomaeki, Paeivi, E-mail: Paivi.Peltomaki@Helsinki.Fi


    Cancer is traditionally viewed as a disease of abnormal cell proliferation controlled by a series of mutations. Mutations typically affect oncogenes or tumor suppressor genes thereby conferring growth advantage. Genomic instability facilitates mutation accumulation. Recent findings demonstrate that activation of oncogenes and inactivation of tumor suppressor genes, as well as genomic instability, can be achieved by epigenetic mechanisms as well. Unlike genetic mutations, epimutations do not change the base sequence of DNA and are potentially reversible. Similar to genetic mutations, epimutations are associated with specific patterns of gene expression that are heritable through cell divisions. Knudson's hypothesis postulates that inactivation of tumor suppressor genes requires two hits, with the first hit occurring either in somatic cells (sporadic cancer) or in the germline (hereditary cancer) and the second one always being somatic. Studies on hereditary and sporadic forms of colorectal carcinoma have made it evident that, apart from genetic mutations, epimutations may serve as either hit or both. Furthermore, recent next-generation sequencing studies show that epigenetic genes, such as those encoding histone modifying enzymes and subunits for chromatin remodeling systems, are themselves frequent targets of somatic mutations in cancer and can act like tumor suppressor genes or oncogenes. This review discusses genetic vs. epigenetic origin of cancer, including cancer susceptibility, in light of recent discoveries. Situations in which mutations and epimutations occur to serve analogous purposes are highlighted.

  5. [A case of metastatic gastric cancer originating from transverse colon cancer]. (United States)

    Nushijima, Youichirou; Nakano, Katsutoshi; Sugimoto, Keishi; Nakaguchi, Kazunori; Kan, Kazuomi; Maruyama, Hirohide; Doi, Sadayuki; Okamura, Shu; Murata, Kohei


    Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

  6. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas (United States)


    progenitor cells (NPCs) by expressing an activated form of Notch1 (N1ICD) or oncogenic PIK3CA (PIK3CA*) in the developing mouse cerebellum, using cell...resistance, pediatric cancer, brain tumor, Notch1, PIK3CA, cell of origin, molecular subtypes, neural stem cells, neural progenitor cells, tumor initiation...neural progenitor cells, tumor initiation. 3. ACCOMPLISHMENTS: Major goals of the project: The stated goals of this project are to: 1) test the

  7. A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer (United States)

    Odoux, Christine; Fohrer, Helene; Hoppo, Toshitaka; Guzik, Lynda; Stolz, Donna Beer; Lewis, Dale W.; Gollin, Susanne M.; Gamblin, T. Clark; Geller, David A.; Lagasse, Eric


    Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and to the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally-derived tumor cells expressed many consistent (clonal), along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability. PMID:18757407

  8. The initial development of the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN)

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Grønvold, Mogens


    To develop a questionnaire for cancer patients' informal caregivers, measuring the caregiving tasks and consequences, and the caregivers' needs with a main focus on the interaction with the health care professionals. Such an instrument is needed to evaluate the efforts directed towards caregivers...

  9. Origins and consequences of tripartite efficacy beliefs within elite athlete dyads. (United States)

    Jackson, Ben; Knapp, Peter; Beauchamp, Mark R


    Drawing from Lent and Lopez's (2002) "tripartite" model of relational efficacy, the overall purpose of this study was to examine antecedents and consequences of self-efficacy, other-efficacy, and relation-inferred self-efficacy (RISE) within six international-level athlete dyads. Semistructured interviews were conducted and data were content analyzed using deductive and inductive procedures. Sources of efficacy emerged in relation to perceptions regarding (i) oneself, (ii) one's partner, (iii) the dyad/relationship, and (iv) external factors. Results also revealed the emergence of a number of salient intrapersonal and interpersonal outcomes, incorporating cognitive, affective, as well as behavioral consequences. Implications for theory development and future research are considered, and applied propositions are discussed with regard to effective relationship management in elite sport.

  10. Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations. (United States)

    Rycaj, Kiera; Tang, Dean G


    A tumor originates from a normal cell that has undergone tumorigenic transformation as a result of genetic mutations. This transformed cell is the cell-of-origin for the tumor. In contrast, an established clinical tumor is sustained by subpopulations of self-renewing cancer cells operationally called cancer stem cells (CSC) that can generate, intraclonally, both tumorigenic and nontumorigenic cells. Identifying and characterizing tumor cell-of-origin and CSCs should help elucidate tumor cell heterogeneity, which, in turn, should help understand tumor cell responses to clinical treatments, drug resistance, tumor relapse, and metastatic spread. Both tumor transplantation and lineage-tracing assays have been helpful in characterizing these cancer cell populations, although each system has its strengths and caveats. In this article, we briefly review and summarize advantages and limitations of both assays in support of a combinatorial approach to accurately define the roles of both cancer-initiating and cancer-propagating cells. As an aside, we also wish to clarify the definitions of cancer cell-of-origin and CSCs, which are often interchangeably used by mistake.

  11. Consequences of the common origin of the knee and ankle in Cosmic Ray Physics

    CERN Document Server

    Codino, Antonio


    The differential energy spectrum of the cosmic radiation from solar modulation energies up to 5x10**19 eV is correctly predicted by a recent theory of the knee and ankle which uses only one normalization point. This remarkable quantitative result, spanning over many decades in energy and intensity, along with the existence of the second knee at 6x10**17 eV, is obtained assuming constant spectral indices of individual ions at the cosmic-ray sources and no other critical hypotheses. In this study the chemical composition of the cosmic radiation is evaluated as a direct consequence of the theory. The computed mean logarithmic mass exhibits a rising trend from 1.8 to 3.0 in the range 10**15-10**17 eV, a maximum value of 3.2 at 3x10**17 eV, and a characteristic lightening above 3x10**17 eV up to 4x10**18 eV. All of these distinctive features are in accord with the data of many experiments. Two additional consequences intrinsic to the theory are qualitatively discussed: (1) some limitative bounds on the mechanism a...

  12. The potential consequences for cancer care and cancer research of Brexit (United States)

    Selby, Peter; Lawler, Mark; Baird, Richard; Banks, Ian; Johnston, Patrick; Nurse, Paul


    Following the UK “Brexit” vote in June 2016, there are many uncertainties and risks for cancer research and cancer care in the UK. These are summarised and the importance of sustained engagement and influence from the cancer community on UK governments is emphasised. PMID:28275394

  13. The potential consequences for cancer care and cancer research of Brexit. (United States)

    Selby, Peter; Lawler, Mark; Baird, Richard; Banks, Ian; Johnston, Patrick; Nurse, Paul


    Following the UK "Brexit" vote in June 2016, there are many uncertainties and risks for cancer research and cancer care in the UK. These are summarised and the importance of sustained engagement and influence from the cancer community on UK governments is emphasised.

  14. Triterpenoids of Marine Origin as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Yong-Xin Li


    Full Text Available Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry as potential anti-cancer drug leads.

  15. The origin of scientific neurology and its consequences for modern and future neuroscience. (United States)

    Steinberg, David A


    John Hughlings Jackson (1835-1911) created a science of brain function that, in scope and profundity, is among the great scientific discoveries of the 19th century. It is interesting that the magnitude of his achievement is not completely recognized even among his ardent admirers. Although thousands of practitioners around the world use the clinical applications of his science every day, the principles from which bedside neurology is derived have broader consequences-for modern and future science-that remain unrecognized and unexploited. This paper summarizes the scientific formalism that created modern neurology, demonstrates how its direct implications affect a current area of neuroscientific research, and indicates how Hughlings Jackson's ideas form a path toward a novel solution to an important open problem of the brain and mind.

  16. On the origin and evolutionary consequences of gene body DNA methylation. (United States)

    Bewick, Adam J; Ji, Lexiang; Niederhuth, Chad E; Willing, Eva-Maria; Hofmeister, Brigitte T; Shi, Xiuling; Wang, Li; Lu, Zefu; Rohr, Nicholas A; Hartwig, Benjamin; Kiefer, Christiane; Deal, Roger B; Schmutz, Jeremy; Grimwood, Jane; Stroud, Hume; Jacobsen, Steven E; Schneeberger, Korbinian; Zhang, Xiaoyu; Schmitz, Robert J


    In plants, CG DNA methylation is prevalent in the transcribed regions of many constitutively expressed genes (gene body methylation; gbM), but the origin and function of gbM remain unknown. Here we report the discovery that Eutrema salsugineum has lost gbM from its genome, to our knowledge the first instance for an angiosperm. Of all known DNA methyltransferases, only CHROMOMETHYLASE 3 (CMT3) is missing from E. salsugineum Identification of an additional angiosperm, Conringia planisiliqua, which independently lost CMT3 and gbM, supports that CMT3 is required for the establishment of gbM. Detailed analyses of gene expression, the histone variant H2A.Z, and various histone modifications in E. salsugineum and in Arabidopsis thaliana epigenetic recombinant inbred lines found no evidence in support of any role for gbM in regulating transcription or affecting the composition and modification of chromatin over evolutionary timescales.

  17. Pecado Original: uma herança agostiniana?: o tema da falta das origens e suas consequências


    Silva, Dayvid da


    O presente estudo tem por objetivo trabalhar o tema da falta das origens e suas consequências para a natureza humana, que, no século 5, será chamado por Santo Agostinho de Pecado Original , fazendo referência direta ao pecado de Adão. Porém, antes de se falar do pecado de Adão, como se encontra nas Escrituras judaico-cristãs, visando responder à questão que dá título à dissertação Pecado Original: uma herança agostiniana? , achou-se por bem ampliar, mesmo que de forma moderada, o campo de...

  18. Addressing the financial consequences of cancer: qualitative evaluation of a welfare rights advice service.

    Directory of Open Access Journals (Sweden)

    Suzanne Moffatt

    Full Text Available BACKGROUND: The onset, treatment and trajectory of cancer is associated with financial stress among patients across a range of health and welfare systems and has been identified as a significant unmet need. Welfare rights advice can be delivered effectively in healthcare settings, has the potential to alleviate financial stress, but has not yet been evaluated. We present an evaluation of a welfare rights advice intervention designed to address the financial consequences of cancer. METHODS: Descriptive study of welfare outcomes among 533 male and 641 female cancer patients and carers aged 4-95 (mean 62 years, who accessed the welfare rights advice service in North East England between April 2009 and March 2010; and qualitative interview study of a maximum variation sample of 35 patients and 9 carers. RESULTS: Over two thirds of cancer patients and carers came from areas of high socio-economic deprivation. Welfare benefit claims were successful for 96% of claims made and resulted in a median increase in weekly income of £70.30 ($109.74, €84.44. Thirty-four different types of benefits or grants were awarded. Additional resources were perceived to lessen the impact of lost earnings, help offset costs associated with cancer, reduce stress and anxiety and increase ability to maintain independence and capacity to engage in daily activities, all of which were perceived to impact positively on well-being and quality of life. Key barriers to accessing benefit entitlements were knowledge, system complexity, eligibility concerns and assumptions that health professionals would alert patients to entitlements. CONCLUSIONS: The intervention proved feasible, effectively increased income for cancer patients and was highly valued. Addressing the financial sequelae of cancer can have positive social and psychological consequences that could significantly enhance effective clinical management and suitable services should be routinely available. Further research

  19. Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin

    DEFF Research Database (Denmark)

    Vikeså, Jonas; Møller, Anne Kirstine H; Kaczkowski, Bogumil;


    BACKGROUND: Cancers of unknown primary (CUPs) constitute ~5% of all cancers. The tumors have an aggressive biological and clinical behavior. The aim of the present study has been to uncover whether CUPs exhibit distinct molecular features compared to metastases of known origin. METHODS: Employing...

  20. Ovarian cancer: the Fallopian tube as the site of origin and opportunities for prevention

    Directory of Open Access Journals (Sweden)

    Sophia HL George, PhD


    Full Text Available High-grade serous carcinoma is the most common and aggressive histotype of epithelial ovarian cancer, and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC. Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option risk-reducing surgery, which involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy. Growing evidence now supports the fallopian tube epithelia as an etiological site for the development of HGSC and consequently, salpingectomy alone is emerging as a prophylactic option. This review discusses the site of origin of epithelial ovarian cancer, the rationale for risk-reducing salpingectomy in the high-risk population and opportunities for salpingectomy in the low-risk population.

  1. What do we know 40 years after Nixon declared the 'war on cancer'? On the origin, prevention and treatment of cancer. (United States)

    Erren, Thomas C; Groß, J Valérie; Koch, Melissa S; Erren, Michael; Meyer-Rochow, V Benno


    Evolutionary principles suggested by Darwin and Wallace some 150 years ago can provide insights into the origins of cancer. Moreover, they can form a basis for answering the question implicitly posed when Nixon declared the war on cancer in 1971: Can we actually 'cure' cancer? As explained lucidly by Greaves in 2001, necessary keys to evolution and thus for the origin of species, including ours, are changes of genes or mutations; but changes of genes are also necessary links in the causal chains which lead to cancer. In effect, cancer is therefore, according to Greaves, an 'evolutionary legacy'. Intriguingly, the realization that cancer is a consequence of changes in genes which are conditiones sine qua non for evolution suggests a mutation paradox on an evolutionary scale: in individuals, mutations may have devastating adverse health effects, including cancer. Populations, however, as a whole can be expected to benefit ultimately from changes of genes to better adapt to environmental challenges. On the basis of premises from evolution theory, it remains for us to interweave growing insights into evolutionary principles with realistic objectives for the primary prevention of and, where the latter fails, coexistence with cancer so that what we do for patients can become more of an art rather than a war.

  2. The origin and evolution of weed beets: consequences for the breeding and release of herbicide-resistant transgenic sugar beets. (United States)

    Boudry, P; Mörchen, M; Saumitou-Laprade, P; Vernet, P; Van Dijk, H


    Populations of weed beets have expanded into European sugar beet production areas since the 1970s, thereby forming a serious new weed problem for this crop. We sampled seeds in different French populations and studied mitochondrial DNA, chloroplast DNA and life-cycle variability. Given the maternal inheritance of the mitochondrial and chloroplastic genomes and the nuclear determinism of the annual habit, we were able to determine the maternal origin and evolution of these weed beet populations. Our study shows that they carry the dominant allele "B" for annual habit at high frequency. The main cytoplasmic DNA type found in northern weed beet populations is the cytoplasmic male-sterile type characteristic of sugar beets. We were able to determine that these populations arise from seeds originating from the accidental pollinations of cultivated beets by adventitious beets in the seed production area, which have been transported to the regions where sugar beets are cultivated. These seeds are supposedly the origin of the weed forms and a frequently disturbed cultivated environment has selected for annual habit and early flowering genotypes. We discuss the consequences of the weed beet populations for the breeding, seed production and release of herbicide-resistant transgenic sugar beets.

  3. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity | Office of Cancer Genomics (United States)

    Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect clones that are present at a ≥10% frequency in 1,165 exome sequences from tumors in The Cancer Genome Atlas. 86% of tumors across 12 cancer types had at least two clones. ITH in the morphology of nuclei was associated with genetic ITH (Spearman's correlation coefficient, ρ = 0.24-0.41; P < 0.001).

  4. Paying Down the Care Deficit: The Health Consequences for Grandmothers Caring for Grandchildren in a Mexican Migrant Community of Origin

    Directory of Open Access Journals (Sweden)

    Mary Alice Scott


    Full Text Available While significant research addresses global chains of care work from the perspective of female migrant workers engaged in low-paid, unstable domestic labor in “receiving” communities, little research has focused on those who substitute for migrant workers to provide care in communities of origin. This article addresses that gap by focusing on the health consequences of care work for grandmothers in southern Veracruz, Mexico who assume the primary responsibility for caring for their grandchildren when the parents migrate out of the community. Based in the literature on care work and transnational families, this ethnographically-based article argues that grandmothers suffer consequences for their own health in three ways. They must deduct from their own health care resources – including time and money – to provide for their grandchildren. They must concede to the exploitation of already ill bodies to engage in the physical care of children and the household. Finally, they must transfer energy for self-care to caring for others thereby exacerbating their own existing health issues in order to meet the physical and emotional needs of their grandchildren. The article calls for further research in this area that aims to develop solutions to the problem of “care substitution” in transnational families.

  5. A case of radiation gastritis required surgical treatment in consequence of radiotherapy for recurrent ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hagino, Daisuke; Arai, Yuko; Komatsu, Atsushi; Inoue, Kumiko; Takechi, Kimihiro [Ibaraki Prefectural Central Hospital, Tomobe (Japan)


    We report a case of radiation gastritis in consequence of radiotherapy for recurrent ovarian cancer. A 61-year-old woman received irradiation of a metastatic lesion of the second lumbar vertebra. Six months later she complained of fatigue and presented with severe anemia, and her diagnosis was hemorrhagic radiation gastritis. She was treated endoscopically, but that failed to control the bleeding, making it necessary to resect surgically. The incidence of radiation gastritis is very low because the stomach is rarely within the treated field, but it is of importance to be aware that the stomach is by no means more radioresistant than other organs. (author)

  6. Increased risks of third primary cancers of non-breast origin among women with bilateral breast cancer

    NARCIS (Netherlands)

    Kwast, A.B.G.; Liu, L.; Roukema, J.A.; Voogd, A.C.; Jobsen, J.J.; Coebergh, J.W.W.; Soerjomataram, I.; Siesling, S.


    Background: This study examined the risk of third cancer of non-breast origin (TNBC) among women with bilateral breast cancer (BBC; either synchronous or metachronous), focussing on the relation with breast cancer treatment. Methods: Risk was assessed, among 8752 Dutch women diagnosed with BBC betw

  7. Uranium exploration, non-governmental organizations, and local communities. The origin, anatomy, and consequences of a new challenge in Finland

    Directory of Open Access Journals (Sweden)

    Eerola, Toni


    Full Text Available The advent of global warming has returned nuclear power to the agenda. Many countries, including Finland, have decided to construct more nuclear power plants. They will need uranium, and its price is rising in the international market. A new uranium exploration boom is going on. Finland is politically and economically stable, with good infrastructure and basic geodata, attracting foreign companies to explore the promising uranium showings of the country. However, this has triggered an extensive anti-uranium campaign in northern, eastern, and southern, but not in central Finland, which is related to anti-nuclear movement, green and leftist parties, and environmental non-governmental organizations (NGOs. The resistance, created mainly by lack of public awareness of geology and mining, surprised mining companies, the geological community, and the Ministry of Trade and Industry, who found themselves in a completely new situation. Here we will examine the origin, anatomy, and consequences of this challenge and how to deal with it. The picture presented herewithin is based on author’s active participation in uranium exploration in Finland, discussions with other geologists and activists, following the issue in newspapers, web-pages, reviews, and participating in NGO meetings.

  8. Origin of Cancer: An Information, Energy, and Matter Disease (United States)

    Hanselmann, Rainer G.; Welter, Cornelius


    Cells are open, highly ordered systems that are far away from equilibrium. For this reason, the first function of any cell is to prevent the permanent threat of disintegration that is described by thermodynamic laws and to preserve highly ordered cell characteristics such as structures, the cell cycle, or metabolism. In this context, three basic categories play a central role: energy, information, and matter. Each of these three categories is equally important to the cell and they are reciprocally dependent. We therefore suggest that energy loss (e.g., through impaired mitochondria) or disturbance of information (e.g., through mutations or aneuploidy) or changes in the composition or distribution of matter (e.g., through micro-environmental changes or toxic agents) can irreversibly disturb molecular mechanisms, leading to increased local entropy of cellular functions and structures. In terms of physics, changes to these normally highly ordered reaction probabilities lead to a state that is irreversibly biologically imbalanced, but that is thermodynamically more stable. This primary change—independent of the initiator—now provokes and drives a complex interplay between the availability of energy, the composition, and distribution of matter and increasing information disturbance that is dependent upon reactions that try to overcome or stabilize this intracellular, irreversible disorder described by entropy. Because a return to the original ordered state is not possible for thermodynamic reasons, the cells either die or else they persist in a metastable state. In the latter case, they enter into a self-driven adaptive and evolutionary process that generates a progression of disordered cells and that results in a broad spectrum of progeny with different characteristics. Possibly, 1 day, one of these cells will show an autonomous and aggressive behavior—it will be a cancer cell. PMID:27909692

  9. Origin of cancer: an information, energy and matter disease

    Directory of Open Access Journals (Sweden)

    Rainer Günter Hanselmann


    Full Text Available Cells are open, highly ordered systems far away from equilibrium. For that reason, the first function of any cell is to prevent the permanent threat of disintegration described by thermo-dynamic laws and to preserve highly ordered cell characteristics like structures, cell cycle and metabolism. In that context, three basic categories play a central role - energy, matter and information. Every single of these three categories is equally important to the cell and depends on the others reciprocally. For that reason, we suggest that either energy loss (e.g. by disturbed mitochondria or disturbance of information (e.g. mutations, aneuploidy or changes in matter composition or exposition (e.g. micro-environmental changes, toxic agents can irreversibly disturb molecular mechanisms leading to increased local entropy of cellular functions and structures. In terms of physics, changes to these normally highly ordered reaction probabilities lead to a biologically irreversibly, imbalanced but thermodynamically more stable state. This primary change independent of the initiator now provokes and drives a complex interplay between energy availability, matter exposition and increasing information disturbance depending on reactions that try to overcome or stabilize this intra-cellular, irreversible disorder described by entropy. Because the return to the original ordered state is not possible due to the thermodynamic reasons cells die, or persist in an meta-stable state and enter into a self-driven adaptive and evolutionary process that generates progressive, disordered cells resulting in a broad spectrum of progeny with different characteristics, and maybe one day one of these cells will show an autonomous and aggressive behavior – a cancer cell.

  10. The amphiphilic nature of saponins and their effects on artificial and biological membranes and potential consequences for red blood and cancer cells. (United States)

    Lorent, Joseph H; Quetin-Leclercq, Joëlle; Mingeot-Leclercq, Marie-Paule


    Saponins, amphiphiles of natural origin with numerous biological activities, are widely used in the cosmetic and pharmaceutical industry. Some saponins exhibit relatively selective cytotoxic effects on cancer cells but the tendency of saponins to induce hemolysis limits their anticancer potential. This review focused on the effects of saponin activity on membranes and consequent implications for red blood and cancer cells. This activity seems to be strongly related to the amphiphilic character of saponins that gives them the ability to self-aggregate and interact with membrane components such as cholesterol and phospholipids. Membrane interactions of saponins with artificial membrane models, red blood and cancer cells are reviewed with respect to their molecular structures. The review considered the mechanisms of these membrane interactions and their consequences including the modulation of membrane dynamics, interaction with membrane rafts, and membrane lysis. We summarized current knowledge concerning the mechanisms involved in the interactions of saponins with membrane lipids and examined the structure activity relationship of saponins regarding hemolysis and cancer cell death. A critical analysis of these findings speculates on their potential to further develop new anticancer compounds.

  11. Constitutive phosphorylation of aurora-a on ser51 induces its stabilization and consequent overexpression in cancer.

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    Shojiro Kitajima

    Full Text Available BACKGROUND: The serine/threonine kinase Aurora-A (Aur-A is a proto-oncoprotein overexpressed in a wide range of human cancers. Overexpression of Aur-A is thought to be caused by gene amplification or mRNA overexpression. However, recent evidence revealed that the discrepancies between amplification of Aur-A and overexpression rates of Aur-A mRNA were observed in breast cancer, gastric cancer, hepatocellular carcinoma, and ovarian cancer. We found that aggressive head and neck cancers exhibited overexpression and stabilization of Aur-A protein without gene amplification or mRNA overexpression. Here we tested the hypothesis that aberration of the protein destruction system induces accumulation and consequently overexpression of Aur-A in cancer. PRINCIPAL FINDINGS: Aur-A protein was ubiquitinylated by APC(Cdh1 and consequently degraded when cells exited mitosis, and phosphorylation of Aur-A on Ser51 was observed during mitosis. Phosphorylation of Aur-A on Ser51 inhibited its APC(Cdh1-mediated ubiquitylation and consequent degradation. Interestingly, constitutive phosphorylation on Ser51 was observed in head and neck cancer cells with protein overexpression and stabilization. Indeed, phosphorylation on Ser51 was observed in head and neck cancer tissues with Aur-A protein overexpression. Moreover, an Aur-A Ser51 phospho-mimetic mutant displayed stabilization of protein during cell cycle progression and enhanced ability to cell transformation. CONCLUSIONS/SIGNIFICANCE: Broadly, this study identifies a new mode of Aur-A overexpression in cancer through phosphorylation-dependent inhibition of its proteolysis in addition to gene amplification and mRNA overexpression. We suggest that the inhibition of Aur-A phosphorylation can represent a novel way to decrease Aur-A levels in cancer therapy.

  12. Epidemiology of cancers of infectious origin and prevention strategies


    Flora, S; LA MAESTRA, S.


    Summary Infectious and parasitic diseases represent the third cause of cancer worldwide. A number of infectious and parasitic agents have been suspected or recognized to be associated with human cancers, including DNA viruses, such as papillomaviruses (several HPV types), herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), and hepadnaviruses (HBV); RNA viruses, such as flaviviruses (HCV), defective viruses (HDV), and retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2,HERV-K, and X...

  13. The molecular and cellular origin of human prostate cancer. (United States)

    Packer, John R; Maitland, Norman J


    Prostate cancer is the most commonly diagnosed male malignancy. Despite compelling epidemiology, there are no definitive aetiological clues linking development to frequency. Pre-malignancies such as proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) yield insights into the initiating events of prostate cancer, as they supply a background "field" for further transformation. An inflammatory aetiology, linked to recurrent prostatitis, and heterologous signalling from reactive stroma and infiltrating immune cells may result in cytokine addiction of cancer cells, including a tumour-initiating population also known as cancer stem cells (CSCs). In prostate tumours, the background mutational rate is rarely exceeded, but genetic change via profound sporadic chromosomal rearrangements results in copy number variations and aberrant gene expression. In cancer, dysfunctional differentiation is imposed upon the normal epithelial lineage, with disruption/disappearance of the basement membrane, loss of the contiguous basal cell layer and expansion of the luminal population. An initiating role for androgen receptor (AR) is attractive, due to the luminal phenotype of the tumours, but alternatively a pool of CSCs, which express little or no AR, has also been demonstrated. Indolent and aggressive tumours may also arise from different stem or progenitor cells. Castrate resistant prostate cancer (CRPC) remains the inevitable final stage of disease following treatment. Time-limited effectiveness of second-generation anti-androgens, and the appearance of an AR-neuroendocrine phenotype imply that metastatic disease is reliant upon the plasticity of the CSC population, and indeed CSC gene expression profiles are most closely related to those identified in CRPCs.

  14. Cellular origin and procoagulant activity of tissue factor-exposing microparticles in cancer patients

    NARCIS (Netherlands)

    Kleinjan, A.; Berckmans, R.J.; Böing, A.N.; Sturk, A.; Büller, H.R.; Kamphuisen, P.W.; Nieuwland, R.


    Background: In patients with cancer, tissue factor-exposing microparticles (TF-exposing MP) have been associated with disease progression and thrombosis. The cellular origin and coagulant activity of TF-exposing MP, however, remain disputed. Therefore, we investigated the cellular origin of the TF-e

  15. Nexrutine Inhibits Cancer Cell Growth as a Consequence of Mitochondrial Damage and Mitophagy

    Directory of Open Access Journals (Sweden)

    Xiang Wu


    Full Text Available Background/Aims: Nexrutine is an herbal extract of Phellodendron amurense and has been used as nutrient supplement in China as well as America. Potential protection effect of Nexrutine has been reported. Methods: To investigate the mechanism of Nexrutine, we used the HeLa, U2OS and HCT116 as a model. Based on the acidification of cell culture media, we examined the lactate, mitochondria damage as well as mitophagy status by corresponding assay. Results: Our data suggest that Nexrutine alters the cellular glucose metabolism to promote lactate production. This effect is caused by mitochondrial damage, not an alteration to lactate dehydrogenase activity. As a result of the mitochondrial damage, cell proliferation was inhibited and was associated with an elevation in p21/p27 proteins, which are both important cell cycle inhibitors. As another consequence of the mitochondrial damage, mitophagy was highly activated in Nexrutine-treated cells in a dose-dependent manner. When the autophagy pathway was blocked by siRNAs against BECN1 or ATG7, the growth inhibition caused by Nexrutine was reversed. Conclusion: Our study revealed that autophagy plays an important role in the inhibition of cancer cell proliferation by Nexrutine.

  16. Cancer caregiving tasks and consequences and their associations with caregiver status and the caregiver's relationship to the patient

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Petersen, Morten Aagaard


    BACKGROUND: Seriously ill patients often depend on their informal caregivers to help and support them through the disease course. This study investigated informal cancer caregivers' experiences of caregiving tasks and consequences and how caregiver status (primary vs. non-primary caregiver......-primary caregivers experienced most problems with getting time off from work. Spouses/partners and/or parents experienced the highest workload, most lack of time for social relations, most financial difficulties, and had the greatest need for seeing a psychologist. They furthermore experienced the highest degree......) and the caregiver's relationship to the patient (spouse/partner, etc.) are related to these experiences. METHODS: In a cross-sectional questionnaire study, randomly selected cancer patients with a range of diagnoses and disease stages were invited to pass on the 'Cancer Caregiving Tasks, Consequences and Needs...

  17. Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives

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    Tomokazu Ohishi


    Full Text Available Bladder cancer (BC, the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC and non-muscle-invasive bladder cancer (NMIBC. MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs, which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory.

  18. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin

    DEFF Research Database (Denmark)

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M


    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform...... on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset...... of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides...

  19. Tracking Origins of Prostate Cancer: An Innovative in Vivo Modeling (United States)


    challenges in management of patients with prostate cancer. To make rapid advances in understanding of disease mechanism that can be translated to clinical...males with Tamoxifen injection (10mg/ml in corn oil, 100µl/adult/day, for five consecutive days). We checked prostate for XFP expression in all of...check whether those signals are background noise, we harvested prostate from non-induced control animal (littermate with same genotype) and did

  20. Posttraumatic stress symptoms in breast cancer: Prevalence, predictors, consequences, and treatment

    DEFF Research Database (Denmark)

    O Connor, Maja; Zachariae, Robert


    This chapter focuses on posttraumatic stress reactions after being diagnosed with and treated for breast cancer. Posttraumatic stress symptoms (PTSS) are evident in a significant proportion of women after having experienced diagnosis and treatment of breast cancer. Several risk factors...... for developing long-term PTSS after breast cancer have been identified. Younger age, low education and income, pre-cancer previous psychiatric history, cancer disease severity, poor physical functioning, and acute symptoms of PTSS are predictors of long-term post-cancer PTSS, with poor physical functioning...

  1. Cancer of unknown primary origin: a case report

    Directory of Open Access Journals (Sweden)

    Elisa De Carlo


    Full Text Available Carcinoma of unknown primary origin (CUP accounts for 2-10% of all malignancies. The apparent absence of the primary tumour, the development of early, uncommon systemic metastases and the resistance to therapy and poor prognosis are hallmarks of this heterogeneous clinical entity and are a challenge for physicians. The diagnostic workup of patients with CUP includes a large amount of histopathological examination, as well as the use of imaging techniques that often fail to identify the primary tumour. Therefore, the optimal workup and treatment for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for "lost" CUP origin and guide the further treatment approach. We report the case of a 66-year-old man, with mediastinal lymph nodes metastasis of carcinoma and neurological syndrome with diplopia and balance disorders, in which many exams have been performed without finding the primary tumour.

  2. Assessment of fatigue using the Identity- Consequence Fatigue Scale in patients with lung cancer

    Directory of Open Access Journals (Sweden)

    Ingrid Correia Nogueira

    Full Text Available ABSTRACT Objective: To evaluate the properties of the Identity-Consequence Fatigue Scale (ICFS in patients with lung cancer (LC, assessing the intensity of fatigue and associated factors. Methods: This was a cross-sectional study involving LC patients, treated at a teaching hospital in Brazil, who completed the ICFS. Patients with chronic heart disease (CHD and healthy controls, matched for age and gender, also completed the scale. Initially, a Brazilian Portuguese-language version of the ICFS was administered to 50 LC patients by two independent interviewers; to test for reproducibility, it was readministered to those same patients. At baseline, the LC patients were submitted to spirometry and the six-minute walk test, as well as completing the Epworth Sleepiness Scale (ESS, Hospital Anxiety and Depression Scale (HADS, Medical Outcomes Study 36-item Short-Form Health Survey (SF-36, and Fatigue Severity Scale (FSS. Inflammatory status was assessed by blood C-reactive protein (CRP levels. To validate the ICFS, we assessed the correlations of its scores with those variables. Results: The sample comprised 50 patients in each group (LC, CHD, and control. In the LC group, the intraclass correlation coefficients for intra-rater and inter-rater reliability regarding ICFS summary variables ranged from 0.94 to 0.76 and from 0.94 to 0.79, respectively. The ICFS presented excellent internal consistency, and Bland-Altman plots showed good test-retest reliability. The ICFS correlated significantly with FSS, HADS, and SF-36 scores, as well as with CRP levels. Mean ICFS scores in the LC group differed significantly from those in the CHD and control groups. Conclusions: The ICFS is a valid, reliable instrument for evaluating LC patients, in whom depression, quality of life, and CRP levels seem to be significantly associated with fatigue.

  3. Identification of new differentially methylated genes that have potential functional consequences in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jin W Kim

    Full Text Available Many differentially methylated genes have been identified in prostate cancer (PCa, primarily using candidate gene-based assays. Recently, several global DNA methylation profiles have been reported in PCa, however, each of these has weaknesses in terms of ability to observe global DNA methylation alterations in PCa. We hypothesize that there remains unidentified aberrant DNA methylation in PCa, which may be identified using higher resolution assay methods. We used the newly developed Illumina HumanMethylation450 BeadChip in PCa (n = 19 and adjacent normal tissues (n = 4 and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in PCa development and progression. We also confirmed our methylation results in an independent data set. Two aberrant DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG sites showed significant differences in DNA methylation (FDR adjusted P<0.05, defined as a mean methylation difference of at least 20% between PCa and normal samples. Furthermore, a total of 122 genes had more than one differentially methylated CpG site in their promoter region and a gene expression pattern that was inverse to the direction of change in DNA methylation (e.g. decreased expression with increased methylation, and vice-versa. Aberrant DNA methylation of two genes, AOX1 and SPON2, were confirmed via bisulfate sequencing, with most of the respective CpG sites showing significant differences between tumor samples and normal tissues. The AOX1 promoter region showed hypermethylation in 92.6% of 54 tested PCa samples in contrast to only three out of 53 tested normal tissues. This study used a new BeadChip combined with gene expression data in PCa to identify novel differentially methylated CpG sites located within genes. The newly identified differentially methylated genes may be used as biomarkers for PCa diagnosis.

  4. Developmental Pathways Direct Pancreatic Cancer Initiation from Its Cellular Origin

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    Maximilian Reichert


    Full Text Available Pancreatic ductal adenocarcinoma (PDA is characterized by an extremely poor prognosis, since it is usually diagnosed at advanced stages. In order to employ tools for early detection, a better understanding of the early stages of PDA development from its main precursors, pancreatic intraepithelial neoplasia (PanIN, and intraductal papillary mucinous neoplasm (IPMN is needed. Recent studies on murine PDA models have identified a different exocrine origin for PanINs and IPMNs. In both processes, developmental pathways direct the initiation of PDA precursors from their cellular ancestors. In this review, the current understanding of early PDA development is summarized.

  5. Origins. (United States)

    Online-Offline, 1999


    Provides an annotated list of resources dealing with the theme of origins of life, the universe, and traditions. Includes Web sites, videos, books, audio materials, and magazines with appropriate grade levels and/or subject disciplines indicated; professional resources; and learning activities. (LRW)

  6. Cancer caregiving tasks and consequences and their associations with caregiver status and the caregiver's relationship to the patient

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Petersen, Morten Aagaard;


    BACKGROUND: Seriously ill patients often depend on their informal caregivers to help and support them through the disease course. This study investigated informal cancer caregivers' experiences of caregiving tasks and consequences and how caregiver status (primary vs. non-primary caregiver...... consequences, most commonly stress (59%). Some caregivers experienced personal growth, but relatively large proportions did not. Caregiver status and the caregiver's relationship to the patient were associated with some caregiving aspects. Primary caregivers experienced the highest caregiving workload, and non-primary...... is burdensome. The primary and the closest caregivers seemed to take on most caregiving tasks, but, contrary to expectations, regarding the majority of caregiving consequences non-primary and more distant caregivers were affected to the same degree as the primary and closest caregivers. Initiatives...

  7. The role of stem cells in airway repair: implications for the origins of lung cancer

    Institute of Scientific and Technical Information of China (English)

    Michael S.Mulvihill; Johannes R.Kratz; Patrick Pham; David M.Jablons; Biao He


    Lung cancer is the leading cause of cancer-related deaths worldwide.Recently,advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis.Much of this research has focused on the use of the airway repair model to study response to injury.In this review,we discuss the primary evidence of the role that cancer stem cells play in lung cancer development.The implications of a stem cell origin of lung cancer are reviewed,and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.

  8. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. (United States)

    Oser, Matthew G; Niederst, Matthew J; Sequist, Lecia V; Engelman, Jeffrey A


    Lung cancer is the most common cause of cancer deaths worldwide. The two broad histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Although NSCLC and SCLC are commonly thought to be different diseases owing to their distinct biology and genomic abnormalities, the idea that these malignant disorders might share common cells of origin has been gaining support. This idea has been supported by the unexpected findings that a subset of NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase inhibitors develops. Additionally, other case reports have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of their distinct lineages. Here, we summarise the published clinical observations and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies pointing to common potential cells of origin, and speculate how the distinct paths of differentiation are determined by the genomics of each disease.

  9. Optimum 3D Matrix Stiffness for Maintenance of Cancer Stem Cells Is Dependent on Tissue Origin of Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Esmaiel Jabbari

    Full Text Available The growth and expression of cancer stem cells (CSCs depend on many factors in the tumor microenvironment. The objective of this work was to investigate the effect of cancer cells' tissue origin on the optimum matrix stiffness for CSC growth and marker expression in a model polyethylene glycol diacrylate (PEGDA hydrogel without the interference of other factors in the microenvironment.Human MCF7 and MDA-MB-231 breast carcinoma, HCT116 colorectal and AGS gastric carcinoma, and U2OS osteosarcoma cells were used. The cells were encapsulated in PEGDA gels with compressive moduli in the 2-70 kPa range and optimized cell seeding density of 0.6x106 cells/mL. Micropatterning was used to optimize the growth of encapsulated cells with respect to average tumorsphere size. The CSC sub-population of the encapsulated cells was characterized by cell number, tumorsphere size and number density, and mRNA expression of CSC markers.The optimum matrix stiffness for growth and marker expression of CSC sub-population of cancer cells was 5 kPa for breast MCF7 and MDA231, 25 kPa for colorectal HCT116 and gastric AGS, and 50 kPa for bone U2OS cells. Conjugation of a CD44 binding peptide to the gel stopped tumorsphere formation by cancer cells from different tissue origin. The expression of YAP/TAZ transcription factors by the encapsulated cancer cells was highest at the optimum stiffness indicating a link between the Hippo transducers and CSC growth. The optimum average tumorsphere size for CSC growth and marker expression was 50 μm.The marker expression results suggest that the CSC sub-population of cancer cells resides within a niche with optimum stiffness which depends on the cancer cells' tissue origin.

  10. Pharmacological consequences of long-term morphine treatment in patients with cancer and chronic non-malignant pain

    DEFF Research Database (Denmark)

    Andersen, Gertrud; Sjøgren, Per; Hansen, Steen Honoré;


    In patients with pain of malignant origin morphine may be administered in high and often increasing doses during extended periods of time. In patients with chronic pain of non-malignant origin morphine may be an important remedy, and in these cases the goal is to keep the morphine dose stable. Th....... The pharmacokinetic as well as the pharmacodynamic consequences of long-term morphine treatment with special reference to the two most important metabolites of morphine morphine-6-glucuronide (M-6-G) and morphine-3-glucuronide (M-3-G) remain to be settled....

  11. Origin of animal multicellularity: precursors, causes, consequences-the choanoflagellate/sponge transition, neurogenesis and the Cambrian explosion. (United States)

    Cavalier-Smith, Thomas


    Evolving multicellularity is easy, especially in phototrophs and osmotrophs whose multicells feed like unicells. Evolving animals was much harder and unique; probably only one pathway via benthic 'zoophytes' with pelagic ciliated larvae allowed trophic continuity from phagocytic protozoa to gut-endowed animals. Choanoflagellate protozoa produced sponges. Converting sponge flask cells mediating larval settling to synaptically controlled nematocysts arguably made Cnidaria. I replace Haeckel's gastraea theory by a sponge/coelenterate/bilaterian pathway: Placozoa, hydrozoan diploblasty and ctenophores were secondary; stem anthozoan developmental mutations arguably independently generated coelomate bilateria and ctenophores. I emphasize animal origin's conceptual aspects (selective, developmental) related to feeding modes, cell structure, phylogeny of related protozoa, sequence evidence, ecology and palaeontology. Epithelia and connective tissue could evolve only by compensating for dramatically lower feeding efficiency that differentiation into non-choanocytes entails. Consequentially, larger bodies enabled filtering more water for bacterial food and harbouring photosynthetic bacteria, together adding more food than cell differentiation sacrificed. A hypothetical presponge of sessile triploblastic sheets (connective tissue sandwiched between two choanocyte epithelia) evolved oogamy through selection for larger dispersive ciliated larvae to accelerate benthic trophic competence and overgrowing protozoan competitors. Extinct Vendozoa might be elaborations of this organismal grade with choanocyte-bearing epithelia, before poriferan water channels and cnidarian gut/nematocysts/synapses evolved.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.

  12. On the origin of the Fundamental Plane and Faber-Jackson relations: consequences for the star formation problem

    CERN Document Server

    D'Onofrio, Mauro; Chiosi, Cesare; Chiosi, Emanuela; Marziani, Paola


    We show that the origin of the Fundamental Plane (FP) relation for early-type galaxies (ETGs) can be traced back to the existence of two distinct virtual planes for each galaxy in the \\muerespace\\ space. The first virtual plane is the Virial Plane (VP) relating the total galaxy mass to the \\muerespace\\ variables, while the other plane (named here BB plane) comes from a relation $L=L'_0 \\sigma^{\\beta}$ with $\\beta=-2$ connecting the luminosity of galaxies with the velocity dispersion through a factor $L'_0$ which varies considerably from galaxy to galaxy. This relation permits to explain the downsizing phenomenon and the Zone of Exclusion (ZOE) visible in the $I_e-R_e$ plane. The intersection of the $L=L'_0 \\sigma^{-2}$ relations in the $L-\\sigma$ plane with the zero-point lines of the VP at each galaxy radius originate the observed $L=L_0 \\sigma^2$ Faber-Jackson relation, where $L_0$ is a constant nearly equal for all ETGs. We show that this relation is the translation of the stellar black body law of Stefan-...

  13. Functional and genetic deconstruction of the cellular origin in liver cancer

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S


    During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

  14. Plate Tectonic Consequences of competing models for the origin and history of the Banda Sea subducted oceanic lithosphere

    CERN Document Server

    Heine, Christian; McKay, Hamish; Müller, R Dietmar


    The Banda Arc, situated west of Irian Jaya and in the easternmost extension of the Sunda subduction zone system, reveals a characteristic bowl-shaped geometry in seismic tomographic images. This indicates that the oceanic lithosphere still remains attached to the surrounding continental margins of northern Australia and the Bird's Head microcontinent. Major controversies exist between authors proposing an allochthonous or autochthonous origin of the Bird's Head block. Either scenario has important implications for plate kinematic models aiming to reconstruct the tectonic evolution of the region and the late Jurassic seaoor spreading geometry of this now subducted Argo-Tanimbar-Seram (ATS) ocean basin. Wider implications affect the tectonic conguration of the Tethyan-Pacic realm, the distribution of plate boundaries as well as the shape and size of continental blocks which have been rifted off the northeastern Gondwana margin during the Late Jurassic and are now accreted to the SE Asia margin. We apply structu...

  15. The Dosimetric Consequences of Intensity Modulated Radiotherapy for Cervix Cancer: The Impact of Organ Motion, Deformation and Tumour Regression (United States)

    Lim, Karen Siah Huey

    Hypothesis: In intensity modulated radiotherapy (IMRT) for cervix cancer, the dose received by the tumour target and surrounding normal tissues is significantly different to that indicated by a single static plan. Rationale: The optimal use of IMRT in cervix cancer requires a greater attention to clinical target volume (CTV) definition and tumour & normal organ motion to assure maximum tumour control with the fewest side effects. Research Aims: 1) Generate consensus CTV contouring guidelines for cervix cancer; 2) Evaluate intra-pelvic tumour and organ dynamics during radiotherapy; 3) Analyze the dose consequences of intra-pelvic organ dynamics on different radiotherapy strategies. Results: Consensus CTV definitions were generated using experts-in-the-field. Substantial changes in tumour volume and organ motion, resulted in significant reductions in accumulated dose to tumour targets and variability in accumulated dose to surrounding normal tissues. Significance: Formalized CTV definitions for cervix cancer is important in ensuring consistent standards of practice. Complex and unpredictable tumour and organ dynamics mandates daily soft-tissue image guidance if IMRT is used. To maximize the benefits of IMRT for cervix cancer, a strategy of adaptation is necessary.

  16. Accuracy and consequences of same-day, invasive lung cancer workup

    DEFF Research Database (Denmark)

    Madsen, Kirsten Riis; Høegholm, Asbjørn; Bodtger, Uffe


    pulmonary disease. Tumour located in right upper lobe was associated with need for resampling. DISCUSSION: Our retrospective study suggests that same-day, invasive workup for lung cancer is safe, accurate, and efficacious in reducing time to therapy, even in patients with small lesions and low tumour burden.......BACKGROUND: Though widely used, little is known about accuracy and efficacy of same-day, invasive workup of suspected lung cancer. OBJECTIVE: To evaluate the accuracy and efficacy of same-day, invasive lung cancer workup (diagnosis and mediastinal staging), and to identify differences between...... patients without (Group A) or with (Group B) need for resampling. METHODS: A retrospective study was performed on all consecutive patients referred for surgical treatment for localised lung cancer after invasive diagnostic and staging workup at our unit. Data were extracted from electronic medical files...

  17. Abnormal connection between lateral and posterior semicircular canal revealed by a new modeling process: origin and physiological consequences. (United States)

    Rousie, Dominique Louise; Deroubaix, Jean Paul; Joly, Olivier; Baudrillard, Jean Claude; Berthoz, Alain


    We developed a modeling procedure using CT scans or MRI data for exploring the bony and lymphatic canals of vestibular patients. We submitted 445 patients with instability and spatial de-orientation to this procedure. Out of the 445 patients, 95 had scoliosis, some of them, because malformations were suspected also had CT-scan modeling and functional tests. We focused on a never described, abnormal connection between the lymphatic lateral and posterior canal (LPCC) with a frequency of 67/445 (15%). In the scoliosis subgroup, the frequency was 52/95 (55%). Three scoliotic patients had CT scans. For each of them, the modeling revealed that LPCC was present on the bony canals. LPCC has pathognomic signs: no rotatory vertigo but frequent instability, transport sickness head tilt on the side of the anomaly, and spatial disorientation in new environment. We evaluated the functional impact of LPCC by testing the vestibulo-ocular reflex (VOR) in horizontal and vertical planes and found reproducible abnormal responses: in the case of left LPCC, during a counterclockwise horizontal rotation or a post clockwise horizontal rotation, added to the expected horizontal nystagmus, we found an unexpected upbeat nystagmus induced by the ampullofugal displacement of the fluid in the posterior canal. As LPCC was found in CT scans and MRI modeling for a same subject, we suggest that it could be a congenital abnormal process of ossification of the canals. The responses to the vestibular tests highlighting constant unexpected nystagmus underline the potential functional consequences of LPCC on vestibular perception and scoliosis.

  18. Adverse psychosocial consequences: Compassion fatigue, burnout and vicarious traumatization: Are nurses who provide palliative and hematological cancer care vulnerable?

    Directory of Open Access Journals (Sweden)

    Brenda M Sabo


    Full Text Available The work environment significantly affects the physical, psychological, emotional and/or spiritual wellbeing of individuals is unquestionable. Adverse effects have been noted among healthcare professionals working with clients experiencing pain and suffering often associated with cancer, palliative or end-of-life care; however, little is known about how or in which manner the nurse-patient-family relationship may affect the psychosocial health and wellbeing of nurses working in these areas. Three concepts have been highlighted as most frequently associated with the adverse consequences of caring work: these are compassion fatigue (secondary traumatic stress, burnout and vicarious traumatization. The following discussion investigates these concepts and their implications on palliative and hematological cancer nursing practice.

  19. Psychosocial consequences in the Danish randomised controlled lung cancer screening trial (DLCST)

    DEFF Research Database (Denmark)

    F. Rasmussen, Jakob; Siersma, V.; H. Pedersen, J.


    on Airway Symptoms, Stigmatisation, Introvert, and Harm of Smoking. Results: 4104 participants were randomised to the DLCST and the COS-LC completion rates for the CT group and the control group were 95.5% and 73.6%, respectively. There was a significant increase in negative psychosocial consequences from...

  20. Consequences of Screening in Breast Cancer (COS-BC): development of a questionnaire

    DEFF Research Database (Denmark)

    Brodersen, John; Thorsen, Hanne


    The aims of the study were to translate and adapt both the negative and positive items of the Psychological Consequences Questionnaire (PCQ) into Danish and to test the translated version for comprehension, suitability, and content coverage by developing new items in a setting of false-positive...

  1. Negative and positive consequences of adolescent cancer 10 years after diagnosis : an interview-based longitudinal study in Sweden

    NARCIS (Netherlands)

    Lehmann, Vicky; Gronqvist, Helena; Engvall, Gunn; Ander, Malin; Tuinman, Marrit A.; Hagedoorn, Mariet; Sanderman, Robbert; Mattsson, Elisabet; von Essen, Louise


    OBJECTIVE: The aim of this study was to provide insight into survivor-reported negative and positive consequences of cancer during adolescence 10 years after diagnosis and compare these with consequences reported 3 and 4 years after diagnosis. METHODS: Three, 4, and 10 years after diagnosis, survivo

  2. The complexities of identifying a cell of origin for human prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Gail P Risbridger; Renea A Taylor


    @@ Prostate cancer(PCa)is the second most common malignancy in men1 and ifloca-lized or confined to the gland at diagnosis,the choice of treatment includes surgery,radiation or watchful waiting.If and when the disease spreads,androgen blockade is effective but inevitably relapse occurs,resulting in incurable castrate-resistant PCa.Understanding the etiology of PCa will underpin the development of better treatment options In particular,the identity of the cell type(s)that are the origin of PCa(or cancer-initiating cells)will enable them to become therapeutic targets that could lead to newer and more sophisticated treatment options.These cells of origin are defined as epithelial cells in the normal prostate,susceptible to malignant transformation and therefore capable of initiating tumourigenesis.However,their identity is unknown.

  3. Origins of DNA Replication and Amplification in the Breast Cancer Genome (United States)


    identified 53,914 origins in the MCF-7 genome, with a median width of 1.5 kb using the methodology as follows: We used BEDTools ( Quinlan et al...are collaborating with David Gilbert (University of Florida – Tallahassee) to determine the replication foci higher order structure in the nucleus...Cancer Cell 10: 515-527. Quinlan AR, Hall IM. (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 26: 841-2

  4. Psychosocial consequences of cancer screening - development and validation of a questionnaire

    DEFF Research Database (Denmark)

    Brodersen, John; Thorsen, H; Kreiner, Svend


    , and reliability were established by item analysis, examining the fit between item responses and Rasch models. Results: Eight themes specifically relevant for participants in lung cancer screening results were identified: “self-blame,” “focus on symptoms,” “stigmatization,” “introvert,” “harm of smoking...... experience in lung cancer screening. Part I: “anxiety,” “behavior,” “dejection,” “sleep,” “selfblame,” “focus on airway symptoms,” “stigmatization,” “introvert,” and “harm of smoking.” Part II: “calm/relax,” “social network,” “existential values,” “impulsivity,” “empathy,” and “regretful of still smoking...

  5. Breast cancer by proxy: Can the microenvironment be both the cause and consequence?

    Energy Technology Data Exchange (ETDEWEB)

    Ronnov-Jessen, Lone; Bissell, Mina J


    Breast cancer is one of the most clear-cut examples of a solid tumor in which systemic cues play a decisive part in its development. The breast tissue is constantly subjected to changes in hormone levels and modifications in the microenvironment. This scenario is even more striking during tumor development because of the dramatic loss or aberration of basement membrane (BM) and myoepithelial cells and the gain of peritumoral myofibroblasts. We suggest that the microenvironment, defined here as all components of the mammary gland other than luminal and/or tumor epithelial cells, might be instrumental in maintaining organ integrity and in promoting, and at times even initiating, breast cancer development. As such, the tumor microenvironment and its constituents, alone or in combination, might serve as promising targets for therapy.

  6. Breast cancer risk among Swedish hemangioma patients and possible consequences of radiation-induced genomic instability

    Energy Technology Data Exchange (ETDEWEB)

    Eidemueller, Markus, E-mail: [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, 85764 Neuherberg (Germany); Holmberg, Erik [Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Goeteborg (Sweden); Jacob, Peter [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, 85764 Neuherberg (Germany); Lundell, Marie [Department of Medical Physics, Radiumhemmet, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Karlsson, Per [Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Goeteborg (Sweden)


    Breast cancer incidence among 17,158 female Swedish hemangioma patients was analyzed with empirical excess relative risk models and with a biologically-based model of carcinogenesis. The patients were treated in infancy mainly by external application of radium-226. The mean and median absorbed doses to the breast were 0.29 and 0.04 Gy, and a total of 678 breast cancer cases have been observed. Both models agree very well in the risk estimates with an excess relative risk and excess absolute risk at the age of 50 years, about the mean age of breast cancer incidence, of 0.25 Gy{sup -1}(95% CI 0.14; 0.37) and 30.7 (10{sup 5}BYRGy){sup -1} (95% CI 16.9; 42.8), respectively. Models incorporating effects of radiation-induced genomic instability were developed and applied to the hemangioma cohort. The biologically-based description of the radiation risk was significantly improved with a model of genomic instability at an early stage of carcinogenesis.

  7. N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Lobna Ouldamer

    Full Text Available The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality.Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality.We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality.These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.

  8. Exosomes are fingerprints of originating cells: potential biomarkers for ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kobayashi M


    Full Text Available Miharu Kobayashi, Gregory E Rice, Jorge Tapia, Murray D Mitchell, Carlos Salomon Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Abstract: The past decade has seen an extraordinary explosion of research in the field of extracellular vesicles, especially in a specific type of extracellular vesicles originating from endosomal compartments, called exosomes. Exosomes are a specific subtype of secreted vesicles that are defined as small (~30–120 nm but very stable membrane vesicles that are released from a wide range of cells, including normal and cancer cells. As the content of exosomes is cell type specific, it is believed that they are a "fingerprint" of the releasing cell and its metabolic status. We hypothesized that the exosomes and their specific exosomal content (eg, microribonucleic acid represent a precious biomedical tool and may be used as biomarkers for the diagnosis and prognosis of malignant tumors. In addition, exosomes may modify the phenotype of the parent and/or target cell by transferring pro-oncogenic molecules to induce cancerous phenotype of recipient cells and contribute to the formation of the premetastatic niche. The mechanism involved in these phenomena remains unclear; however, inclusion of signaling mediators into exosomes or exosome release may reduce their intracellular bioavailability in the parent cell, thereby altering cell phenotype and their metastatic potential. The aim of this review therefore is to analyze the biogenesis and role of exosomes from tumor cells, focusing primarily on ovarian cancer. Ovarian cancer is the most lethal gynecologic cancer, and an effective early diagnosis has the potential to improve patient survival. Ovarian cancer currently lacks a reliable method for early detection, however, exosomes have received great attention as potential biomarkers and mediators

  9. Origin and distribution of the BRCA2-8765delAG mutation in breast cancer

    Directory of Open Access Journals (Sweden)

    Baldinu Paola


    Full Text Available Abstract Background The BRCA2-8765delAG mutation was firstly described in breast cancer families from French-Canadian and Jewish-Yemenite populations; it was then reported as a founder mutation in Sardinian families. We evaluated both the prevalence of the BRCA2-8765delAG variant in Sardinia and the putative existence of a common ancestral origin through a haplotype analysis of breast cancer family members carrying such a mutation. Methods Eight polymorphic microsatellite markers (D13S1250, centromeric, to D13S267, telomeric spanning the BRCA2 gene locus were used for the haplotype analysis. Screening for the 8765delAG mutation was performed by PCR-based amplification of BRCA2-exon 20, followed by automated sequencing. Results Among families with high recurrence of breast cancer (≥ 3 cases in first-degree relatives, those from North Sardinia shared the same haplotype whereas the families from French Canadian and Jewish-Yemenite populations presented distinct genetic assets at the BRCA2 locus. Screening for the BRCA2-8765delAG variant among unselected and consecutively-collected breast cancer patients originating from the entire Sardinia revealed that such a mutation is present in the northern part of the island only [9/648 (1.4% among cases from North Sardinia versus 0/493 among cases from South Sardinia]. Conclusion The BRCA2-8765delAG has an independent origin in geographically and ethnically distinct populations, acting as a founder mutation in North but not in South Sardinia. Since BRCA2-8765delAG occurs within a triplet repeat sequence of AGAGAG, our study further confirmed the existence of a mutational hot-spot at this genomic position (additional genetic factors within each single population might be involved in generating such a mutation.

  10. Oxidative Stress in the Pathogenesis of Colorectal Cancer: Cause or Consequence?

    Directory of Open Access Journals (Sweden)

    Martina Perše


    Full Text Available There is a growing support for the concept that reactive oxygen species, which are known to be implicated in a range of diseases, may be important progenitors in carcinogenesis, including colorectal cancer (CRC. CRC is one of the most common cancers worldwide, with the highest incidence rates in western countries. Sporadic human CRC may be attributable to various environmental and lifestyle factors, such as dietary habits, obesity, and physical inactivity. In the last decades, association between oxidative stress and CRC has been intensively studied. Recently, numerous genetic and lifestyle factors that can affect an individual's ability to respond to oxidative stress have been identified. The aim of this paper is to review evidence linking oxidative stress to CRC and to provide essential background information for accurate interpretation of future research on oxidative stress and CRC risk. Brief introduction of different endogenous and exogenous factors that may influence oxidative status and modulate the ability of gut epithelial cells to cope with damaging metabolic challenges is also provided.

  11. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice. (United States)

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien


    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards.

  12. The validity and reliability of the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN)

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Petersen, Morten A;


    and reliability of the multi-item scales in the CaTCoN using psychometric analyses as well as tests of convergent and discriminant validity with the existing instruments FAMCARE and Family Inventory of Needs (FIN). Material and methods. Based on theoretical considerations, a subscale structure in the Ca......TCoN and the existing questionnaires FAMCARE and FIN. Conclusion. Taken together the psychometric analyses and tests of convergent and discriminant validity indicate that the validity and reliability of the CaTCoN are satisfactory.......Background. Caregivers are often involved in and affected by the patient's disease. The questionnaire 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN) was developed to measure caregivers' experiences. The aim of this study is to evaluate the construct validity...

  13. Conflicting consequences of immunity to cancer versus autoimmunity to neurons: insights from paraneoplastic disease. (United States)

    Steinman, Lawrence


    Immunologists are well aware that cancer regression and increased patient survival with the use of checkpoint inhibitors, such as ipilimumab, an antibody directed against cytotoxic T-lymphocyte-associated antigen 4, CTLA-4 (CD152), is accompanied by concomitant autoimmunity. For over 30 years, a small group of investigators have shown that the rare paraneoplastic syndromes are caused by immunity to shared antigens found on both tumors and on components of the nervous system. In this issue of the European Journal of Immunology, Blachère et al. [Eur. J. Immunol. 2014. 44: 3240-3251] elucidate some of the molecular mechanisms underlying the tolerance to neuronal antigens which share epitopes with oncologic antigens, observed in the context of paraneoplastic syndromes in mice. The presence of the shared tumor antigen on a nonhematopoietic cell underlies the basis for a certain level of tolerance in CD4+ and CD8+ T cells, preventing these cells from attacking the brain, but allowing them to lyse the tumor upon transfer into tumor-bearing recipient mice. Comparisons between the paraneoplastic syndromes and the new autoimmune conditions seen with antibodies to immune checkpoints at CD152 or at CD279 are likely to illuminate shared mechanisms and solutions to these vexing diseases.

  14. Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Ander Abarrategi


    Full Text Available Osteosarcoma (OS is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.

  15. The Molecular Fingerprint of High Grade Serous Ovarian Cancer Reflects Its Fallopian Tube Origin

    Directory of Open Access Journals (Sweden)

    Thomas Meyer


    Full Text Available High grade serous ovarian cancer (HGSC, the most lethal and frequent type of epithelial ovarian cancer (EOC, has poor long term prognosis due to a combination of factors: late detection, great metastatic potential and the capacity to develop resistance to available therapeutic drugs. Furthermore, there has been considerable controversy concerning the etiology of this malignancy. New studies, both clinical and molecular, strongly suggest that HGSC originates not from the surface of the ovary, but from the epithelial layer of the neighboring fallopian tube fimbriae. In this paper we summarize data supporting the central role of fallopian tube epithelium in the development of HGSC. Specifically, we address cellular pathways and regulatory mechanisms which are modulated in the process of transformation, but also genetic changes which accumulate during disease progression. Similarities between fallopian tube mucosa and the malignant tissue of HGSC warrant a closer analysis of homeostatic mechanisms in healthy epithelium in order to elucidate key steps in disease development. Finally, we highlight the importance of the cancer stem cell (CSC identification and understanding of its niche regulation for improvement of therapeutic strategies.

  16. HER2 Analysis in Sporadic Thyroid Cancer of Follicular Cell Origin

    Directory of Open Access Journals (Sweden)

    Rosaria M. Ruggeri


    Full Text Available The Epidermal Growth Factor Receoptor (EGFR family member human epidermal growth factor receptor 2 (HER2 is overexpressed in many human epithelial malignancies, representing a molecular target for specific anti-neoplastic drugs. Few data are available on HER2 status in differentiated thyroid cancer (DTC. The present study was aimed to investigate HER2 status in sporadic cancers of follicular cell origin to better clarify the role of this receptor in the stratification of thyroid cancer. By immunohistochemistry and fluorescence in-situ hybridization, HER2 expression was investigated in formalin-fixed paraffin-embedded surgical specimens from 90 DTC patients, 45 follicular (FTC and 45 papillary (PTC histotypes. No HER2 immunostaining was recorded in background thyroid tissue. By contrast, overall HER2 overexpression was found in 20/45 (44% FTC and 8/45 (18% PTC, with a significant difference between the two histotypes (p = 0.046. Five of the six patients who developed metastatic disease during a median nine-year follow-up had a HER2-positive tumor. Therefore, we suggest that HER2 expression may represent an additional aid to identify a subset of patients who are characterized by a worse prognosis and are potentially eligible for targeted therapy.

  17. Hemodynamic Consequences of Malignant Ascites in Epithelial Ovarian Cancer Surgery*: A Prospective Substudy of a Randomized Controlled Trial. (United States)

    Hunsicker, Oliver; Fotopoulou, Christina; Pietzner, Klaus; Koch, Mandy; Krannich, Alexander; Sehouli, Jalid; Spies, Claudia; Feldheiser, Aarne


    Malignant ascites (MA) is most commonly observed in patients scheduled for epithelial ovarian cancer (EOC) surgery and is supposed as a major risk factor promoting perioperative hemodynamic deterioration. We aimed to assess the hemodynamic consequences of MA on systemic circulation in patients undergoing cytoreductive EOC surgery.This study is a predefined post-hoc analysis of a randomized controlled pilot trial comparing intravenous solutions within a goal-directed algorithm to optimize hemodynamic therapy in patients undergoing cytoreductive EOC surgery. Ascites was used to stratify the EOC patients prior to randomization in the main study. We analyzed 2 groups according to the amount of ascites (NLAS: none or low ascites [500 mL]). Differences in hemodynamic variables with respect to time were analyzed using nonparametric analysis for longitudinal data and multivariate generalized estimating equation adjusting the analysis for the randomized study groups of the main study.A total of 31 patients in the NLAS and 16 patients in the HAS group were analyzed. Although cardiac output was not different between groups suggesting a similar circulatory blood flow, the HAS group revealed higher heart rates and lower stroke volumes during surgery. There were no differences in pressure-based hemodynamic variables. In the HAS group, fluid demands, reflected by the time to reindication of a fluid challenge after preload optimization, increased steadily, whereas stroke volume could not be maintained at baseline resulting in hemodynamic instability after 1.5 h of surgery. In contrast, in the NLAS group fluid demands were stable and stroke volume could be maintained during surgery. Clinically relevant associations of the type of fluid replacement with hemodynamic consequences were particularly observed in the HAS group, in which transfusion of fresh frozen plasma (FFP) was associated to an improved circulatory flow and reduced vasopressor and fluid demands, whereas the

  18. Noxa determines localization and stability of MCL-1 and consequently ABT-737 sensitivity in small cell lung cancer. (United States)

    Nakajima, W; Hicks, M A; Tanaka, N; Krystal, G W; Harada, H


    The sensitivity to ABT-737, a prototype BH3 mimetic drug, varies in a broad range in small cell lung cancer (SCLC) cells. We have previously shown that the expression of Noxa, a BH3-only pro-apoptotic BCL-2 family protein, is the critical determinant of ABT-737 sensitivity. We show here that Noxa regulates the localization and stability of MCL-1, an anti-apoptotic member, which results in modulating ABT-737 sensitivity. Mutations in Noxa within the BH3 domain, the carboxyl terminus mitochondrial targeting domain, or of ubiquitinated lysines not only change the localization and stability of Noxa itself but also affect the mitochondrial localization and phosphorylation/ubiquitination status of MCL-1 and consequently modulate sensitivity to ABT-737. Results of studies utilizing these mutant proteins indicate that Noxa recruits MCL-1 from the cytosol to the mitochondria. Translocation of MCL-1 initiates its phosphorylation and subsequent ubiquitination, which triggers proteasome-mediated degradation. The precise regulatory mechanisms of Noxa/MCL-1 expression and stability could provide alternative targets to modulate apoptosis induced by BH3 mimetic drugs or other chemotherapeutic reagents.

  19. Analysis of origin and protein-protein interaction maps suggests distinct oncogenic role of nuclear EGFR during cancer evolution (United States)

    Sharip, Ainur; Abdukhakimova, Diyora; Wang, Xiao; Kim, Alexey; Kim, Yevgeniy; Sharip, Aigul; Orakov, Askarbek; Miao, Lixia; Sun, Qinglei; Chen, Yue; Chen, Zhenbang; Xie, Yingqiu


    Receptor tyrosine kinase EGFR usually is localized on plasma membrane to induce progression of many cancers including cancers in children (Bodey et al. In Vivo. 2005, 19:931-41), but it contains a nuclear localization signal (NLS) that mediates EGFR nuclear translocation (Lin et al. Nat Cell Biol. 2001, 3:802-8). Here we report that NLS of EGFR has its old evolutionary origin. Protein-protein interaction maps suggests that nEGFR pathways are different from membrane EGFR and EGF is not found in nEGFR network while androgen receptor (AR) is found, which suggests the evolution of prostate cancer, a well-known AR driven cancer, through changes in androgen- or EGF-dependence. Database analysis suggests that nEGFR correlates with the tumor grades especially in prostate cancer patients. Structural predication analysis suggests that NLS can compromise the differential protein binding to EGFR through stretch linkers with evolutionary mutation from N to V. In experiment, elevation of nEGFR but not membrane EGFR was found in castration resistant prostate cancer cells. Finally, systems analysis of NLS and transmembrane domain (TM) suggests that NLS has old origin while NLS neighboring domain of TM has been undergone accelerated evolution. Thus nEGFR has an old origin resembling the cancer evolution but TM may interfere with NLS driven signaling for natural selection of survival to evade NLS induced aggressive cancers. Our data suggest NLS is a dynamic inducer of EGFR oncogenesis during evolution for advanced cancers. Our model provides novel insights into the evolutionary role of NLS of oncogenic kinases in cancers.

  20. Allergies and risk of head and neck cancer: an original study plus meta-analysis.

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    Jenn-Ren Hsiao

    Full Text Available BACKGROUND: Although the relationship between allergy and cancer has been investigated extensively, the role of allergy in head and neck cancer (HNC appears less consistent. It is not clear whether allergies can independently influence the risk of HNC in the presence of known strong environmental risk factors, including consumption of alcohol, betel quid, and cigarette. METHODS: THE CURRENT PAPER REPORTS RESULTS FROM: 1 an original hospital-based case-control study, which included 252 incident cases of HNC and 236 controls frequency-matched to cases on sex and age; and 2 a meta-analysis combining the results of the current case-control study and 13 previously published studies (9 cohort studies with 727,569 subjects and 550 HNC outcomes and 5 case-control studies with 4,017 HNC cases and 10,928 controls. RESULTS: In the original case-control study, we observed a strong inverse association between allergies and HNC [odds ratio = 0.41, 95% confidence interval (CI: 0.27-0.62]. The meta-analysis also indicated a statistically significant inverse association between HNC and allergies [meta-relative risk (RR = 0.76, 95% CI: 0.63-0.91], particularly strong for allergic rhinitis (meta-RR = 0.55, 95% CI: 0.40-0.76. In addition, the inverse association between allergies and HNC was observed only among men (meta-RR = 0.67, 95% CI: 0.54-0.84 but not among women (meta-RR = 0.98, 95% CI: 0.81-1.18. CONCLUSIONS: These findings suggest that immunity plays an influential role in the risk of HNC. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are warranted to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help devise effective strategies to reduce and treat HNC.

  1. Nuclear insertions of mitochondrial origin: Database updating and usefulness in cancer studies. (United States)

    Ramos, Amanda; Barbena, Elena; Mateiu, Ligia; del Mar González, María; Mairal, Quim; Lima, Manuela; Montiel, Rafael; Aluja, Maria Pilar; Santos, Cristina


    Nuclear insertions of mitochondrial origin (NUMTs) can be useful tools in evolution and population studies. However, due to their similarity to mitochondrial DNA (mtDNA), NUMTs may also be a source of contamination in mtDNA studies. The main goal of this work is to present a database of NUMTs, based on the latest version of the human genome-GRCh37 draft. A total of 755 insertions were identified. There are 33 paralogous sequences with over 80% sequence similarity and of a greater length than 500bp. The non-identical positions between paralogous sequences are listed for the first time. As an application example, the described database is used to evaluate the impact of NUMT contamination in cancer studies. The evaluation reveals that 220 positions from 256 with zero hits in the current mtDNA phylogeny could in fact be traced to one or more nuclear insertions of mtDNA. This is due to they are located in non-identical positions between mtDNA and nuclear DNA (nDNA). After in silico primer validation of each revised cancer study, risk of co-amplification between mtDNA and nDNA was detected in some cases, whereas in others no risk of amplification was identified. This approach to cancer studies clearly proves the potential of our NUMT database as a valuable new tool to validate mtDNA mutations described in different contexts. Moreover, due to the amount of information provided for each nuclear insertion, this database should play an important role in designing evolutionary, phylogenetic and epidemiological studies.

  2. Clinicopathological study of cardiac tamponade due to pericardial metastasis originating from gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Michiya Kobayashi; Takehiro Okabayashi; Ken Okamoto; Tsutomu Namikawa; Keijiro Araki


    AIM: To review the cases reported in the literature,examined their clinicopathological features, and evaluated the efficacy of different therapeutic modalities for this rare condition.METHODS: A search of the MEDLINE database revealed 16 cases of pericarditis carcinomatosa (PC)originating from GC reported in the literature between1982 and 2005. Additional detailed data were obtained from the authors of these studies for subsequent clinicopathological investigation. We have also described about a case study from our own clinic.RESULTS: The mean age of cases with pericarditis carcinomatosa originating from GC was 54 years.Females were diagnosed at a younger age (46.3 years)compared to males (58 years). The mean survival period after diagnosis was 4.5 mo. No statistical differences in the length of survival time were found between different therapeutic modalities, such as drainage, and local and/or systemic chemotherapy after drainage. However,three cases who underwent systemic chemotherapy survived for more than 10 mo. Cases that developed metachronous cardiac tamponade for more than 2years after the diagnosis of GC generally survived for a longer period of time, although this was not statistically significant. Multivariate analysis revealed that low levels of carcinoembryonic antigen (CEA), and CEA and/or cancer antigen 19-9 (CA 19-9) were associated with longer survival.CONCLUSION: Cases with low levels of CEA, and CEA and/or CA 19-9 should undergo systemic chemotherapy with or without local chemotherapy after drainage.

  3. 92-Gene molecular profiling in identification of cancer origin: a retrospective study in Chinese population and performance within different subgroups.

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    Fei Wu

    Full Text Available BACKGROUND: After cancer diagnosis, therapy for the patient is largely dependent on the tumor origin, especially when a metastatic tumor is being treated. However, cases such as untypical metastasis, poorly differentiated tumors or even a limited number of tumor cells may lead to challenges in identifying the origin. Moreover, approximately 3% to 5% of total solid tumor patients will not have to have their tumor origin identified in their lifetime. The THEROS CancerTYPE ID® is designed for identifying the tumor origin with an objective, rapid and standardized procedure. METHODOLOGY AND PRINCIPAL FINDINGS: This is a blinded retrospective study to evaluate performance of the THEROS CancerTYPE ID® in a Chinese population. In total, 184 formalin-fixed paraffin-embedded (FFPE samples of 23 tumor origins were collected from the tissue bank of Fudan University Shanghai Cancer Center (FDUSCC. A standard tumor cell enrichment process was used, and the prediction results were compared with reference diagnosis, which was confirmed by two experienced pathologists at FDUSCC. All of the 184 samples were successfully analyzed, and no tumor specimens were excluded because of sample quality issues. In total, 151 samples were correctly predicted. The agreement rate was 82.1%. A Pearson Chi-square test shows that there is no difference between this study and the previous evaluation test performed by bioTheranostics Inc. No statistically significant decrease was observed in either the metastasis group or tumors with high grades. CONCLUSIONS: A comparable result with previous work was obtained. Specifically, specimens with a high probability score (>0.85 have a high chance (agreement rate = 95% of being correctly predicted. No performance difference was observed between primary and metastatic specimens, and no difference was observed among three tumor grades. The use of laser capture micro-dissection (LCM makes the THEROS CancerTYPE ID® accessible to almost all

  4. Breast cancer screening disparities among immigrant women by world region of origin: a population-based study in Ontario, Canada. (United States)

    Vahabi, Mandana; Lofters, Aisha; Kumar, Matthew; Glazier, Richard H


    Rates of mammography screening for breast cancer are disproportionately low in certain subgroups including low-income and immigrant women. The purpose of the study was to examine differences in rates of appropriate breast cancer screening (i.e., screening mammography every 2 years) among Ontario immigrant women by world region of origin and explore the association between appropriate breast cancer screening among these women groups and individual and structural factors. A cohort of 183,332 screening-eligible immigrant women living in Ontario between 2010 and 2012 was created from linked databases and classified into eight world regions of origin. Appropriate screening rates were calculated for each region by age group and selected sociodemographic, immigration, and healthcare-related characteristics. The association between appropriate screening across the eight regions of origin and selected sociodemographic, immigration, and health-related characteristics was explored using multivariate Poisson regression. Screening varied by region of origin, with South Asian women (48.5%) having the lowest and Caribbean and Latin American women (63.7%) the highest cancer screening rates. Factors significantly associated with lower screening across the world regions of origin included living in the lowest income neighborhoods, having a refugee status, being a new immigrant, not having a regular physical examination, not being enrolled in a primary care patient enrollment model, having a male physician, and having an internationally trained physician. Multiple interventions entailing cross-sector collaboration, promotion of patient enrollment models, community engagement, comprehensive and intensive outreach to women, and knowledge translation and transfer to physicians should be considered to address screening disparities among immigrant population. Consideration should be given to design and delivery of culturally appropriate and easily accessible cancer screening programs

  5. Cervical cancer epidemiology in foreign women in Northern Italy: role of human papillomavirus prevalence in country of origin. (United States)

    Di Felice, Enza; Caroli, Stefania; Paterlini, Luisa; Campari, Cinzia; Prandi, Sonia; Giorgi Rossi, Paolo


    This study compares the incidence and treatments of cervical neoplasia in foreigners from high migration countries and Italians in the Reggio Emilia province (Northern Italy) in 2002-2009. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CI) for cervical intraepithelial neoplasia grade 3 (CIN3) and cancer were calculated for foreigners versus Italian women; foreigners were also classified according to the prevalence of human papillomavirus (HPV) in their country of origin. The proportion of hysterectomies is presented as an indicator of inappropriate surgery in CIN3 and microinvasive cancers. A higher risk was observed in women from high human papillomavirus prevalence countries (HHPVC) both for cancer and for CIN3 (SIR=4.1, 95% CI=2.2-6.9; SIR=2.0, 95% CI 1.7-2.5, respectively), whereas in those from low human papillomavirus prevalence countries (LHPVC), no difference for cancer and a lower risk for CIN3 were observed (SIR=1.0, 95% CI 0.2-2.2; SIR=0.6, 95% CI 0.4-0.8, respectively). A lower CIN3/cancer ratio was found in women from HHPVC (2.6) and in women from LHPVC (3.6) than in Italians (7.4). The percentage of hysterectomies for CIN3 or microinvasive cancers was 3.4 in foreigners and 4.7 in Italians. A higher risk of cervical cancer was found in women from HHPVC compared with Italians and women from LHPVC, suggesting a role of HPV prevalence in the country of origin in the excess risk. The CIN3/cancer ratio was lower for both women from HHPVC and women from LHPVC, also suggesting a role of low screening uptake for cervical cancer incidence in immigrants.

  6. Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase (United States)

    Song, Xinhua; Yin, Shutao; Zhang, Enxiang; Fan, Lihong; Ye, Min; Zhang, Yong; Hu, Hongbo


    Glycycoumarin (GCM) is a major bioactive coumarin compound isolated from licorice and the anti-cancer activity of GCM has not been scientifically addressed. In the present study, we have tested the anti-liver cancer activity of GCM using both in vitro and in vivo models and found for the first time that GCM possesses a potent activity against liver cancer evidenced by cell growth inhibition and apoptosis induction in vitro and tumor reduction in vivo. Mechanistically, GCM was able to bind to and inactivate oncogenic kinase T-LAK cell-originated protein kinase (TOPK), which in turn led to activation of p53 pathway. Our findings supported GCM as a novel active compound that contributed to the anti-cancer activity of licorice and TOPK could be an effective target for hepatocellular carcinoma (HCC) treatment. PMID:27582549

  7. A new theory of the origin of cancer: quantum coherent entanglement, centrioles, mitosis, and differentiation. (United States)

    Hameroff, Stuart R


    Malignant cells are characterized by abnormal segregation of chromosomes during mitosis ("aneuploidy"), generally considered a result of malignancy originating in genetic mutations. However, recent evidence supports a century-old concept that maldistribution of chromosomes (and resultant genomic instability) due to abnormalities in mitosis itself is the primary cause of malignancy rather than a mere byproduct. In normal mitosis chromosomes replicate into sister chromatids which are then precisely separated and transported into mirror-like sets by structural protein assemblies called mitotic spindles and centrioles, both composed of microtubules. The elegant yet poorly understood ballet-like movements and geometric organization occurring in mitosis have suggested guidance by some type of organizing field, however neither electromagnetic nor chemical gradient fields have been demonstrated or shown to be sufficient. It is proposed here that normal mirror-like mitosis is organized by quantum coherence and quantum entanglement among microtubule-based centrioles and mitotic spindles which ensure precise, complementary duplication of daughter cell genomes and recognition of daughter cell boundaries. Evidence and theory supporting organized quantum states in cytoplasm/nucleoplasm (and quantum optical properties of centrioles in particular) at physiological temperature are presented. Impairment of quantum coherence and/or entanglement among microtubule-based mitotic spindles and centrioles can result in abnormal distribution of chromosomes, abnormal differentiation and uncontrolled growth, and account for all aspects of malignancy. New approaches to cancer therapy and stem cell production are suggested via non-thermal laser-mediated effects aimed at quantum optical states of centrioles.

  8. The Consequence of Immune Suppressive Cells in the Use of Therapeutic Cancer Vaccines and Their Importance in Immune Monitoring

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    Matteo Vergati


    Full Text Available Evaluating the number, phenotypic characteristics, and function of immunosuppressive cells in the tumor microenvironment and peripheral blood could elucidate the antitumor immune response and provide information to evaluate the efficacy of cancer vaccines. Further studies are needed to evaluate the correlation between changes in immunosuppressive cells and clinical outcomes of patients in cancer vaccine clinical trials. This paper focuses on the role of T-regulatory cells, myeloid-derived suppressor cells, and tumor-associated macrophages in cancer and cancer immunotherapy and their role in immune monitoring.

  9. Hazardous Consequences of Polygamy, Contraceptives and Number of Childs on cervical cancer in a low incoming country: Bangladesh

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    Full Text Available Background: Cervical cancer is the one of the most alarming disease among female in the low incoming country like Bangladesh. The societies of Bangladesh are conservative because of lacking education and consciousness. The information on Bangladeshi female’s cervical cancer factors is not available. Purpose: To retrieve the associations among the factors with cervical cancer and to raise awareness among the women of society. Methods: A case-control study has been acquitted on 426 participants of both patients and non-patients from February 2014 till July 2014. Through a precise questionnaire based on former study the whole data collection process done. For analyzing of data some tasks like binary logistic regression, odds ratio, crosstabs and p-value tests have executed. Results: Factors like First sex at the age below 16, Lack of knowledge about cervical cancer, number of children above 3, STI (Sexually Transmitted Infection affection, previous cervical cancer history are founded highly significant on the other hand oral contraception taken, contraception used and vaccine taken factors are significantly lower than the previous factors. Conclusions: The analysis would help to predict the risk factors of the cervical cancer and may help to diminish the cancer not only from Bangladesh but all over the world.

  10. SU-E-J-170: Dosimetric Consequences of Uncorrected Rotational Setup Errors During Stereotactic Body Radiation Therapy (SBRT) Treatment of Pancreatic Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Di Maso, L [Chicago, IL (United States); Forbang, R Teboh; Zhang, Y; Herman, J; Lee, J [John Hopkins University, Baltimore, MD (United States)


    Purpose: To explore the dosimetric consequences of uncorrected rotational setup errors during SBRT for pancreatic cancer patients. Methods: This was a retrospective study utilizing data from ten (n=10) previously treated SBRT pancreas patients. For each original planning CT, we applied rotational transformations to derive additional CT images representative of possible rotational setup errors. This resulted in 6 different sets of rotational combinations, creating a total of 60 CT planning images. The patients’ clinical dosimetric plans were then applied to their corresponding rotated CT images. The 6 rotation sets encompassed a 3, 2 and 1-degree rotation in each rotational direction and a 3-degree in just the pitch, a 3-degree in just the yaw and a 3-degree in just the roll. After the dosimetric plan was applied to the rotated CT images, the resulting plan was then evaluated and compared with the clinical plan for tumor coverage and normal tissue sparing. Results: PTV coverage, defined here by V33 throughout all of the patients’ clinical plans, ranged from 92–98%. After an n degree rotation in each rotational direction that range decreased to 68–87%, 85–92%, and 88– 94% for n=3, 2 and 1 respectively. Normal tissue sparing defined here by the proximal stomach V15 throughout all of the patients’ clinical plans ranged from 0–8.9 cc. After an n degree rotation in each rotational direction that range increased to 0–17 cc, 0–12 cc, and 0–10 cc for n=3, 2, and 1 respectively. Conclusion: For pancreatic SBRT, small rotational setup errors in the pitch, yaw and roll direction on average caused under dosage to PTV and over dosage to proximal normal tissue. The 1-degree rotation was on average the least detrimental to the normal tissue and the coverage of the PTV. The 3-degree yaw created on average the lowest increase in volume coverage to normal tissue. This research was sponsored by the AAPM Education Council through the AAPM Education and Research

  11. On the cells of origin of radiogenic thyroid cancer: New studies based on an old idea

    Energy Technology Data Exchange (ETDEWEB)

    Clifton, K.H.; Domann, F.E.; Groch, K.M.


    We have presented evidence that the functional thyroid follicles (follicular units, FU) which are formed in grafts of monodispersed rat thyroid cells, and hence the thyroid tumors which later develop in such grafts, are clonal in origin. Recent studies have been designed to investigate: whether cell number-dependent inhibition of promotion-progression is mediated by remote hormonal feed-back, local cell-cell interactions, or both; the cell population kinetics of the clonogen subpopulation during goitrogenesis and goiter involution; and the effect of prolonged exposure to high levels of TSH (thyrotropin) on the capacity of the clonogens to give rise to functional FU. The results indicate that local cell-cell interactions play an important role in the cell number-dependent suppression of neoplastic promotion-progression. They also show that if sufficient thyroid cells are grafted, the thyroid-pituitary axis can be reestablished in thyroidectomized rats fed normal diets. In such animals given iodine deficient diets, the FU that develop in the thyroid grafts shift their secretory pattern to increase the ratio of T3 (triiodothyronine) to T4 (thyroxine), and thus conserve the available iodine. Finally, the clonogenic subpopulation is conserved during both goitrogenesis and goiter involution. When they are transplanted to thyroidectomized recipients, clonogens from two types of goiters form FU that are morphologically indistinguishable from those that develop in grafts of normal thyroid clonogens. Furthermore, the secretion of T3 and T4 by such grafts is dependent on the grafted clonogen number, and hence FU formation, and not on the total number of thyroid cells transplanted. We conclude that the thyroid clonogens, the presumptive cancer progenitor cells, have many of the characteristics of stem cells.

  12. On the cells of origin of radiogenic thyroid cancer: New studies based on an old idea

    Energy Technology Data Exchange (ETDEWEB)

    Clifton, K.H.; Domann, F.E.; Groch, K.M.


    We have presented evidence that the functional thyroid follicles (follicular units, FU) which are formed in grafts of monodispersed rat thyroid cells, and hence the thyroid tumors which later develop in such grafts, are clonal in origin. Recent studies have been designed to investigate: whether cell number-dependent inhibition of promotion-progression is mediated by remote hormonal feed-back, local cell-cell interactions, or both; the cell population kinetics of the clonogen subpopulation during goitrogenesis and goiter involution; and the effect of prolonged exposure to high levels of TSH (thyrotropin) on the capacity of the clonogens to give rise to functional FU. The results indicate that local cell-cell interactions play an important role in the cell number-dependent suppression of neoplastic promotion-progression. They also show that if sufficient thyroid cells are grafted, the thyroid-pituitary axis can be reestablished in thyroidectomized rats fed normal diets. In such animals given iodine deficient diets, the FU that develop in the thyroid grafts shift their secretory pattern to increase the ratio of T3 (triiodothyronine) to T4 (thyroxine), and thus conserve the available iodine. Finally, the clonogenic subpopulation is conserved during both goitrogenesis and goiter involution. When they are transplanted to thyroidectomized recipients, clonogens from two types of goiters form FU that are morphologically indistinguishable from those that develop in grafts of normal thyroid clonogens. Furthermore, the secretion of T3 and T4 by such grafts is dependent on the grafted clonogen number, and hence FU formation, and not on the total number of thyroid cells transplanted. We conclude that the thyroid clonogens, the presumptive cancer progenitor cells, have many of the characteristics of stem cells.

  13. Possible participation of receptor for advanced glycation end products (RAGE) in the origin of cancer stem cells in diabetic patients with colon cancer. (United States)

    Hu, Xiang; Cheng, Yong


    The association between diabetes and the associated increased risk of several solid malignancies has been the subject of investigation for many years, while potential biologic links between the two diseases are incompletely understood. The receptor for advanced glycation end-products (RAGE) signal transduction may represent a focal point in their respective contributions to malignant transformation associated diabetes. While the physiopathology of RAGE axis in promoting malignancies cannot be explained completely by the available mechanism as perpetuating inflammation at tumor microenvironment. In addition, experimental researches revealed a crucial role for upstreams of RAGE signaling pathway in maintaining the stemness properties and tumorigenicity of cancer stem cells. Hence, we hypothesized that RAGE inducing cancer stem cells may be a key determinant in the origin and progression of colon malignant tumors concomitant diabetes. Such an opinion not only bands together the seemingly disparate various complications in diabetes and colon cancers, but also has future implications for risk assessment and biopharmaceutical treatment.

  14. Do Carcinoma-Associated Fibroblasts Adjacent to Breast Cancer Cells Originate from Circulating Mesenchymal Stem Cells? (United States)


    D., Gorringe , K., Haviv, I., Desmond, P.V., et al. (2003). Distinctive Patterns of Gene Expression in Premalignant Gastric Mucosa and Gastric Cancer...Hu, M., Shipitsin, M., Trivett, M., Thompson, E.R., Ramakrishna, M., Gorringe , K., et al. (2008). No evidence of genomic alterations in cancer

  15. Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage and consequent cell death: A putative cancer chemotherapy mechanism. (United States)

    Sarwar, Tarique; Zafaryab, Md; Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Rehman, Sayeed Ur; Rizvi, M Moshahid Alam; Tabish, Mohammad


    Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we have shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS.

  16. Insulin resistance, its consequences for the clinical course of the disease, and possibilities of correction in endometrial cancer

    NARCIS (Netherlands)

    Berstein, LM; Kvatchevskaya, JO; Poroshina, TE; Kovalenko, IG


    Objectives: To study the frequency of insulin resistance (IR) in endometrial cancer patients, its relation to the clinical course of the disease and DNA damage, and to evaluate possible approaches to the pharmacological correction of IR in the patients studied. Methods: The signs of insulin resistan

  17. Cancer (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  18. A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin

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    Judith Klotz


    Full Text Available Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available.

  19. [Downstaging after neoadjuvant therapy for rectal cancer modifies the planned original surgery]. (United States)

    Scutari, F; Tramutola, G; Morlino, A; Rossi, M T; Manzione, L; Rosati, G; Sopranzi, A


    Cancer of the rectum has been for more years burdened with a heavy rate of local relapse about 30%. The introduction of total meso-rectum excision has reduced the rate of up to 5-8%. Later more studies proved how the preoperative radiotherapy was able to reduce the rate of local relapse. The Authors introduce studies about downstaging after neoadjuvant chemoradiotherapy for rectal cancer and discuss about their own series from 2005 to 2007.

  20. History, Pathogenesis, and Management of Familial Gastric Cancer: Original Study of John XXIII's Family

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    Giovanni Corso


    Full Text Available Background. Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma. Methods. In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines. Results. Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN was classified as cT4bN3a (IV stage. In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively. Conclusions. Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer’s development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members.

  1. The holistic management of consequences of cancer treatment by a gastrointestinal and nutrition team: a financially viable approach to an enormous problem? (United States)

    Muls, Ann C; Lalji, Amyn; Marshall, Christopher; Butler, Lewis; Shaw, Clare; Vyoral, Susan; Mohammed, Kabir; Andreyev, H Jervoise N


    There is no national NHS tariff to fund services for patients experiencing long-term bowel and nutritional problems after cancer treatment. In this paper, we report the clinical characteristics and outcomes of patients referred to our service and the estimated cost of a completed episode of care. Patient characteristics, symptom severity, investigations, diagnoses, number of clinic visits and referrals elsewhere were recorded in a prospective cohort study. During 2013-14, 325 patients completed assessment and treatment. The majority of original cancer diagnoses were urological (43%) and gynaecological (21%). A median of six investigations were requested. 62% were found to have three or more new diagnoses including small intestinal bacterial overgrowth (46%), vitamin D deficiency (38%), bile acid malabsorption (28%), gastritis (22%), radiation-induced bleeding (20%), vitamin B12 deficiency (17%), pelvic floor weakness (17%), colorectal polyps (13%) and pancreatic insufficiency (5%). A median of three visits were required and all commonly reported gastrointestinal symptoms improved by discharge. The mean episode of care per patient was costed at £1,563. Effective amelioration of chronic gastrointestinal toxicity after cancer treatment costs substantially less than treating the cancer in the first place and requires an NHS tariff.

  2. Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells. (United States)

    Shin, Ji-Ae; Shim, Jung-Hyun; Choi, Eun-Sun; Leem, Dae-Ho; Kwon, Ki Han; Lee, Syng-Ook; Safe, Stephen; Cho, Nam-Pyo; Cho, Sung-Dae


    Diindolylmethane (DIM), an isothiocyanate found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC6H5, which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC6H5 decreased the number of viable KB cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of death receptor 5 and the cleavage of Bid and caspase 8. Studies on the mechanism of action showed that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC6H5 was mediated by endoplasmic reticulum stress. In addition, C-DIMs inhibited cell proliferation and induced PARP cleavage through death receptor 5 and CHOP in HEp-2 and HN22 cells. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in human oral cancer cells through the endoplasmic reticulum stress pathway.

  3. Phase II study of concurrent capecitabine and external beam radiotherapy for pain control of bone metastases of breast cancer origin.

    Directory of Open Access Journals (Sweden)

    Yulia Kundel

    Full Text Available Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer.Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m(2 twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial at 12 weeks was 86%. Side effects were of mild intensity (grade I or II and included nausea (38% of patients, weakness (24%, diarrhea (24%, mucositis (10%, and hand and foot syndrome (7%.External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is NCT01784393NCT01784393.

  4. Cytotoxicity of nickel zinc ferrite nanoparticles on cancer cells of epithelial origin. (United States)

    Al-Qubaisi, Mothanna Sadiq; Rasedee, Abdullah; Flaifel, Moayad Husein; Ahmad, Sahrim H J; Hussein-Al-Ali, Samer; Hussein, Mohd Zobir; Eid, Eltayeb E M; Zainal, Zulkarnain; Saeed, Mohd; Ilowefah, Muna; Fakurazi, Sharida; Mohd Isa, Norhaszalina; El Zowalaty, Mohamed Ezzat


    In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6-1,000 μg/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells.

  5. The conditioned place preference test for assessing welfare consequences and potential refinements in a mouse bladder cancer model. (United States)

    Roughan, John V; Coulter, Claire A; Flecknell, Paul A; Thomas, Huw D; Sufka, Kenneth J


    Most pre-clinical analgesic efficacy assays still involve nociceptive testing in rodents. This is despite concerns as to the relevance of these tests for evaluating the pain-preventative properties of drugs. More appropriate methods would target pain rather than nociception, but these are currently not available, so it remains unknown whether animal pain equates to the negatively affective and subjective/emotional state it causes in humans. Mouse cancer models are common despite the likelihood of substantial pain. We used Conditioned Place Preference (CPP) testing, assessments of thermal hyperalgesia and behaviour to determine the likelihood that MBT-2 bladder cancer impacts negatively on mouse welfare, such as by causing pain. There was no CPP to saline, but morphine preference in tumour bearing mice exceeded that seen in tumour-free controls. This occurred up to 10 days before the study end-point alongside reduced body weight, development of hyperalgesia and behaviour changes. These effects indicated mice experienced a negative welfare state caused by malaise (if not pain) before euthanasia. Due to the complexity of the assessments needed to demonstrate this, it is unlikely that this approach could be used for routine welfare assessment on a study-by-study basis. However, our results show mice in sufficiently similar studies are likely to benefit from more intensive severity assessment and re-evaluation of end-points with a view to implementing appropriate refinements. In this particular case, a refinement would have been to have euthanased mice at least 7 days earlier or possibly by provision of end-stage pain relief. CPP testing was found to be a helpful method to investigate the responses of mice to analgesics, possibly on a subjective level. These findings and those of other recent studies show it could be a valuable method of screening candidate analgesics for efficacy against cancer pain and possibly other pain or disease models.

  6. Emergence of cytotoxic resistance in cancer cell populations: Single-cell mechanisms and population-level consequences (United States)

    Lorenzi, Tommaso; Chisholm, Rebecca H.; Lorz, Alexander; Larsen, Annette K.; de Almeida, Luís Neves; Escargueil, Alexandre; Clairambault, Jean


    We formulate an individual-based model and a population model of phenotypic evolution, under cytotoxic drugs, in a cancer cell population structured by the expression levels of survival-potential and proliferation-potential. We apply these models to a recently studied experimental system. Our results suggest that mechanisms based on fundamental laws of biology can reversibly push an actively-proliferating, and drug-sensitive, cell population to transition into a weakly-proliferative and drug-tolerant state, which will eventually facilitate the emergence of more potent, proliferating and drug-tolerant cells.

  7. Potential long-term consequences of fad diets on health, cancer, and longevity: lessons learned from model organism studies. (United States)

    Ruden, Douglas M; Rasouli, Parsa; Lu, Xiangyi


    While much of the third world starves, many in the first world are undergoing an obesity epidemic, and the related epidemics of type II diabetes, heart disease, and other diseases associated with obesity. The amount of economic wealth being directly related to a decline in health by obesity is ironic because rich countries contribute billions of dollars to improve the health of their citizens. Nevertheless, nutritional experiments in model organisms such as yeast, C. elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is defined generally as a 30-40% decrease in caloric intake, a famine-like condition for humans seen only in the poorest of countries, promotes good health and increases longevity in model organisms. Because caloric restriction, and dieting in general, requires a great deal of will power to deal with the feelings of deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power, have been developed which allow people to lose weight purportedly without the severe feelings of deprivation. However, the long-term effects of such fad diets are not known and few experiments have been performed in the laboratory to investigate possible side affects and adverse consequences. In this paper, we review studies with fad-like dietary conditions in humans and model organisms, and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary supplements, and drugs for potential long-term health consequences in model organisms.

  8. Broader utilization of origins of DNA replication in cancer cell lines along a 78 kb region of human chromosome 2q34. (United States)

    Valenzuela, Manuel S; Hu, Lan; Lueders, John; Walker, Robert; Meltzer, Paul S


    Human DNA replication depends on the activation of thousands of origins distributed within the genome. The actual distribution of origins is not known, nor whether this distribution is unique to a cell type, or if it changes with the proliferative state of the cell. In this study, we have employed a real-time PCR-based nascent strand DNA abundance assay, to determine the location of origins along a 78 kb region on Chr2q34. Preliminary studies using nascent DNA strands isolated from either HeLa and normal skin fibroblast cells showed that in both cell lines peaks of high origin activity mapped in similar locations. However, the overall origin profile in HeLa cells corresponded to broad origin activation zones, whereas in fibroblasts a more punctuated profile of origin activation was observed. To investigate the relevance of this differential origin profile, we compared the origin distribution profiles in breast cancer cell lines MDA-MB-231, BT-474, and MCF-7, to their normal counterpart MCF-10A. In addition, the CRL7250 cell line was also used as a normal control. Our results validated our earlier observation and showed that the origin profile in normal cell lines exhibited a punctuated pattern, in contrast to broader zone profiles observed in the cancer cell lines. A quantitative analysis of origin peaks revealed that the number of activated origins in cancer cells is statistically larger than that obtained in normal cells, suggesting that the flexibility of origin usage is significantly increased in cancer cells compared to their normal counterparts.

  9. The nanomechanical signature of liver cancer tissues and its molecular origin (United States)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong


    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus

  10. Origin and age of zircon-bearing chromitite layers from the Finero phlogopite peridotite (Ivrea-Verbano Zone, Western Alps) and geodynamic consequences (United States)

    Zanetti, Alberto; Giovanardi, Tommaso; Langone, Antonio; Tiepolo, Massimo; Wu, Fu-Yuan; Dallai, Luigi; Mazzucchelli, Maurizio


    An investigation has been performed on three chromitite layers segregated in dunite bodies of the Phlogopite Peridotite mantle unit in the Finero complex (FPP, Ivrea-Verbano Zone, Southern Alps) aimed at providing new constraints to their origin and evolution. Field relationships, the sub-chondritic Hf isotopic composition of the zircons (εHf(188) as low as - 5.4), the heavy O isotopic composition of zircons and pyroxenes (δ18O up to 6.9‰), the strict similarity of the trace element composition between the clinopyroxenes and amphiboles from the chromitites and those from the phlogopite harzburgites and pyroxenites forming the typical FPP association, as well as the REE composition of zircons, which approaches equilibrium with the associate clinopyroxene, suggest that the studied chromitites were segregated from melts, highly contaminated from continental crust, during the pervasive cycle of metasomatism recorded by the FPP. An LA-ICP-HRMS survey of chromitite zircon grains has provided Early Jurassic U-Pb ages mostly between 199 ± 3 Ma and 178 ± 2 Ma, with a pronounced peak at 187 Ma. Relevant exceptions are inherited domains of two grains giving Triassic ages of 242 ± 7 Ma and 229 ± 7 Ma, and a third homogeneous zircon giving 208 ± 3 Ma. Our geochronological data and those reported in the literature show that the FPP chromitites have zircon populations with different internal CL textures, but the same sub-chondritic Hf isotopic composition, which define an overall U-Pb age span from ~ 290 Ma to 180. The segregation of the chromitite layers and the main pervasive metasomatism likely occurred in the Early Permian (in a post-collisional, transtensional setting) or before (possibly, in a subduction-related setting). The rejuvenation of the zircon ages was accompanied by a progressive disappearance of the internal zoning, interpreted as the result of a prolonged residence at mantle depths with progressive re-equilibration of the U-Pb system due to thermal

  11. The origin of serous ovarian cancer may be found in the uterus: a novel hypothesis.

    NARCIS (Netherlands)

    Massuger, L.F.A.G.; Roelofsen, T.; Ham, M. van der; Bulten, J.


    Since 1971 the incessant ovulation theory by Fathalla is widely accepted as theory for ovarian carcinogenesis, supported mainly by epidemiological findings. However, this theory cannot explain the protective effect of hysterectomy and tubal ligation on the incidence of ovarian cancer. Furthermore, n

  12. The nanomechanical signature of liver cancer tissues and its molecular origin. (United States)

    Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong


    Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the "gold standard" in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.

  13. Transmissible [corrected] dog cancer genome reveals the origin and history of an ancient cell lineage. (United States)

    Murchison, Elizabeth P; Wedge, David C; Alexandrov, Ludmil B; Fu, Beiyuan; Martincorena, Inigo; Ning, Zemin; Tubio, Jose M C; Werner, Emma I; Allen, Jan; De Nardi, Andrigo Barboza; Donelan, Edward M; Marino, Gabriele; Fassati, Ariberto; Campbell, Peter J; Yang, Fengtang; Burt, Austin; Weiss, Robin A; Stratton, Michael R


    Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.

  14. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging (United States)

    Kaczanowski, Szymon


    Programmed cell death is a basic cellular mechanism. Apoptotic-like programmed cell death (called apoptosis in animals) occurs in both unicellular and multicellular eukaryotes, and some apoptotic mechanisms are observed in bacteria. Endosymbiosis between mitochondria and eukaryotic cells took place early in the eukaryotic evolution, and some of the apoptotic-like mechanisms of mitochondria that were retained after this event now serve as parts of the eukaryotic apoptotic machinery. Apoptotic mechanisms have several functions in unicellular organisms: they include kin-selected altruistic suicide that controls population size, sharing common goods, and responding to viral infection. Apoptotic factors also have non-apoptotic functions. Apoptosis is involved in the cellular aging of eukaryotes, including humans. In addition, apoptosis is a key part of the innate tumor-suppression mechanism. Several anticancer drugs induce apoptosis, because apoptotic mechanisms are inactivated during oncogenesis. Because of the ancient history of apoptosis, I hypothesize that there is a deep relationship between mitochondrial metabolism, its role in aerobic versus anaerobic respiration, and the connection between apoptosis and cancer. Whereas normal cells rely primarily on oxidative mitochondrial respiration, most cancer cells use anaerobic metabolism. According to the Warburg hypothesis, the remodeling of the metabolism is one of the processes that leads to cancer. Recent studies indicate that anaerobic, non-mitochondrial respiration is particularly active in embryonic cells, stem cells, and aggressive stem-like cancer cells. Mitochondrial respiration is particularly active during the pathological aging of human cells in neurodegenerative diseases. According to the reversed Warburg hypothesis formulated by Demetrius, pathological aging is induced by mitochondrial respiration. Here, I advance the hypothesis that the stimulation of mitochondrial metabolism leads to pathological aging.

  15. Origins of DNA Replication and Amplification in the Breast Cancer Genome (United States)


    Our findings underscore the importance of using orthogonal approaches (i.e., assays not involving Lexo, such as nascent strand extrusion , bubble...2009). Analysis of re-replication from redregulated origin licensing by DNA fiber spreading . Nucleic Acids Res. 37:60-69. Dutta A. (2007). Chaotic

  16. Bioequivalence study with lapatinib powder for oral suspension and the original tablet formulation in cancer patients. (United States)

    Koch, Kevin M; Ferron-Brady, Geraldine; Lemmon, Colleen; Cartee, Leanne; Hollyfield, Hedy; D'Amelio, Anthony M; Piepszak, Alexandra; Swaby, Ramona F; Curran, David; Arya, Niki


    Lapatinib is approved for use in various therapeutic combinations for treating metastatic breast cancers that over-express HER2. To deliver the approved doses, up to six large tablets need to be ingested with the current 250-mg tablets. For ease of ingestion, a powder for oral suspension was developed. This study was an open-label, randomized, adaptive design, two-period crossover bioequivalence study of the powder for suspension relative to the commercial tablet at steady state following once daily dosing for 7 days in patients with advanced cancer. To minimize the number of cancer patients required for a pivotal bioequivalence study (144 in this case), a four-stage adaptive group sequential design with interim analyses after every 36 subjects was implemented to allow for early termination. Bioequivalence for the oral suspension relative to the commercial tablet was demonstrated in both the first (and only) interim analysis and the final analysis, as the 90% confidence intervals for the treatment comparison ratios for both AUC0-24 and Cmax were contained within the acceptance criteria (0.80, 1.25). Additionally, there was no statistical difference in tlag or tmax , suggesting no difference in the absorption rate between treatments. There were no unexpected safety findings during this study.

  17. Chemotherapy for Liver Metastasis Originating from Colorectal Cancer with Portal Vein Tumor Thrombosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Atsushi Kawasaki


    Full Text Available The patient was a male in his 70s with a history of chronic renal failure and dilated cardiomyopathy. In January 2011, he underwent abdominoperineal resection of the rectum, right hepatic lobectomy, and resection of a portal vein tumor thrombus with a diagnosis of rectal cancer and metastatic liver cancer accompanied by portal vein tumor thrombosis. Although 5-fluorouracil + l-leucovorin therapy (RPMI regimen was carried out as postoperative adjuvant chemotherapy, the tumor marker (CEA and VA19-9 levels increased 8 months after surgery. Since the functions of major organs were impaired, UFT® + UZEL® therapy was started. The tumor marker levels decreased temporarily, but increased again 12 months after surgery, and so intravenous instillation of panitumumab was initiated. Nine administrations have been performed to date, with no increase in tumor marker levels or exacerbation of the condition. Also, no grade 2 or severer adverse event has been noted according to CTCAE v.4.0. The experience with this patient suggests the possibility that exacerbation of the condition of patients with liver metastasis of colorectal cancer accompanied by portal vein tumor thrombosis with abnormalities in the functions of major organs can be controlled temporarily by the administration of panitumumab alone.

  18. Aging in chalcohalide glasses: Origin and consequences

    DEFF Research Database (Denmark)

    Jensen, Martin; Smedskjær, Morten Mattrup; Wang, W.;


    The application of chalcogenide and chalcohalide glasses is limited by their uncontrolled drift in properties over time due to aging processes. In the present work, we perform aging experiments on some chalcohalide glasses in oxidizing, inert and reducing atmospheres and afterwards we measure the...

  19. Cervical cancer screening among immigrant Hispanics: an analysis by country of origin. (United States)

    Shelton, Rachel C; Jandorf, Lina; King, Sheba; Thelemaque, Linda; Erwin, Deborah O


    As the largest and most diverse ethnic minority population in the U.S., it is important to examine differences in and correlates of Pap test adherence among Hispanics by country of origin. The data for these analyses are baseline responses from a Randomized Controlled Trial. Bivariate and multivariable logistic regression models were conducted among Hispanic immigrant women who identified as Mexican, Puerto Rican, Dominican, or Central/South American (n = 1,305). There were significant differences in Pap test adherence: Dominicans (81.6%), Mexicans (77.5%), Central/South Americans (71.2%), and Puerto Ricans (69.3%). In multivariable analyses, there were different correlates of Pap test adherence for each country of origin. For example, marriage status (P = .0001) and younger age (P = .006) were positively associated with adherence among Mexican women. This research provides insight into the variability that exists among Hispanics and can help improve understanding of important determinants that may influence Pap test screening among diverse Hispanics.

  20. Teeth and irradiation in head and neck cancer; Dent et irradiation: denture et consequences sur la denture de la radiotherapie des cancers de la tete et du cou

    Energy Technology Data Exchange (ETDEWEB)

    Thariat, J.; Ortholan, C. [Centre Antoine-Lacassagne, Service de radiotherapie, 06 - Nice (France); Thariat, J.; Darcourt, V.; Poissonnet, G.; Dassonville, O.; Marcy, P.Y.; Bozec, A.; Ortholan, C.; Santini, J. [Universite de Nice Sophia-Antipolis, 06 - Nice (France); Thariat, J. [IBDC CNRS UMR 6543, 06 - Nice (France); Mones, E. de [CHU de Bordeaux, Service ORL, 33 - Bordeaux (France); Darcourt, V. [Centre Antoine-Lacassagne, Service de radiotherapie-dentisterie, 06 - Nice (France); Poissonnet, G.; Dassonville, O.; Bozec, A.; Santini, J. [Centre Antoine-Lacassagne, Service ORL, 06 - Nice (France); Savoldelli, C.; Odin, G.; Guevara, N. [CHU, Service ORL et de chirurgie maxillofaciale, 06 - Nice (France); Marcy, P.Y. [Centre Antoine-Lacassagne, Service de radiologie, 06 - Nice (France); Bensadoun, R.J. [CHU, Service de radiotherapie, 86 - Poitiers (France)


    Pre-irradiation dental care depends on teeth health, fields and dose of irradiation, compliance to fluorides, cessation of tobacco and psycho-social cofactors. Dental care aims at preventing complications and preserving the quality of life (eating, speech and aesthetics). Approximately 11% of patients do not require any pre-irradiation dental care. Dental complications vary from slight colorations of the teeth to major complication such as osteoradionecrosis. Osteoradionecrosis rates vary from 1 to 9%, and may be decreased by using a 21-day delay between extractions and irradiation, provided that it does not postpone cancer treatment, with a dose-dependent risk (<6% if <40 Gy; 14% between 40 et 60 Gy; =20% if >60 Gy). Osteoradionecrosis occurs spontaneously (35%), mostly involves the mandible (85%). (authors)

  1. Choice & Consequence

    DEFF Research Database (Denmark)

    Khan, Azam

    between cause and effect in complex systems complicates decision making. To address this issue, we examine the central role that data-driven decision making could play in critical domains such as sustainability or medical treatment. We developed systems for exploratory data analysis and data visualization...... of data analysis and instructional interface design, to both simulation systems and decision support interfaces. We hope that projects such as these will help people to understand the link between their choices and the consequences of their decisions....

  2. Confined trisomy 8 mosaicism of meiotic origin: a rare cause of aneuploidy in childhood cancer. (United States)

    Valind, Anders; Pal, Niklas; Asmundsson, Jurate; Gisselsson, David; Holmquist Mengelbier, Linda


    Whether chromosome abnormalities observed in tumor cells may in some cases reflect low-grade somatic mosaicism for anomalies present already at zygote formation, rather than acquired somatic mutations, has for long remained a speculation. We here report a patient with Wilms tumor, where constitutional somatic mosaicism of trisomy 8 was detected in a previously healthy 2 ½-year-old boy. Single Nucleotide Polymorphism (SNP) array analysis of tumor tissue revealed a complex distribution of allele frequencies for chromosome 8 that could not be explained solely by mitotic events. Combined analysis of allele frequencies, chromosome banding, and fluorescence in situ hybridization revealed that the majority of tumor cells contained four copies of chromosome 8, with three distinct haplotypes at a 2:1:1 ratio. Because the patient had not been subject to organ transplantation, these findings indicated that the tumor karyotype evolved from a cell with trisomy 8 of meiotic origin, with subsequent somatic gain of one additional chromosome copy. Haplotype analysis was consistent with trisomy 8 through nondisjunction at meiosis I. Matched normal renal tissue or peripheral blood did not contain detectable amounts of cells with trisomy 8, consistent with the complete lack of mosaic trisomy 8 syndrome features in the patient. This case provides proof of principle for the hypothesis that tumor genotypes may in rare cases reflect meiotic rather than mitotic events, also in patients lacking syndromic features. © 2014 Wiley Periodicals, Inc.

  3. Bias explains most of the parent-of-origin effect on breast cancer risk in BRCA1/2 mutation carriers

    NARCIS (Netherlands)

    Vos, Janet R; Oosterwijk, Jan C; Aalfs, Cora M; Rookus, Matti A; Adank, Muriel A; van der Hout, Annemarie H; van Asperen, Christi J; Gomez-Garcia, Encarna B; Mensenkamp, Arjen R; Jager, Agnes; Ausems, Margreet G E M; Mourits, Marian J; de Bock, Geertruida H


    BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1

  4. The consequences of "Culture's consequences"

    DEFF Research Database (Denmark)

    Knudsen, Fabienne; Loloma Froholdt, Lisa


    , but it may also have unintentional outcomes. It may lead to a deterministic view of other cultures, thereby reinforcing prejudices and underestimating other forms of differences; it risks blinding the participants of the specific context of a given communicative situation. The article opens with a critical...... review of the theory of Geert Hofstede, the most renowned representative of this theoretical approach. The practical consequences of using such a concept of culture is then analysed by means of a critical review of an article applying Hofstede to cross-cultural crews in seafaring. Finally, alternative...... views on culture are presented. The aim of the article is, rather than to promote any specific theory, to reflect about diverse perspectives of cultural sense-making in cross-cultural encounters. Udgivelsesdato: Oktober...

  5. A study of the anatomic changes and dosimetric consequences in adaptive CRT of non-small-cell lung cancer using deformable CT and CBCT image registration. (United States)

    Ma, Changsheng; Hou, Yong; Li, Hongsheng; Li, Dengwang; Zhang, Yingjie; Chen, Siye; Yin, Yong


    The aim of this study is to evaluate anatomic lung tumor changes and dosimetric consequences utilizing the deformable daily kilovolt (KV) cone-beam computer tomography (CBCT) image registration. Five patients diagnosed with NSCLC were treated with three-dimensional conformal radiotherapy (3D CRT) and 10 daily KV CBCT image sets were acquired for each patient. Each CBCT image and plan CT were imported into the deformable image registration (DIR) system. The plan CT image was deformed by the DIR system and a new contour on CBCT was obtained by using the auto-contouring function of the DIR. These contours were individually marked as CBCT f1, CBCT f2,..., and CBCT f10, and imported into a treatment planning system (TPS). The daily CBCT plan was individually generated with the same planning criteria based on new contours. These plans were individually marked as CBCTp1, CBCTp2,..., and CBCTp10, followed by generating a dose accumulation plan (DA plan) in original pCT image contour sets by adding all CBCT plans using Varian Eclipse TPS. The maximum, minimum and mean doses to the plan target volume (PTV) in the 5 DA plans were the same with the CT plans. However, the volume of radiation 5, 10, 20, 30, and 50 Gy of the total lungs in DA plans were less than those of the CT plans. The maximum dose of the spinal cord in the DA plans were average 27.96% less than the CT plans. The mean dose for the left, right, and total lungs in the DA plans were reduced by 13.80%, 23.65%, and 12.96%, respectively. The adaptive 3D CRT based on the deformable registration can reduce the dose to the lung and the spinal cord with the same PTV dose coverage. Moreover, it provides a method for further adaptive radiotherapy exploration.

  6. Nanoquartz in Late Permian C1 coal and the high incidence of female lung cancer in the Pearl River Origin area: a retrospective cohort study - article no. 398

    Energy Technology Data Exchange (ETDEWEB)

    Tian, L.W.; Dai, S.F.; Wang, J.F.; Huang, Y.C.; Ho, S.C.; Zhou, Y.; Lucas, D.; Koshland, C.P. [Chinese University of Hong Kong, Hong Kong (China). School of Public Health


    The Pearl River Origin area, Qujing District of Yunnan Province, has one of the highest female lung cancer mortality rates in China. Smoking was excluded as a cause of the lung cancer excess because almost all women were non-smokers. Crystalline silica embedded in the soot emissions from coal combustion was found to be associated with the lung cancer risk in a geographical correlation study. Lung cancer rates tend to be higher in places where the Late Permian C1 coal is produced. Therefore, we have hypothesized the two processes: C1 coal combustion {yields} nanoquartz in ambient air {yields} lung cancer excess in non-smoking women. To estimate the study subjects' retrospective exposure, we will reconstruct the historical exposure scenario by burning the coal samples, collected from operating or deserted coal mines by coal geologists, in a traditional firepit of an old house. Indoor air particulate samples will be collected for nanoquartz and polycyclic aromatic hydrocarbons (PAHs) analyses. Bulk quartz content will be quantified by X-ray diffraction analysis. Size distribution of quartz will be examined by electron microscopes and by centrifugation techniques. Lifetime cumulative exposure to nanoquartz will be estimated for each subject. Using the epidemiology data, we will examine whether the use of C1 coal and the cumulative exposure to nanoquartz are associated with an elevated risk of lung cancer. If nanoquartz is found to be the main underlying cause of the lung cancer epidemic in the study area, cancer potency estimates for PAHs by the international agencies based on the lung cancer data in this study setting should then be updated.

  7. The origin of Cenozoic basalts from central Inner Mongolia, East China: The consequence of recent mantle metasomatism genetically associated with seismically observed paleo-Pacific slab in the mantle transition zone (United States)

    Guo, Pengyuan; Niu, Yaoling; Sun, Pu; Ye, Lei; Liu, Jinju; Zhang, Yu; Feng, Yue-xing; Zhao, Jian-xin


    We present new major element, trace element and Sr-Nd-Hf isotope data on Cenozoic basalts from central Inner Mongolia (CIM) in eastern China to study the origin of the incompatible-element enriched component in these basalts by testing whether or not the paleo-Pacific plate lying in the mantle transition zone beneath eastern China is the immediate cause. The Cenozoic CIM basalts have a large variation in major element, trace element and isotope compositions. Fractional crystallization of olivine and clinopyroxene can readily explain much of the major element compositional variation, while trace element and isotope ratio variation largely reflect source heterogeneities and source histories. The variably low 87Sr/86Sr, high εNd, high εHf and elevated ratios of high field strength element over large ion lithophile element (HFSE/LILE, e.g., Nb/U, Nb/La) indicate that the CIM basalts are of asthenospheric origin, which is characterized by mixing between DMM and EM1. However, the CIM basalts are enriched in incompatible elements and enriched in the progressively more incompatible elements (e.g., variably high [La/Sm]N = 1.66-3.38), suggesting that the magma source(s) must have been enriched prior to the major episode of the magmatism. Participation of subducted ocean crust in the mantle source region of these basalts is recognized, but cannot be the major source material because the subducted ocean crust is expectedly too depleted in incompatible elements (e.g., [La/Sm]N ≪ 1) to produce magmas highly enriched in incompatible elements with [La/Sm]N ≫ 1. With the new data, we consider that low mass fraction (low-F) melt metasomatism in the seismic low velocity zone (LVZ) beneath eastern China as the most likely process to generate incompatible-element enriched source(s) for mantle melts parental to the Cenozoic CIM basalts. The low-F metasomatic agent most likely resulted from dehydration melting of the transition-zone paleo-Pacific slab, which has been taking place

  8. Nanoquartz in Late Permian C1 coal and the high incidence of female lung cancer in the Pearl River Origin area: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Zhou Yiping


    Full Text Available Abstract Background The Pearl River Origin area, Qujing District of Yunnan Province, has one of the highest female lung cancer mortality rates in China. Smoking was excluded as a cause of the lung cancer excess because almost all women were non-smokers. Crystalline silica embedded in the soot emissions from coal combustion was found to be associated with the lung cancer risk in a geographical correlation study. Lung cancer rates tend to be higher in places where the Late Permian C1 coal is produced. Therefore, we have hypothesized the two processes: C1 coal combustion --> nanoquartz in ambient air --> lung cancer excess in non-smoking women. Methods/Design We propose to conduct a retrospective cohort study to test the hypothesis above. We will search historical records and compile an inventory of the coal mines in operation during 1930–2009. To estimate the study subjects' retrospective exposure, we will reconstruct the historical exposure scenario by burning the coal samples, collected from operating or deserted coal mines by coal geologists, in a traditional firepit of an old house. Indoor air particulate samples will be collected for nanoquartz and polycyclic aromatic hydrocarbons (PAHs analyses. Bulk quartz content will be quantified by X-ray diffraction analysis. Size distribution of quartz will be examined by electron microscopes and by centrifugation techniques. Lifetime cumulative exposure to nanoquartz will be estimated for each subject. Using the epidemiology data, we will examine whether the use of C1 coal and the cumulative exposure to nanoquartz are associated with an elevated risk of lung cancer. Discussion The high incidence rate of lung cancer in Xuan Wei, one of the counties in the current study area, was once attributed to high indoor air concentrations of PAHs. The research results have been cited for qualitative and quantitative cancer risk assessment of PAHs by the World Health Organization and other agencies. If

  9. Medical consequences of obesity. (United States)

    Lawrence, Victor J; Kopelman, Peter G


    The obese are subject to health problems directly relating to the carriage of excess adipose tissue. These problems range from arthritis, aches and pains, sleep disturbance, dyspnea on mild exertion, and excessive sweating to social stigmatization and discrimination, all of which may contribute to low quality of life and depression (Table 1). The most serious medical consequences of obesity are a result of endocrine and metabolic changes, most notably type 2 diabetes mellitus, cardiovascular disease, and increased risk of cancer. Not all obesity comorbidities are fully reversed by weight loss. The degree and duration of weight loss required may not be achievable by an individual patient. Furthermore, "weight cycling" may be more detrimental to both physical and mental health than failure to achieve weight loss targets with medical and lifestyle advice.

  10. MicroRNA-375 Functions as a Tumor-Suppressor Gene in Gastric Cancer by Targeting Recepteur d’Origine Nantais (United States)

    Lian, Sen; Park, Jung Sun; Xia, Yong; Nguyen, Thi Thinh; Joo, Young Eun; Kim, Kyung Keun; Kim, Hark Kyun; Jung, Young Do


    Emerging evidence supports a fundamental role for microRNAs (miRNA) in regulating cancer metastasis. Recently, microRNA-375 (miR-375) was reported to be downregulated in many types of cancers, including gastric cancer. Increase in the expression of Recepteur d’Origine Nantais (RON), a receptor tyrosine kinase, has been reported in tumors. However, the function of miR-375 and RON expression in gastric cancer metastasis has not been sufficiently studied. In silico analysis identified miR-375 binding sites in the 3′-untranslated regions (3′-UTR) of the RON-encoding gene. Expression of miR-375 resulted in reduced activity of a luciferase reporter containing the 3′-UTR fragments of RON-encoding mRNA, confirming that miR-375 directly targets the 3′-UTR of RON mRNA. Moreover, we found that overexpression of miR-375 inhibited mRNA and protein expression of RON, which was accompanied by the suppression of cell proliferation, migration, and invasion in gastric cancer AGS and MKN-28 cells. Ectopic miR-375 expression also induced G1 cell cycle arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of retinoblastoma (Rb). Knockdown of RON by RNAi, similar to miR-375 overexpression, suppressed tumorigenic properties and induced G1 arrest through a decrease in the expression of cyclin D1, cyclin D3, and in the phosphorylation of Rb. Thus, our study provides evidence that miR-375 acts as a suppressor of metastasis in gastric cancer by targeting RON, and might represent a new potential therapeutic target for gastric cancer. PMID:27689991

  11. Unintended consequences of expensive cancer therapeutics—the pursuit of marginal indications and a me-too mentality that stifles innovation and creativity: the John Conley Lecture. (United States)

    Fojo, Tito; Mailankody, Sham; Lo, Andrew


    Cancer is expected to continue as a major health and economic problem worldwide. Several factors are contributing to the increasing economic burden imposed by cancer, with the cost of cancer drugs an undeniably important variable. The use of expensive therapies with marginal benefits for their approved indications and for unproven indications is contributing to the rising cost of cancer care. We believe that expensive therapies are stifling progress by (1) encouraging enormous expenditures of time, money, and resources on marginal therapeutic indications and (2) promoting a me-too mentality that is stifling innovation and creativity. The modest gains of Food and Drug Administration-approved therapies and the limited progress against major cancers is evidence of a lowering of the efficacy bar that, together with high drug prices, has inadvertently incentivized the pursuit of marginal outcomes and a me-too mentality evidenced by the duplication of effort and redundant pharmaceutical pipelines. We discuss the economic realities that are driving this process and provide suggestions for radical changes to reengineer our collective cancer ecosystem to achieve better outcomes for society.

  12. Estimation of plasma lipids and its significance on histopathological grades in oral cancer: Prognostic significance an original research

    Directory of Open Access Journals (Sweden)

    Eugenia J Sherubin


    Full Text Available Background Objectives: Alterations in the lipid profile have long been associated with various cancers because lipids play a key role in maintenance of cell integrity. This study was to estimate the plasma lipid levels in patients with oral cancer and to correlate the values with the histopathological grades. Materials and Methods: The study group included 50 patients with oral cancer aged between 20 and 60 years who had visited the Department of Oral Medicine and Radiology during the period of September 2005 to July 2007. After the histotopathological confirmation, their plasma lipid levels were estimated using auto analyzer and the data was statistically analyzed. Results: The study revealed a significant decrease in the total plasma lipid levels in patients with oral cancer in comparison with the standard values. Comparing the plasma lipid levels with the histopathological grades, we observed a significant variation in the levels of total cholesterol, very low density lipoprotein, low-density lipoprotein, high-density lipoprotein and triglycerides Conclusion: The variation in the levels of plasma cholesterol and other lipid constituents in patients with cancer might be due to their increased utilization by neoplastic cells for new membrane biosynthesis. This study was an attempt to estimate the plasma lipids in oral cancer patients and its significance on histopathological grades. We observed a relationship between lower plasma lipids and oral cancer. The result of our study strongly warrants an in-depth research with larger samples and a longer follow-up to consider the low plasma lipid status in oral cancer patients as a useful indicator to assess the course and prognosis of the disease.

  13. Engagement of Patients With Advanced Cancer (United States)


    End of Life; Advanced Cancer; Lung Neoplasm; Gastric Cancer; Colon Cancer; Glioblastoma Multiforme; Head and Neck Neoplasms; Rectum Cancer; Melanoma; Kidney Cancer; Prostate Cancer; Testicular Neoplasms; Liver Cancer; Cancer of Unknown Origin

  14. Breast cancer in women at high risk: the role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies. (United States)

    Francken, Anne Brecht; Schouten, Philip C; Bleiker, Eveline M A; Linn, Sabine C; Rutgers, Emiel J Th


    Specific clinical questions rise when patients, who are diagnosed with breast cancer, are at risk of carrying a mutation in BRCA1 and -2 gene due to a strong family history or young age at diagnosis. These questions concern topics such as 1. Timing of genetic counseling and testing, 2. Choices to be made for BRCA1 or -2 mutation carriers in local treatment, contralateral treatment, (neo)adjuvant systemic therapy, and 3. The psychological effects of rapid testing. The knowledge of the genetic status might have several advantages for the patient in treatment planning, such as the choice whether or not to undergo mastectomy and/or prophylactic contralateral mastectomy. The increased risk of developing a second breast cancer in the ipsilateral breast in mutation carriers, is only slightly higher after primary cancer treatment, than in the general population. Prophylactic contralateral mastectomy provides a substantial reduction of contralateral breast cancer, although only a small breast cancer specific survival benefit. Patients should be enrolled in clinical trials to investigate (neo)-adjuvant drug regimens, that based on preclinical and early clinical evidence might be targeting the homologous recombination defect, such as platinum compounds and PARP inhibitors. If rapid testing is performed, the patient can make a well-balanced decision. Although rapid genetic counseling and testing might cause some distress, most women reported this approach to be worthwhile. In this review the literature regarding these topics is evaluated. Answers and suggestions, useful in clinical practice are discussed.

  15. On the Origin of Prostate Cancer Stem Cells through Transmissible ER Stress-Mediated Epithelial to Mesenchymal Transition (United States)


    UPR, Grp78, is a necessary component for prostate cancer tumorigenesis. UPR activation is often elicited by noxae in the tumor microenvironment...Collectively, these results suggest TERS priming may play an insidious role in protecting tumor cells from a variety of noxae , both tumor borne and therapeutic

  16. Detection of primary breast cancer presenting as metastatic carcinoma of unknown primary origin by 111In-pentetreotide scan. (United States)

    Lenzi, R; Kim, E E; Raber, M N; Abbruzzese, J L


    Women with isolated metastatic carcinoma or adenocarcinoma involving axillary lymph nodes are a well-recognized group of unknown primary carcinoma (UPC) patients with a favorable prognosis. This group of patients are generally treated based on the assumption that they have occult breast cancer. However, to facilitate patient access to the whole spectrum of therapies available for patients with breast cancer, including strategies involving the use of high-dose chemotherapy, a precise diagnosis is increasingly important. In this clinical case we report the detection of a primary breast cancer by 111In-pentetreotide scanning in a woman who presented with metastatic carcinoma in axillary nodes, no palpable breast lesion, a nondiagnostic mammogram, and negative breast ultrasonography. Previous outcomes analysis of patients with UPC have emphasized the value of identifying women with breast cancer. This report suggests that the 111In-pentetreotide scan can contribute specific, clinically useful information in the evaluation of women presenting with metastatic carcinoma in axillary nodes and an occult primary and deserves prospective study in women with UPC presenting with isolated axillary metastases.

  17. Early planetary differentiation: Geophysical consequences (United States)

    Schubert, G.


    Differentiation of a planet can have profound consequences for its structure and thermal evolution, including core formation and crystal growth. Recent theories for the origin and evolution of the terrestrial planets and the Moon have all these bodies forming hot and cooling thereafter. Early core formation, and in the cases of Earth and Moon, a deep magma ocean possibly encompassing the entire mantle are characteristic features of these models. Secular cooling of Mars from a hot origin and cooling of Moon from a hot initial state with a deep magma ocean have been criticized on the basis of their tectonic implications. The cases of Mars and the Moon are discussed.

  18. Mineralogical and compositional characteristics of Late Permian coals from an area of high lung cancer rate in Xuan Wei, Yunnan, China: Occurrence and origin of quartz and chamosite (United States)

    Dai, S.; Tian, L.; Chou, C.-L.; Zhou, Y.; Zhang, M.; Zhao, L.; Wang, Jingyuan; Yang, Z.; Cao, H.; Ren, D.


    Some townships in Xuan Wei County, Yunnan Province, have one of the highest lung cancer mortality rates in China and the epidemic disease in the area has generally been attributed to the polycyclic aromatic hydrocarbons (PAHs) released from domestic coal burning. However, the cancer-causing culprit is not settled as Tian [Tian, L., 2005. Coal Combustion Emissions and Lung Cancer in Xuan Wei, China. Ph.D. thesis, University of California, Berkeley.] found nanometer quartz in these coals, soot emissions, and lung cancer tissues. We have conducted mineralogical and geochemical studies of the coals from Xuan Wei for the purpose of shedding light on the minerals which may be related to the epidemic lung cancer. In this paper, abundances, modes of occurrence, and origins of minerals and elements in the coals from two mines in Xuan Wei have been studied using optical microscope, low-temperature ashing, X-ray diffraction analysis, scanning electron microscope equipped with energy-dispersive X-ray spectrometer, and inductively-coupled plasma mass spectrometry. The minerals in the coals are mainly composed of quartz, chamosite, kaolinite, and calcite. The particle size of quartz is rather small, mostly less than 20????m and it is of authigenic origin. Chamosite occurs mainly as cell-fillings. The occurrence of quartz and chamosite indicates that they were derived from the hydrothermal fluids. Epigenetic calcite is derived from calcic fluids. Kaolinite is derived mainly from sediment source region of Kangdian Oldland to the west of coal basin. The composition of Xuan Wei coal is high in SiO2, Fe2O3, TiO2, CaO, MnO, V, Co, Ni, Cu, and Zn. The high SiO2 content is attributed to quartz, and the Fe2O3 content to chamosite. The high Mn and low Mg contents in the coal indicate the inputs of hydrothermal fluids. CaO occurs mainly in epigenetic calcite. Elements Ti, Co, Ni, Cu, Zn, and rare earth elements were derived from the basaltic rocks at sediment source region. ?? 2008

  19. <Original>A basic study of intraoperative photodynamic therapy for lung cancer : photodynamic therapy for lymphogenous metastases in nude rats


    MIZUTANI,Eiki; Inoue, Hidenori; Shimada,Osamu; Matsubara,Hirochika; Kobayashi, Masami; Matsumoto,Masahiko


    Background: We designed a new photodynamic therapy (PDT) protocol in which Pheophorbide a (Pba) accumulates in the lymph nodes following local administration around lung cancer tumors, followed by lobectomy and irradiation of the lymph nodes with lasers. As the fi rst step, we evaluated whether administering PDT for metastatic lymph nodes is possible in a rat model.Materials and Methods: Human lung squamous cell carcinoma (RERF-LC-AI) cells were subcutaneously injected into the foot pads of n...

  20. An integral approach to the etiopathogenesis of human neurodegenerative diseases (HNDDs and cancer. Possible therapeutic consequences within the frame of the trophic factor withdrawal syndrome (TFWS

    Directory of Open Access Journals (Sweden)

    Enrique Meléndez Hevia


    Full Text Available Salvador Harguindey1, Gorka Orive2,6, Ramón Cacabelos3, Enrique Meléndez Hevia4, Ramón Díaz de Otazu5, et al1Institute of Clinical Biology and Metabolism, Vitoria, Spain; 2Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of The Basque Country, Vitoria, Spain; 3Department of Clinical Neuroscience, EuroEspes Biomedical Research Center, Bergondo, La Coruña, Spain; 4Institute for Cellular Metabolism, Tenerife, Spain; 5Department of Pathology, Hospital Txagorritxu, Vitoria, Spain; 6Biotechnology Institute (BTI, Vitoria, SpainAbstract: A novel and integral approach to the understanding of human neurodegenerative diseases (HNDDs and cancer based upon the disruption of the intracellular dynamics of the hydrogen ion (H+ and its physiopathology, is advanced. From an etiopathological perspective, the activity and/or deficiency of different growth factors (GFs in these pathologies are studied, and their relationships to intracellular acid-base homeostasis reviewed. Growth and trophic factor withdrawal in HNDDs indicate the need to further investigate the potential utilization of certain GFs in the treatment of Alzheimer disease and other neurodegenerative diseases.  Platelet abnormalities and the therapeutic potential of platelet-derived growth factors in these pathologies, either through platelet transfusions or other clinical methods, are considered. Finally, the etiopathogenic mechanisms of apoptosis and antiapoptosis in HNDDs and cancer are viewed as opposite biochemical and biological disorders of cellular acid-base balance and their secondary effects on intracellular signaling pathways and aberrant cell metabolism are considered in the light of the both the seminal and most recent data available. The “trophic factor withdrawal syndrome” is described for the first time in English-speaking medical literature, as well as a Darwinian-like interpretation of cellular behavior related to specific and nonspecific

  1. Melanin-originated carbonaceous dots for triple negative breast cancer diagnosis by fluorescence and photoacoustic dual-mode imaging. (United States)

    Xiao, Wei; Li, Yuan; Hu, Chuan; Huang, Yuan; He, Qin; Gao, Huile


    Carbonaceous dots exhibit increasing applications in diagnosis and drug delivery due to excellent photostability and biocompatibility properties. However, relative short excitation and emission of melanin carbonaceous dots (MCDs) limit the applicability in fluorescence bioimaging. Furthermore, the generally poor spatial resolution of fluorescence imaging limits potential in vivo applications. Due to a variety of beneficial properties, in this study, MCDs were prepared exhibiting great potential in fluorescence and photoacoustic dual-mode bioimaging. The MCDs exhibited a long excitation peak at 615nm and emission peak at 650nm, further highlighting the applicability in fluorescence imaging, while the absorbance peak at 633nm renders MCDs suitable for photoacoustic imaging. In vivo, the photoacoustic signal of MCDs was linearly correlated with the concentration of MCDs. Moreover, the MCDs were shown to be taken up into triple negative breast cancer cell line 4T1 in both a time- and concentration-dependent manner. In vivo fluorescence and photoacoustic imaging of subcutaneous 4T1 tumor demonstrated that MCDs could passively target triple negative breast cancer tissue by enhanced permeability and retention effects and may therefore be used for tumor dual-mode imaging. Furthermore, fluorescence distribution in tissue slices suggested that MCDs may distribute in 4T1 tumor with high efficacy. In conclusion, the MCDs studied offer potential application in fluorescence and photoacoustic dual-mode imaging.

  2. Molecular Consequences of Proprotein Convertase 1/3 (PC1/3) Inhibition in Macrophages for Application to Cancer Immunotherapy: A Proteomic Study* (United States)

    Duhamel, Marie; Rodet, Franck; Delhem, Nadira; Vanden Abeele, Fabien; Kobeissy, Firas; Nataf, Serge; Pays, Laurent; Desjardins, Roxanne; Gagnon, Hugo; Wisztorski, Maxence; Fournier, Isabelle; Day, Robert; Salzet, Michel


    Macrophages provide the first line of host immune defense. Their activation triggers the secretion of pro-inflammatory cytokines and chemokines recruiting other immune cells. In cancer, macrophages present an M2 anti-inflammatory phenotype promoting tumor growth. In this way, strategies need to be develop to reactivate macrophages. Previously thought to be expressed only in cells with a neural/neuroendocrine phenotype, the proprotein convertase 1/3 has been shown to also be expressed in macrophages and regulated as a function of the Toll-like receptor immune response. Here, we investigated the intracellular impact of the down-regulation of the proprotein convertase 1/3 in NR8383 macrophages and confirmed the results on macrophages from PC1/3 deficient mice. A complete proteomic study of secretomes and intracellular proteins was undertaken and revealed that inhibition of proprotein convertase 1/3 orient macrophages toward an M1 activated phenotype. This phenotype is characterized by filopodial extensions, Toll-like receptor 4 MyD88-dependent signaling, calcium entry augmentation and the secretion of pro-inflammatory factors. In response to endotoxin/lipopolysaccharide, these intracellular modifications increased, and the secreted factors attracted naïve T helper lymphocytes to promote the cytotoxic response. Importantly, the application of these factors onto breast and ovarian cancer cells resulted in a decrease viability or resistance. Under inhibitory conditions using interleukin 10, PC1/3-knockdown macrophages continued to secrete inflammatory factors. These data indicate that targeted inhibition of proprotein convertase 1/3 could represent a novel type of immune therapy to reactivate intra-tumoral macrophages. PMID:26330543

  3. European trends in the frequency of original research in acne vulgaris, rosacea, dermatitis, psoriasis, skin cancer, and skin infections, 1970-2010. (United States)

    Choi, Young M; Garcha, Jaspreet K; Wu, Jashin J


    We analyzed trends in the frequency of original publications into common dermatologic topics in two premier European journals, the British Journal of Dermatology and the Journal of the European Academy of Dermatology and Venereology. Most notably, we found that psoriasis publications peaked around the mid-to-late 1980's as well as demonstrated an upward trend since the 21st century. Skin cancer research witnessed a gradual increase in the frequency of publications since 1970. These findings were consistent with a prior study analyzing trends in two American dermatology journals. We attempted to analyze these results from a historical perspective as well as provide an outlook on the future of research into these common dermatologic topics.

  4. Time trends in incidence and prognosis of primary liver cancer and liver metastases of unknown origin in a Danish region, 1985-2004

    DEFF Research Database (Denmark)

    Erichsen, Rune; Jepsen, Peter; Jacobsen, Jacob;


    OBJECTIVES: Changes, over the last 20 years, in the diagnostic procedures and treatment of primary liver cancer (PLC) and liver metastases of unknown origin (LMUO) may have affected the clinical course of both cancers. Few longitudinal studies examined this issue. In a population-based setting, we...... studied changes in the incidence and prognosis of PLC and LMUO over time. METHODS: Between 1985 and 2004, we identified 2675 patients with PLC and LMUO in three Danish counties, with a population of 1.4 million. We computed the standardized incidence rate (SIR), ratio of PLC to LMUO diagnoses, median...... survival, and estimated mortality rate ratio adjusted for age, sex, and comorbidity. RESULTS: The SIR of PLC increased from 3.2 in 1985 to 5.0 in 2003, and the SIR of LMUO increased from 3.7 to 6.4. No increase was noted in the PLC-to-LMUO ratio over time (P=0.1 for trend). From 1985 to 2004, the median...

  5. A Cell ELISA for the quantification of MUC1 mucin (CD227) expressed by cancer cells of epithelial and neuroectodermal origin. (United States)

    Falahat, Rana; Wiranowska, Marzenna; Gallant, Nathan D; Toomey, Ryan; Hill, Robert; Alcantar, Norma


    Quantitative analysis of MUC1, a cell membrane associated mucin, expressed by intact cells of epithelial origin previously has been limited to flow cytometry, which requires using large quantities of cells and antibodies. Here, for the first time, we report the development of a novel Cellular-based Enzyme Linked Immunosorbent Assay (Cell ELISA) to quantify the expression of MUC1 by cell lines of epithelial and neuroectodermal origin using an antibody recognizing a specific tandem repeat found in the extracellular domain of MUC1. In contrast to flow cytometry, this method requires a much lower number of cells. We report here the results obtained from two variants of this Cell ELISA in live and fixed cells. We found that the Cell ELISA in live cells was not sensitive enough to detect a difference in MUC1 levels between the normal cells and tumor cells. However, we found that Cell ELISA in fixed cells followed by whole cell staining was a dependable method of MUC1 level detection in the normal and tumor cells showing significantly higher levels of MUC1 receptor in the tumor cells when compared to the normal controls. Therefore, we conclude that the Cell ELISA in fixed cells is an efficient method for quantifying the expression of MUC1 by epithelial and neuroectodermal cancer cell lines.

  6. Consequences of contamination of the spacecraft environment: immunologic consequences (United States)

    Shearer, W. T.


    Long-term space voyages pose numerous known and unknown health hazards, to the human immune system. Well-studied clinical examples of secondary immunodeficiencies created on Earth, lead one to predict that the conditions of prolonged space flight would weaken the human immune responses that normally hold infection and cancer in check. From evidence gathered from humans flown for prolonged periods in space and from human models of space flight studied on Earth it is reasonable to suspect that space travelers to the planet Mars would experience a weakening of immunity. Subtle defects of immune cell structure and function have been observed in astronauts, such as weakening of specific T-lymphocyte recall of specific antigens. Ground-based models also have demonstrated alterations of immune function, such as the elevation of neuroendocrine immune system messengers, interleukin-6, and soluble tumor necrosis factor-alpha receptor in sleep deprivation. Since severe immune compromise the clinical consequences of reactivation of latent virus infections and the development of cancer, has yet to be seen in space flight or in the Earth models, it is extremely important to begin to quantify early changes in immunity to predict the development of immune system collapse with poor clinical outcomes. This approach is designed to validate a number of surrogate markers that will predict trouble ahead. Inherent in this research is the development of countermeasures to reduce the risks of infection and cancer in the first humans going to Mars.

  7. Cancer (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  8. Do changes in surgical procedures for breast cancer have consequences for hospital mean length of stay? A study of women operated on for breast cancer in Sweden, 1980-95

    DEFF Research Database (Denmark)

    Lindqvist, Rikard; Möller, Torgil R; Stenbeck, Magnus;


    BACKGROUND: Between 1986 and 1996, the overall mean overnight length of stay for all diagnoses in Sweden decreased from 20.8 to 7.1 days. OBJECTIVES: The study describes changes in surgical technique, from mastectomy to breast-conserving surgery, in treatment of female breast cancer and the paral......BACKGROUND: Between 1986 and 1996, the overall mean overnight length of stay for all diagnoses in Sweden decreased from 20.8 to 7.1 days. OBJECTIVES: The study describes changes in surgical technique, from mastectomy to breast-conserving surgery, in treatment of female breast cancer...... and the parallel change in average length of hospital stay, and discusses the possible link between the trends. RESEARCH DESIGN: The study was performed as a descriptive register study on hospital admission data from the Swedish Hospital Discharge Register over a 16-year period (1980-95). RESULTS: During the study...

  9. Dosimetric consequences of tumor volume changes after kilovoltage cone-beam computed tomography for non-operative lung cancer during adaptive intensity-modulated radiotherapy or fractionated stereotactic radiotherapy

    Institute of Scientific and Technical Information of China (English)

    Jian Hu; Ximing Xu; Guangjin Yuan; Wei Ge; Liming Xu; Aihua Zhang; Junjian Deng


    Objective The aim of this study was to investigate tumor volume changes with kilovoltage cone-beam computed tomography (kV-CBCT) and their dosimetric consequences for non-operative lung cancer during intensity-modulated radiotherapy (IMRT) or fractionated stereotactic radiotherapy. Methods Eighteen patients with non-operative lung cancer who received IMRT consisting of 1.8-2.2 Gy/fraction and five fractions per week or stereotactic radiotherapy with 5-8 Gy/fraction and three fractions a week were studied. kV-CBCT was performed once per week during IMRT and at every fraction during stereotactic radiotherapy. The gross tumor volume (GTV) was contoured on the kV-CBCT images, and adaptive treatment plans were created using merged kV-CBCT and primary planning computed tomogra-phy image sets. Tumor volume changes and dosimetric parameters, including the minimum dose to 95%(D95) or 1% (D1) of the planning target volume (PTV), mean lung dose (MLD), and volume of lung tissue that received more than 5 (V5), 10 (V10), 20 (V20), and 30 (V30) Gy were retrospectively analyzed. Results The average maximum change in GTV observed during IMRT or fractionated stereotactic radio-therapy was -25.85% (range, -13.09% --56.76%). The D95 and D1 of PTV for the adaptive treatment plans in all patients were not significantly different from those for the initial or former adaptive treatment plans. In patients with tumor volume changes of >20% in the third or fourth week of treatment during IMRT, adap-tive treatment plans offered clinically meaningful decreases in MLD and V5, V10, V20, and V30; however, in patients with tumor volume changes of 20% in the third or fourth week of treatment.

  10. The MSSA consequence tables

    Energy Technology Data Exchange (ETDEWEB)

    Sacks, I.J.


    The Master Safeguards and Security Agreement (MSSA) is the mechanism through which the U.S. Department of Energy is implementing a policy of graded safeguards. Under this concept, the level of protection provided to a target is proportional to the ''cost'' of the loss of the target. Cost is measured by use of the conditional risk equation in which the protection system ineffectiveness is multiplied by the consequence to society of a successful adversary attempt. The consequences which are used in the MSSA process were developed in the summer of the 1986 by a consensus of DOE personnel and contractors. There are separate consequence tables for theft of SNM, radiological sabotage. The consequence values in the tables were deliberately not cross-normalized. The consequence values in each table correspond to a societal or DOE cost, for example, the consequence values for SNM theft compared to a normalized estimate of the expected number of fatalities from a successful use of the stolen material times an estimate of the likelihood of successfully using the material. Consequence values for radiological sabotage correspond very roughly to a similar expected fatality level. Values for industrial sabotage are an estimate of the impact on DOE weapons production or impact on the nuclear weapons stockpile. Problems have arisen in the use of these tables and are discussed in the paper.

  11. It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain. (United States)

    Janssens, Derek H; Lee, Cheng-Yu


    During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion.

  12. Consequences of Accounting Standards

    Institute of Scientific and Technical Information of China (English)

    Cai Mingyue


    The first part of this article consists in attempting to highlight the importance of concerning about the economic consequences and introducing the foundation of economic consequence theory, proposing that the accounting standard is not only a kind of technical standard, it also has the economic consequences, so it becomes the object which all quarters special interest group gambles to get latent profit. After general characterization of the economic consequences in the second part, the article gives a description of the influences the change of accounting standards bring to the government, the ordinary investors and creditors, the auditors, and the enterprise, establishing a framework that how those groups react as the economic consequences in the third part. The fourth section compare technical theory and accounting standards theory, links the basic norms of accounting such as conservatism, relevance and reliability to the methods of escaping the harm of economic consequences, then proposes some specific methods in the formuhtion of accounting standard. Finally, the article utilizes the methods to settle the problems appearing in Chinese market.

  13. Interdependence of cell growth and gene expression: origins and consequences. (United States)

    Scott, Matthew; Gunderson, Carl W; Mateescu, Eduard M; Zhang, Zhongge; Hwa, Terence


    In bacteria, the rate of cell proliferation and the level of gene expression are intimately intertwined. Elucidating these relations is important both for understanding the physiological functions of endogenous genetic circuits and for designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing the allocation of resources toward protein synthesis and other aspects of cell growth. A theory incorporating these constraints can accurately predict how cell proliferation and gene expression affect one another, quantitatively accounting for the effect of translation-inhibiting antibiotics on gene expression and the effect of gratuitous protein expression on cell growth. The use of such empirical relations, analogous to phenomenological laws, may facilitate our understanding and manipulation of complex biological systems before underlying regulatory circuits are elucidated.

  14. Labor market institutions in OECD countries : Origins and consequences

    NARCIS (Netherlands)

    Belot, M.V.K.


    This thesis is a contribution to the field of labor economics. It investigates the effects of labor market institutions, such as the labor taxes, unemployment benefits, labor standards and industrial relations systems on the labor market performance. It also raises the question of their legitimacy,

  15. Evolutionary origin and consequences of uniparental mitochondrial inheritance

    NARCIS (Netherlands)

    Hoekstra, R.F.


    In the great majority of sexual organisms, cytoplasmic genomes such as the mitochondrial genome are inherited (almost) exclusively through only one, usually the maternal, parent. This rule probably evolved to minimize the potential spread of selfish cytoplasmic genomic mutations through a species. M

  16. Brain lesions in preterms: origin, consequences and compensation

    DEFF Research Database (Denmark)

    Krageloh-Mann, I; Toft, P; Lunding, J;


    , with the exception that symptoms of attention deficit hyperactivity disorder were related to mild MRI abnormalities. This could mean that with respect to cognitive functions, mild or unilateral periventricular MRI lesions could be compensated. However, as among preterms without mental retardation (n = 19), IQ...... in terms of neurology and neuropsychology. Abnormal MRI was found in 19 children. Low oxygen delivery to the brain was found in 63% of them, in contrast to 12.5% in those with normal MRI, indicating neonatal hypoxia-ischemia as an important factor. The MRI abnormalities were mainly periventricular lesions...... of motor tracts), mental retardation (bilateral extensive white matter reduction or cerebellar atrophy) and severe visual impairment (severe optic radiation involvement). A morphological correlate for minor disabilities, i.e. functional variations in motor performance or intelligence, was not found...

  17. Evolutionary origins and ecological consequences of endophyte symbiosis with grasses. (United States)

    Clay, Keith; Schardl, Christopher


    Over the past 20 yr much has been learned about a unique symbiotic interaction between fungal endophytes and grasses. The fungi (Clavicipitaceae, Ascomycota) grow intercellularly and systemically in aboveground plant parts. Vertically transmitted asexual endophytes forming asymptomatic infections of cool-season grasses have been repeatedly derived from sexual species that abort host inflorescences. The phylogenetic distribution of seed-transmitted endophytes is strongly suggestive of cocladogenesis with their hosts. Molecular evidence indicates that many seed-transmitted endophytes are interspecific hybrids. Superinfection may result in hyphal fusion and parasexual recombination. Most endophytes produce one or more alkaloid classes that likely play some role in defending the host plant against pests. Hybridization may have led to the proliferation of alkaloid-production genes among asexual endophytes, favoring hybrids. The ergot alkaloid ergovaline, lolitrems, and lolines are produced by only a single sexual species, Epichloë festucae, but they are common in seed-transmitted endophytes, suggesting that E. festucae contributed genes for their synthesis. Asexual hybrids may also be favored by the counteracting of the accumulation of deleterious mutations (Muller's rachet). Endophyte infection can provide other benefits, such as enhanced drought tolerance, photosynthetic rate, and growth. Estimates of infection frequency have revealed variable levels of infection with especially high prevalence in the subfamily Pooideae. Longitudinal studies suggest that the prevalence of seed-transmitted endophytes can increase rapidly over time. In field experiments, infected tall fescue suppressed other grasses and forbs relative to uninfected fescue and supported lower consumer populations. Unlike other widespread plant/microbial symbioses based on the acquisition of mineral resources, grass/endophyte associations are based primarily on protection of the host from biotic and abiotic stresses.

  18. Rossi Prize Lecture: Gamma Ray Bursts: Origins and Consequences (United States)

    Meszaros, P.


    Some of the major stepping stones towards uncovering the mystery of gamma ray bursts will be discussed. This is an unfinished process, new observations being expected in the near future. I will review the current observational status, and discuss the present theoretical understanding of GRB, as well as the possible impact of future missions and experiments.

  19. Determinants and Consequences of Obesity (United States)

    Hruby, Adela; Manson, JoAnn E.; Qi, Lu; Malik, Vasanti S.; Rimm, Eric B.; Sun, Qi; Willett, Walter C.


    Objectives. To review the contribution of the Nurses’ Health Studies (NHS and NHS II) in addressing hypotheses regarding risk factors for and consequences of obesity. Methods. Narrative review of the publications of the NHS and NHS II between 1976 and 2016. Results. Long-term NHS research has shown that weight gain and being overweight or obese are important risk factors for type 2 diabetes, cardiovascular diseases, certain types of cancers, and premature death. The cohorts have elucidated the role of dietary and lifestyle factors in obesity, especially sugar-sweetened beverages, poor diet quality, physical inactivity, prolonged screen time, short sleep duration or shift work, and built environment characteristics. Genome-wide association and gene–lifestyle interaction studies have shown that genetic factors predispose individuals to obesity but that such susceptibility can be attenuated by healthy lifestyle choices. This research has contributed to evolving clinical and public health guidelines on the importance of limiting weight gain through healthy dietary and lifestyle behaviors. Conclusions. The NHS cohorts have contributed to our understanding of the risk factors for and consequences of obesity and made a lasting impact on clinical and public health guidelines on obesity prevention. PMID:27459460

  20. Acromegaly : irreversible clinical consequences

    NARCIS (Netherlands)

    Wassenaar, Monica Johanna Elisabeth


    This thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the considerable prevalence of diverse morbidity in these patients, during the active phase of the disease but even

  1. Hepatic steatosis : metabolic consequences

    NARCIS (Netherlands)

    Boer, Adriana Maria den


    In this thesis we focused on the causes and consequences of hepatic steatosis. Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance and type 2 diabetes mellitus. The mechanism unde

  2. Culturing in serum-free culture medium on collagen type-I-coated plate increases expression of CD133 and retains original phenotype of HT-29 cancer stem cell

    Directory of Open Access Journals (Sweden)

    Zahra Arab-Bafrani


    Conclusion: Finding of this study suggested that CSCs derived from colon cancer cell line (HT-29 can be propagated and form colonospheres in serum-free culture medium on collagen type-I. According to maintenance of their original phenotype in these conditions, it seems serum-free culture medium on collagen type-I is a suitable way to drug screening of HT-29 CSCs.

  3. A novel de novo BRCA2 mutation of paternal origin identified in a Spanish woman with early onset bilateral breast cancer. (United States)

    Diez, Orland; Gutiérrez-Enríquez, Sara; Mediano, Carmen; Masas, Miriam; Saura, Cristina; Gadea, Neus; Balmaña, Judith


    Germ line mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mutations in any of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary breast/ovarian cancer, we identified a novel germ line mutation in the BRCA2 gene (c.51dupA) in a patient with early onset bilateral breast cancer and no family history of the disease. None of her parents carried the mutation, and paternity was confirmed. Subsequent molecular analysis demonstrated that the mutation was a novel de novo germ line mutation located in the paternal allele of the BRCA2 gene.

  4. BRCA1--conductor of the breast stem cell orchestra: the role of BRCA1 in mammary gland development and identification of cell of origin of BRCA1 mutant breast cancer. (United States)

    Buckley, Niamh E; Mullan, Paul B


    Breast cancer treatment has been increasingly successful over the last 20 years due in large part to targeted therapies directed against different subtypes. However, basal-like breast cancers still represent a considerable challenge to clinicians and scientists alike since the pathogenesis underlying the disease and the target cell for transformation of this subtype is still undetermined. The considerable similarities between basal-like and BRCA1 mutant breast cancers led to the hypothesis that these cancers arise from transformation of a basal cell within the normal breast epithelium through BRCA1 dysfunction. Recently, however, a number of studies have called this hypothesis into question. This review summarises the initial findings which implicated the basal cell as the cell of origin of BRCA1 related basal-like breast cancers, as well as the more recent data which identifies the luminal progenitor cells as the likely target of transformation. We compare a number of key studies in this area and identify the differences that could explain some of the contradictory findings. In addition, we highlight the role of BRCA1 in breast cell differentiation and lineage determination by reviewing recent findings in the field and our own observations suggesting a role for BRCA1 in stem cell regulation through activation of the p63 and Notch pathways. We hope that through an increased understanding of the BRCA1 role in breast differentiation and the identification of the cell(s) of origin we can improve treatment options for both BRCA1 mutant and basal-like breast cancer subgroups.

  5. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can


    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  6. Cancer (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  7. Phenomenological consequences of supersymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Hinchliffe, I.; Littenberg, L.


    This report deals with the phenomenological consequences of supersymmetric theories, and with the implications of such theories for future high energy machines. It is concerned only with high energy predictions of supersymmetry; low energy consequences (for example in the K/sub o/anti K/sub o/ system) are discussed in the context of future experiments by another group, and will be mentioned briefly only in the context of constraining existing models. However a brief section is included on the implication for proton decay, although detailed experimental questions are not discussed. The report is organized as follows. Section I consists of a brief review of supersymmetry and the salient features of existing supersymmetric models; this section can be ignored by those familiar with such models since it contains nothing new. Section 2 deals with the consequences for nucleon decay of SUSY. The remaining sections then discuss the physics possibilities of various machines; e anti e in Section 3, ep in Section 4, pp (or anti pp) colliders in Section 5 and fixed target hadron machines in Section 6.

  8. Coagulant activity and cellular origin of circulating tissue factor exposing microparticles in cancer patients - two forms of TF-exposing microparticles

    NARCIS (Netherlands)

    Kleinjan, A.; Boing, A. N.; Di Nisio, M.; Twint, D.; Kamphuisen, P. W.; Nanayakkara, P.; Buller, H. R.; Nieuwland, R.


    Background: Because plasma of cancer patients presenting with venous thrombosis contains high numbers of tissue factor (TF)-exposing microparticles (TF-MP1), TF-MP have been causally linked to the occurrence of venous thrombosis in cancer patients. The relationship between numbers of TF-exposing MP

  9. Dana-Farber Cancer Institute | Office of Cancer Genomics (United States)

    Functional Annotation of Cancer Genomes Principal Investigator: William C. Hahn, M.D., Ph.D. The comprehensive characterization of cancer genomes has and will continue to provide an increasingly complete catalog of genetic alterations in specific cancers. However, most epithelial cancers harbor hundreds of genetic alterations as a consequence of genomic instability. Therefore, the functional consequences of the majority of mutations remain unclear.

  10. Intraperitoneal chemotherapy hyperthermia (HIPEC) for peritoneal carcinomatosis of ovarian cancer origin by fluid and CO2 recirculation using the closed abdomen technique (PRS-1.0 Combat): A clinical pilot study. (United States)

    Sánchez-García, Susana; Villarejo-Campos, Pedro; Padilla-Valverde, David; Amo-Salas, Mariano; Martín-Fernández, Jesús


    Background This paper reports a study of 21 patients with peritoneal carcinomatosis from ovarian cancer who underwent cytoreductive surgery and HIPEC by means of PRS-1.0 Combat®, a new model for closed abdomen HIPEC aimed at improving fluid distribution with assistance from a CO2 recirculation system. This new technology has been previously shown to be successful in an experimental study (pig model) performed by our group, and has been approved for use in our hospital. Methods Twenty-one patients with peritoneal carcinomatosis of ovarian cancer origin were included in the study. Cytoreductive surgery and HIPEC were performed by a closed abdomen fluid and CO2 recirculation technique using the PRS-1.0 Combat(®) model. We analysed the intraoperative safety tolerance and post-operative morbidity and mortality during the first 30 days. Results Between November 2011 and March 2014 21 patients with epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stage II-IV, were included in the study. During the procedure there were no significant haemodynamic or analytical disturbances. Complication rates were 38.1% and 57.14% for grade III/IV and minor (grade I/II) complications, respectively. Post-operative mortality was 4.76% (one patient). Complete cytoreductive surgery and intraperitoneal chemotherapy improved overall survival and disease-free survival in women with advanced ovarian cancer. The association of intra-abdominal hyperthermia with chemotherapy (HIPEC) increased the therapeutic benefit. Conclusions This study has shown that closed abdomen intraperitoneal chemohyperthermia by a fluid and CO2 recirculation system (PRS-1.0 Combat(®)) can be a safe and feasible model for the treatment of peritoneal carcinomatosis of ovarian cancer origin.

  11. An examination of the consequences in high consequence operations

    Energy Technology Data Exchange (ETDEWEB)

    Spray, S.D.; Cooper, J.A.


    Traditional definitions of risk partition concern into the probability of occurrence and the consequence of the event. Most safety analyses focus on probabilistic assessment of an occurrence and the amount of some measurable result of the event, but the real meaning of the ``consequence`` partition is usually afforded less attention. In particular, acceptable social consequence (consequence accepted by the public) frequently differs significantly from the metrics commonly proposed by risk analysts. This paper addresses some of the important system development issues associated with consequences, focusing on ``high consequence operations safety.``

  12. Original pedagogues

    DEFF Research Database (Denmark)

    Schmidt, Christina Haandbæk

    Original pedagogues Distention between competences and originality By Christina Haandbæk Schmidt, ph. d. student Aarhus University, Denmark This presentation concerns a Ph.D. project (Sept. 2012 –Sept. 2015) about pedagogues in day care facilities and their struggles to develop and retain...... of pedagogues and in everyday life in daycare facilities. The competence term includes at least two discourses of interest; a pedagogical competence discourse and a political jurisdiction discourse which forms a distention between authenticity and competence. In order that pedagogues may regain their autonomy I...

  13. "Origin," "creation," and "origin of life" some conceptual considerations. (United States)

    Charpa, Ulrich


    This paper opens by drawing attention to the fact that there is some conceptual confusion with regard to "origin" and "creation." This has its historical roots in the beginnings of modern science and undoubtedly affects our positioning towards the evolutionism/creationism-debate. This article argues that there are relevant ontological, epistemological, thematic, methodological, and logical differences between "origin" and "creation." As a result, the analysis suggests keeping the usage of both concepts strictly quite separate. Creation is not simply another word for origin nor does it stand for an (from a rigid scientific point of view) awkward example of an origin. Irrespective of the apparent similarities as explanatory factors, origin and creation belong to fundamentally different types of concepts. Consequently, "origin of life" and those scientific projects connected to it present themselves as something distinct that neither competes nor meshes with thinking about creation.

  14. Unintended Consequences of Remittance

    Directory of Open Access Journals (Sweden)

    Adediran Daniel Ikuomola


    Full Text Available Research on migrants’ remittance in Nigeria has largely focused on the contribution to national development and economic well-being of family members. In contrast, this article explores the way in which remittance serves as potential sources of conflict within migrant households. The article investigates intra-household conflicts related to migrant remittances, revealing the contradictory and unintended consequences of remittances destabilizing cordial relationships between migrants and family members. Within the family (mainly extended families, the sharing of remittance is often accompanied with envy, distrust, and accusation of witch hunt. While improper utilization and accountability of remittances strain relationships, migrants are forced to re-strategize on how remittances get to their relatives and sometimes cut off communication and remittances with family members. Based on the qualitative data collected in Benin City (Edo State in Nigeria, the article investigates intra-household conflicts emanating from migrant remittances, from the perspectives of migrants on holidays.

  15. Original Copies

    DEFF Research Database (Denmark)

    Sørensen, Tim Flohr


    of similarity by looking at artefactual similarity as the results of prototyping and as a production of simulacra. In this light, the concept of copying turns out to be more than simply a matter of trying to imitate an exotic or prestigious original, and it fundamentally raises the question how different a copy...

  16. The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy. (United States)

    Fan, Ping; Maximov, Philipp Y; Curpan, Ramona F; Abderrahman, Balkees; Jordan, V Craig


    During the past 20 years our understanding of the control of breast tumor development, growth and survival has changed dramatically. The once long forgotten application of high dose synthetic estrogen therapy as the first chemical therapy to treat any cancer has been resurrected, refined and reinvented as the new biology of estrogen-induced apoptosis. High dose estrogen therapy was cast aside once tamoxifen, from its origins as a failed "morning after pill", was reinvented as the first targeted therapy to treat any cancer. The current understanding of the mechanism of estrogen-induced apoptosis is described as a consequence of acquired resistance to long term antihormone therapy in estrogen receptor (ER) positive breast cancer. The ER signal transduction pathway remains a target for therapy in breast cancer despite "antiestrogen" resistance, but becomes a regulator of resistance. Multiple mechanisms of resistance come into play: Selective ER modulator (SERM) stimulated growth, growth factor/ER crosstalk, estrogen-induced apoptosis and mutations of ER. But it is with the science of estrogen-induced apoptosis that the next innovation in women's health will be developed. Recent evidence suggests that the glucocorticoid properties of medroxyprogesterone acetate blunt estrogen-induced apoptosis in estrogen deprived breast cancer cell populations. As a result breast cancer develops during long-term hormone replacement therapy (HRT). A new synthetic progestin with estrogen-like properties, such as the 19 nortestosterone derivatives used in oral contraceptives, will continue to protect the uterus from unopposed estrogen stimulation but at the same time, reinforce apoptosis in vulnerable populations of nascent breast cancer cells.

  17. The Chernobyl catastrophe: Consequences on human health

    Energy Technology Data Exchange (ETDEWEB)

    Yablokov, A.; Labunska, I.; Blokov, I.; Santillo, D.; Johnston, P.; Stringer, R.; Sadownichik, T. (eds.); Antipkin, Yu.G. [Institute of Paediatrics, Obstetrics and Gynaecology, Academy of Medical Sciences, Kiev (Ukraine); Arabskaya, L.P. [Institute of Paediatrics, Obstetrics and Gynaecology, Academy of Medical Sciences, Kiev (Ukraine); Bazyka, D.A. [Research Centre for Radiation Medicine, Academy of Medical Sciences, Kiev (Ukraine)] (and others)


    This new Greenpeace report estimates that the full consequences of the Chernobyl disaster could top a quarter of a million cancers cases and nearly 100,000 fatal cancers. It reports that the report involved 52 respected scientists and includes information never before published in English. It challenges the International Atomic Energy Agency Chernobyl Forum report, which predicted 4,000 additional deaths attributable to the accident as a gross simplification of the real breadth of human suffering. Their data, based on Belarus national cancer statistics, predicts approximately 270,000 cancers and 93,000 fatal cancer cases caused by Chernobyl. The report also concludes that on the basis of demographic data, during the last 15 years, 60,000 people have additionally died in Russia because of the Chernobyl accident, and estimates of the total death toll for the Ukraine and Belarus could reach another 140,000. The report also looks into the ongoing health impacts of Chernobyl and concludes that radiation from the disaster has had a devastating effect on survivors; damaging immune and endocrine systems, leading to accelerated ageing, cardiovascular and blood illnesses, psychological illnesses, chromosomal aberrations and an increase in foetal deformations.

  18. Missense mutations (p.H371Y, p.D438Y) in gene CHEK2 are associated with breast cancer risk in women of Balochistan origin. (United States)

    Baloch, Abdul Hameed; Daud, Shakeela; Raheem, Nafeesa; Luqman, Muhammad; Ahmad, Adeel; Rehman, Abdul; Shuja, Jameela; Rasheed, Saeeda; Ali, Akhtar; Kakar, Naseebullah; Naseeb, Hafiz Khush; Mengal, Mohammad Alam; Awan, Muhammad Arif; Wasim, Muhammad; Baloch, Dost Mohammad; Ahmad, Jamil


    CHEK2 encodes a serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways. CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1. Most women with breast and/or ovarian cancer are not carriers of mutant BRCA1 or BRCA2. Multiple studies have shown that a CHEK2*1100delC confers about a two-fold increased risk of breast cancer in unselected females and a tenfold increase in males. Moreover, studies have shown that first-degree relatives of bilateral breast cancer cases who carried the CHEK2*1100delC allele had an eight-fold increased risk of breast cancer. It has been suggested that CHEK2 functions as a low-penetrance susceptibility gene for cancers and multiplies the risks associated with other gene(s) to increase cancer risk. The main goal of this study was to evaluate and to compare the role of truncating mutations, splice junction mutations and rare missense substitutions in breast cancer susceptibility gene CHEK2. Present study was performed on 140 individuals including 70 breast cancer patients both with and without family history and 70 normal individuals. Written consent was obtained and 3 ml intravenous blood was drawn from all the subjects. DNA was extracted from all the samples through inorganic method published already. Primers were synthesized for all the 14 exons of CHEK2 gene. Coding and adjacent intronic sequences of CHEK2 gene were amplified and sequenced. Two genetic variants (p.H371Y, p.D438Y) were found in exon 10 and exon 11 of gene CHEK2 which were not found in any of the 70 control individuals from same geographical area and ethnic group. The genetic variant c.1312G>T (p.D438Y) identified in a patient with a family history of breast cancer. To our knowledge, this is first mutation scanning study of gene CHEK2 from Balochistan population.

  19. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi


    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  20. Developmental origins of disruptive behaviour problems: the 'original sin' hypothesis, epigenetics and their consequences for prevention. (United States)

    Tremblay, Richard E


    This paper reviews publications on developmental trajectories of disruptive behaviour (DB) problems (aggression, opposition-defiance, rule breaking, and stealing-vandalism) over the past decade. Prior to these studies two theoretical models had strongly influenced research on DB: social learning and disease onset. According to these developmental perspectives, children learn DB from their environment and onset of the disease is triggered by accumulated exposition to disruptive models in the environment, including the media. Most of the evidence came from studies of school age children and adolescents. Longitudinal studies tracing developmental trajectories of DB from early childhood onwards suggest an inversed developmental process. DB are universal during early childhood. With age, children learn socially acceptable behaviours from interactions with their environment. A 'disease' status is given to children who fail to learn the socially acceptable behaviours. The mechanisms that lead to deficits in using socially accepted behaviours are strongly intergenerational, based on complex genetic and environmental contributions, including epigenetic mechanisms. Prevention of these deficits requires early, intensive and long-term support to parents and child. Newly discovered epigenetic mechanisms suggest that intensive perinatal interventions will have impacts on numerous aspects of physical and mental health, including DB. This review also concludes that: a) subtypes of disruptive behaviours should not be aggregated because they have different developmental trajectories and require specific corrective interventions; b) the overt-covert and destructive-nondestructive dimensions appear the most useful to create DB subtypes; c) overt DB onset before covert DB because the latter require more brain maturation; d) DB subtype taxonomies are more useful for clinicians than developmental taxonomies because the latter are post mortem diagnoses and clinicians' retrospective information is unreliable; e) we need large-scale collaborative preventive experimental interventions starting during early pregnancy to advance knowledge on causes and prevention of DB problems.

  1. Seismic Consequence Abstraction

    Energy Technology Data Exchange (ETDEWEB)

    M. Gross


    The primary purpose of this model report is to develop abstractions for the response of engineered barrier system (EBS) components to seismic hazards at a geologic repository at Yucca Mountain, Nevada, and to define the methodology for using these abstractions in a seismic scenario class for the Total System Performance Assessment - License Application (TSPA-LA). A secondary purpose of this model report is to provide information for criticality studies related to seismic hazards. The seismic hazards addressed herein are vibratory ground motion, fault displacement, and rockfall due to ground motion. The EBS components are the drip shield, the waste package, and the fuel cladding. The requirements for development of the abstractions and the associated algorithms for the seismic scenario class are defined in ''Technical Work Plan For: Regulatory Integration Modeling of Drift Degradation, Waste Package and Drip Shield Vibratory Motion and Seismic Consequences'' (BSC 2004 [DIRS 171520]). The development of these abstractions will provide a more complete representation of flow into and transport from the EBS under disruptive events. The results from this development will also address portions of integrated subissue ENG2, Mechanical Disruption of Engineered Barriers, including the acceptance criteria for this subissue defined in Section of the ''Yucca Mountain Review Plan, Final Report'' (NRC 2003 [DIRS 163274]).


    Directory of Open Access Journals (Sweden)

    Chernyshov Alexander V.


    Full Text Available The article investigates the origins of music in electronic regular broadcasting, which conditions have appeared in the XIX century. They stand out in the "telephone concerts", "phonograph concerts" and the proto-sound films (T.Edison, W.Dickson, Ch.Pathé, O.Messter. In the early twentieth century, a clear prototype of mediamusic playing by the music of "silent" films, which has been divided on the on-screen and offscreen sound layers, the method of compilation, the basics of synchronization between musical sound and off-music montage-structures. In addition, the origins of music of electronic mass media can be regarded as attempts to understand the "musical" noise features, which subsequently materialize in the phenomenon of "noisemusic" of media audio-score (L.Russolo, Ars.Avraamov, D.Vertov, W.Ruttmann, N.Voinov, P.Schaeffer. Are considered Russian, European and North American experiences.

  3. Mitochondrial origins.


    Yang, D.; Oyaizu, Y; Oyaizu, H; Olsen, G J; Woese, C R


    The 16S ribosomal RNA sequences from Agrobacterium tumefaciens and Pseudomonas testosteroni have been determined to further delimit the origin of the endosymbiont that gave rise to the mitochondrion. These two prokaryotes represent the alpha and beta subdivisions, respectively, of the so-called purple bacteria. The endosymbiont that gave rise to the mitochondrion belonged to the alpha subdivision, a group that also contains the rhizobacteria, the agrobacteria, and the rickettsias--all prokary...

  4. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

    NARCIS (Netherlands)

    S. Blein (Sophie); C. Bardel (Claire); V. Danjean (Vincent); L. McGuffog (Lesley); S. Healey (Sue); D. Barrowdale (Daniel); A. Lee (Andrew); J. Dennis (Joe); K.B. Kuchenbaecker (Karoline); P. Soucy (Penny); M.B. Terry (Mary Beth); W. Chung (Wendy); D. Goldgar (David); S.S. Buys (Saundra); R. Janavicius (Ramunas); L. Tihomirova (Laima); N. Tung (Nadine); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); A-M. Gerdes (Anne-Marie); B. Ejlertsen (Bent); F. Nielsen (Finn); T.V.O. Hansen (Thomas); A. Osorio (Ana); J. Benítez (Javier); R.A. Conejero (Raquel Andrés); E. Segota (Ena); J.N. Weitzel (Jeffrey); M. Thelander (Margo); P. Peterlongo (Paolo); P. Radice (Paolo); V. Pensotti (Valeria); R. Dolcetti (Riccardo); B. Bonnani (Bernardo); B. Peissel (Bernard); D. Zaffaroni (D.); G. Scuvera (Giulietta); S. Manoukian (Siranoush); L. Varesco (Liliana); G.L. Capone (Gabriele L.); L. Papi (Laura); L. Ottini (Laura); D. Yannoukakos (Drakoulis); I. Konstantopoulou (I.); J. Garber (Judy); U. Hamann (Ute); A. Donaldson (Alan); A. Brady (A.); C. Brewer (Carole); C. Foo (Claire); D.G. Evans (Gareth); D. Frost (Debra); D. Eccles (Diana); F. Douglas (Fiona); J. Cook (Jackie); L. Adlard; J. Barwell (Julian); L.J. Walker (Lisa); L. Izatt (Louise); L. Side (Lucy); M.J. Kennedy (John); M. Tischkowitz (Marc); M.T. Rogers (Mark); M.E. Porteous (Mary); P.J. Morrison (Patrick); R. Platte (Radka); R. Eeles (Ros); R. Davidson (Rosemarie); S. Hodgson (Shirley); T.J. Cole (Trevor); A.K. Godwin (Andrew); C. Isaacs (Claudine); K.B.M. Claes (Kathleen B.M.); K. De Leeneer (Kim); A. Meindl (Alfons); P.A. Gehrig (Paola A.); B. Wapenschmidt (Barbara); C. Sutter (Christian); C. Engel (Christoph); D. Niederacher (Dieter); D. Steinemann (Doris); H. Plendl (Hansjoerg); K. Kast (Karin); K. Rhiem (Kerstin); N. Ditsch (Nina); N. Arnold (Norbert); R. Varon-Mateeva (Raymonda); R.K. Schmutzler (Rita); S. Preisler-Adams (Sabine); N.B. Markov (Nadja Bogdanova); S. Wang-Gohrke (Shan); A. de Pauw (Antoine); C. Lefol (Cédrick); C. Lasset (Christine); D. Leroux (Dominique); E. Rouleau (Etienne); F. Damiola (Francesca); H. Dreyfus (Hélène); L. Barjhoux (Laure); L. Golmard (Lisa); N. Uhrhammer (Nancy); V. Bonadona (Valérie); V. Sornin (Valérie); Y.-J. Bignon (Yves-Jean); J. Carter (Jonathan); L. van Le (Linda); M. Piedmonte (Marion); P. DiSilvestro (Paul); M. de La Hoya (Miguel); T. Caldes (Trinidad); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); A. Jager (Agnes); A.M.W. van den Ouweland (Ans); C.M. Kets; C.M. Aalfs (Cora); F.E. van Leeuwen (F.); F.B.L. Hogervorst (Frans); E.J. Meijers-Heijboer (Hanne); J.C. Oosterwijk (Jan); K.E. van Roozendaal (Kees); M.A. Rookus (M.); P. Devilee (Peter); R.B. van der Luijt (Rob); E. Olah; O. Díez (Orland); A. Teulé (A.); C. Lazaro (Conxi); I. Blanco (Ignacio); J. Del Valle (Jesús); A. Jakubowska (Anna); G. Sukiennicki (Grzegorz); J. Gronwald (Jacek); J. Lubinski (Jan); K. Durda (Katarzyna); K. Jaworska-Bieniek (Katarzyna); B.A. Agnarsson (Bjarni); C. Maugard; A. Amadori (Alberto); M. Montagna (Marco); P.J. Teixeira; A.B. Spurdle (Amanda); W.D. Foulkes (William); C. Olswold (Curtis); N.M. Lindor (Noralane); V.S. Pankratz (Shane); C. Szabo (Csilla); A. Lincoln (Anne); L. Jacobs (Lauren); M. Corines (Marina); M. Robson (Mark); J. Vijai (Joseph); A. Berger (Andreas); A. Fink-Retter (Anneliese); C.F. Singer (Christian); C. Rappaport (Christine); D.G. Kaulich (Daphne Gschwantler); G. Pfeiler (Georg); M.-K. Tea; M.H. Greene (Mark); P.L. Mai (Phuong); G. Rennert (Gad); E.N. Imyanitov (Evgeny); A.M. Mulligan (Anna Marie); G. Glendon (Gord); I.L. Andrulis (Irene); S. Tchatchou (Sandrine); A.E. Toland (Amanda); I.S. Pedersen (Inge Sokilde); M. Thomassen (Mads); T.A. Kruse (Torben); U.B. Jensen; M.A. Caligo (Maria); E. Friedman (Eitan); J. Zidan (Jamal); Y. Laitman (Yael); A. Lindblom (Annika); B. Melin (Beatrice); B. Arver (Brita Wasteson); N. Loman (Niklas); R. Rosenquist (R.); O.I. Olopade (Olofunmilayo); R. Nussbaum (Robert); S.J. Ramus (Susan); K.L. Nathanson (Katherine); S.M. Domchek (Susan); R. Rebbeck (Timothy); B.K. Arun (Banu); G. Mitchell (Gillian); B. Karlan; K.J. Lester (Kathryn); S. Orsulic (Sandra); D. Stoppa-Lyonnet (Dominique); G. Thomas (Gilles); J. Simard (Jacques); F.J. Couch (Fergus); K. Offit (Kenneth); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S. Mazoyer (Sylvie); C. Phelan (Catherine); O. Sinilnikova (Olga); D.G. Cox (David)


    textabstractIntroduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of whi

  5. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

    NARCIS (Netherlands)

    Blein, S.; Bardel, C.; Danjean, V.; McGuffog, L.; Healey, S.; Barrowdale, D.; Lee, A.; Dennis, J.; Kuchenbaecker, K.B.; Soucy, P.; Terry, M.B.; Chung, W.K.; Goldgar, D.E.; Buys, S.S.; Janavicius, R.; Tihomirova, L.; Tung, N.; Dorfling, C.M.; Rensburg, E.J. van; Neuhausen, S.L.; Ding, Y.C.; Gerdes, A.M.; Ejlertsen, B.; Nielsen, F.C.; Hansen, T.V.; Osorio, A.; Benitez, J.; Conejero, R.A.; Segota, E.; Weitzel, J.N.; Thelander, M.; Peterlongo, P.; Radice, P.; Pensotti, V.; Dolcetti, R.; Bonanni, B.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Manoukian, S.; Varesco, L.; Capone, G.L.; Papi, L.; Ottini, L.; Yannoukakos, D.; Konstantopoulou, I.; Garber, J.; Hamann, U.; Donaldson, A.; Brady, A.; Brewer, C.; Foo, C.; Evans, D.G.; Frost, D.; Eccles, D.; Douglas, F.; Cook, J.; Adlard, J.; Barwell, J.; Walker, L.; Izatt, L.; Side, L.E.; Kennedy, M.J.; Tischkowitz, M.; Rogers, M.T.; Porteous, M.E.; Morrison, P.J.; Platte, R.; Eeles, R.; Davidson, R.; Hodgson, S.; Cole, T.; Godwin, A.K.; Isaacs, C.; Claes, K.; Leeneer, K. De; Meindl, A.; Gehrig, A.; Wappenschmidt, B.; Sutter, C.; Engel, C.; Niederacher, D.; Steinemann, D.; Plendl, H.; Kast, K.; Rhiem, K.; Ditsch, N.; Arnold, N.; Varon-Mateeva, R.; Schmutzler, R.K.; Preisler-Adams, S.; Markov, N.B.; Wang-Gohrke, S.; Pauw, A. de; Lefol, C.; Lasset, C.; Leroux, D.; Rouleau, E.; Damiola, F.; Dreyfus, H.; Barjhoux, L.; Golmard, L.; Uhrhammer, N.; Bonadona, V.; Sornin, V.; Bignon, Y.J.; Carter, J.; Le, L; Piedmonte, M.; DiSilvestro, P.A.; Hoya, M. de la; Caldes, T.; Nevanlinna, H.; Aittomaki, K.; Jager, A.; Ouweland, A.M. van den; Kets, C.M.; Aalfs, C.M.; Leeuwen, F.E. van; Hogervorst, F.B.; Meijers-Heijboer, H.E.; Oosterwijk, J.C.; Roozendaal, K.E. van; Rookus, M.A.; Devilee, P.; Luijt, R.B. van der; Olah, E.; Diez, O.; Teule, A.; Lazaro, C.; Blanco, I.; Valle, J.; Jakubowska, A.; Sukiennicki, G.; Gronwald, J.; Lubinski, J.; Durda, K.; Jaworska-Bieniek, K.; Agnarsson, B.A.; Maugard, C.; Amadori, A.; Montagna, M.; Teixeira, M.R.; Spurdle, A.B.; Foulkes, W.; Olswold, C.; Lindor, N.M.; Pankratz, V.S.; Szabo, C.I.; Lincoln, A.; Jacobs, L.; Corines, M.; Robson, M.; Vijai, J.; Berger, A.; Fink-Retter, A.; Singer, C.F.; Rappaport, C.; Kaulich, D.G.; Pfeiler, G.; Tea, M.K.; Greene, M.H.; Mai, P.L.; Rennert, G.; Imyanitov, E.N.; Mulligan, A.M.; Glendon, G.; Andrulis, I.L.; Tchatchou, S.; Toland, A.E.; Pedersen, I.S.; Thomassen, M.; Kruse, T.A.; Jensen, U.B.; Caligo, M.A.; Friedman, E.; Zidan, J.; Laitman, Y.; Lindblom, A.; Melin, B.; Arver, B.; Loman, N.; Rosenquist, R.; Olopade, O.I.; Nussbaum, R.L.; Ramus, S.J.; Nathanson, K.L.; Domchek, S.M.; Rebbeck, T.R.; Arun, B.K.; Mitchell, G.; Karlan, B.Y.; Lester, J.; Orsulic, S.; Stoppa-Lyonnet, D.; Thomas, G; Simard, J.; Couch, F.J.; Offit, K.; Easton, D.F.; Chenevix-Trench, G.; Antoniou, A.C.; Mazoyer, S.; Phelan, C.M.; Sinilnikova, O.M.; Cox, D.G.


    INTRODUCTION: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitoc

  6. Comparison of a gene expression profiling strategy to standard clinical work-up for determination of tumour origin in cancer of unknown primary (CUP)

    DEFF Research Database (Denmark)

    Ades, Felipe; de Azambuja, Evandro; Daugaard, Gedske;


    CupPrint® is a genomic signature able to identify 47 different cancer types. The aim of our study was to compare the accuracy of this genomic signature to that of a full clinical work-up in diagnosing the primary tumour site. Patients with newly diagnosed, untreated metastatic tumours were eligib...

  7. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

    NARCIS (Netherlands)

    Blein, Sophie; Bardel, Claire; Danjean, Vincent; McGuffog, Lesley; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B.; Soucy, Penny; Terry, Mary Beth; Chung, Wendy K.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Neuhausen, Susan L.; Ding, Yuan Chun; Gerdes, Anne-Marie; Ejlertsen, Bent; Nielsen, Finn C.; Hansen, Thomas V. O.; Osorio, Ana; Benitez, Javier; Andres Conejero, Raquel; Segota, Ena; Weitzel, Jeffrey N.; Thelander, Margo; Peterlongo, Paolo; Radice, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Bonanni, Bernardo; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush; Varesco, Liliana; Capone, Gabriele L.; Papi, Laura; Ottini, Laura; Yannoukakos, Drakoulis; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brady, Angela; Brewer, Carole; Foo, Claire; Evans, D. Gareth; Frost, Debra; Eccles, Diana; Douglas, Fiona; Cook, Jackie; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Tischkowitz, Marc; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Cole, Trevor; Godwin, Andrew K.; Isaacs, Claudine; Claes, Kathleen; De Leeneer, Kim; Meindl, Alfons; Gehrig, Andrea; Wappenschmidt, Barbara; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Schmutzler, Rita K.; Preisler-Adams, Sabine; Markov, Nadja Bogdanova; Wang-Gohrke, Shan; de Pauw, Antoine; Lefol, Cedrick; Lasset, Christine; Leroux, Dominique; Rouleau, Etienne; Damiola, Francesca; Dreyfus, Helene; Barjhoux, Laure; Golmard, Lisa; Uhrhammer, Nancy; Bonadona, Valerie; Sornin, Valerie; Bignon, Yves-Jean; Carter, Jonathan; Van Le, Linda; Piedmonte, Marion; DiSilvestro, Paul A.; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Aittomaki, Kristiina; Jager, Agnes; van den Ouweland, Ans M. W.; Kets, Carolien M.; Aalfs, Cora M.; van Leeuwen, Flora E.; Hogervorst, Frans B. L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Roozendaal, Kees E. P.; Rookus, Matti A.; Devilee, Peter; van der Luijt, Rob B.; Olah, Edith; Diez, Orland; Teule, Alex; Lazaro, Conxi; Blanco, Ignacio; Del Valle, Jesus; Jakubowska, Anna; Sukiennicki, Grzegorz; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Agnarsson, Bjarni A.; Maugard, Christine; Amadori, Alberto; Montagna, Marco; Teixeira, Manuel R.; Spurdle, Amanda B.; Foulkes, William; Olswold, Curtis; Lindor, Noralane M.; Pankratz, Vernon S.; Szabo, Csilla I.; Lincoln, Anne; Jacobs, Lauren; Corines, Marina; Robson, Mark; Vijai, Joseph; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Imyanitov, Evgeny N.; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L.; Tchatchou, Sandrine; Toland, Amanda Ewart; Pedersen, Inge Sokilde; Thomassen, Mads; Kruse, Torben A.; Jensen, Uffe Birk; Caligo, Maria A.; Friedman, Eitan; Zidan, Jamal; Laitman, Yael; Lindblom, Annika; Melin, Beatrice; Arver, Brita; Loman, Niklas; Rosenquist, Richard; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Ramus, Susan J.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Mitchell, Gillian; Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Stoppa-Lyonnet, Dominique; Thomas, Gilles; Simard, Jacques; Couch, Fergus J.; Offit, Kenneth; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Mazoyer, Sylvie; Phelan, Catherine M.; Sinilnikova, Olga M.; Cox, David G.


    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitoc

  8. RhoC a new target for therapeutic vaccination against metastatic cancer

    DEFF Research Database (Denmark)

    Wenandy, L.; Sorensen, R.B.; Straten, P.T.


    Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...

  9. Diagnostic Invasiveness and Psychosocial Consequences of False-Positive Mammography

    DEFF Research Database (Denmark)

    Heleno, Bruno M.; Siersma, Volkert Dirk; Brodersen, John


    of a cohort study of 454 womenwith abnormal screening mammography and 908 matched control women withnormal results. Using a condition-specific questionnaire (Consequences of Screening in Breast Cancer), we assessed 12 psychosocial consequences at 5 time points (0, 1, 6, 18, and 36 months after final diagnosis......) and compared the 2 groups of women with false-positives (invasive and noninvasive management groups). RESULTS: Among the 252 women with false-positive mammography eligible forthis study, psychosocial consequences were similar for those managed invasivelyand those managed noninvasively during the 36 months...... between those of women withnormal mammography and those of women determined to have breast cancer. CONCLUSIONS: We found no evidence that use of more invasive diagnosticswas associated with worse psychosocial consequences. It is therefore reasonableto pool subgroups of women with false...

  10. Original Thinking

    Directory of Open Access Journals (Sweden)

    Ashok Natarajan


    Full Text Available History that comes to us as a chronology of events is really a collective existence that is evolving through several stages to develop Individuality in all members of the society. The human community, nation states, linguistic groups, local castes and classes, and families are the intermediate stages in development of the Individual. The social process moves through phases of survival, growth, development and evolution. In the process it organizes the consciousness of its members at successive levels from social external manners, formed behavior, value-based character and personality to culminate in the development of Individuality. Through this process, society evolves from physicality to Mentality. The power of accomplishment in society and its members develops progressively through stages of skill, capacity, talent, and ability. Original thinking is made possible by the prior development of thinking that organizes facts into information. The immediate result of the last world war was a shift in reliance from physical force and action to mental conception and mental activity on a global scale. At such times no problem need defy solution, if only humanity recognizes the occasion for thinking and Original Thinking. The apparently insoluble problems we confront are an opportunity to formulate a comprehensive theory of social evolution. The immediate possibility is to devise complete solutions to all existing problems, if only we use the right method of thought development.

  11. A Report of Disseminated Carcinomatosis of the Bone Marrow Originating from Transverse Colon Cancer Successfully Treated with Chemotherapy Using XELOX plus Bevacizumab

    Directory of Open Access Journals (Sweden)

    Masayasu Naito


    Full Text Available A 61-year-old male, who had been admitted to another hospital due to disseminated intravascular coagulation (DIC, was referred to our hospital. Total colonoscopy, abdominal dynamic CT and positron-emission tomography revealed bone metastasis and multiple lymphocytic metastases from transverse colon cancer in addition to disseminated carcinomatosis of the bone marrow (DCBM. We immediately performed chemotherapy with XELOX + bevacizumab and denosumab against DCBM from transverse colon cancer in order to avoid radical surgery. In addition, we initiated the administration of recombinant human soluble thrombomodulin for 1 week to treat DIC. The patient was able to tolerate and receive 4 cycles of chemotherapy without any severe side effects. After receiving the 4 cycles of treatment, he recovered from DIC, and the bone and multiple lymphocytic metastases disappeared.

  12. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Roberto Hegg

    Full Text Available OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI for the rate of neutropenia between the two groups (12.61% was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯.

  13. A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients (United States)

    Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie


    OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

  14. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin | Office of Cancer Genomics (United States)

    Morin et al. describe recurrent somatic mutations in EZH2, a polycomb group oncogene. The mutation, found in the SET domain of this gene encoding a histone methyltransferase, is found only in a subset of lymphoma samples. Specifically, EZH2 mutations are found in about 12% of follicular lymphomas (FL) and almost 23% of diffuse large B-cell lymphomas (DLBCL) of germinal center origin. This paper goes on to demonstrate that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays.

  15. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Blein, Sophie; Bardel, Claire; Danjean, Vincent


    or unaffected individuals. RESULTS: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is......, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. CONCLUSIONS: This study illustrates how...

  16. The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer. (United States)

    Podlutsky, Andrej; Valcarcel-Ares, Marta Noa; Yancey, Krysta; Podlutskaya, Viktorija; Nagykaldi, Eszter; Gautam, Tripti; Miller, Richard A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan


    Experimental, clinical, and epidemiological findings support the concept of developmental origins of health and disease (DOHAD), suggesting that early-life hormonal influences during a sensitive period around adolescence have a powerful impact on cancer morbidity later in life. The endocrine changes that occur during puberty are highly conserved across mammalian species and include dramatic increases in circulating GH and IGF-1 levels. Importantly, patients with developmental IGF-1 deficiency due to GH insensitivity (Laron syndrome) do not develop cancer during aging. Rodents with developmental GH/IGF-1 deficiency also exhibit significantly decreased cancer incidence at old age, marked resistance to chemically induced carcinogenesis, and cellular resistance to genotoxic stressors. Early-life treatment of GH/IGF-1-deficient mice and rats with GH reverses the cancer resistance phenotype; however, the underlying molecular mechanisms remain elusive. The present study was designed to test the hypothesis that developmental GH/IGF-1 status impacts cellular DNA repair mechanisms. To achieve that goal, we assessed repair of γ-irradiation-induced DNA damage (single-cell gel electrophoresis/comet assay) and basal and post-irradiation expression of DNA repair-related genes (qPCR) in primary fibroblasts derived from control rats, Lewis dwarf rats (a model of developmental GH/IGF-1 deficiency), and GH-replete dwarf rats (GH administered beginning at 5 weeks of age, for 30 days). We found that developmental GH/IGF-1 deficiency resulted in persisting increases in cellular DNA repair capacity and upregulation of several DNA repair-related genes (e.g., Gadd45a, Bbc3). Peripubertal GH treatment reversed the radiation resistance phenotype. Fibroblasts of GH/IGF-1-deficient Snell dwarf mice also exhibited improved DNA repair capacity, showing that the persisting influence of peripubertal GH/IGF-1 status is not species-dependent. Collectively, GH/IGF-1 levels during a critical period

  17. Balancing truth-telling: relatives acting as translators for older adult cancer patients of Turkish or northwest African origin in Belgium. (United States)

    van Eechoud, I; Grypdonck, M; Leman, J; Van Den Noortgate, N; Deveugele, M; Verhaeghe, S


    The first generation of Turkish and Northwest African immigrants in Belgium are ageing and at risk for developing cancer. Relatives play an important role and provide both emotional and practical care, including mental support and acting as a contact person and/or a translator for improving access to healthcare, as most patients and their spouses have only a limited command of the language. Although access to professional interpreters has shown to be the best guarantee for qualitative healthcare, oncology health providers working with relatives as interpreters is much more common than professional interpreters. The aim of this study was to provide insight into the process wherein relatives balance truth-telling in translating for an older family member diagnosed with cancer. This was a qualitative research study, with elements of constructivist grounded theory. Twenty-eight loosely structured interviews were conducted. Most relatives consider it their responsibility to contribute to a positive attitude of the patient. Relatives decided to what extent they inform the patient, based on several motives and embedded in their assessment of the patient's emotional strength, understanding and need to be informed. What they decide influences the way they act as a translator and/or a contact person between the patient and health professional(s). Some considered it best to omit medical information while others considered it best to inform the patient fully. The results emphasise the importance for healthcare providers to take into account the complexity and unpredictable character of the process of balancing truth-telling when family members translate for their ill older relative.

  18. LgR5 expression and cancer stem cell hypothesis: clue to define the true origin of esophageal adenocarcinomas with and without Barrett's Esophagus?

    Directory of Open Access Journals (Sweden)

    Otto Christoph


    Full Text Available Abstract Background Investigation of the expression of an intestinal stem cell marker in esophageal adenocarcinomas (EAC with and without Barrett's Esophagus (BE, with respect to a cancer stem cell (CSC hypothesis. Materials and methods Expression of a putative intestinal stem cell marker LgR5 was analyzed in esophageal cancer specimen (n = 70: 41 EAC with BE, 19 EAC without BE, and n = 10 esophageal squamous-cell carcinomas, ESCC and in the adenocarcinoma cell line OE-33. Ki-67 and Cdx-2 were co-labelled with LgR5 in double staining experiments. Immunhistochemical expression results were confirmed by RT-PCR and correlated with tumor stage and five-year survival rates. Results LgR5was found expressed in 35 of 41 (85% EAC with BE and in 16 of 19 (81% EAC without BE. By contrast, LgR5 was not found to be expressed in ESCC. Quantification of immunolabeling showed 15% LgR5+ cells in EAC with BE, 32% LgR5+ cells in adjacent BE and 13% in EAC without BE. Immunofluorescence double staining experiments with LgR5 and Ki-67 revealed a subpopulation (~5% of proliferating LgR+/Ki-67+ cells. On mRNA-level, expression of LgR5 was higher in BE in comparison to EAC (p = 0.0159. High levels of LgR5 expression in BE associated EAC were associated with poorer survival in univariate analysis. Conclusion The stem cell marker LgR5 is expressed in EAC, irrespective of association with BE, and appears to have negative impact on survival. The subset of proliferating LgR5+ cells (

  19. Global consequences of unsafe abortion. (United States)

    Singh, Susheela


    Unsafe abortion is a significant cause of death and ill health in women in the developing world. A substantial body of research on these consequences exists, although studies are of variable quality. However, unsafe abortion has a number of other significant consequences that are much less widely recognized. These include the economic consequences, the immediate costs of providing medical care for abortion-related complications, the costs of medical care for longer-term health consequences, lost productivity to the country, the impact on families and the community, and the social consequences that affect women and families. This article will review the scientific evidence on the consequences of unsafe abortion, highlight gaps in the evidence base, suggest areas where future research efforts are needed, and speculate on the future situation regarding consequences and evidence over the next 5-10 years. The information provided is useful and timely given the current heightened interest in the issue of unsafe abortion, growing from the recent focus of national and international agencies on reducing maternal mortality by 75% by 2015 (as one of the Millennium Development Goals established in 2000).

  20. Consequence Prioritization Process for Potential High Consequence Events (HCE)

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Sarah G. [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    This document describes the process for Consequence Prioritization, the first phase of the Consequence-Driven Cyber-Informed Engineering (CCE) framework. The primary goal of Consequence Prioritization is to identify potential disruptive events that would significantly inhibit an organization’s ability to provide the critical services and functions deemed fundamental to their business mission. These disruptive events, defined as High Consequence Events (HCE), include both events that have occurred or could be realized through an attack of critical infrastructure owner assets. While other efforts have been initiated to identify and mitigate disruptive events at the national security level, such as Presidential Policy Directive 41 (PPD-41), this process is intended to be used by individual organizations to evaluate events that fall below the threshold for a national security. Described another way, Consequence Prioritization considers threats greater than those addressable by standard cyber-hygiene and includes the consideration of events that go beyond a traditional continuity of operations (COOP) perspective. Finally, Consequence Prioritization is most successful when organizations adopt a multi-disciplinary approach, engaging both cyber security and engineering expertise, as in-depth engineering perspectives are required to recognize and characterize and mitigate HCEs. Figure 1 provides a high-level overview of the prioritization process.


    Directory of Open Access Journals (Sweden)

    Viorel ROŞ


    Full Text Available The Doctrine defines originality as a combination of fancy, audacity, individuality and novelty. This ensemble of ideas meant to define originality appeals to the patents/ certificates Law for which novelty/ innovation is not enough. It shall be accompanied by inventive activity. The aim of the paper below is to clarify the question of the scientific works originality, by referring to the two appearantly contradictory norms and to their consequences over counterfeit/ imitation.

  2. Resource footprints and their ecosystem consequences (United States)

    Verones, Francesca; Moran, Daniel; Stadler, Konstantin; Kanemoto, Keiichiro; Wood, Richard


    A meaningful environmental impact analysis should go beyond the accounting of pressures from resource use and actually assess how resource demand affects ecosystems. The various currently available footprints of nations report the environmental pressures e.g. water use or pollutant emissions, driven by consumption. However, there have been limited attempts to assess the environmental consequences of these pressures. Ultimately, consequences, not pressures, should guide environmental policymaking. The newly released LC-Impact method demonstrates progress on the path to providing this missing link. Here we present “ecosystem impact footprints” in terms of the consequences for biodiversity and assess the differences in impact footprint results from MRIO-based pressure footprints. The new perspective reveals major changes in the relative contribution of nations to global footprints. Wealthy countries have high pressure footprints in lower-income countries but their impact footprints often have their origin in higher-income countries. This shift in perspective provides a different insight on where to focus policy responses to preserve biodiversity.

  3. Early Life Exposures and Cancer (United States)

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  4. Waiting time and the psychosocial consequences of false-positive mammography

    DEFF Research Database (Denmark)

    Heleno, Bruno M.; Siersma, Volkert; Brodersen, John


    Background: There is wide variation in the psychosocial response to false-positive mammography. We aimed to assess whether women having to wait longer to exclude cancer had increased psychosocial consequences that persisted after cancer was ruled out. Findings: We selected women with false......-positive mammography (n = 272), screened for breast cancer in Copenhagen and Funen (Denmark) over a 1-year period. We measured psychosocial consequences immediately before women attended their recall visit and 1, 6, 18 and 36 months after women received their final diagnosis. After women were told that cancer had been...

  5. Nutritional consequences of the African diaspora. (United States)

    Luke, A; Cooper, R S; Prewitt, T E; Adeyemo, A A; Forrester, T E


    Along with their foods and dietary customs, Africans were carried into diaspora throughout the Americas as a result of the European slave trade. Their descendants represent populations at varying stages of the nutrition transition. West Africans are in the early stage, where undernutrition and nutrient deficiencies are prevalent. Many Caribbean populations represent the middle stages, with undernutrition and obesity coexisting. African-Americans and black populations in the United Kingdom suffer from the consequences of caloric excess and diets high in fat and animal products. Obesity, non-insulin-dependent diabetes mellitus, hypertension, coronary heart disease, and certain cancers all follow an east-to-west gradient of increasing prevalence. Public health efforts must focus not only on eradicating undernutrition in West Africa and the Caribbean but also on preventing obesity, hypercholesterolemia, and their consequences. Fortunately, a coherent and well-supported set of recommendations exists to promote better nutrition. Implementation of it founders primarily as a result of the influence of commercial and political interests.

  6. Emotional consequences of nuclear power plant disasters. (United States)

    Bromet, Evelyn J


    The emotional consequences of nuclear power plant disasters include depression, anxiety, post-traumatic stress disorder, and medically unexplained somatic symptoms. These effects are often long term and associated with fears about developing cancer. Research on disasters involving radiation, particularly evidence from Chernobyl, indicates that mothers of young children and cleanup workers are the highest risk groups. The emotional consequences occur independently of the actual exposure received. In contrast, studies of children raised in the shadows of the Three Mile Island (TMI) and Chernobyl accidents suggest that although their self-rated health is less satisfactory than that of their peers, their emotional, academic, and psychosocial development is comparable. The importance of the psychological impact is underscored by its chronicity and by several studies showing that poor mental health is associated with physical health conditions, early mortality, disability, and overuse of medical services. Given the established increase in mental health problems following TMI and Chernobyl, it is likely that the same pattern will occur in residents and evacuees affected by the Fukushima meltdowns. Preliminary data from Fukushima indeed suggest that workers and mothers of young children are at risk of depression, anxiety, psychosomatic, and post-traumatic symptoms both as a direct result of their fears about radiation exposure and an indirect result of societal stigma. Thus, it is important that non-mental health providers learn to recognize and manage psychological symptoms and that medical programs be designed to reduce stigma and alleviate psychological suffering by integrating psychiatric and medical treatment within the walls of their clinics.Introduction of Emotional Consequences of Nuclear Power Plant Disasters (Video 2:15,

  7. Uncertainties in offsite consequence analysis

    Energy Technology Data Exchange (ETDEWEB)

    Young, M.L.; Harper, F.T.; Lui, C.H.


    The development of two new probabilistic accident consequence codes, MACCS and COSYMA, was completed in 1990. These codes estimate the consequences from the accidental releases of radiological material from hypothesized accidents at nuclear installations. In 1991, the U.S. Nuclear Regulatory Commission and the European Commission began co-sponsoring a joint uncertainty analysis of the two codes. The ultimate objective of this joint effort was to systematically develop credible and traceable uncertainty distributions for the respective code input variables using a formal expert judgment elicitation and evaluation process. This paper focuses on the methods used in and results of this on-going joint effort.

  8. Chernobyl accident and its consequences

    Energy Technology Data Exchange (ETDEWEB)

    Gittus, J.H.; Bonell, P.G.; Hicks, D.


    The USSR power reactor programme is first described. The reasons for the accident at the Chernobyl-4 RBMK nuclear reactor on 26 April 1986, the sequence of events that took place, and the immediate and long-term consequences are considered. A description of the RBMK-type reactors is given and the design changes resulting from the experience of the accident are explained. The source terms describing the details of the radioactivity release associated with the accident and the environmental consequences are covered in the last two sections of the report. Throughout the text comments referring to the UK Nuclear Installations Inspectorate Safety assessment principles have been inserted. (U.K.).

  9. Cancer rehabilitation in Denmark

    DEFF Research Database (Denmark)

    Hansen, Helle Ploug; Tjørnhøj-Thomsen, Tine


    A fundamental assumption behind cancer rehabilitation in many Western societies is that cancer survivors can return to normal life by learning to deal with the consequences of their illness and their treatment. This assumption is supported by increasing political attention to cancer rehabilitation...... and a growth in residential cancer-rehabilitation initiatives in Denmark (Danish Cancer Society 1999; Government of Denmark 2003). On the basis of their ethnographic fieldwork in residential-cancer rehabilitation courses, the authors examine the new rehabilitation discourse. They argue that this discourse has...

  10. Genetics and consequences of crop domestication. (United States)

    Flint-Garcia, Sherry A


    Phenotypic variation has been manipulated by humans during crop domestication, which occurred primarily between 3000 and 10000 years ago in the various centers of origin around the world. The process of domestication has profound consequences on crops, where the domesticate has moderately reduced genetic diversity relative to the wild ancestor across the genome, and severely reduced diversity for genes targeted by domestication. The question that remains is whether reduction in genetic diversity has affected crop production today. A case study in maize ( Zea mays ) demonstrates the application of understanding relationships between genetic diversity and phenotypic diversity in the wild ancestor and the domesticate. As an outcrossing species, maize has tremendous genetic variation. The complementary combination of genome-wide association mapping (GWAS) approaches, large HapMap data sets, and germplasm resources is leading to important discoveries of the relationship between genetic diversity and phenotypic variation and the impact of domestication on trait variation.

  11. Literacy in Somali: Linguistic Consequences. (United States)

    Biber, Douglas; Hared, Mohamed


    Linguistic consequences of literacy in Somalia are examined in a review of the literature and through a study of five dimensions of variation among Somali registers and the expansion of linguistic variation in Somali resulting from the introduction of written registers. (36 references) (LB)

  12. Economic consequences of biological variation

    DEFF Research Database (Denmark)

    Otto, Lars


    We present an economic decision support model, based on a Bayesian network, for Mycoplasma infection in slaughter swine production. The model describes the various risk factors for Mycoplasma infection and their interactions. This leads to a stochastic determination of the consequences of product...

  13. Emerging Technologies: Biosecurity and Consequence Management Implications (United States)

    Perkins, Dana; Nordmann, Brian

    The natural outbreaks of disease and pandemics are transnational threats that create international challenges when detection and containment are not timely due to scarce human and material resources. Whether the cause of those outbreaks is natural or intentional in origin, the main goal of consequence management operations is to save lives. The consequence management process is a continuum of inter-connected phases such as planning, preparation, response, and recovery. The rapid advances of life sciences and the emergence of dual-use technologies such as synthetic biology and nanotechnology pose additional challenges in terms of planning for the unknown potential threats whether they may be synthetic microorganisms with unpredictable dissemination patterns or nanoscale-manipulated biological agents evading current detection capabilities. The US National Strategy for Countering Biological Threats is emphasizing prevention while continuing to support the national preparedness goals and response/recovery capabilities. The recent policies, guidelines, and recommendations on overhauling the biological risk management in the United States are a proactive stance to a rapidly changing global environment. They include optimization of the current oversight frameworks and active engagement of the industry and academia in order to reduce the risk that individuals with ill intent may exploit the commercial application of nucleic acid synthesis technology to access genetic material derived from or by encoding Biological Select Agents or Toxins. We are also actively seeking to increase our knowledge of health effects of various types of nanomaterials, and how to assess, control, and prevent harmful exposure, taking into consideration the numerous gaps that currently exist with regard to the distinct behavior of nanoparticles compared to the same chemical or material at "macro-scale". Fundamentally, a biological incident, whether it is of natural, accidental, or deliberate origin

  14. Abortion — facts and consequences


    Perinčić, Robert


    The author sets forth some of the most recent demographic data, important directions of legal documents as regards abortion, tackling medical and ethical problems of abortion. Some essentials particulars are also given as to the embryonic and foetal development. The whole paper concerns the problems of legal abortion during the first three months of pregnancy. The second part of the paper relates to the consequences of abortion affecting the physical and mental health of a woman as show...

  15. Performance consequences of psychological empowerment


    Tuuli, MM; Rowlinson, S


    The relationship between psychological empowerment and job performance, and whether three intermediate performance determinants; motivation, ability, and opportunity to perform hold the key to unlocking the empowerment-performance relationship dilemma are addressed. Using hierarchical linear modeling to analyze responses from 380 project management-level staff, the results show that psychological empowerment not only has direct and positive performance consequences, but also indirect effects,...

  16. Country of Origin: Globalised Consumer Perception


    Steffensen, Lars Schmidt; Sørensen, Mikkel


    The project report consists of an exploratory description and a discussion illustrating the consequences of the Country of Origin effect. This is done using Malcolm Waters theoretical framework on globalisation, Adam Smith and Michael Porters theories on economic advantages in a globalised economy, and own research and theories on cognitive perception in Country of Origin effect. The qualitative empirical data collected stems interviews conducted with Royal Copenhagen consumers. The theories ...

  17. Chemical consequences of cutaneous photoageing

    Directory of Open Access Journals (Sweden)

    Thurstan Sarah A


    Full Text Available Abstract Human skin, in common with other organs, ages as a consequence of the passage of time, but in areas exposed to solar ultraviolet radiation, the effects of this intrinsic ageing process are exacerbated. In particular, both the severity and speed of onset of age-related changes, such as wrinkle formation and loss of elasticity, are enhanced in photoaged (also termed extrinsically aged as compared with aged, photoprotected, skin. The anatomy of skin is characterised by two major layers: an outer, avascular, yet highly cellular and dynamic epidermis and an underlying vascularised, comparatively static and cell-poor, dermis. The structural consequences of photoageing are mainly evident in the extracellular matrix-rich but cell-poor dermis where key extracellular matrix proteins are particularly susceptible to photodamage. Most investigations to date have concentrated on the cell as both a target for and mediator of, ultraviolet radiation-induced photoageing. As the main effectors of dermal remodelling produced by cells (extracellular proteases generally have low substrate specificity, we recently suggested that the differential susceptibility of key extracellular matrix proteins to the processes of photoageing may be due to direct, as opposed to cell-mediated, photodamage. In this review, we discuss the experimental evidence for ultraviolet radiation (and related reactive oxygen species-mediated differential degradation of normally long lived dermal proteins including the fibrillar collagens, elastic fibre components, glycoproteins and proteoglycans. Whilst these components exhibit highly diverse primary and hence macro- and supra-molecular structures, we present evidence that amino acid composition alone may be a useful predictor of age-related protein degradation in both photoexposed and, as a consequence of differential oxidation sensitivity, photoprotected, tissues.

  18. Lifecycle Problems in Consequence Estimation

    Directory of Open Access Journals (Sweden)

    Lehman William


    Full Text Available The United States Army Corps of Engineers (USACE guidance documents require economists and planners to meet a very high standard when evaluating consequences resulting from flood events. The guidance documents require analysts to evaluate how government action changes the consequences over time, in addition to evaluating how government inaction changes consequences over time as well. Corps guidance (Engineering Regulation 1105-2-100, Section 2-3.c.4 and Engineering Regulation 1105-2-100, Section 2-3.b respectively require the evaluation of direct and indirect economic impacts, life risk impacts, and agricultural impacts for both current conditions and future most likely conditions across a range of alternatives. Evaluating the potential for impacts from flooding across time, and how time impacts their existence or vulnerability, is considered a “lifecycle approach”. Little to no guidance is available on the process of calculating this “lifecycle approach” regarding changes in the value and number of assets within the floodplain over time. Performing a lifecycle analysis of a project over durations from 30 to 100 years, depending on the project purpose, requires evaluation of the changes in human behavior caused by changes in the floodplain such as reconstruction of structures, maintenance of structures, construction of new structures, population growth, and what type of structures are being built within the study area. This type of evaluation is not fully supported by most of the software programs utilized for flood risk management in the planning context. This paper is intended to describe pros and cons of economic lifecycle evaluation techniques to address the needs stated by policy, and tools that are being developed to support this analysis.

  19. Physical Consequences of Mathematical Principles

    Directory of Open Access Journals (Sweden)

    Comay E.


    Full Text Available Physical consequences are derived from the following mathematical structures: the variational principle, Wigner’s classifications of the irreducible representations of the Poincar ́ e group and the duality invariance of the homogeneous Maxwell equations. The analysis is carried out within the validity domain of special relativity. Hierarchical re- lations between physical theories are used. Some new results are pointed out together with their comparison with experimental data. It is also predicted that a genuine Higgs particle will not be detected.

  20. Quantum Consequences of Parameterizing Geometry (United States)

    Wanas, M. I.


    The marriage between geometrization and quantization is not successful, so far. It is well known that quantization of gravity , using known quantization schemes, is not satisfactory. It may be of interest to look for another approach to this problem. Recently, it is shown that geometries with torsion admit quantum paths. Such geometries should be parameterizied in order to preserve the quantum properties appeared in the paths. The present work explores the consequences of parameterizing such geometry. It is shown that quantum properties, appeared in the path equations, are transferred to other geometric entities.

  1. Chernobyl accident and its consequences

    Energy Technology Data Exchange (ETDEWEB)

    Gittus, J.H.


    The paper concerns the Chernobyl reactor accident, with emphasis on the design of the RBMK reactor and nuclear safety. A description is given of the Chernobyl nuclear power plant, including details of the RMBK reactor and safety systems. Comments on the design of the RBMK by UK experts prior to the accident are summarized, along with post-accident design changes to improve RBMK safety. Events of the Chernobyl accident are described, as well as design deficiencies highlighted by the accident. Differences between the USSR and UK approaches to nuclear safety are commented on. Finally source terms, release periods and environmental consequences are briefly discussed.

  2. Chernobyl: what sanitary consequences?; Tchernobyl: quelles consequences sanitaires?

    Energy Technology Data Exchange (ETDEWEB)

    Aurengo, A. [Assistance Publique, Hopitaux de Parix (AP-HP), 75 - Paris (France)


    Because of its public health, ecological and industrial consequences, the Chernobyl accident has become a myth which serves as the focus of many fears, justified or not. no one can question the seriousness of the event, but after fifteen years there is still no agreement about the effect it has had or will have on public health. For example, the total number of deaths attributed to Chernobyl varies from less than a hundred to several millions and congenital malformations from negligible to cataclysmic. Effects on public health may be calculated from data on contamination, from the dose received and from the risk, all three of which are likely to be very roughly known; or they may be evaluated on the spot, either by epidemiological studies or by examining medical registers. This report makes an inventory of the different risks and takes stock on them. (N.C.)


    Directory of Open Access Journals (Sweden)



    Full Text Available Major dysfunctionalities can arise from the demographic decline, both on a social level and from the perspective of the economic-financial evolution of the world’s states. The obvious aging of the industrialized states’ population overlapping the import of cheap workforce in the developing countries can start mutations whose consequences are somewhat predictable but discouraging. An accelerated urbanization of the states is foreseen, as well as the decrease of birthrates, negative external migration, increase of mortality and its stagnation in a larger value than that of the birthrate, and not least the population’s aging will hinder a part of the developing countries to sustain a high rhythm of long-term economical increase. The socialeconomic consequences will be reflected in the labor market, the householders’ amount of income as well as in the education’s level. All of these aspects call for a rethinking of the public politics, especially of the social insurance’s system and of the education, a reorientation of the economy based on the increase of specializing in production and productivity, as well as a financial stability unburdened by the politics’ interference in the business environment.

  4. Environmental Degradation: Causes and Consequences

    Directory of Open Access Journals (Sweden)

    Swati Tyagi


    Full Text Available The subject of environmental economics is at the forefront of the green debate: the environment can no longer be viewed as an entity separate from the economy. Environmental degradation is of many types and have many consequences. To address this challenge a number of studies have been conducted in both developing and developed countries applying different methods to capture health benefits from improved environmental quality. Minimizing exposure to environmental risk factors by enhancing air quality and access to improved sources of drinking and bathing water, sanitation and clean energy is found to be associated with significant health benefits and can contribute significantly to the achievement of the Millennium Development Goals of environmental sustainability, health and development. In this paper, I describe the national and global causes and consequences of environmental degradation and social injustice. This paper provides a review of the literature on studies associated with reduced environmental risk and in particular focusing on reduced air pollution, enhanced water quality and climate change mitigation.

  5. Individual Consequences of Internal Marketing

    Directory of Open Access Journals (Sweden)

    Naghi Remus Ionut


    Full Text Available Since the emergence of the concept of internal marketing in the literature there have been almost 40 years. This period was marked by a constant increase of the concerns in the internal marketing area, these efforts being evidenced by the publication of a consistent number of articles (conceptual and empirical which analyze this subject. Considering the previous empirical studies, most of them have focused on studying the relationship between internal marketing and employee satisfaction and / or organizational commitment. However, the relationship between internal marketing and its consequences has been less analyzed in the context of emergent economies. In this paper we aimed to analyze the individual consequences of the internal marketing in the Romanian economy context, focusing our attention on three constructs: employee satisfaction, organizational commitment and organizational citizenship behavior. The research was conducted on a sample of 83 medium and large companies in various sectors of the Romanian economy. In order to proceed with the statistical data analyses we followed these steps: verifying the scales reliability, determining factor loadings and research hypotheses testing. Our research results are consistent with results of previous studies showing that the adoption of internal marketing practice has a positive effect on employee satisfaction, organizational commitment and organizational citizenship behavior

  6. Psychosomatic aspects of the behavior of cancer patients that should be considered in the rehabilitation

    Directory of Open Access Journals (Sweden)

    S. A. Misiak


    Full Text Available The article is dedicated to the psychological aspects of the relationship of the organisms of patients suffering from malignisation, and neoplasms, for further study of the disease during the rehabilitation period after standard treatment. If during the treatment of neoplastic disease doctors are encountering with the consequences of illness then the rehabilitation team need to identify the reasons of the disease occurrence. This helps to give the patient rehabilitation in full to improve the life quality and to provide effective socialization. The article analyzes the problems of the psychological characteristics of the origin and course of cancer, psychosomatic theories to explain the origin of the tumor during the illness. Also theories of the models of the patient’s psychological reactions to the presence of the cancer were studied in the article. The rehabilitation period in the cancer patients should include technological methods of psychotherapy.

  7. Proteomics in epigenetics: new perspectives for cancer research. (United States)

    Bartke, Till; Borgel, Julie; DiMaggio, Peter A


    The involvement of epigenetic processes in the origin and progression of cancer is now widely appreciated. Consequently, targeting the enzymatic machinery that controls the epigenetic regulation of the genome has emerged as an attractive new strategy for therapeutic intervention. The development of epigenetic drugs requires a detailed knowledge of the processes that govern chromatin regulation. Over the recent years, mass spectrometry (MS) has become an indispensable tool in epigenetics research. In this review, we will give an overview of the applications of MS-based proteomics in studying various aspects of chromatin biology. We will focus on the use of MS in the discovery and mapping of histone modifications and how novel proteomic approaches are being utilized to identify and study chromatin-associated proteins and multi-subunit complexes. Finally, we will discuss the application of proteomic methods in the diagnosis and prognosis of cancer based on epigenetic biomarkers and comment on their future impact on cancer epigenetics.

  8. Cancer-associated lysosomal changes

    DEFF Research Database (Denmark)

    Kallunki, T; Olsen, O D; Jaattela, Marja


    Rapidly dividing and invasive cancer cells are strongly dependent on effective lysosomal function. Accordingly, transformation and cancer progression are characterized by dramatic changes in lysosomal volume, composition and cellular distribution. Depending on one's point of view, the cancer-associated......-targeting anti-cancer drugs. In this review we compile our current knowledge on cancer-associated changes in lysosomal composition and discuss the consequences of these alterations to cancer progression and the possibilities they can bring to cancer therapy.Oncogene advance online publication, 9 July 2012; doi...

  9. Hand eczema - prognosis and consequences

    DEFF Research Database (Denmark)

    Petersen, A. H.; Johansen, J D; Hald, M


    BACKGROUND: Hand eczema is recognized as a long-lasting disease with personal and societal repercussions. Long-term studies are required to generate information on factors contributing to a poor outcome. OBJECTIVES: The aims of this 7-year follow-up study were to evaluate the clinical course...... of patients with hand eczema, the occupational consequences and to identify risk factors associated with a poor prognosis. MATERIALS AND METHODS: In all, 536 patients with hand eczema participated and were examined by a dermatologist. The clinical severity was assessed at baseline and 7 years later using...... a self-administrated photographic guide. Additional information was obtained from a questionnaire. RESULTS: Based on the photographic guide, 73% experienced a clinical improvement. Notably, 20% had moderate to very severe hand eczema at follow-up. Severe hand eczema or frequent eruptions at baseline...

  10. Hydrological consequences of global warming

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Norman L.


    The 2007 Intergovernmental Panel for Climate Change indicates there is strong evidence that the atmospheric concentration of carbon dioxide far exceeds the natural range over the last 650,000 years, and this recent warming of the climate system is unequivocal, resulting in more frequent extreme precipitation events, earlier snowmelt runoff, increased winter flood likelihoods, increased and widespread melting of snow and ice, longer and more widespread droughts, and rising sea level. The effects of recent warming has been well documented and climate model projections indicate a range of hydrological impacts with likely to very likely probabilities (67 to 99 percent) of occurring with significant to severe consequences in response to a warmer lower atmosphere with an accelerating hydrologic cycle.

  11. Antecedents and Consequences of Envy. (United States)

    Thompson, Geir; Glasø, Lars; Martinsen, Øyvind


    The aim of this study was to examine the relationship between individual attributes and envy, and to determine how envy may impact personal response variables in the workplace. To address these issues we apply Vecchio's theory on antecedents and consequences of envy (1995) as a theoretical framework. The present study relied on a cross-sectional measurement design. A total of 135 leaders and 772 followers employed in business organizations participated. SEM analysis shows that span of supervision serves as an important antecedent of envy, where span of supervision is significantly associated to envy via supportive leadership. Furthermore, envy seems to be indirectly and negatively related to self-esteem via distress and directly related to social loafing. The implications of these findings are discussed, and suggestions for future research are outlined.

  12. Studying health consequences of microchimerism

    DEFF Research Database (Denmark)

    Olsen, J.; Campi, Rita; Frydenberg, Morten;


    Abstract. A pregnancy requires a reasonably good health and may have positive as well as negative health consequences for the woman. Part of these health effects may depend on the immune response to the exchange of fetal cells (microchimerism). The number of biological fathers to a woman’s children...... may thus have a health effect beyond the parity effect. A possible design for studying this is to compare health effects for women with or without multiple partners but with the same parity. We compared total and cause specific mortality in these two groups in order to estimate their comparability...... one partner had a higher relative mortality rate, which was even higher if she had more than two partners. This finding persisted after excluding unnatural deaths and did not depend on time from exposure. Although some of the findings were adjusted for parity, age and social factors, it is highly...

  13. The immunological consequences of injury.

    LENUS (Irish Health Repository)

    Ni Choileain, N


    Immediate and early trauma death rates are determined by "first hits" such as hypoxia, hypotension and organ injury, while late mortality correlates closely with "second hits" such as infection. An imbalance between the early systemic inflammatory response (SIRS), and the later compensatory counter-inflammatory response (CARS), is considered to be responsible for much post-traumatic morbidity and mortality. From a clinical perspective, this remains a significant healthcare problem, which has stimulated decades of experimental and clinical research aimed at understanding the functional effects of injury on the immune system. This review describes the impact of injury on the innate and adaptive immune systems. Though it is worth noting that the features of the immune response to injury overlap in many areas with immune dysregulation in sepsis, we attempt here to elucidate the mechanism by which injury predisposes to infection rather than to describe the alterations in host immunity consequent to established sepsis.

  14. A significant association between rs8067378 at 17q12 and invasive cervical cancer originally identified by a genome-wide association study in Han Chinese is replicated in a Japanese population. (United States)

    Miura, Kiyonori; Mishima, Hiroyuki; Yasunami, Michio; Kaneuchi, Masanori; Kitajima, Michio; Abe, Shuhei; Higashijima, Ai; Fuchi, Naoki; Miura, Shoko; Yoshiura, Koh-Ichiro; Masuzaki, Hideaki


    In this study, associations between invasive cervical cancer and four cervical cancer susceptibility loci (rs13117307 at 4q12, rs8067378 at 17q12, and rs4282438 and rs9277952 at 6p21.32) in the Han Chinese population were investigated in a Japanese population. Human leukocyte antigen (HLA)-DPB1 alleles were also investigated for their association with cervical cancer risk in the Japanese population. After receiving written informed consent, 214 unrelated Japanese women with invasive cervical cancer and 288 cancer-free Japanese women were recruited, and DNA samples were obtained (study protocol approved by Institutional Review Board of Nagasaki University). Of the four single-nucleotide polymorphisms, rs8067378 showed a significant association with invasive cervical cancer (P=0.0071). Under a recessive model, the minor allele G of rs8067378 contributed to the risk of invasive cervical cancer (odds ratio=2.92, 95% confidence interval=1.40-6.36; P=0.0021). No association was detected between HLA-DPB1 alleles and cervical cancer risk in the Japanese population. In conclusion, we show for the first time, to the best of our knowledge, that an association between increased risk of invasive cervical cancer and rs8067378 in the Han Chinese population is replicated in a Japanese population. In addition, Japanese women with the GG genotype of rs8067378 are a candidate high-risk group for invasive cervical carcinoma.

  15. Long-Term Consequences of Radioactive Fallout From Conflicts Involving Nuclear Explosions (United States)

    Simon, S. L.; Bouville, A.


    This presentation will summarize past exposures of the public to radioactive fallout from nuclear testing and extrapolate to the possible fallout-related consequences from detonation of multiple warheads that might accompany international conflicts. Long-term consequences could be of three distinct types: (1) the abandonment of living areas that might be heavily contaminated; (2) the necessity to curtail use of particular agricultural products and foods, and (3) life-shortening due to increased rates of cancer and possibly some non-cancer diseases among the exposed populations. While the actual health and economic impact on the surviving public after such conflicts could vary tremendously depending on the number and sizes of explosions (fission yields), height of detonations, and the public's proximity to explosion sites, it is clear that multiple detonations would disperse radioactive products over large geographic areas. Our understanding of radioactive fallout is based on studies carried out for more than five decades on weapons testing fallout that originated from sites worldwide including Nevada, the Soviet Union, four locations in the Pacific, and elsewhere. Those studies have led to an understanding of the composition of radioactive fallout, of its radioactive qualities, and of its capacity to contaminate ground and agricultural products, as well as dwellings and workplaces located from a few km to tens of thousands of km from the explosion site. Though the most severe individual health consequences from exposure to fallout would most likely develop relatively close to the detonation sites (within a few hundred km), wide geographic distribution of fallout, well beyond the borders of the nations involved in the conflict, would affect much larger populations and would likely cause elevated cancer rates and cancer-related deaths among them for many decades following. While acute radiation symptoms (and even death) can result from very high short-term exposures

  16. Psychological consequences of lymphoedema associated with breast cancer

    DEFF Research Database (Denmark)

    Vassard, Ditte; Olsen, Maja Halgren; Zinckernagel, Line


    BACKGROUND: The aim of this prospective cohort study of women attending a rehabilitation course at the Dallund Rehabilitation Centre was to explore the emotional and psychological aspects of living with lymphoedema, expressed as psychological distress, poorer quality of life and poorer self...

  17. What is the origin of pancreatic adenocarcinoma?

    Directory of Open Access Journals (Sweden)

    Pandey Krishan K


    Full Text Available Abstract The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.

  18. The consequences of abortion legislation. (United States)

    Braude, M


    This article examines the consequences of the 1973 US Supreme Court decision legalizing abortion as well as potential implications of proposed legilation aimed at nullifying this decision. In addition to giving women the right to determine their own reproduction, legal abortion had had beneficial health effects for both mothers and infants. The partial reversal of abortion gains due to restrictions on public funding and limitations on how and where abortions can be performed has produced a slight increase in abortion mortality, but the impact has not been dramatic. Moreover, each year since 1973, women have been obtaining abortions earlier in pregnancy. Abortion may be experienced as a loss by the mother, but there is no evidence of serious psychological sequelae. In contrast, a large body of evidence supports the physical, psychological, and social benefits of legal abortion to women, children, and families. However, proponents of the proposed Human Life Amendment place protection of the rights of the fetus over all other considerations. Their antiabortion actions have challenged the medical tradition of privacy and the confidentiality of the doctor-patient relationship. Most supporters of legal abortion would prefer that there be fewer abortions; such a decrease is more likely as a result of better education and contraceptive methods rather than coercion.

  19. Pain management in cancer survivorship

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Sjøgren, Per


    BACKGROUND: The number of patients surviving cancer disease has increased in last decades. Consequently, an emerging population with different needs due to long-term or late effects of cancer disease and/or treatment, e.g. chronic pain, is of major concern. EPIDEMIOLOGY: Chronic pain is one...... survivors. Pain management strategies are discussed according to the biopsychosocial model and with the rapidly growing number of cancer survivors the establishment of multidisciplinary clinics as a part of comprehensive cancer centers are proposed....

  20. Medical consequences of Chernobyl accident

    Directory of Open Access Journals (Sweden)

    Galstyan I.A.


    Full Text Available Aim: to study the long-term effects of acute radiation syndrome (ARS, developed at the victims of the Chernobyl accident. Material and Methods. 237 people were exposed during the accident, 134 of them were diagnosed with ARS. Dynamic observation implies a thorough annual examination in a hospital. Results. In the first 1.5-2 years after the ARS mean group indices of peripheral blood have returned to normal. However, many patients had transient expressed moderate cytopenias. Granulocytopenia, thrombocytopenia, lymphopenia and erythropenia were the most frequently observed things during the first 5 years after the accident. After 5 years their occurences lowered. In 11 patients the radiation cataract was detected. A threshold dose for its development is a dose of 3.2 Gy Long-term effects of local radiation lesions (LRL range from mild skin figure smoothing to a distinct fibrous scarring, contractures, persistently recurrent late radiation ulcers. During all years of observation we found 8 solid tumors, including 2 thyroid cancers. 5 hematologic diseases were found. During 29 years 26 ARS survivors died of various causes. Conclusion. The health of ones with long-term ARS effects is determined by the evolution of the LRL effects on skin, radiation cataracts, hema-tological diseases and the accession of of various somatic diseases, not caused by radiation.

  1. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter


    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... are only ameliorated to a minor degree by a healthy diet....

  2. Economic Consequences Of Climate Change (United States)

    Szlávik, János; Füle, Miklós


    Even though the climate conflict resulting from green houses gases (GHG) emissions was evident by the Nineties and the well-known agreements made, their enforcement is more difficult than that of other environmental agreements. That is because measures to reduce GHG emissions interfere with the heart of the economy and the market: energy (in a broader sense than the energy sector as defined by statistics) and economical growth. Analyzing the environmental policy responses to climate change the conclusion is that GHG emission reduction can only be achieved through intensive environmental policy. While extensive environmental protection complements production horizontally, intensive environmental protection integrates into production and the environment vertically. The latter eliminates the source of the pollution, preventing damage. It utilizes the biochemical processes and self-purification of the natural environment as well as technical development which not only aims to produce state-of-the-art goods, but to make production more environmentally friendly, securing a desired environmental state. While in extensive environmental protection the intervention comes from the outside for creating environmental balance, in intensive environmental protection the system recreates this balance itself. Instead of dealing with the consequences and the polluter pays principle, the emphasis is on prevention. It is important to emphasize that climate strategy decisions have complex effects regarding the aspects of sustainability (economical, social, ecological). Therefore, all decisions are political. At present, and in the near future, market economy decisions have little to do with sustainability values under normal circumstances. Taking social and ecological interests into consideration can only be successful through strategic political aims.

  3. Natural products as potential cancer therapy enhancers: A preclinical update. (United States)

    Agbarya, Abed; Ruimi, Nili; Epelbaum, Ron; Ben-Arye, Eran; Mahajna, Jamal


    Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  4. Natural products as potential cancer therapy enhancers: A preclinical update

    Directory of Open Access Journals (Sweden)

    Abed Agbarya


    Full Text Available Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  5. Basal stamcellebiologi og cancer

    DEFF Research Database (Denmark)

    Porse, Bo T; Petersen, Ole W; Helin, Kristian


    The finding that tumours, like normal tissues, are endowed with varying degrees of cellular heterogeneity has far-reaching consequences for our understanding of cancer. The cancer stem cell and clonal evolution models have both been proposed to explain tumour-associated cellular heterogeneity. Here......, we briefly review these two non-exclusive models with special emphasis on how they aid our understanding of cancer and their implications for therapeutic strategies. Finally, we discuss the close association between basic stem cell biology and cancer, focusing on the role of self-renewal....

  6. The digitisation of cultural heritage: originality, derivative works and (non) original photographs

    NARCIS (Netherlands)

    Margoni, T.


    The purpose of this paper is to explore the legal consequences of the digitisation of cultural heritage institutions' archives and in particular to establish whether digitisation processes involve the originality required to trigger new copyright or copyright-related protection. As the European Comm

  7. Multiple origins of asteroid pairs

    CERN Document Server

    Jacobson, Seth A


    Rotationally fissioned asteroids produce unbound daughter asteroids that have very similar heliocentric orbits. Backward integration of their current heliocentric orbits provides an age of closest proximity that can be used to date the rotational fission event. Most asteroid pairs follow a predicted theoretical relationship between the primary spin period and the mass ratio of the two pair members that is a direct consequence of the YORP-induced rotational fission hypothesis. If the progenitor asteroid has strength, asteroid pairs may have high mass ratios with possibly fast rotating primaries. However, secondary fission leaves the originally predicted trend unaltered. We also describe the characteristics of pair members produced by four alternative routes from a rotational fission event to an asteroid pair. Unlike direct formation from the event itself, the age of closest proximity of these pairs cannot generally be used to date the rotational fission event since considerable time may have passed.

  8. Clinical Holistic Medicine: Metastatic Cancer

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt


    Full Text Available We believe that the consciousness-based/holistic medical toolbox has a serious additional offer to cancer patients and, as a consequence, designed a treatment for the patient with metastasized cancer. From a holistic perspective, cancer can be understood as a simple disturbance of the cells, arising from the tissue holding on to a trauma with strong emotional content. This is called “a blockage”, where the function of the cells is allocated from their original function in the tissue to a function of holding emotions. We hope to be able not only to improve the quality of life, but also to improve survival and in some cases even induce spontaneous remission of the metastasized cancer. This paper describes how work with a patient with metastasized cancer can be done in the holistic clinical practice in 14 days on an individual basis, helping the patient to recover her human character, purpose of life, coherence, and will to live, thus improving quality of life and possibly also survival time. The holistic therapeutic work includes (1 teaching existential theory, (2 working with life perspective and philosophy of life, (3 helping the patient to acknowledge the state of the disease and the feelings connected to it, and finally (4 getting the patient into the holistic state of healing: (a feeling old repressed emotions, (b understanding why she got sick from a holistic point of view, and finally (c letting go of the negative beliefs and decisions that made her sick according to the holistic theory of nongenetic diseases. The theory of the human character, the quality of life theories, the holistic theory of cancer, the holistic process theory of healing, the theory of (Antonovsky coherence, and the life mission theory are the most important theories for the patient to find hope and mobilize the will to fight the cancer and survive. The patient went through the following phases: (1 finding the purpose of life and hidden resources; (2 confronting

  9. Multiple origins of life (United States)

    Raup, D. M.; Valentine, J. W.


    There is some indication that life may have originated readily under primitive earth conditions. If there were multiple origins of life, the result could have been a polyphyletic biota today. Using simple stochastic models for diversification and extinction, we conclude: (1) the probability of survival of life is low unless there are multiple origins, and (2) given survival of life and given as many as 10 independent origins of life, the odds are that all but one would have gone extinct, yielding the monophyletic biota we have now. The fact of the survival of our particular form of life does not imply that it was unique or superior.

  10. Consequences of Assessment: What is the Evidence?

    Directory of Open Access Journals (Sweden)

    William A. Mehrens


    Full Text Available Attention is here directed toward the prevalence of large scale assessments (focusing primarily on state assessments. I examine the purposes of these assessment programs; enumerate both potential dangers and benefits of such assessments; investigate what the research evidence says about assessment consequences (including a discussion of the quality of the evidence; discuss how to evaluate whether the consequences are good or bad; present some ideas about what variables may influence the probabilities for good or bad consequences; and present some tentative conclusions about the whole issue of the consequences of assessment and the amount of evidence available and needed.

  11. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska


    Full Text Available Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  12. HSV-1/HSV-2 Infection-Related Cancers in Bantu Populations Driving HIV-1 Prevalence in Africa: Tracking the Origin of AIDS at the Onset of the 20th Century

    Directory of Open Access Journals (Sweden)

    Jacqueline Le Goaster


    Full Text Available Introduction: At the onset of the 20th century, ancient clinical observations of cancer epidemics in Bantu populations of Sub-Saharan Africa were discovered. They were reported from 1914 to 1960, but remained unexplained. In 1983, in San Francisco, Calif., USA, cancer epidemics were related to infections by the human immunodeficiency virus type 1 (HIV-1 known as AIDS disease. Yet since 1996, it is known that HIV-1 strains are not the only ones involved. In Sub-Saharan Africa, recurrent orobuccal herpes simplex virus type 1 (HSV-1 and genital recurrent herpes simplex virus type 2 (HSV-2 appeared many times prior to infection by HIV-1. Case Reports: Data on these ancient medical observations regarding African cancer epidemics can today be referred to as the relationship between the unfortunate immune deficiency of herpes in Bantu populations and HIV-1 viral strains. For centuries, the Bantu populations dispersed in forests were living in close proximity to chimpanzees infected by simian immunodeficiency virus (SIV and were exposed to SIV contamination which became HIV-1 in human beings. Presently, these unexplained Bantu cancer epidemics can be linked to the viral partnership of HSV-1/HSV-2 to HIV-1 strains. Conclusion: The key issue is now to prevent HSV-1/HSV-2 diseases related to HIV-1. An anti-herpes treatment administered early during childhood to Bantu populations will offer a mean of preventing herpes diseases related to HIV-1 infection and hence avoid cancer epidemics.

  13. Chemical Origins of Life (United States)

    Fox, J. Lawrence


    Reviews ideas and evidence bearing on the origin of life. Shows that evidence to support modifications of Oparin's theories of the origin of biological constituents from inorganic materials is accumulating, and that the necessary components are readily obtained from the simple gases found in the universe. (AL)

  14. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter


    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

  15. Colon cancer (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  16. The Origin and Consequences of Excess Competition in Education: A Mainland Chinese Perspective (United States)

    Kai, Jiang


    At present in mainland China, competition in education has become excessive; competition has been increasing, and a competitive mentality is on the rise. The formative causes of excess competition in education are complex; with both practical and conceptual causes. Its roots can be traced to intensifying social competition, a one-sided…

  17. Supernovae from yellow, blue supergiants: origin and consequences for stellar evolution (United States)

    Meynet, Georges; Georgy, Cyril; Saio, Hideyuki; Kudritzki, Rolf-Peter; Groh, Jose


    A few core collapse supernovae progenitors have been found to be yellow or blue supergiants. We shall discuss possible scenarios involving single and close binary evolution allowing to explain this kind of core collapse supernova progenitors. According to stellar models for both single and close binaries, blue supergiants, at the end of their nuclear lifetimes and thus progenitors of core collapse supernovae, present very different characteristics for what concerns their surface compositions, rotational surface velocities and pulsational properties with respect to blue supergiants in their core helium burning phase. We discuss how the small observed scatter of the flux-weighted gravity-luminosity (FWGL) relation of blue supergiants constrains the evolution of massive stars after the Main-Sequence phase and the nature of the progenitors of supernovae in the mass range between 12 and 40 solar masses. The present day observed surface abundances of blue supergiants, of their pulsational properties, as well as the small scatter of the FWGL relation provide strong constraints on both internal mixing and mass loss in massive stars and therefore on the end point of their evolution.

  18. Origins and kinetic consequences of diversity in Sup35 yeast prion fibers. (United States)

    DePace, Angela H; Weissman, Jonathan S


    A remarkable feature of prions is that infectious particles composed of the same prion protein can give rise to different phenotypes. This strain phenomenon suggests that a single prion protein can adopt multiple infectious conformations. Here we use a novel single fiber growth assay to examine the heterogeneity of amyloid fibers formed by the yeast Sup35 prion protein. Sup35 spontaneously forms multiple, distinct and faithfully propagating fiber types, which differ dramatically both in their degrees of polarity and overall growth rates. Both in terms of the number of distinct self-propagating fiber types, as well as the ability of these differences to dictate the rate of prion growth, this diversity is well suited to account for the range of prion strain phenotypes observed in vivo.

  19. The bright side of hierarchies : The origins and consequences of social stratification in organizations

    NARCIS (Netherlands)

    Cantimur, Yeliz


    The pursuit of status or influence is inherent to human nature. We all strive to stand out in aspects that society, or the groups to which we belong, deem valuable; let it be wealth, educational attainment, a prestigious job, or affiliation with favored groups (e.g., based on ethnic groups or gender

  20. Targeting Notch to target cancer stem cells. (United States)

    Pannuti, Antonio; Foreman, Kimberly; Rizzo, Paola; Osipo, Clodia; Golde, Todd; Osborne, Barbara; Miele, Lucio


    The cellular heterogeneity of neoplasms has been at the center of considerable interest since the "cancer stem cell hypothesis", originally formulated for hematologic malignancies, was extended to solid tumors. The origins of cancer "stem" cells (CSC) or tumor-initiating cells (TIC; henceforth referred to as CSCs) and the methods to identify them are hotly debated topics. Nevertheless, the existence of subpopulations of tumor cells with stem-like characteristics has significant therapeutic implications. The stem-like phenotype includes indefinite self-replication, pluripotency, and, importantly, resistance to chemotherapeutics. Thus, it is plausible that CSCs, regardless of their origin, may escape standard therapies and cause disease recurrences and/or metastasis after apparently complete remissions. Consequently, the idea of selectively targeting CSCs with novel therapeutics is gaining considerable interest. The Notch pathway is one of the most intensively studied putative therapeutic targets in CSC, and several investigational Notch inhibitors are being developed. However, successful targeting of Notch signaling in CSC will require a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to prove safe and effective. Additionally, to determine which patients are most likely to benefit from treatment with Notch-targeting therapeutics, reliable biomarkers to measure pathway activity in CSC from specific tumors will have to be identified and validated. This article summarizes the most recent developments in the field of Notch-targeted cancer therapeutics, with emphasis on CSC.

  1. Keeping Secrets : Quantity, Quality and Consequences

    NARCIS (Netherlands)

    Frijns, T.


    Keeping Secrets deals with the consequences of an elusive yet everyday phenomenon. It addresses both the quantity and quality of secret-keeping. With respect to quantity, it presents research on the intra- and interpersonal consequences of keeping secrets from parents in adolescence. With respect t

  2. Targeting Breast Cancer Metastasis



    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  3. The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

    Directory of Open Access Journals (Sweden)

    Tamara Potapova


    Full Text Available Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.

  4. Educational Issues in Childhood Cancer. (United States)

    Armstrong, Daniel F.; Horn, Marianna


    Describes school issues for children with cancer. Presents the relationship between school performance and both the acute and long-term consequences of the type of cancer, radiation therapy, and chemotherapy. Reviews the results of the studies of the cognitive and academic effects of cranial radiation and chemotherapy, and a developmental model…

  5. Planetary Environments and Origins of Life

    Directory of Open Access Journals (Sweden)

    Ollivier Marc


    Full Text Available The present strategies proposed for the search for the origins of life and for extra-terrestrial life are mainly based on Earth-life and its adaptation along geological eras to the Earth environment. These strategies should however face the difficulty that one cannot as yet accurately date the appearance of life on Earth, and consequently one cannot identify a chronology of phenomena related to the transition from the non-living to the living and the dependence of these phenomena on the Earth environment. In this paper, we present new approaches to search for the origins of life on the Earth and next, for life on exoplanets. This study is based on our experience gained at the head of the CNRSc interdisciplinary research initiative "Environnements Planétaires et Origines de la Vie (EPOVd, and on the analysis of the projects the initiative funded.

  6. Development of A Mouse Model of Menopausal Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Smith


    Full Text Available Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; questions of the cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology.A potentially useful model is the germ cell-deficient Wv (white spotting variant mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1-5% (it is not a null mutation. Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer.Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention.

  7. Long-term psychosocial consequences of false-positive screening mammography

    DEFF Research Database (Denmark)

    Brodersen, John; Siersma, Volkert Dirk


    Cancer screening programs have the potential of intended beneficial effects, but they also inevitably have unintended harmful effects. In the case of screening mammography, the most frequent harm is a false-positive result. Prior efforts to measure their psychosocial consequences have been limited...

  8. Echoes of the embryo: using the developmental biology toolkit to study cancer

    Directory of Open Access Journals (Sweden)

    Nicole M. Aiello


    Full Text Available The hallmark of embryonic development is regulation – the tendency for cells to find their way into organized and ‘well behaved’ structures – whereas cancer is characterized by dysregulation and disorder. At face value, cancer biology and developmental biology would thus seem to have little to do with each other. But if one looks beneath the surface, embryos and cancers share a number of cellular and molecular features. Embryos arise from a single cell and undergo rapid growth involving cell migration and cell-cell interactions: features that are also seen in the context of cancer. Consequently, many of the experimental tools that have been used to study embryogenesis for over a century are well-suited to studying cancer. This article will review the similarities between embryogenesis and cancer progression and discuss how some of the concepts and techniques used to understand embryos are now being adapted to provide insight into tumorigenesis, from the origins of cancer cells to metastasis.

  9. Perspectives from older adults receiving cancer treatment about the cancer-related information they receive



    Objective: Cancer patients have reported that information plays a significant role in their capacity to cope with cancer and manage the consequences of treatment. This study was undertaken to identify the importance older adults receiving cancer treatment assign to selected types of cancer-related information, their satisfaction with the cancer-related information they received, and the barriers to effective information provision for this age group. Methods: This study was conducted in two ph...

  10. Consequences of Obstructive Sleep Apnea in Children. (United States)

    Blechner, Michael; Williamson, Ariel A


    Obstructive sleep apnea syndrome (OSAS) has various negative health and behavioral consequences in the pediatric population. As shown in adults, there are metabolic derangements such as obesity, insulin sensitivity, dyslipidemia, and metabolic syndrome, as well as cardiovascular derangements like hypertension, chronic inflammation, endothelial dysfunction, ventricular size/function abnormalities, and even elevated pulmonary arterial pressures, that can be seen in children with OSAS. The first two sections will discuss the metabolic and cardiovascular consequences on OSAS in children. The last section summarizes selected studies and reviews on the behavioral, neurocognitive and academic consequences of OSAS in children.

  11. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J


    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...

  12. [Hypotension from endocrine origin]. (United States)

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie


    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  13. PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth. (United States)

    Vishchuk, Olesia S; Sun, Huimin; Wang, Zhe; Ermakova, Svetlana P; Xiao, JuanJuan; Lu, Tao; Xue, PeiPei; Zvyagintseva, Tatyana N; Xiong, Hua; Shao, Chen; Yan, Wei; Duan, Qiuhong; Zhu, Feng


    The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo.

  14. Comparative expression study of the endo-G protein coupled receptor (GPCR repertoire in human glioblastoma cancer stem-like cells, U87-MG cells and non malignant cells of neural origin unveils new potential therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Marie Fève

    Full Text Available Glioblastomas (GBMs are highly aggressive, invasive brain tumors with bad prognosis and unmet medical need. These tumors are heterogeneous being constituted by a variety of cells in different states of differentiation. Among these, cells endowed with stem properties, tumor initiating/propagating properties and particularly resistant to chemo- and radiotherapies are designed as the real culprits for tumor maintenance and relapse after treatment. These cells, termed cancer stem-like cells, have been designed as prominent targets for new and more efficient cancer therapies. G-protein coupled receptors (GPCRs, a family of membrane receptors, play a prominent role in cell signaling, cell communication and crosstalk with the microenvironment. Their role in cancer has been highlighted but remains largely unexplored. Here, we report a descriptive study of the differential expression of the endo-GPCR repertoire in human glioblastoma cancer stem-like cells (GSCs, U-87 MG cells, human astrocytes and fetal neural stem cells (f-NSCs. The endo-GPCR transcriptome has been studied using Taqman Low Density Arrays. Of the 356 GPCRs investigated, 138 were retained for comparative studies between the different cell types. At the transcriptomic level, eight GPCRs were specifically expressed/overexpressed in GSCs. Seventeen GPCRs appeared specifically expressed in cells with stem properties (GSCs and f-NSCs. Results of GPCR expression at the protein level using mass spectrometry and proteomic analysis are also presented. The comparative GPCR expression study presented here gives clues for new pathways specifically used by GSCs and unveils novel potential therapeutic targets.

  15. Consequence Reasoning in Multilevel Flow Modelling

    DEFF Research Database (Denmark)

    Zhang, Xinxin; Lind, Morten; Ravn, Ole


    Consequence reasoning is a major element for operation support system to assess the plant situations. The purpose of this paper is to elaborate how Multilevel Flow Models can be used to reason about consequences of disturbances in complex engineering systems. MFM is a modelling methodology...... for representing process knowledge for complex systems. It represents the system by using means-end and part-whole decompositions, and describes not only the purposes and functions of the system but also the causal relations between them. Thus MFM is a tool for causal reasoning. The paper introduces MFM modelling...... syntax and gives detailed reasoning formulas for consequence reasoning. The reasoning formulas offers basis for developing rule-based system to perform consequence reasoning based on MFM, which can be used for alarm design, risk monitoring, and supervision and operation support system design....

  16. The redistributive consequences of monetary policy


    Nakajima, Makoto


    Monetary policy is not intended to benefit one segment of the population at the expense of another by redistributing income and wealth. But as Makoto Nakajima explains, it is probably impossible to avoid such redistributive consequences.

  17. Stochastic Consequence Analysis for Waste Leaks

    Energy Technology Data Exchange (ETDEWEB)

    HEY, B.E.


    This analysis evaluates the radiological consequences of potential Hanford Tank Farm waste transfer leaks. These include ex-tank leaks into structures, underneath the soil, and exposed to the atmosphere. It also includes potential misroutes, tank overflow

  18. Causes and Consequences of Youth Unemployment. (United States)

    Stevenson, Wayne


    The author discusses the state of unemployment in the 1970s among teenagers, some reasons for its existence, the long-term consequences, and the net impact of the teenage experience on joblessness. (RK)

  19. Avoid the Consequences of High Blood Pressure (United States)

    ... Thromboembolism Aortic Aneurysm More Avoid the Consequences of High Blood Pressure Infographic Updated:Oct 31,2016 View a downloadable version of this infographic High Blood Pressure • Home • Get the Facts About HBP • Know Your ...

  20. Antecedents and Consequences of Affective Commitment

    NARCIS (Netherlands)

    Bloemer, J.M.M.; Odekerken-Schröder, G.J.


    The primary objective of this study is to assess the impact of three psychological antecedents (position involvement, volitional choice and informational complexity) on affective commitment in a financial service setting. Furthermore, this study addresses the consequences of affective commitment on

  1. Consequences of use of anabolic androgenic steroids. (United States)

    Casavant, Marcel J; Blake, Kathleen; Griffith, Jill; Yates, Andrew; Copley, LaRae M


    Whether providing anticipatory guidance to the young adolescent patient, conducting a preparticipation examination on a young athlete, or treating a sick user of anabolic androgenic steroids (AASs), the primary care physician must be familiar with the adverse consequences of the use of these compounds. This article reviews the endocrine, cardiovascular, neuropsychiatric, musculoskeletal, hematologic, hepatic, and miscellaneous effects of AASs, highlighting effects reported in children and adolescents, and relying on consequences in adults when pediatric data is unavailable.

  2. Consequences of Assessment: What is the Evidence?


    William A. Mehrens


    Attention is here directed toward the prevalence of large scale assessments (focusing primarily on state assessments). I examine the purposes of these assessment programs; enumerate both potential dangers and benefits of such assessments; investigate what the research evidence says about assessment consequences (including a discussion of the quality of the evidence); discuss how to evaluate whether the consequences are good or bad; present some ideas about what variables may influence the pro...

  3. The consequences of Israel's counter terrorism policy


    Jansen, Pia Therese


    The main focus of this thesis is to examine Israel's counter terrorism methods and their consequences and to debate the effectiveness of Israel's counter terrorism policy. By stimulating a debate on these issues it is possible to identify a more effective counter terrorism policy. In order to examine Israel's counter terrorism methods, their consequences and effectiveness, it is necessary to first explore the overall concepts of terrorism and counter terrorism. Then, because...

  4. Drinking Water Consequences Tools. A Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Pasqualini, Donatella [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    In support of the goals of Department of Homeland Security’s (DHS) National Protection and Programs Directorate and the Federal Emergency Management Agency, the DHS Office of Science and Technology is seeking to develop and/or modify consequence assessment tools to enable drinking water systems owner/operators to estimate the societal and economic consequences of drinking water disruption due to the threats and hazards. This work will expand the breadth of consequence estimation methods and tools using the best-available data describing water distribution infrastructure, owner/assetlevel economic losses, regional-scale economic activity, and health. In addition, this project will deploy the consequence methodology and capability within a Web-based platform. This report is intended to support DHS effort providing a review literature review of existing assessment tools of water and wastewater systems consequences to disruptions. The review includes tools that assess water systems resilience, vulnerability, and risk. This will help to understand gaps and limitations of these tools in order to plan for the development of the next-generation consequences tool for water and waste water systems disruption.

  5. Origins: science inspires art

    CERN Multimedia

    CERN Bulletin


    From 8 December 2011 to 17 February 2012, Geneva University's physics faculty will be holding an exhibition called "L'Origine – un voyage entre la Science et l'Art". Thirty artists from Europe and Africa will be exhibiting their work.   The aim of the exhibition is to take the visitor on an imaginary journey to the origins of mankind and to show how science and art approach the same theme from different angles. The works on display will include pieces of Makonde art, a traditional art form native to Mozambique, created by artists of the Nairucu Arts centre. The cultural programme that will run alongside the exhibition will include lectures on contemporary scientific themes aimed at the general public. Visitors will also have the opportunity to discover "L’Origine", a book of poetry by Beatrice Bressan (Ed. Loreleo, Geneva, 2010), which was awarded the third prize in the “Poeti nella società&...

  6. Origins Space Telescope (United States)

    Cooray, Asantha R.; Origins Space Telescope Study Team


    The Origins Space Telescope (OST) is the mission concept for the Far-Infrared Surveyor, a study in development by NASA in preparation for the 2020 Astronomy and Astrophysics Decadal Survey. Origins is planned to be a large aperture, actively-cooled telescope covering a wide span of the mid- to far-infrared spectrum. Its spectrographs will enable 3D surveys of the sky that will discover and characterize the most distant galaxies, Milky-Way, exoplanets, and the outer reaches of our Solar system. Origins will enable flagship-quality general observing programs led by the astronomical community in the 2030s. The Science and Technology Definition Team (STDT) would like to hear your science needs and ideas for this mission. The team can be contacted at I will summarize the OST STDT, mission design and instruments, key science drivers, and the study plan over the next two years.

  7. Cancer and orofacial pain (United States)

    Salvemini, Daniela


    Background Cancer pain is a devastating condition. Pain in the orofacial region, may be present as the single symptom of cancer or as a symptom of cancer in its later stages. This manuscript revises in a comprehensive manner the content of the conference entitled “Orofacial Pain and Cancer” (Dolor Orofacial y Cancer) given at the VI Simposio International “Advances in Oral Cancer” on the 22 July, 2016 in Donostia. Material and Methods We have reviewed (pubmed-medline) from the most relevant literature including reviews, systematic reviews and clinical cases, the significant and evidence-based mechanisms and mediators of cancer-associated facial pain, the diverse types of cancers that can be present in the craniofacial region locally or from distant sites that can refer to the orofacial region, cancer therapy that may induce pain in the orofacial region as well as discussed some of the new advancements in cancer pain therapy. Results There is still a lack of understanding of cancer pain pathophysiology since depends of the intrinsic heterogeneity, type and anatomic location that the cancer may present, making more challenging the creation of better therapeutic options. Orofacial pain can arise from regional or distant tumor effects or as a consequence of cancer therapy. Conclusions The clinician needs to be aware that the pain may present the characteristics of any other orofacial pain disorder so a careful differential diagnosis needs to be given. Cancer pain diagnosis is made by exclusion and only can be reached after a thorough medical history, and all the common etiologies have been carefully investigated and ruled out. The current management tools are not optimal but there is hope for new, safer and effective therapies coming in the next years. Key words:Pain, orofacial, facial, cancer. PMID:27694791

  8. Origins and Evolution of Life (United States)

    Gargaud, Muriel; López-García, Purificación; Martin, Hervé


    Part I. What Is Life?: 1. Problems raised by a definition of life M. Morange; 2. Some remarks about uses of cosmological anthropic 'principles' D. Lambert; 3. Minimal cell: the biologist point of view C. Brochier-Armanet; 4. Minimal cell: the computer scientist point of view H. Bersini; 5. Origins of life: computing and simulation approaches B. Billoud; Part II. Astronomical and Geophysical Context of the Emergence of Life: 6. Organic molecules in interstellar medium C. Ceccarelli and C. Cernicharo; 7. Cosmochemical evolution and the origin of life: insights from meteorites S. Pizzarello; 8. Astronomical constraints on the emergence of life M. Gounelle and T. Montmerle; 9. Formation of habitable planets J. Chambers; 10. The concept of galactic habitable zone N. Prantzos; 11. The young Sun and its influence on planetary atmospheres M. Güdel and J. Kasting; 12. Climates of the Earth G. Ramstein; Part III. Role of Water in the Emergence of Life: 13. Liquid water: a necessary condition to all forms of life K. Bartik, G. Bruylants, E. Locci and J. Reisse; 14. The role of water in the formation and evolution of planets T. Encrenaz; 15. Water on Mars J. P. Bibring; Part IV. From Non-Living Systems to Life: 16. Energetic constraints on prebiotic pathways: application to the emergence of translation R. Pascal and L. Boiteau; 17. Comparative genomics and early cell evolution A. Lazcano; 18. Origin and evolution of metabolisms J. Peretó; Part V. Mechanisms for Life Evolution: 19. Molecular phylogeny: inferring the patterns of evolution E. Douzery; 20. Horizontal gene transfer: mechanisms and evolutionary consequences D. Moreira; 21. The role of symbiosis in eukaryotic evolution A. Latorre, A. Durbán, A. Moya and J. Peretó; Part VI. Life in Extreme Conditions: 22. Life in extreme conditions: Deinococcus radiodurans, an organism able to survive prolonged desiccation and high doses of ionising radiation S. Sommer and M. Toueille; 23. Molecular effects of UV and ionizing

  9. Conscientiousness: Origins in Childhood? (United States)

    Eisenberg, Nancy; Duckworth, Angela L.; Spinrad, Tracy L.; Valiente, Carlos


    In this review, we evaluate developmental and personality research with the aim of determining whether the personality trait of conscientiousness can be identified in children and adolescents. After concluding that conscientiousness does emerge in childhood, we discuss the developmental origins of conscientiousness with a specific focus on…

  10. The Origin of Species

    NARCIS (Netherlands)

    Darwin, Charles


    In The Origin of Species Darwin outlined his theory of evolution, which proposed that species had been evolving and differentiating over time under the influence of natural selection. On its publication it became hugely influential, bringing about a seismic shift in the scientific view of humanitys

  11. The Origin of Life (United States)

    Hodson, D.


    Presents an outline of lectures given on this topic to British secondary students. Man's various ideas about the origin of life are included in three categories: those that consider life to have been created by a Divine Being; those that consider life to have developed from non-living matter; and those that consider life to be eternal. (MLH)

  12. The Consequences of Divorce for Attitudes toward Divorce and Gender Roles. (United States)

    Amato, Paul R.; Booth, Alan


    Examined consequences of divorce for attitudes toward divorce and gender roles among national sample of adults (n=2,033). Individuals from divorced families of origin revealed more positive attitudes toward divorce than did those who grew up in happy intact families. Those who recalled their parents' marriage as being unhappy had relatively…

  13. Argument z důsledku a jeho varianty (Argument from Consequences and its variants

    Directory of Open Access Journals (Sweden)

    Martina Juříková


    Full Text Available The article examines the use and evaluation of the argument from consequences, its historical origins since Aristotle through Blaise Pascal, David Hume until the inclusion of this argument into the textbooks of modern logic. The article also recapitulates current evaluation of this argument by Douglas Walton and along with Walton presents its two variants and criteria for evaluating their validity.

  14. Mechanisms and consequences of paternally transmitted chromosomal abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, F; Wyrobek, A J


    Paternally transmitted chromosomal damage has been associated with pregnancy loss, developmental and morphological defects, infant mortality, infertility, and genetic diseases in the offspring including cancer. There is epidemiological evidence linking paternal exposure to occupational or environmental agents with an increased risk of abnormal reproductive outcomes. There is also a large body of literature on germ cell mutagenesis in rodents showing that treatment of male germ cells with mutagens has dramatic consequences on reproduction producing effects such as those observed in human epidemiological studies. However, we know very little about the etiology, transmission and early embryonic consequences of paternally-derived chromosomal abnormalities. The available evidence suggests that: (1) there are distinct patterns of germ cell-stage differences in the sensitivity of induction of transmissible genetic damage with male postmeiotic cells being the most sensitive; (2) cytogenetic abnormalities at first metaphase after fertilization are critical intermediates between paternal exposure and abnormal reproductive outcomes; and, (3) there are maternally susceptibility factors that may have profound effects on the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and directly affect the risk for abnormal reproductive outcomes.

  15. Software development methodology for high consequence systems

    Energy Technology Data Exchange (ETDEWEB)

    Baca, L.S.; Bouchard, J.F.; Collins, E.W.; Eisenhour, M.; Neidigk, D.D.; Shortencarier, M.J.; Trellue, P.A.


    This document describes a Software Development Methodology for High Consequence Systems. A High Consequence System is a system whose failure could lead to serious injury, loss of life, destruction of valuable resources, unauthorized use, damaged reputation or loss of credibility or compromise of protected information. This methodology can be scaled for use in projects of any size and complexity and does not prescribe any specific software engineering technology. Tasks are described that ensure software is developed in a controlled environment. The effort needed to complete the tasks will vary according to the size, complexity, and risks of the project. The emphasis of this methodology is on obtaining the desired attributes for each individual High Consequence System.

  16. Exploring antismoking ads: appeals, themes, and consequences. (United States)

    Beaudoin, Christopher E


    In this study we seek a descriptive understanding of antismoking television advertising in light of the problem cigarette consumption poses for society today. We establish relationships between ad characteristics and whether ads have a youth or adult orientation, based on a content analysis of 197 antismoking television advertisements produced between 1991 and 1999. The study finds that youth-oriented ads have youth characters, sociability, and humor as common appeals, and social and short-term consequences. In contrast, adult-oriented ads relied on fear appeals and long-term, health-related consequences.

  17. Child sexual abuse: consequences and implications. (United States)

    Hornor, Gail


    Sexual abuse is a problem of epidemic proportions in the United States. Given the sheer numbers of sexually abused children, it is vital for pediatric nurse practitioners to understand both short-term and long-term consequences of sexual abuse. Understanding consequences of sexual abuse can assist the pediatric nurse practitioner in anticipating the physical and mental health needs of patients and also may assist in the identification of sexual abuse victims. Sexual abuse typically does not occur in isolation. Implications for practice will be discussed.

  18. Selective Accelerated Proliferation of Malignant Breast Cancer Cells on Planar Graphene Oxide Films. (United States)

    Kenry; Chaudhuri, Parthiv Kant; Loh, Kian Ping; Lim, Chwee Teck


    Graphene nanomaterials have been actively investigated for biomedical and biological applications, including that of cancer. Despite progress made, most of such studies are conducted on dispersed graphene nanosheets in solution. Consequently, the use of planar graphene films, especially in cancer research, has not been fully explored. Here, we investigate the cellular interactions between the graphene material films and breast cancer cell lines, specifically the effects these films have on cellular proliferation, spreading area, and cytotoxicity. We demonstrate that the graphene oxide (GO) film selectively accelerates the proliferation of both metastatic (MDA-MB-231) and nonmetastatic (MCF-7) breast cancer cells, but not that of noncancer breast epithelial cells (MCF-10A). Contrastingly, this accelerated proliferation is not observed with the use of graphene (G) film. Moreover, GO induces negligible cytotoxicity on these cells. We suggest that the observed phenomena originate from the synergistic effect resulted from the high loading capacity and conformational change of cellular attachment proteins on the GO film, and the high amount of oxygenated groups present in the material. We anticipate that our findings can further shed light on the graphene-cancer cellular interactions and provide better understanding for the future design and application of graphene-based nanomaterials in cancer research.

  19. Origin of Life

    CERN Document Server

    Lal, Ashwini Kumar


    The evolution of life has been a big enigma despite rapid advancements in the field of astrobiology, astrophysics and genetics in recent years. The answer to this puzzle has been as mindboggling as the riddle relating to evolution of Universe itself. Despite the fact that panspermia has gained considerable support as a viable explanation for origin of life on the Earth and elsewhere in the Universe, the issue however, remains far from a tangible solution. This paper examines the various prevailing hypotheses regarding origin of life like abiogenesis, RNA(ribonucleic acid) world, iron-sulphur world, panspermia, and concludes that delivery of life-bearing organic molecules by the comets in the early epoch of the Earth alone possibly was not responsible for kickstarting the process of evolution of life on our planet.

  20. Thermodynamic Origin of Life

    CERN Document Server

    Michaelian, K


    Understanding the thermodynamic function of life may shed light on its origin. Out of equilibrium structuring in space and time is contingent on continuous entropy production. Entropy production is a measure of the rate of the natural tendency of Nature to explore all available microstates. The process producing the greatest amount of entropy in the biosphere is the absorption and transformation of sunlight, leading to the transpiration of water by plants and cyanobacteria. Here we hypothesize that life began, and exists today, as a dynamic catalyst for the absorption and transformation of sunlight into heat, which could then be efficiently harvested by the water cycle, hurricanes, and ocean and wind currents. RNA and DNA are the most efficient of all known molecules for absorbing the ultraviolet light that could have penetrated the dense early atmosphere, and are extremely rapid in transforming this light into heat that can be readily absorbed by liquid water. The origin and evolution of life was thus driven...

  1. Authentic, Original, and Valuable

    DEFF Research Database (Denmark)

    Tupasela, Aaro Mikael; Tamminen, Sakari


    The idea of genetic authenticity and origin has been an important issue within genetics for decades for scientific, political, and economic reasons. The question of where species and populations come from, as well as the linking of genetic traits to particular geographical locations, has resurfaced...... as both a scientific and political site of interest more recently through the study of population genetics in both humans and non-humans. This article explores the ways in which genetics and notions of ‘authentic’, ‘indigenous’, and ‘endemic’ have become intertwined with everyday practices in research....... Using the case of human and non-human genetics to compare and contrast the various facets associated with genetic identity, we seek to develop a broader picture of the ways in which genetics plays an important role in stabilizing categories of origin....

  2. The Origins of Art

    Directory of Open Access Journals (Sweden)

    Aleksandre P. Lobodanov


    Full Text Available The origins of artistic activities or rather art, and in recent decades the processing and consolidation of a new field in art history, art semiotics, are grouped together in the semiotic systems of applied and non-applied arts.In this paper, in particular, an analysis is made of the non-applied arts, in which non-verbal signs are used to express the form of human thought.The discussion focuses on the origins of non-applied arts, the image-forming process, the psychology of perception, the perception of sound and reproduction of sounds, the development of music and the development of dance in their entirety, as an expression of the inner condition that influences the body through movement: it thus provides a valuable contribution to the study of the non-applied arts.

  3. Toothache of cardiac origin. (United States)

    Kreiner, M; Okeson, J P


    Pain referred to the orofacial structures can sometimes be a diagnostic challenge for the clinician. In some instances, a patient may complain of tooth pain that is completely unrelated to any dental source. This poses a diagnostic and therapeutic problem for the dentist. Cardiac pain most commonly radiates to the left arm, shoulder, neck, and face. In rare instances, angina pectoris may present as dental pain. When this occurs, an improper diagnosis frequently leads to unnecessary dental treatment or, more significantly, a delay of proper treatment. This delay may result in the patient experiencing an acute myocardial infarction. It is the dentist's responsibility to establish a proper diagnosis so that the treatment will be directed toward the source of pain and not to the site of pain. This article reviews the literature concerning referred pain of cardiac origin and presents a case report of toothache of cardiac origin.

  4. Conscientiousness: Origins in Childhood?


    Eisenberg, Nancy; Duckworth, Angela L.; Spinrad, Tracy L.; Valiente, Carlos


    In this review, we evaluate developmental and personality research with the aim of determining if the personality trait of conscientiousness can be identified in children and adolescents. After concluding that conscientiousness does emerge in childhood, we discuss the developmental origins of conscientiousness with a specific focus on self-regulation, academic motivation, and internalized compliance/internalization of standards. Based on the accumulated body of evidence, we conclude that self...

  5. Origin of Hawking Radiation: Firewall or Atmosphere?

    CERN Document Server

    Kim, Wontae


    The Unruh vacuum not admitting any outgoing flux at the horizon implies that the origin of the outgoing Hawking radiation would be the atmosphere of a near-horizon quantum region without resort to the firewall; however, the existence of the firewall of superplanckian excitations at the horizon might be supported by the infinite Tolman temperature of the infinitely blueshifted Hawking temperature at the horizon. Using an exactly soluble model, we show that the firewall necessarily emerges out of the Unruh vacuum such that the Tolman temperature in the Unruh vacuum is divergent in essence due to the infinitely blueshifted negative ingoing flux crossing the horizon rather than the outgoing flux. It is also shown that the outgoing Hawking radiation in the Unruh vacuum indeed originates from the atmosphere, not just at the horizon, which is of no relevance to the infinite blueshift. Consequently, we find that the firewall induced from the infinite Tolman temperature and the Hawking radiation coming from the atmosp...

  6. Carotenoids and lung cancer prevention (United States)

    Understanding the molecular actions of carotenoids is critical for human studies involving carotenoids for prevention of lung cancer and cancers at other tissue sites. While the original hypothesis prompting the beta-carotene intervention trials was that beta-carotene exerts beneficial effects thro...

  7. Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms. (United States)

    Cobb, Lauren Patterson; Gaillard, Stephanie; Wang, Yihong; Shih, Ie-Ming; Secord, Angeles Alvarez


    Traditionally, epithelial ovarian, tubal, and peritoneal cancers have been viewed as separate entities with disparate origins, pathogenesis, clinical features, and outcomes. Additionally, previous classification systems for ovarian cancer have proposed two primary histologic groups that encompass the standard histologic subtypes. Recent data suggest that these groupings no longer accurately reflect our knowledge surrounding these cancers. In this review, we propose that epithelial ovarian, tubal, and peritoneal carcinomas represent a spectrum of disease that originates in the Mullerian compartment. We will discuss the incidence, classification, origin, molecular determinants, and pathologic analysis of these cancers that support the conclusion they should be collectively referred to as adenocarcinomas of Mullerian origin. As our understanding of the molecular and pathologic profiling of adenocarcinomas of Mullerian origin advances, we anticipate treatment paradigms will shift towards genomic driven therapeutic interventions.

  8. Ghrelin and cancer. (United States)

    Chopin, Lisa; Walpole, Carina; Seim, Inge; Cunningham, Peter; Murray, Rachael; Whiteside, Eliza; Josh, Peter; Herington, Adrian


    Ghrelin is a peptide hormone that was originally isolated from the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin has many functions, including the regulation of appetite and gut motility, growth hormone release from the anterior pituitary and roles in the cardiovascular and immune systems. Ghrelin and its receptor are expressed in a number of cancers and cancer cell lines and may play a role in processes associated with cancer progression, including cell proliferation, apoptosis, and cell invasion and migration.

  9. Cerebral asymmetry and language development: cause, correlate, or consequence? (United States)

    Bishop, Dorothy V M


    In most people, language is processed predominantly by the left hemisphere of the brain, but we do not know how or why. A popular view is that developmental language disorders result from a poorly lateralized brain, but until recently, evidence has been weak and indirect. Modern neuroimaging methods have made it possible to study normal and abnormal development of lateralized function in the developing brain and have confirmed links with language and literacy impairments. However, there is little evidence that weak cerebral lateralization has common genetic origins with language and literacy impairments. Our understanding of the association between atypical language lateralization and developmental disorders may benefit if we reconceptualize the nature of cerebral asymmetry to recognize its multidimensionality and consider variation in lateralization over developmental time. Contrary to popular belief, cerebral lateralization may not be a highly heritable, stable characteristic of individuals; rather, weak lateralization may be a consequence of impaired language learning.

  10. Original BPC3 Research Plan (United States)

    The Breast and Prostate Cancer and Hormone-Related Gene Variant Study allows large-scale analyses of breast and prostate cancer risk in relation to genetic polymorphisms and gene-environment interactions that affect hormone metabolism.

  11. Weaning the pig - Concepts and consequences

    NARCIS (Netherlands)

    Pluske, J.R.; Dividich, Le J.; Verstegen, M.W.A.


    Weaning the Pig: Concepts and Consequences addresses the major issues surrounding the weaning process, both for piglets and the breeding herd, in modern-day pig production. The post-weaned pig presents many challenges to the manager, stockperson and nutritionist, and as such is a critical phase in t

  12. Paternal Alcoholism: Consequences for Female Children (United States)

    Dehn, Julia


    The consequences of substance abuse and addiction are profound and depredating. The desolation is incalculable in estimating the psychological damage and trauma inflicted on the children of addicted parents. According to studies and statistics gathered by the National Association for Children of Alcoholics, "there are more than 20 million children…

  13. Cognitive Consequences of Formal and Informal Education (United States)

    Scribner, Sylvia; Cole, Michael


    Discusses the cognitive consequences of education, and reviews evidence which supports the hypothesis that differences in the social organization of education promote differences in the organization of learning and thinking skills in the individual. Proposes that new accommodations are needed between school-based learning and learning experiences…

  14. Consequences and complications of peritoneal adhesions

    NARCIS (Netherlands)

    Goor, H. van


    Consequences and complications of postsurgical intra-abdominal adhesion formation not including small bowel obstruction and secondary infertility are substantial but are under-exposed in the literature. Inadvertent enterotomy during reopening of the abdomen or subsequent adhesion dissection is a fea

  15. Common consequence effects in pricing and choice

    NARCIS (Netherlands)

    Schmidt, U.; Trautmann, S.T.


    This paper presents an experimental study of common consequence effects in binary choice, willingness-to-pay (WTP) elicitation, and willingness-to-accept (WTA) elicitation. We find strong evidence in favor of the fanning out hypothesis (Machina, Econometrica 50:277–323, 1982) for both WTP and WTA. I

  16. Violence against Teachers: Prevalence and Consequences (United States)

    Wilson, Catherine M.; Douglas, Kevin S.; Lyon, David R.


    Data collected from 731 teachers were used to examine the consequences of violence directed toward teachers while in the workplace. Analyses showed that the majority of respondents (n = 585, 80.0%) had experienced school-related violence--broadly defined--at one point in their careers. Serious violence (actual, attempted, or threatened physical…

  17. Physiological consequences : Cardiopulmonary, vestibular, and sensory aspects

    NARCIS (Netherlands)

    Welsch, H.; Albery, W.; Banks, R.D.; Bles, W.


    Discussing the physiological consequences of enhanced fighter manoeuvrability (EFM), aspects of cardiopulmonary reactions will be seen during high G manoeuvres, especially the combination of negative G-load followed by high G-onset manoeuvres ("push-pull"). The aircraft's capability to reach high al

  18. Consequences of Assessment: What Is the Evidence? (United States)

    Mehrens, William A.


    Examines the purposes of large-scale assessment programs, outlines the dangers and benefits of these assessments, considers the research evidence about the consequences of assessment, discusses how to evaluate assessment quality, and presents some ideas about the variables that influence the probabilities for good and bad assessment. (SLD)

  19. Climate change consequences for the indoor environment

    NARCIS (Netherlands)

    Ariës, M.B.C.; Bluyssen, P.M.


    Scientists warn us about climate change and its effects on the outdoor environment. These effects can have significant consequences for the indoor environment, also in the Netherlands. Climate changes will affect different aspects of the indoor environment as well as the stakeholders of that indoor

  20. Separation: consequences for wealth in later life

    NARCIS (Netherlands)

    Dewilde, C.; van den Bosch, K.; van den Heede, A.; Börsch-Supan, A.; Brandt, M.; Hank, K.; Schröder, M.


    Over the course of their lives, a substantial minority of elderly European men and women have experienced the dissolution of one or more partner relationships through divorce or the ending of cohabitation. So far, most research into the economic consequences of (marital) separation has been based on

  1. Low-Incidence, High-Consequence Pathogens

    Centers for Disease Control (CDC) Podcasts


    Dr. Stephan Monroe, a deputy director at CDC, discusses the impact of low-incidence, high-consequence pathogens globally.  Created: 2/21/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 2/26/2014.

  2. Explosion risks and consequences for tunnels

    NARCIS (Netherlands)

    Weerheijm, J.; Berg, A.C. van den


    Tunnel accidents with transports of dangerous goods may lead to explosions. Risk assessment for these accidents is complicated because of the low probability and the unknown, but disastrous effects expected. Especially the lack of knowledge on the strength of the explosion and the consequences for t

  3. Health consequences of the September 11 World Trade Center attacks: a review. (United States)

    Moline, Jacqueline; Herbert, Robin; Nguyen, Ngoctram


    In the aftermath of the September 11 World Trade Center (WTC) attack, a large number of people sustained potential exposures to smoke, dust, particulate matter, and a variety of toxins, including asbestos, pulverized concrete, glass fibers, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated furans and dioxins. Additionally, many had exposure to psychological traumatogens. The most common effects seen to date are respiratory and mental health consequences. The long-term consequences of exposures are not yet known, and there remains concern about the potential for late-emerging diseases such as cancers. This article reviews WTC-related health effects, the spectrum of exposures and how they were documented, and discusses future preventive efforts.

  4. The origin of life--how long did it take? (United States)

    Orgel, L. E.; Bada, J. L. (Principal Investigator)


    We do not understand the steps leading from the abiotic early earth to the RNA world. Consequently, we cannot estimate the time required for the origins of life. Attempts to circumvent this essential difficulty are based on misunderstandings of the nature of the problem.

  5. Noisy clues to the origin of life. (United States)

    Krakauer, David C; Sasaki, Akira


    The origin of stable self-replicating molecules represents a fundamental obstacle to the origin of life. The low fidelity of primordial replicators places restrictions on the quantity of information encoded in a primitive nucleic acid alphabet. Further difficulties for the origin of life are the role of drift in small primordial populations, reducing the rate of fixation of superior replicators, and the hostile conditions increasing developmental noise. Thus, mutation, noise and drift are three different stochastic effects that are assumed to make the evolution of life improbable. Here we show, to the contrary, how noise present in hostile early environments can increase the probability of faithful replication, by amplifying selection in finite populations. Noise has negative consequences in infinite populations, whereas in finite populations, we observe a synergistic interaction among noise sources. Hence, two factors formerly considered inimical to the origin of life-developmental noise and drift in small populations-can in combination give rise to conditions favourable to robust replication.

  6. Big bang or continuous creation: does life have multiple origins? (United States)

    Konesky, Gregory A.


    The generally accepted notion of a single origin of life from a primordial soup on the early Earth has been challenged recently by the suggestion of a "second life," "shadow life," and even "biological dark matter." The problem in classifying these microorganisms is in the difficulty or complete failure of the 16s genetic fingerprinting process, suggesting a different underlying biochemistry resulting from at least a second origin of life. We consider an extension of this concept to include continuous origination of life throughout Earth's history, up to the present. The consequences for interpreting the "tree of life" are also considered.


    Directory of Open Access Journals (Sweden)

    Mellina da Silva Tertes


    Full Text Available Individuals in their day-to-day are demanded to make choices in contexts of services with mild and severeconsequences. Decisions with severe consequences are difficult situations where choices are dilemmas thatcause stress and severe emotional reactions (botti et al, 2009; Kahn, luce, 2003. The mild decisions, in turn,involve situations that represent a low risk and uncertainty to decision maker. However, despite thedifferences seen in the literature, the consequences of decisions - mild and severe - have rarely been seen inconsumer behavior studies. This theoretical essay aims to investigate the moderator effect of theconsequences of the exchange of relations between trust and its antecedents and consequences in the contextof provision of medical services. Consumer confidence plays a key role, especially in situations of severechanges, as it reduces the perception of risk, since it helps the individual to form consistent expectationsregarding the service provider. Comparing exchanges with mild versus severe consequences, affection willhave a greater impact on confidence in exchanges with severe consequences comparing with mildexchanges. In turn, the cognition effect will be moderated by the type of exchange, because it is believed thatin both exchanges, with mild and severe consequences, cognition will play an important role in reducinguncertainty and increasing confidence. Regarding the consequences of confidence, it is believed that themore severe are the consequences of the exchanges, the strongest will be the relationship between trust andthe treatment continuity intent, word-of-mouth and search for a second opinion.

  8. On the Mathematical Consequences of Binning Spike Trains. (United States)

    Cessac, Bruno; Le Ny, Arnaud; Löcherbach, Eva


    We initiate a mathematical analysis of hidden effects induced by binning spike trains of neurons. Assuming that the original spike train has been generated by a discrete Markov process, we show that binning generates a stochastic process that is no longer Markov but is instead a variable-length Markov chain (VLMC) with unbounded memory. We also show that the law of the binned raster is a Gibbs measure in the DLR (Dobrushin-Lanford-Ruelle) sense coined in mathematical statistical mechanics. This allows the derivation of several important consequences on statistical properties of binned spike trains. In particular, we introduce the DLR framework as a natural setting to mathematically formalize anticipation, that is, to tell "how good" our nervous system is at making predictions. In a probabilistic sense, this corresponds to condition a process by its future, and we discuss how binning may affect our conclusions on this ability. We finally comment on the possible consequences of binning in the detection of spurious phase transitions or in the detection of incorrect evidence of criticality.

  9. On the mathematical consequences of binning spike trains

    CERN Document Server

    Cessac, B; Loecherbach, E


    We initiate a mathematical analysis of hidden effects induced by binning spike trains of neurons. Assuming that the original spike train has been generated by a discrete Markov process, we show that binning generates a stochastic process which is not Markov any more, but is instead a Variable Length Markov Chain (VLMC) with unbounded memory. We also show that the law of the binned raster is a Gibbs measure in the DLR (Dobrushin-Lanford-Ruelle) sense coined in mathematical statistical mechanics. This allows the derivation of several important consequences on statistical properties of binned spike trains. In particular, we introduce the DLR framework as a natural setting to mathematically formalize anticipation, i.e. to tell "how good" our nervous system is at making predictions. In a probabilistic sense, this corresponds to condition a process by its future and we discuss how binning may affect our conclusions on this ability. We finally comment what could be the consequences of binning in the detection of spu...

  10. Malnutrition and obesity in pediatric oncology patients: causes, consequences, and interventions. (United States)

    Co-Reyes, Erica; Li, Rhea; Huh, Winston; Chandra, Joya


    In children with cancer, suboptimal nutrition states are common consequences of the disease and its treatment. These nutrition states have been attributed to a number of etiologies dependent on the patient's tumor type and treatment, and are associated with increased morbidity and mortality. Interventions vary from psychosocial to pharmacological and surgical management. Further research is necessary to understand the epidemiology and etiology of these nutrition states. Of great importance is the development and implementation of effective interventions to optimize nutritional status among children with cancer during and after therapy.

  11. Integrated genomic analysis of breast cancers. (United States)

    Addou-Klouche, L; Adélaïde, J; Cornen, S; Bekhouche, I; Finetti, P; Guille, A; Sircoulomb, F; Raynaud, S; Bertucci, F; Birnbaum, D; Chaffanet, M


    Breast cancer is the most frequent and the most deadly cancer in women in Western countries. Different classifications of disease (anatomoclinical, pathological, prognostic, genetic) are used for guiding the management of patients. Unfortunately, they fail to reflect the whole clinical heterogeneity of the disease. Consequently, molecularly distinct diseases are grouped in similar clinical classes, likely explaining the different clinical outcome between patients in a given class, and the fact that selection of the most appropriate diagnostic or therapeutic strategy for each patient is not done accurately. Today, treatment is efficient in only 70.0-75.0% of cases overall. Our repertoire of efficient drugs is limited but is being expanded with the discovery of new molecular targets for new drugs, based on the identification of candidate oncogenes and tumor suppressor genes (TSG) functionally relevant in disease. Development of new drugs makes therapeutical decisions even more demanding of reliable classifiers and prognostic/predictive tests. Breast cancer is a complex, heterogeneous disease at the molecular level. The combinatorial molecular origin and the heterogeneity of malignant cells, and the variability of the host background, create distinct subgroups of tumors endowed with different phenotypic features such as response to therapy and clinical outcome. Cellular and molecular analyses can identify new classes biologically and clinically relevant, as well as provide new clinically relevant markers and targets. The various stages of mammary tumorigenesis are not clearly defined and the genetic and epigenetic events critical to the development and aggressiveness of breast cancer are not precisely known. Because the phenotype of tumors is dependent on many genes, a large-scale and integrated molecular characterization of the genetic and epigenetic alterations and gene expression deregulation should allow the identification of new molecular classes clinically

  12. Nuclear catastrophe in Japan. Health consequences resulting from Fukushima; Atomkatastrophe in Japan. Gesundheitliche Folgen von Fukushima

    Energy Technology Data Exchange (ETDEWEB)

    Paulitz, Henrik; Eisenberg, Winfrid; Thiel, Reinhold


    On 11 March 2011, a nuclear catastrophe occurred at the Fukushima Dai-ichi nuclear power plant in Japan in the wake of an earthquake and due to serious safety deficiencies. This resulted in a massive and prolonged release of radioactive fission and decay products. Approximately 20% of the radioactive substances released into the atmosphere have led to the contamination of the landmass of Japan with 17,000 becquerels per square meter of cesium-137 and a comparable quantity of cesium-134. The initial health consequences of the nuclear catastrophe are already now, after only two years, scientifically verifiable. Similar to the case of Chernobyl, a decline in the birth rate was documented nine months after the nuclear catastrophe. Throughout Japan, the total drop in number of births in December 2011 was 4362, with the Fukushima Prefecture registering a decline of 209 births. Japan also experienced a rise in infant mortality, with 75 more children dying in their first year of life than expected statistically. In the Fukushima Prefecture alone, some 55,592 children were diagnosed with thyroid gland nodules or cysts. In contrast to cysts and nodules found in adults, these findings in children must be classified as precancerous. There were also the first documented cases in Fukushima of thyroid cancer in children. The present document undertakes three assessments of the expected incidence of cancer resulting from external exposure to radiation. These are based on publications in scientific journals on soil contamination in 47 prefectures in Japan, the average total soil contamination, and, in the third case, on local dose rate measurements in the fall of 2012. Taking into consideration the shielding effect of buildings, the medical organization IPPNW has calculated the collective lifetime doses for individuals at 94,749 manSv, 206,516 manSv, and 118,171 manSv, respectively. In accordance with the risk factors set by the European Committee on Radiation Risk (ECRR) for death

  13. DNA replication origins in archaea


    Zhenfang eWu; Jingfang eLiu; Haibo eYang; Hua eXiang


    DNA replication initiation, which starts at specific chromosomal site (known as replication origins), is the key regulatory stage of chromosome replication. Archaea, the third domain of life, use a single or multiple origin(s) to initiate replication of their circular chromosomes. The basic structure of replication origins is conserved among archaea, typically including an AT-rich unwinding region flanked by several conserved repeats (origin recognition box, ORB) that are located adjacent to ...

  14. Origin of earth's moon (United States)

    Wood, J. A.


    The major geochemical properties of the moon are briefly considered along with the significant facts of the moon's geologic history, and then the three current hypotheses regarding the moon's origin, namely, fission, capture, and binary accretion, are reviewed. The individual merits and improbabilities associated with each mechanism are taken into consideration. Special attention is given to the binary accretion model as the most promising one. In the variants of this model, of crucial importance is the nature of the more general hypothesis assumed for planetary formation from the solar nebula. The two main models differ considerably in the amount of chemical fractionation they allow to accompany planetary formation.

  15. Geochemical Origin of Biological Molecules (United States)

    Bassez, Marie-Paule


    A model for the geochemical origin of biological molecules is presented. Rocks such as peridotites and basalts, which contain ferromagnesian minerals, evolve in the presence of water. Their hydrolysis is an exothermic reaction which generates heat and a release of H2 and of minerals with modified structures. The hydrogen reacts with the CO2 embedded inside the rock or with the CO2 of the environment to form CO in an hydrothermal process. With the N2 of the environment, and with an activation source arising from cosmic radiation, ferromagnesian rocks might evolve towards the abiotic formation of biological molecules, such as peptide like macromolecules which produce amino acids after acid hydrolysis. The reactions concerned are described. The production of hydrothermal CO is discussed in geological sites containing ferromagnesian silicate minerals and the low intensity of the Earth's magnetic field during Paleoarchaean Era is also discussed. It is concluded that excitation sources arising from cosmic radiation were much more abundant during Paleoarchaean Era and that macromolecular structures of biological relevance might consequently form during Archaean Eon, as a product of the chemical evolution of the rocks and of their mineral contents. This synthesis of abiotically formed biological molecules is consecutively discussed for meteorites and other planets such as Mars. This model for the geochemical origin of biological molecules has first been proposed in 2008 in the context of reactions involving catalysers such as kaolinite [Bassez 2008a] and then presented in conferences and articles [Bassez 2008b, 2009, 2012; Bassez et al. 2009a to 2012b]. BASSEZ M.P. 2008a Synthèse prébiotique dans les conditions hydrothermales, CNRIUT'08, Lyon 29-30/05/2008, Conf. and open access article: 29 mai 11h-12h40. BASSEZ M.P. 2008b Prebiotic synthesis under hydrothermal conditions, ISSOL'08, P2-6, Firenze-Italy, 24-29/08/2008. Poster at the

  16. The Origins of Neuroticism. (United States)

    Barlow, David H; Ellard, Kristen K; Sauer-Zavala, Shannon; Bullis, Jacqueline R; Carl, Jenna R


    In this article, we provide a fresh perspective on the developmental origins of neuroticism--a dimension of temperament marked by elevated stress reactivity resulting in the frequent experience of negative emotions. This negative affectivity is accompanied by a pervasive perception that the world is a dangerous and threatening place, along with beliefs about one's inability to manage or cope with challenging events. Historically, neuroticism has been viewed as a stable, genetically based trait. However, recent understanding of ongoing gene-environment interactions that occur throughout the life span suggests there may be a more complex and dynamic etiology. Thus, the purpose of this article is to offer a theory for understanding the development of neuroticism that integrates genetic, neurobiological, and environmental contributions to this trait. Given the strong correlation between neuroticism and the development of negative health outcomes--most notably, the full range of anxiety and mood disorders--an enhanced understanding of how neuroticism originates has implications for the treatment and prevention of a broad range of pathologies and, perhaps, even for the prevention of neuroticism itself.

  17. Partial migration in fishes: causes and consequences. (United States)

    Chapman, B B; Hulthén, K; Brodersen, J; Nilsson, P A; Skov, C; Hansson, L-A; Brönmark, C


    Partial migration, where only some individuals from a population migrate, has been widely reported in a diverse range of animals. In this paper, what is known about the causes and consequences of partial migration in fishes is reviewed. Firstly, the ultimate and proximate drivers of partial migration are reflected upon: what ecological factors can shape the evolution of migratory dimorphism? How is partial migration maintained over evolutionary timescales? What proximate mechanisms determine whether an individual is migratory or remains resident? Following this, the consequences of partial migration are considered, in an ecological and evolutionary context, and also in an applied sense. Here it is argued that understanding the concept of partial migration is crucial for fisheries and ecosystem managers, and can provide information for conservation strategies. The review concludes with a reflection on the future opportunities in this field, and the avenues of research that are likely to be fruitful to shed light on the enduring puzzle of partial migration in fishes.

  18. Partial migration in fishes: causes and consequences

    DEFF Research Database (Denmark)

    Chapman, B.B.; Hulthén, K.; Brodersen, J.;


    migration are reflected upon: what ecological factors can shape the evolution of migratory dimorphism? How is partial migration maintained over evolutionary timescales? What proximate mechanisms determine whether an individual is migratory or remains resident? Following this, the consequences of partial...... with a reflection on the future opportunities in this field, and the avenues of research that are likely to be fruitful to shed light on the enduring puzzle of partial migration in fishes......Partial migration, where only some individuals from a population migrate, has been widely reported in a diverse range of animals. In this paper, what is known about the causes and consequences of partial migration in fishes is reviewed. Firstly, the ultimate and proximate drivers of partial...

  19. Galectins in angiogenesis: consequences for gestation. (United States)

    Blois, Sandra M; Conrad, Melanie L; Freitag, Nancy; Barrientos, Gabriela


    Members of the galectin family have been shown to exert several roles in the context of reproduction. They contribute to placentation, maternal immune regulation and facilitate angiogenesis encompassing decidualisation and placenta formation during pregnancy. In the context of neo-vascularisation, galectins have been shown to augment signalling pathways that lead to endothelial cell activation, cell proliferation, migration and tube formation in vitro in addition to angiogenesis in vivo. Angiogenesis during gestation ensures not only proper foetal growth and development, but also maternal health. Consequently, restriction of placental blood flow has major consequences for both foetus and mother, leading to pregnancy diseases. In this review we summarise both the established and the emerging roles of galectin in angiogenesis and discuss the possible implications during healthy and pathological gestation.

  20. FIRE simulations: galactic outflows and their consequences (United States)

    Keres, Dusan; FIRE Team


    We study gaseous outflows and their consequences in high-resolution galaxy formation simulations with explicit stellar feedback from the Feedback in Realistic Environments project. Collective, galaxy scale, effect of stellar feedback results in episodic ejections of large amount of gas and heavy elements into the circum-galactic medium. Gas ejection episodes follow strong bursts of star formation. Properties of galactic star formation and ejection episodes depend on galaxy mass and redshift and, together with gas infall and recycling, shape the evolution of the circum-galactic medium and galaxies. As a consequence, our simulated galaxies have masses, star formation histories and heavy element content in good agreement with the observed population of galaxies.

  1. Consequences of infertility in developing countries. (United States)

    Rouchou, Brittany


    Infertility affects more than 10% of the world's population. In developing countries, there are severe social, psychological and economic consequences for infertile men and women. All of the cited references are compiled from primary peer-reviewed research articles that were conducted through one-to-one interviews or focus groups in countries of developing regions, such as Africa, Asia and the Middle East. The following paper seeks to raise awareness of the consequences of infertility in developing nations and identify infertility as an under-observed, but significant public health issue. It is proposed that education programmes tailored to each society's specific religious beliefs and grounded traditions must be implemented in order to reverse the social stigma, detrimental psychological effects, and loss of economic security that results from infertility.

  2. Review of methodology for accident consequence assessment

    Energy Technology Data Exchange (ETDEWEB)

    Strenge, D.L.; Soldat, J.K.; Watson, E.C.


    This report reviews current methodologies for reactor accident consequence analysis and describes areas where modifications are warranted. Methodologies reviewed are: (1) Models in Regulatory Guides 1.109, 1.111 and 1.113 used for evaluation of compliance with 10 CFR 50 Appendix I; (2) Models in Regulatory Guides used for evaluation of consequences from accidents of Classes 3-8; (3) Models for evaluation of Class 9 accidents presented in the Reactor Safety Study; and (4) Models in the Liquid Pathway Generic Study. The review is designed to aid in the ultimate goal of selection of a comprehensive set of models to extend the Class 9 methodology of the Reactor Safety Study to the analysis of Classes 3-8 accidents.

  3. Assuring quality in high-consequence engineering

    Energy Technology Data Exchange (ETDEWEB)

    Hoover, Marcey L.; Kolb, Rachel R.


    In high-consequence engineering organizations, such as Sandia, quality assurance may be heavily dependent on staff competency. Competency-dependent quality assurance models are at risk when the environment changes, as it has with increasing attrition rates, budget and schedule cuts, and competing program priorities. Risks in Sandia's competency-dependent culture can be mitigated through changes to hiring, training, and customer engagement approaches to manage people, partners, and products. Sandia's technical quality engineering organization has been able to mitigate corporate-level risks by driving changes that benefit all departments, and in doing so has assured Sandia's commitment to excellence in high-consequence engineering and national service.

  4. EPEC-O Self-Study - Original Version (United States)

    The EPEC-O (Education in Palliative and End-of-Life Care for Oncology) Self-Study Original Version is a free comprehensive multimedia curricula for health professionals caring for persons with cancer and their families. The curricula is available as an online Self-Study Section and as a CD-ROM you can order.

  5. Origins of XMRV deciphered, undermining claims for role in humans (United States)

    Delineation of the origin of the retrovirus known as XMRV from the genomes of laboratory mice indicates that the virus is unlikely to be responsible for either prostate cancer or chronic fatigue syndrome in humans, as has been widely published. The virus arose because of genetic recombination of two mouse viruses.

  6. Consequences of long-term hyperparathyroidism. (United States)

    Graal, M B; Wolffenbuttel, B H


    We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates.

  7. Consequences of Confinement in Zeolite Acid Catalysis


    Gounder, Rajamani Pachayappan


    The catalytic consequences of confinement within zeolite voids were examined for several elimination (alkane cracking and dehydrogenation, alkene cracking, alkanol dehydration) and addition (alkene hydrogenation, alkylation and oligomerization) reactions catalyzed by Brønsted solid acids. These reactions are mediated by cationic transition states that are confined within voids of molecular dimensions (0.4-1.3 nm) and proceed at rates that reflect the Gibbs free energies of late ion-pairs at t...

  8. Central Bank Transparency: Causes, Consequences and Updates


    Nergiz Dincer; Barry Eichengreen


    We present updated estimates of central bank for 100 countries up through 2006 and use them to analyze both the determinants and consequences of monetary policy transparency in an integrated econometric framework. We establish that there has been significant movement in the direction of greater central bank transparency in recent years. Transparent monetary policy arrangements are more likely in countries with strong and stable political institutions. They are more likely in democracies, with...

  9. Consequences of Helicobacter pylori infection in children

    Institute of Scientific and Technical Information of China (English)

    Lucia; Pacifico; Caterina; Anania; John; F; Osborn; Flavia; Ferraro; Claudio; Chiesa


    Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the hu-man stomach for many decades without adverse con-sequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent a...

  10. Consequences of Helicobacter pylori infection in children


    Pacifico, Lucia; Anania, Caterina; Osborn, John F.; Ferraro, Flavia; Chiesa, Claudio


    Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the human stomach for many decades without adverse consequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children wit...

  11. Planning of elimination of emergency consequences

    Directory of Open Access Journals (Sweden)

    S. Kovalenko


    Full Text Available Introduction. The volume of useful information in the planning of elimination of emergency consequences process is reasonable to assess with calculatory problems and mathematical models. Materials and methods. The expert survey method is used to calculate quantitative values of probability and to determine the optimal solution before the information in condition is received. Results. It is determined that the quality of the solution of elimination emergency consequences depends primarily on the number of factors that are taken into account in particular circumstances of the situation; on the level of information readiness of control bodies to take decision to eliminate emergency consequences as soon as possible and to consider several options for achieving reasonableness and concreteness of a particular decision. The ratio between volume of useful information collected and processed during operation planning which is required for identifying optimal solution is calculated. This ratio allows to construct a graph of probability of identifying a solution in existing environment and probability value of identifying optimal solution before information in P*condition is obtained. This graph also shows the ratio volume of useful information collected and processed during operation planning and necessary volume of information for identifying optimal solution. Conclusion. The results of this research can be used for improving control bodies decisions to ensure safe working conditions for employees of food industry.

  12. 6 Common Cancers - Lung Cancer (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

  13. 6 Common Cancers - Skin Cancer (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  14. 人源Fab抗体库的构建和抗hPRLR抗体的筛选鉴定%Screening and identification of human Fab antibody against hPRLR from large phage-display library originated from breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    屈芫; 魏钦俊; 姚俊; 鲁雅洁; 王天明; 曹新; 冯振卿


    cWe aim to get specific Fab antibody against human prolactin receptor (hPRLR) from the human Fab antibody library constructed by phage display technology. Human lymphocytes were collected from peripheral blood of 24 breast cancer patients. And then the total RNA was extracted and reversely transcribed to cDNA. Genes of light and heavy chains of human antibody were amplified by RT-PCR to construct anti-hPRLR immunized human antibody library. After three rounds of panning and one round of crossed-panning with against his-hPRLR fusion protein, BSA-polypeptide (epitopes of hPRLR) and GST-hPRLR fusion protein, positive clones were chosen by Phage-ELISA and DNA sequencing. Then the positive clones were transformed into E. coli Top 10' and induced to express antibody protein. The results indicated that the human Fab phage-display library consisting of l.0×l09 clones were successfully constructed, and six clones were selected after four rounds. One of them named FabG2 expressed protein correctly. ELISA and Western blot analysis showed that FabG2 could bind hPRLR specifically. We concluded that the hPRLR specific Fab antibody selected from large phage-display library could be used as candidates for therapy agent of breast cancer which over-expresses hPRLR.%目的 构建人源Fab噬菌体抗体库,筛选抗hPRLR抗体片段并进行初步鉴定.方法 从乳腺癌患者外周血提取总RNA,通过RT-PCR扩增人抗体轻链和重链基因,构建抗hPRLR人源Fab抗体库.分别以His-hPRLR融合蛋白、BSA-hPRLR表位多肽融合蛋白和GST-hPRLR融合蛋白作为抗原包板,经过3轮循环的吸附一洗脱一扩增的筛选及1轮交叉筛选,挑单克隆用Phage-ELISA、DNA测序筛选阳性克隆,将筛选到的阳性克隆Fabc2转化至Top10’受体菌,诱导表达可溶性Fab抗体,通过Western blot和ELISA进行特异性的鉴定.结果 构建的人源Fab库容为1.0×109,4轮的筛选,获得6株能与hPRLR结合的人源抗体克隆.选取的Fabc2能够进行

  15. First molecules, biological chirality, origin(s) of life. (United States)

    Caglioti, Luciano; Micskei, Károly; Pályi, Gyula


    Origin(s) of biological chirality appear(s) to be intimately connected to origin(s) of life. Prebiotic evolution toward these important turning points can be traced back to single chiral molecules. These can be small (monomeric) units as amino acids or monosaccharides or oligomers as oligo-RNA type molecules. Earlier speculations about these two kinds of entries to biological chirality are critically reviewed.

  16. Microscopic origin of magnetoresistance

    Directory of Open Access Journals (Sweden)

    Christian Heiliger


    Full Text Available Tunneling magnetoresistance is one of the basic effects of spintronics with the potential for applications in sensors and IT, where the spin degree of freedom of electrons is exploited. Successful application requires control of the materials and processes involved on the atomic scale. To support experimental developments, predict new materials, and optimize the effect, first-principle electronic structure calculations based on density functional theory are the most powerful tool. The method gives an insight into the microscopic origin of spin-dependent tunneling. The main components of a planar tunnel junction – barrier, leads, and their interface – and their specific role for tunneling magnetoresistance are discussed for one of the standard systems, Fe/MgO/Fe.

  17. The Origin of Mercury (United States)

    Benz, W.; Anic, A.; Horner, J.; Whitby, J. A.

    Mercury's unusually high mean density has always been attributed to special circumstances that occurred during the formation of the planet or shortly thereafter, and due to the planet's close proximity to the Sun. The nature of these special circumstances is still being debated and several scenarios, all proposed more than 20 years ago, have been suggested. In all scenarios, the high mean density is the result of severe fractionation occurring between silicates and iron. It is the origin of this fractionation that is at the centre of the debate: is it due to differences in condensation temperature and/or in material characteristics (e.g. density, strength)? Is it because of mantle evaporation due to the close proximity to the Sun? Or is it due to the blasting off of the mantle during a giant impact?

  18. Origins of hydration lubrication. (United States)

    Ma, Liran; Gaisinskaya-Kipnis, Anastasia; Kampf, Nir; Klein, Jacob


    Why is friction in healthy hips and knees so low? Hydration lubrication, according to which hydration shells surrounding charges act as lubricating elements in boundary layers (including those coating cartilage in joints), has been invoked to account for the extremely low sliding friction between surfaces in aqueous media, but not well understood. Here we report the direct determination of energy dissipation within such sheared hydration shells. By trapping hydrated ions in a 0.4-1 nm gap between atomically smooth charged surfaces as they slide past each other, we are able to separate the dissipation modes of the friction and, in particular, identify the viscous losses in the subnanometre hydration shells. Our results shed light on the origins of hydration lubrication, with potential implications both for aqueous boundary lubricants and for biolubrication.

  19. Origins of adaptive immunity. (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister


    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity.

  20. Mechanical origin of aftershocks. (United States)

    Lippiello, E; Giacco, F; Marzocchi, W; Godano, C; de Arcangelis, L


    Aftershocks are the most striking evidence of earthquake interactions and the physical mechanisms at the origin of their occurrence are still intensively debated. Novel insights stem from recent results on the influence of the faulting style on the aftershock organisation in magnitude and time. Our study shows that the size of the aftershock zone depends on the fault geometry. We find that positive correlations among parameters controlling aftershock occurrence in time, energy and space are a stable feature of seismicity independently of magnitude range and geographic areas. We explain the ensemble of experimental findings by means of a description of the Earth Crust as an heterogeneous elastic medium coupled with a Maxwell viscoelastic asthenosphere. Our results show that heterogeneous stress distribution in an elastic layer combined with a coupling to a viscous flow are sufficient ingredients to describe the physics of aftershock triggering.

  1. Origins of Stellar Halos (United States)

    Johnston, Kathryn V.


    This contribution reviews ideas about the origins of stellar halos. It includes discussion of the theoretical understanding of and observational evidence for stellar populations formed ``in situ'' (meaning formed in orbits close to their current ones), ``kicked-out'' (meaning formed in the inner galaxy in orbits unlike their current ones) and ``accreted'' (meaning formed in a dark matter halo other than the one they currently occupy). At this point there is general agreement that a significant fraction of any stellar halo population is likely ``accreted''. There is modest evidence for the presence of a ``kicked-out'' population around both the Milky Way and M31. Our theoretical understanding of and the observational evidence for an ``in situ'' population are less clear.

  2. Original and Derived Judgment

    DEFF Research Database (Denmark)

    Foss, Kirsten; Foss, Nicolai Juul; Klein, Peter G.


    Recent work links entrepreneurship to the economic theory of the firm, using the concept of entrepreneurship as judgment introduced by Frank Knight. When judgment is complementary to other assets, it makes sense for entrepreneurs to hire labour and to own assets. The entrepreneur's role, then......, is to arrange or organize the human and capital assets under his or her control. We extend this Knightian concept of the firm by developing a theory of delegation under Knightian uncetainty. What we call original judgment belongs exclusively to owners, but owners may delegate a wide range of decision rights...... to subordinates, who exercise derived judgment. We call these employees `proxy-entrepreneurs', and ask how the firm's organizational structure - its formal and informal systems of rewards and punishments, rules for settling disputes and renegotiating agreements, means of evaluating performance and so on - can...

  3. Original and Derived Judgment

    DEFF Research Database (Denmark)

    Foss, Kirsten; Foss, Nicolai Juul; Klein, Peter G.

    Recent work links entrepreneurship to the economic theory of firm using the Knightian concept of entrepreneurship as judgment. When judgment is complementary to other as-sets, and these assets or their services are traded in well-functioning markets, it makes sense for entrepreneurs to hire labor...... and own assets. The entrepreneur's role, then, is to arrange or organize the human and capital assets under his control. We extend this Knightian concept of the firm by developing a theory of delegation under Knightian uncertainty. What we call original judgment belongs exclusively to owners, but owners...... may delegate a wide range of decision rights to subordinates, who exercise derived judgment. We call these employees "proxy-entrepreneurs," and ask how the firm's or-ganizational structure — its formal and informal systems of rewards and punishments, rules for settling disputes and renegotiating...

  4. Origins of Mindfulness & Meditation

    DEFF Research Database (Denmark)

    Singla, Rashmi


    Mindfulness & meditation are gaining popularity in the Western psychological practice in the past 3-4 decades, especially within psychotherapeutic approaches, health promotion, and stress reduction. The origins and the broader context, however, seem to be overlooked in some of these practices......- mind, centrality of consciousness and meditation as a part of daily conduct are presented. The basic constructs of Buddhism, an integral part of Indian psychology, in relation to mindfulness and meditation, are also delineated as illustrations of these assumptions. The second part reflects...... on the application of the meditative practices through cognitive existential study of mindfulness (Kabat-Zinn, 2003) and a study on the phenomenology of meditation (Madsen, 2007). Both emphasise an experienced instructor, regular practice as a part of daily life, conceptual consciousness understandings...

  5. The origin of humor. (United States)

    Howe, N E


    Humor is spread throughout every culture on earth and occupies a large portion of our literature and social interaction. It is so deeply rooted in our culture that it may be a defining characteristic of our species. Yet there has been comparatively little effort to understand its origin. According to the Accepted Theory of Humor all jokes begin with a buildup of tension while an initial paradigm is formed. When the punch line occurs the subject must realign his thinking to accommodate the differences between the initial paradigm and the sudden burst of new information. The Mind Reading Hypothesis extends the accepted theory of humor to include a relationship between the observer and the subject of the humor. The actual source of amusement is the observation of the resolution in the mind of the subject of the collision between old perception and new reality.

  6. Origin of Prometheus Eccentricity (United States)

    Rappaport, N. J.; Longaretti, P.


    A number of Saturn's small satellites, from Atlas to the coorbital satellites Janus and Epimetheus, move on orbits just outside the main rings of the planet. These satellites undergo extremely rapid resonant interaction with the rings and outward motion, strongly suggesting that they originated in Saturn's A ring. However, their eccentricities, of the order of 1/1000 are several orders of magnitude larger than what could be expected if the small satellites formed in the ring. This paper represents a first step to providing an explanation for this phenomenon, by focusing on the dynamical processes that have affected the eccentricity of Prometheus. The explanation invokes past resonances with the coorbital satellites combined with chaos due to overlapping of these resonances.

  7. The Pained Original

    Institute of Scientific and Technical Information of China (English)

    Cay Dollerup


    Arguing that, outside class-rooms, discussions on the relationship between translated product and the ‘original' do not advance our US, change according to the country of publication. Finally, the article points out that at many international organisations, most obviously so at the European Union with eleven official languages, there is a division of labour. In this division one or two versions of texts(in English or French)are used first as repositories of the negotiations and as a record of agreements, then as the source text for the ten or nine other language versions, and in the end as one of the eleven equally authoritative texts of which none can claim superiority over the others.

  8. Death certification in cancer of the breast.



    The cause of death entered on the death certificates of 193 patients originally diagnosed as having cancer of the breast was compared with information obtained from clinical records, cancer registry records, and necropsy findings to determine the accuracy of death certification and the proportion of patients who, though dying from another cause, still had overt signs of cancer of the breast. It was found that the overall error in certifying cause of death as breast cancer was small, being an ...

  9. Occupational cancer in Britain. Preventing occupational cancer. (United States)

    Chen, Yiqun; Osman, John


    Although only a relatively small proportion of cancer is attributable to occupational exposure to carcinogenic agents, the estimated number of deaths due to occupational cancer is high when compared to other deaths due to work-related ill health and injury. However, risk from occupational exposure to carcinogens can be minimised through proportionate but effective risk management. The Health and Safety Executive (HSE) is the regulator of workplace health and safety in Great Britain. As part of its aim to reduce ill health arising from failures to control properly exposure to hazards at work, HSE commissioned the research presented elsewhere in this supplement to enable it to identify priorities for preventing occupational cancer. The research has shown that occupational cancer remains a key health issue and that low-level exposure of a large number of workers to carcinogens is important. The finding that a small number of carcinogens have been responsible for the majority of the burden of occupational cancer provides key evidence in the development of priorities for significant reduction of occupational cancer. Although the research presented in this supplement reflects the consequences of past exposures to carcinogens, occupational cancer remains a problem. The potential for exposure to the agents considered in this research is still present in the workplace and the findings are relevant to prevention of future disease. In this article, the principle approaches for risk reduction are described. It provides supporting information on some of the initiatives already being undertaken, or those being put in place, to reduce occupational cancer in Great Britain. The need also for systematic collection of exposure information and the importance of raising awareness and changing behaviours are discussed.

  10. Actinides and Life's Origins. (United States)

    Adam, Zachary


    There are growing indications that life began in a radioactive beach environment. A geologic framework for the origin or support of life in a Hadean heavy mineral placer beach has been developed, based on the unique chemical properties of the lower-electronic actinides, which act as nuclear fissile and fertile fuels, radiolytic energy sources, oligomer catalysts, and coordinating ions (along with mineralogically associated lanthanides) for prototypical prebiotic homonuclear and dinuclear metalloenzymes. A four-factor nuclear reactor model was constructed to estimate how much uranium would have been required to initiate a sustainable fission reaction within a placer beach sand 4.3 billion years ago. It was calculated that about 1-8 weight percent of the sand would have to have been uraninite, depending on the weight percent, uranium enrichment, and quantity of neutron poisons present within the remaining placer minerals. Radiolysis experiments were conducted with various solvents with the use of uraniumand thorium-rich minerals (metatorbernite and monazite, respectively) as proxies for radioactive beach sand in contact with different carbon, hydrogen, oxygen, and nitrogen reactants. Radiation bombardment ranged in duration of exposure from 3 weeks to 6 months. Low levels of acetonitrile (estimated to be on the order of parts per billion in concentration) were conclusively identified in 2 setups and tentatively indicated in a 3(rd) by gas chromatography/mass spectrometry. These low levels have been interpreted within the context of a Hadean placer beach prebiotic framework to demonstrate the promise of investigating natural nuclear reactors as power production sites that might have assisted the origins of life on young rocky planets with a sufficiently differentiated crust/mantle structure. Future investigations are recommended to better quantify the complex relationships between energy release, radioactive grain size, fissionability, reactant phase, phosphorus

  11. Individual Consequences of Plant Closures and Cutbacks

    DEFF Research Database (Denmark)

    Andersen, Steen


    This thesis describes the segment of unemployment which has its origin in major closures and cutbacks. The argument for this is to make it possible to describe and to analyse a flow into and a flow out of a population of unemployed. Given a major dismissal the following questions are to be answer...

  12. Troubling Consequences of Online Political Rumoring (United States)

    Garrett, R. Kelly


    Fear that the Internet promotes harmful political rumoring is merited but not for reasons originally anticipated. Although the network accelerates and widens rumor circulation, on the whole, it does not increase recipient credulity. E-mail, however, which fosters informal political communication within existing social networks, poses a unique…

  13. Genome organization, instabilities, stem cells, and cancer

    Directory of Open Access Journals (Sweden)

    Senthil Kumar Pazhanisamy


    Full Text Available It is now widely recognized that advances in exploring genome organization provide remarkable insights on the induction and progression of chromosome abnormalities. Much of what we know about how mutations evolve and consequently transform into genome instabilities has been characterized in the spatial organization context of chromatin. Nevertheless, many underlying concepts of impact of the chromatin organization on perpetuation of multiple mutations and on propagation of chromosomal aberrations remain to be investigated in detail. Genesis of genome instabilities from accumulation of multiple mutations that drive tumorigenesis is increasingly becoming a focal theme in cancer studies. This review focuses on structural alterations evolve to raise a variety of genome instabilities that are manifested at the nucleotide, gene or sub-chromosomal, and whole chromosome level of genome. Here we explore an underlying connection between genome instability and cancer in the light of genome architecture. This review is limited to studies directed towards spatial organizational aspects of origin and propagation of aberrations into genetically unstable tumors.

  14. Consequences to health of the Chernobyl accident; Helbredsmaessige konsekvenser af reaktorulykken i Tjernobyl

    Energy Technology Data Exchange (ETDEWEB)

    Sewerin, I. [Royal Dental College, Dept. of Radiology, Copenhagen (Denmark)


    The Chernobyl accident in 1986 has been and still is the subject of great interest. Journalistic reports often contain exaggerations and undocumented statements and much uncertainty about the true consequences of the accident prevails in the population. This article reviews the current literature with the focus on reports from official commissions and documentation in the form of controlled studies. The fatal deterministic consequences comprise about 30 victims. The most important outcome is a marked increase in the incidence of thyroid cancer in children and adolescents in the most heavily contaminated area. Furthermore, pronounced psychosocial problems are dominant in the population of the contaminated area. Other significant and documented health consequences are not seen. (au)


    Directory of Open Access Journals (Sweden)

    Gregory Lee


    Full Text Available Immunoglobulins are typically expressed by B cells in our normal immune system. However, certain normal human tissues, such as hyperplastic epithelial cells, cells of the immunologically privileged sites and the majority of cancer cells, have also been found to be sites of immunoglobulin production. Current research is lacking in regards to the differential immunoglobulin expression, the underling mechanisms of action and the biological implications of these cancerous immunoglobulins in cancer immunology. This article reviews the etiology of atypical immunoglobulin expression in normal non-B cells and cancer cells, with emphasis on the exploration of the possible mechanisms of action and biological function of these atypical immunoglobulins, by means of specific biological probes. In contrast to immunoglobulins of B cell origins, atypical immunoglobulins were found to carry additional post-translational modifications, including a unique carbohydrateassociated epitope recognized by RP215 monoclonal antibody. This unique RP215-specific epitope enables us to differentiate between these two types of immunoglobulins. Atypical immunoglobulins expressed by cancer cells have been a common subject of interest in cancer immunology. Furthermore, the recent accumulation of experimental evidence has indicated that these atypical immunoglobulins are essential for the growth and proliferation of cancer cells under our normal immune environment. RP215 monoclonal antibody also reacts with many other cancer cell-expressed glycoproteins, known as CA215, on the cancer cell surface. Apoptosis of cultured cancer cells can be induced and growth inhibition of implanted tumors can be observed in nude mouse animal models. Therefore, humanized RP215 monoclonal antibody, which reacts mainly with surface bound CA215, may have the potential to be developed as an anti-cancer drug for the treatment of human cancers. A better understanding of cancer cell

  16. Metabolic consequences of Helicobacter pylori infection and eradication. (United States)

    Buzás, György Miklós


    Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future.

  17. [The origin of homoiothermy--unsolved problem]. (United States)

    Dol'nik, V P


    The analysis of allometric dependence of energy expenditure on body mass among reptiles, birds and mammals has shown that standard metabolic rate of reptiles when they are warmed up to the temperature of homoiothermic animals is an order of magnitude lower than that of birds and mammals. Basal metabolism is originated as special feature historically related to the metabolism during active behavior, rather than thermal regulation. Facultative endothermy was not advantageous for large animals because of long time needed to warm up the body. The ancestors of birds and animals escaped negative consequences of van't-Hoff equation by choosing constant body temperature. Heat conductivity of reptile's covers is so great, that it cannot keep endogenous warm of resting animal at any temperature of the body. Reptile "dressed" in covers of bird or mammal would be able to keep warm under conditions of maximal aerobic muscular activity and body temperature similar to that of homoiothermic animals. The base of chemical thermoregulation in birds and mammals is a thermoregulatory muscle tonus which remains unknown. One can suppose that during evolution of birds and mammals the saltation-liked origin of endothermy "fixed" the level of metabolism typical for running reptile and transformed in into the basal metabolism. This event took place at the cell and tissue level. The absence of palaeontological evidences and intermediate forms among recent species does not allow easy understanding of homoiothermy origin.


    Directory of Open Access Journals (Sweden)

    Mihaela IAVORSCHI


    Full Text Available The importance of money and the role they hold in the economy can be seen as the keystone of economic life. For a better understanding of the essence of the monetary phenomena it is especially important to turn to history and see how money was born. By turning to their origins, we discover the real fundaments of monetary issues. Only after such a systematic analysis we will be able to suggest the appropriate solutions for the current monetary issues. Therefore, in this study I will research the origin of money and their functionality on the market.The aim of this paper is to analyse the origin of money as a social institution. The appearance and use of money has prehistoric roots. People have turned to the usage of money out of need to facilitate trade. During thousands of years money has known different forms going from money as merchandise, to coins and later to paper money and electronic currency. In this study I have analysed the role of natural money, as well as their production and functionality on the market. The main questionto be answered is whether the production and functionality of paper money nowadays is the consequence of the free market, having the Austrian’s School liberal perspective as a starting point. This methodological approach demonstrates that money is and will remain a social institution and the implication of the authorities in the currency issuing, even from ancient times, has caused distortions in the economic activity.

  19. Origin of Hawking radiation: firewall or atmosphere? (United States)

    Kim, Wontae


    The Unruh vacuum not admitting any outgoing flux at the horizon implies that the origin of the outgoing Hawking radiation is the atmosphere of a near-horizon quantum region without resort to the firewall; however, the existence of the firewall of superplanckian excitations at the horizon can be supported by the infinite Tolman temperature at the horizon. In an exactly soluble model, we explicitly show that the firewall necessarily emerges out of the Unruh vacuum so that the Tolman temperature in the Unruh vacuum is divergent in essence due to the infinitely blueshifted negative ingoing flux crossing the horizon rather than the outgoing flux. We also show that the outgoing Hawking radiation in the Unruh vacuum indeed originates from the atmosphere, not just at the horizon, which is of no relevance to the infinite blueshift. Consequently, the firewall from the infinite Tolman temperature and the Hawking radiation from the atmosphere turn out to be compatible, once we waive the claim that the Hawking radiation in the Unruh vacuum originates from the infinitely blueshifted outgoing excitations at the horizon.

  20. Consequences of Predicted or Actual Asteroid Impacts (United States)

    Chapman, C. R.


    Earth impact by an asteroid could have enormous physical and environmental consequences. Impactors larger than 2 km diameter could be so destructive as to threaten civilization. Since such events greatly exceed any other natural or man-made catastrophe, much extrapolation is necessary just to understand environmental implications (e.g. sudden global cooling, tsunami magnitude, toxic effects). Responses of vital elements of the ecosystem (e.g. agriculture) and of human society to such an impact are conjectural. For instance, response to the Blackout of 2003 was restrained, but response to 9/11 terrorism was arguably exaggerated and dysfunctional; would society be fragile or robust in the face of global catastrophe? Even small impacts, or predictions of impacts (accurate or faulty), could generate disproportionate responses, especially if news media reports are hyped or inaccurate or if responsible entities (e.g. military organizations in regions of conflict) are inadequately aware of the phenomenology of small impacts. Asteroid impact is the one geophysical hazard of high potential consequence with which we, fortunately, have essentially no historical experience. It is thus important that decision makers familiarize themselves with the hazard and that society (perhaps using a formal procedure, like a National Academy of Sciences study) evaluate the priority of addressing the hazard by (a) further telescopic searches for dangerous but still-undiscovered asteroids and (b) development of mitigation strategies (including deflection of an oncoming asteroid and on- Earth civil defense). I exemplify these issues by discussing several representative cases that span the range of parameters. Many of the specific physical consequences of impact involve effects like those of other geophysical disasters (flood, fire, earthquake, etc.), but the psychological and sociological aspects of predicted and actual impacts are distinctive. Standard economic cost/benefit analyses may not

  1. Banting lecture 2011: hyperinsulinemia: cause or consequence? (United States)

    Corkey, Barbara E


    The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Dr. Barbara E. Corkey received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 71st Scientific Sessions, 24-28 June 2011, San Diego, California. She presented the Banting Lecture, "Hyperinsulinemia: Cause or Consequence?" on Sunday, 26 June 2011.

  2. [Fetal pain: immediate and long term consequences]. (United States)

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent


    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  3. Ionization of bovine meat products. Microbiological, nutritional and organoleptic consequences; L`ionisation des produits carnes d`origine bovine. Consequences microbiologiques, nutritionnelles et organoleptiques

    Energy Technology Data Exchange (ETDEWEB)

    Desmonts, M.H.


    In this thesis, the author analyses simultaneously the characteristics of sliced beef steaks, of minced beef steaks from industrial making and of beef and calf ionized liver rounds: microbiological quality, nutritional quality, and organoleptic quality. These analyses are systematically effected during 3 to 4 weeks on vacuum packaged products and stored at 3-4 deg C. The influence of ionization on microbiological, nutritional and organoleptic qualities is studied. These products are vacuum packaged in oxygen-porous films, ionized under accelerated electron with radiation doses from 1 to 5 kGy and stored at 3-4 deg C during 3-4 weeks. Then, other parameters are studied : fats rate of minced steaks (5 and 10%), packing quality (oxygen-tight packing and oxygen-porous film) and finally, the radiation dose rate (X or gamma-radiation and accelerated electrons). In conclusion, the ionization allows to improve the preservation time of vacuum packaged beef and calf liver rounds. Meat can be preserved during 10-14 days after having received a radiation dose of 3-4 kGy, without nutritional quality alteration.

  4. Cancer modelling in the NGS era - Part I: Emerging technology and initial modelling. (United States)

    Rovigatti, Ugo


    It is today indisputable that great progresses have been made in our molecular understanding of cancer cells, but an effective implementation of such knowledge into dramatic cancer-cures is still belated and yet desperately needed. This review gives a snapshot at where we stand today in this search for cancer understanding and definitive treatments, how far we have progressed and what are the major obstacles we will have to overcome both technologically and for disease modelling. In the first part, promising 3rd/4th Generation Sequencing Technologies will be summarized (particularly IonTorrent and OxfordNanopore technologies). Cancer modelling will be then reviewed from its origin in XIX Century Germany to today's NGS applications for cancer understanding and therapeutic interventions. Developments after Molecular Biology revolution (1953) are discussed as successions of three phases. The first, PH1, labelled "Clonal Outgrowth" (from 1960s to mid 1980s) was characterized by discoveries in cytogenetics (Nowell, Rowley) and viral oncology (Dulbecco, Bishop, Varmus), which demonstrated clonality. Treatments were consequently dominated by a "cytotoxic eradication" strategy with chemotherapeutic agents. In PH2, (from the mid 1980s to our days) the description of cancer as "Gene Networks" led to targeted-gene-therapies (TGTs). TGTs are the focus of Section 3: in view of their apparent failing (Ephemeral Therapies), alternative strategies will be discussed in review part II (particularly cancer immunotherapy, CIT). Additional Pitfalls impinge on the concepts of tumour heterogeneity (inter/intra; ITH). The described pitfalls set the basis for a new phase, PH3, which is called "NGS Era" and will be also discussed with ten emerging cancer models in the Review 2nd part.

  5. DHCP Origin Traceback (United States)

    Majumdar, Saugat; Kulkarni, Dhananjay; Ravishankar, Chinya V.

    Imagine that the DHCP server is under attack from malicious hosts in your network. How would you know where these DHCP packets are coming from, or which path they took in the network? This paper investigates the problem of determining the origin of a DHCP packet in a network. We propose a practical method for adding a new option field that does not violate any RFC's, which we believe should be a crucial requirement while proposing any related solution. The new DHCP option will contain the ingress port and the switch MAC address. We recommend that this new option be added at the edge so that we can use the recorded value for performing traceback. The computational overhead of our solution is low, and the related network management tasks are low as well. We also address issues related to securing the field in order to maintain privacy of switch MAC addresses, fragmentation of packets, and possible attack scenarios. Our study shows that the traceback scheme is effective and practical to use in most network environments.

  6. The Cosmic Origins Spectrograph

    CERN Document Server

    Green, James C; Osterman, Steve; Ebbets, Dennis; Heap, Sara H; Linsky, Claus Leitherer Jeffrey L; Savage, Blair D; Sembach, Kenneth; Shull, J Michael; Siegmund, Oswald H W; Snow, Theodore P; Spencer, John; Stern, S Alan; Stocke, John; Welsh, Barry; Beland, Stephane; Burgh, Eric B; Danforth, Charles; France, Kevin; Keeney, Brian; McPhate, Jason; Penton, Steven V; Andrews, John; Brownsberger, Kenneth; Morse, Jon; Wilkinson, Erik


    The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F_lambda ~ 1.0E10-14 ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011....

  7. Looking at our origins

    CERN Multimedia

    Nairucu Arts


    Exhibition by Nairucu-Arts, in collaboration with the Anthropology Museum Giuseppe Sergi, Università la Sapienza, Roma, Italy and ECOLINT, Campus des Nations. The exhibition comprises: posters (in English and French) intended for a large audience with text from Prof. Giorgio Manzi, Julia Rizzo, Fabio Di Vincenzo, illustrated with art drawings from Carlo Ranzi, Italy. The exhibition will also present drawings from the students of the Art Classes of Karin Bain and Fabien Bruttin at ECOLINT,Geneva. On 2nd March at 5 p.m. you will be welcomed with a drink before the conference that will be given in English at 6 p.m in the CERN Council Room by Wim De Geest, a retired Professor from KUB (Catholic University of Brussels). Title: There's no language like our language, like no language we know. But how did it evolve? A summary in French will be made available for the public.

  8. Determinants of increased primary health care use in cancer survivors.

    NARCIS (Netherlands)

    Heins, M.; Schellevis, F.; Rijken, M.; Hoek, L. van der; Korevaar, J.


    Purpose: The number of cancer survivors is increasing, and patients with cancer often experience long-lasting consequences of cancer and its treatment. Because of the variety of health problems and high prevalence of comorbidity, primary care physicians (PCPs) seem obvious candidates to take care of

  9. Coping with cancer : The perspective of patients' relatives

    NARCIS (Netherlands)

    Hagedoorn, Mariet; Kreicbergs, Ulrika; Appel, Charlotte


    Cancer affects not only patients but also their loved ones. Material and methods. This paper presents a selective, narrative review of psychosocial consequences of cancer and its treatment for relatives of patients, including parents and siblings of children with cancer, children of parents with can

  10. Health consequences of child marriage in Africa. (United States)

    Nour, Nawal M


    Despite international agreements and national laws, marriage of girls Child marriage is a human rights violation that prevents girls from obtaining an education, enjoying optimal health, bonding with others their own age, maturing, and ultimately choosing their own life partners. Child marriage is driven by poverty and has many effects on girls' health: increased risk for sexually transmitted diseases, cervical cancer, malaria, death during childbirth, and obstetric fistulas. Girls' offspring are at increased risk for premature birth and death as neonates, infants, or children. To stop child marriage, policies and programs must educate communities, raise awareness, engage local and religious leaders, involve parents, and empower girls through education and employment.

  11. The effect of CTB on P53 protein acetylation and consequence apoptosis on MCF-7 and MRC-5 cell lines

    Directory of Open Access Journals (Sweden)

    Mehdi Nikbakht Dastjerdi


    Conclusion: CTB could induce acetylation of P53 protein through increasing expression of P300 and consequently induce the significant cell death in MCF-7 but it could be well tolerated in MRC-5. Therefore, CTB could be used as an anti-cancer agent.

  12. Phenotypic consequences of aneuploidy in Arabidopsis thaliana. (United States)

    Henry, Isabelle M; Dilkes, Brian P; Miller, Eric S; Burkart-Waco, Diana; Comai, Luca


    Aneuploid cells are characterized by incomplete chromosome sets. The resulting imbalance in gene dosage has phenotypic consequences that are specific to each karyotype. Even in the case of Down syndrome, the most viable and studied form of human aneuploidy, the mechanisms underlying the connected phenotypes remain mostly unclear. Because of their tolerance to aneuploidy, plants provide a powerful system for a genome-wide investigation of aneuploid syndromes, an approach that is not feasible in animal systems. Indeed, in many plant species, populations of aneuploid individuals can be easily obtained from triploid individuals. We phenotyped a population of Arabidopsis thaliana aneuploid individuals containing 25 different karyotypes. Even in this highly heterogeneous population, we demonstrate that certain traits are strongly associated with the dosage of specific chromosome types and that chromosomal effects can be additive. Further, we identified subtle developmental phenotypes expressed in the diploid progeny of aneuploid parent(s) but not in euploid controls from diploid lineages. These results indicate long-term phenotypic consequences of aneuploidy that can persist after chromosomal balance has been restored. We verified the diploid nature of these individuals by whole-genome sequencing and discuss the possibility that trans-generational phenotypic effects stem from epigenetic modifications passed from aneuploid parents to their diploid progeny.

  13. [Legal consequences in cases of child abuse]. (United States)

    Clauß, D; Richter, C; Klohs, G; Heide, S


    Medical child protection includes besides interdisciplinary diagnostics and treatment of physical and psychological symptoms also a discussion that looks at the ensuing legal consequences.This study analyses 21 criminally investigated cases of suspected child abuse from a 2 year study period and compares severity of injury to legal outcome.7 of those 21 criminal proceedings were already dropped by the prosecution and never went to trial. 4 of the 8 cases that led to a trial ended with a conviction. In all of the 4 cases that resulted in an acquittal the judges had been convinced that the child had been abused but found themselves unable to exactly identify the perpetrator. Our study's cases did not show a positive correlation between severity of injury and legal outcome.Diagnosing and treating children and minors within the context of medical child protection should always also include the ques-tion of possible legal consequences. The judicial process in cases of serious child abuse requires high medical expertise. Such expertise particularly includes the ability to determine the time of injury as exactly as possible and to provide precise written documentation of any medical findings. However, our study also shows that medical assessment is only one of many aspects in the legal response to child abuse.

  14. Population consequences of environmental sex reversal. (United States)

    Cotton, Samuel; Wedekind, Claus


    When sex determination in a species is predominantly genetic but environmentally reversible, exposure to (anthropogenic) changes in the environment can lead to shifts in a population's sex ratio. Such scenarios may be common in many fishes and amphibians, yet their ramifications remain largely unexplored. We used a simple model to study the (short-term) population consequences of environmental sex reversal (ESR). We examined the effects on sex ratios, sex chromosome frequencies, and population growth and persistence after exposure to environmental forces with feminizing or masculinizing tendencies. When environmental feminization was strong, X chromosomes were driven to extinction. Analogously, extinction of normally male-linked genetic factors (e.g., Y chromosomes) was caused by continuous environmental masculinization. Although moderate feminization was beneficial for population growth in the absence of large viability effects, our results suggest that the consequences of ESR are generally negative in terms of population size and the persistence of sex chromosomes. Extreme sex ratios resulting from high rates of ESR also reduced effective population sizes considerably. This may limit any evolutionary response to the deleterious effects of ESR. Our findings suggest that ESR changes population growth and sex ratios in some counter-intuitive ways and can change the predominant factor in sex determination from genetic to fully environmental, often within only a few tens of generations. Populations that lose genetic sex determination may quickly go extinct if the environmental forces that cause sex reversal cease.

  15. Metabolic consequences of polycystic ovary syndrome. (United States)

    Churchill, S J; Wang, E T; Pisarska, M D


    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and the leading cause of anovulatory infertility. The prevalence of the syndrome ranges between 6 to 15% based on broader Rotterdam diagnostic criteria verses strict NIH diagnostic criteria.1 The condition is characterized by a combination of ovulatory dysfunction, hyperandrogenism and the presence of polycystic ovaries. PCOS has been associated with multiple metabolic alterations and consequences including impaired glucose tolerance, insulin resistance, hyperinsulinemia, type II diabetes, dyslipidemia, metabolic syndrome, obesity and subclinical cardiovascular disease. It remains unclear however if these associations lead to an increased risk of clinically significant long-term cardiovascular disease. Large prospective studies to date have not detected significant differences in overall cardiovascular morbidity and mortality in PCOS. The phenotypical variability in PCOS has made researching each of these associations challenging as different aspects of the syndrome may be contributing, opposing or confounding factors. The ability to detect significant differences in long-term cardiovascular outcomes may also be due to the variable nature of the syndrome. In this review, we attempt to describe a summary of the current literature concerning the metabolic alterations and cardiovascular consequences of polycystic ovary syndrome.

  16. Perceptual consequences of "hidden" hearing loss. (United States)

    Plack, Christopher J; Barker, Daphne; Prendergast, Garreth


    Dramatic results from recent animal experiments show that noise exposure can cause a selective loss of high-threshold auditory nerve fibers without affecting absolute sensitivity permanently. This cochlear neuropathy has been described as hidden hearing loss, as it is not thought to be detectable using standard measures of audiometric threshold. It is possible that hidden hearing loss is a common condition in humans and may underlie some of the perceptual deficits experienced by people with clinically normal hearing. There is some evidence that a history of noise exposure is associated with difficulties in speech discrimination and temporal processing, even in the absence of any audiometric loss. There is also evidence that the tinnitus experienced by listeners with clinically normal hearing is associated with cochlear neuropathy, as measured using Wave I of the auditory brainstem response. To date, however, there has been no direct link made between noise exposure, cochlear neuropathy, and perceptual difficulties. Animal experiments also reveal that the aging process itself, in the absence of significant noise exposure, is associated with loss of auditory nerve fibers. Evidence from human temporal bone studies and auditory brainstem response measures suggests that this form of hidden loss is common in humans and may have perceptual consequences, in particular, regarding the coding of the temporal aspects of sounds. Hidden hearing loss is potentially a major health issue, and investigations are ongoing to identify the causes and consequences of this troubling condition.

  17. [Fetal pain - neurobiological causes and consequences]. (United States)

    Gonçalves, Nuno; Rebelo, Sandra; Tavares, Isaura


    The existence of putatively painful situations to the fetus demands a careful evaluation of the issue of fetal pain. Several indirect approaches are used to evaluate the existence of fetal pain. Neurobiological studies showed that from the 30th week on, the anatomical and physiological system for pain transmission is already developed, with the connections from the periphery to the cortex being successively established. Stress responses to a painful stimulation are complex but they can be detected from the 16th week on. There is activation of the hypothalamus-pituitary-adrenal axis, autonomic nervous system and hemodynamic changes in response to nociceptive stimulation. In prematures exposed to pain there are significant increases of adrenaline, noradrenaline and cortisol, hemodynamic changes, motor reflexes and facial reactions. The changes induced by strong nociceptive stimulation of newborns have important postnatal consequences since they affect future reactions to noxious stimuli. Central sensitization and immaturity of the pain inhibitory system are the main neurobiological explanations for the increased pain. Detailed studies of the neurobiological mechanisms of the transmission of painful stimuli along with follow-up studies of the consequences of exposure to pain during the development of the fetus are necessary to fully understand fetal pain.

  18. Early institutionalization: neurobiological consequences and genetic modifiers. (United States)

    Sheridan, Margaret; Drury, Stacy; McLaughlin, Kate; Almas, Alisa


    Children raised in the profound deprivation associated with institutionalization are at elevated risk for negative outcomes across a host of social and cognitive domains. This risk appears to be mitigated by early foster care or adoption into a family setting. Although pervasive developmental problems have been noted in a substantial proportion of previously institutionalized children, marked variation exists in the nature and severity of these deficits. Increasing evidence suggests that institutional deprivation impacts the developing brain, potentially underlying the wide range of outcomes with which it is associated. In the current review we examine the neural consequences of institutionalization and genetic factors associated with differences in outcome in an effort to characterize the consequences of early deprivation at a neurobiological level. Although the effects of institutional deprivation have been studied for more than 50 years much remains unanswered regarding the pathways through which institutionalization impacts child development. Through a more complete and nuanced assessment of the neural correlates of exposure and recovery as well as a better understanding of the individual factors involved we will be better able to delineate the impact of early adversity in the setting of severe social deprivation.

  19. YORP: Its origin (United States)

    Paddack, Stephen; Rubincam, David P.


    It’s all about photons and their behavior. Yarkovsky (1844-1902) did not have the knowledge we have today about photons and radiation pressure. Nevertheless, he published a pamphlet in 1901 that small rotating celestial bodies could absorb sunlight and reradiate it as heat after a delay, resulting in possible orbital changes, setting the stage for radiation effects in celestial mechanics. Yarkovsly’s work remained obscure until Öpik recalled having read Yarkovsky’s pamphlet. Öpik brought Yarkovsky’s idea to the attention of John A. O’Keefe in the late 1960s. O’Keefe, the mentor for two aspiring PhD students, Paddack and Rubincam, told them about Yarkovsky. In 1968 Paddack postulated that the reflection of sunlight off of small, irregularly shaped celestial bodies could have a significant effect on their spin rates. He referred to this as a windmill effect. Paddack and O’Keefe tested the idea of windmill shapes causing spin by dropping crushed stones with irregular shapes into a swimming pool and watching them twirl. Paddack then mimicked the space environment by placing windmill-shaped artificial objects and tektites in a vacuum chamber on an almost frictionless bearing and spinning them up with a strong source of light, conclusively showing the relation of shape to spin. Earlier in 1954 Radzievskii wrote about the effects radiation pressure on variations in the albedo of small celestial bodies as a means of changing their spin rates. The uniform color of Paddack’s test bodies ruled out Radzievskii’s effect as the cause for the observed spin-up. The Yarkovsky effect was minimized because the test object had a coating of vapor-deposited aluminum with a very high albedo and consequently did not heat up. In 2000 Rubincam applied Paddack’s idea to small asteroids and called it the YORP effect (YORP = Yarkovsky-O’Keefe-Radzievskii-Paddack), to give it a catchy name and sell the idea. In 2007 results were published in Science about the observed

  20. Moon (Form-Origin) (United States)

    Tsiapas, Elias


    When the Earth was formed, it was in a state of burning heat. As time went by, temperature on the planet's surface was falling due to radiation and heat transfer, and various components (crusts) began taking solid form at the Earth's poles. The formation of crusts took place at the Earth's poles, because the stirring of burning and fluid masses on the surface of the Earth was significantly slighter there than it was on the equator. Due to centrifugal force and Coriolis Effect, these solid masses headed towards the equator; those originating from the North Pole followed a south-western course, while those originating from the South Pole followed a north-western course and there they rotated from west to east at a lower speed than the underlying burning and liquid earth, because of their lower initial linear velocity, their solid state and inertia. Because inertia is proportional to mass, the initially larger solid body swept all new solid ones, incorporating them to its western side. The density of the new solid masses was higher, because the components on the surface would freeze and solidify first, before the underlying thicker components. As a result, the western side of the initial islet of solid rocks submerged, while the east side elevated. . As a result of the above, this initial islet began to spin in reverse, and after taking on the shape of a sphere, it formed the "heart" of the Moon. The Moon-sphere, rolling on the equator, would sink the solid rocks that continued to descend from the Earth's poles. The sinking rocks partially melted because of higher temperatures in the greater depths that the Moon descended to, while part of the rocks' mass bonded with the Moon and also served as a heat-insulating material, preventing the descended side of the sphere from melting. Combined with the Earth's liquid mass that covered its emerging eastern surface, new sphere-shaped shells were created, with increased density and very powerful structural cohesion. During the

  1. The Cosmic Origins Spectrograph (United States)

    Green, James C.; Froning, Cynthia S.; Osterman, Steve; Ebbets, Dennis; Heap, Sara H.; Leitherer, Claus; Linsky, Jeffrey L.; Savage, Blair D.; Sembach, Kenneth; Shull, J. Michael; Siegmund, Oswald H. W.; Snow, Theodore P.; Spencer, John; Stern, S. Alan; Stocke, John; Welsh, Barry; Beland, Stephane; Burgh, Eric B.; Danforth, Charles; France, Kevin; Keeney, Brian; McPhate, Jason; Penton, Steven V; Andrews, John; Morse, Jon


    The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F(sub lambda) approximates 1.0 X 10(exp -14) ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy.


    Energy Technology Data Exchange (ETDEWEB)

    Green, James C.; Michael Shull, J.; Snow, Theodore P.; Stocke, John [Department of Astrophysical and Planetary Sciences, University of Colorado, 391-UCB, Boulder, CO 80309 (United States); Froning, Cynthia S.; Osterman, Steve; Beland, Stephane; Burgh, Eric B.; Danforth, Charles; France, Kevin [Center for Astrophysics and Space Astronomy, University of Colorado, 389-UCB, Boulder, CO 80309 (United States); Ebbets, Dennis [Ball Aerospace and Technologies Corp., 1600 Commerce Street, Boulder, CO 80301 (United States); Heap, Sara H. [NASA Goddard Space Flight Center, Code 681, Greenbelt, MD 20771 (United States); Leitherer, Claus; Sembach, Kenneth [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Linsky, Jeffrey L. [JILA, University of Colorado and NIST, Boulder, CO 80309-0440 (United States); Savage, Blair D. [Department of Astronomy, University of Wisconsin-Madison, 475 North Charter Street, Madison, WI 53706 (United States); Siegmund, Oswald H. W. [Astronomy Department, University of California, Berkeley, CA 94720 (United States); Spencer, John; Alan Stern, S. [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Welsh, Barry [Space Sciences Laboratory, University of California, 7 Gauss Way, Berkeley, CA 94720 (United States); and others


    The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in 2009 May, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F{sub {lambda}} Almost-Equal-To 1.0 Multiplication-Sign 10{sup -14} erg cm{sup -2} s{sup -1} A{sup -1}, COS can achieve comparable signal to noise (when compared to Space Telescope Imaging Spectrograph echelle modes) in 1%-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (2009 September-2011 June) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is nine times than sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of 2011 June. COS has measured, for the first time with high reliability, broad Ly{alpha} absorbers and Ne VIII in the intergalactic medium, and observed the He II reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy.

  3. Childhood Cancer (United States)

    ... Cancer? Cancer Treatment Coping With Cancer en español Cáncer infantil Every cell in the body has a system that controls its growth, interaction with other cells, and even its life span. ... cancer . Different kinds of cancer have different signs, symptoms, ...

  4. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Information Advance Directives Using Trusted Resources Cancer Types Adolescents and Young Adults with Cancer Reports, Research, and ... of Cancers Cancers by Body Location Childhood Cancers Adolescent & Young Adult Cancers Metastatic Cancer Recurrent Cancer Research ...

  5. What Is Thymus Cancer? (United States)

    ... Cancer? Thymus Cancer About Thymus Cancer What Is Thymus Cancer? Cancer starts when cells in the body ... Research and Treatment for Thymus Cancer? More In Thymus Cancer About Thymus Cancer Causes, Risk Factors, and ...


    Institute of Scientific and Technical Information of China (English)

    Song Shumei; Wujian; Shou Chengchao


    Objective: To detect the expression of KDR in different originated carcinomas and to explore its expressed ways and the relationship with tumor progression. Methods: KDR cDNA (Ⅴ-Ⅶ domains)fragment was cloned from human umbilical vein with RTPCR and was expressed in Ecoli.Jm109. The fusion protein of GST-KDR was used for immunizing Balb/c mice to prepare monoclonal antibodies against KDR.The different tumor tissues and related normal tissues were examined with KDR McAb by S-P immunohistochemistry. Results: the rate and intensification of KDR expression among different originated cancers are very different, bladder cancers from transmigrated epidermis are 100% positive and highest intensification.The expression of KDR in breast cancer and intestinal cancer lie in the second-rate, the weakest expression of KDR is in lung squamous carcinoma. Moreover,expression of KDR in tumor tissues lie both in endothelial cells (EC) of tumor blood vessels and tumor cells.Conclusion: VEGF may be not only the para-secretory factor making EC proliferation but also auto-secretory factor stimulating the proliferation of tumor cells to benefit the growth and metastasis of malignant tumors.The different expression of KDR in different originated carcinomas may relate with malignant degree of tumor.

  7. Consequences of severe nuclear accidents in Europe (United States)

    Seibert, Petra; Arnold, Delia; Mraz, Gabriele; Arnold, Nikolaus; Gufler, Klaus; Kromp-Kolb, Helga; Kromp, Wolfgang; Sutter, Philipp


    A first part of the presentation is devoted to the consequences of the severe accident in the 1986 Chernobyl NPP. It lead to a substantial radioactive contaminated of large parts of Europe and thus raised the awareness for off-site nuclear accident consequences. Spatial patterns of the (transient) contamination of the air and (persistent) contamination of the ground were studied by both measurements and model simulations. For a variety of reasons, ground contamination measurements have variability at a range of spatial scales. Results will be reviewed and discussed. Model simulations, including inverse modelling, have shown that the standard source term as defined in the ATMES study (1990) needs to be updated. Sensitive measurements of airborne activities still reveal the presence of low levels of airborne radiocaesium over the northern hemisphere which stems from resuspension. Over time scales of months and years, the distribution of radionuclides in the Earth system is constantly changing, for example relocated within plants, between plants and soil, in the soil, and into water bodies. Motivated by the permanent risk of transboundary impacts from potential major nuclear accidents, the multidisciplinary project flexRISK (see has been carried out from 2009 to 2012 in Austria to quantify such risks and hazards. An overview of methods and results of flexRISK is given as a second part of the presentation. For each of the 228 NPPs, severe accidents were identified together with relevant inventories, release fractions, and release frequencies. Then, Europe-wide dispersion and dose calculations were performed for 2788 cases, using the Lagrangian particle model FLEXPART. Maps of single-case results as well as various aggregated risk parameters were produced. It was found that substantial consequences (intervention measures) are possible for distances up to 500-1000 km, and occur more frequently for a distance range up to 100-300 km, which is in

  8. Evaluation of radiological dispersion/consequence codes supporting DOE nuclear facility SARs

    Energy Technology Data Exchange (ETDEWEB)

    O`Kula, K.R.; Paik, I.K. [Westinghouse Savannah River Site, Aiken, SC (United States); Chung, D.Y. [Dept. of Energy, Germantown, MD (United States)


    Since the early 1990s, the authorization basis documentation of many U.S. Department of Energy (DOE) nuclear facilities has been upgraded to comply with DOE orders and standards. In this process, many safety analyses have been revised. Unfortunately, there has been nonuniform application of software, and the most appropriate computer and engineering methodologies often are not applied. A DOE Accident Phenomenology and Consequence (APAC) Methodology Evaluation Program was originated at the request of DOE Defense Programs to evaluate the safety analysis methodologies used in nuclear facility authorization basis documentation and to define future cost-effective support and development initiatives. Six areas, including source term development (fire, spills, and explosion analysis), in-facility transport, and dispersion/ consequence analysis (chemical and radiological) are contained in the APAC program. The evaluation process, codes considered, key results, and recommendations for future model and software development of the Radiological Dispersion/Consequence Working Group are summarized in this paper.

  9. Implications of a Neotropical Origin of the Genus Leishmania

    Directory of Open Access Journals (Sweden)

    Noyes Harry


    Full Text Available The hypothesis of a Neotropical origin of the Leishmania/Endotrypanum clade is reviewed. The position of the L. (Sauroleishmania external to the subgenus L. (Leishmania is not consistent with the Neotropical origin of the latter subgenus. It is suggested that this may be a consequence of a faster evolutionary rate in the L. (Sauroleishmania. The implications for the classsification of the phlebotomine sandflies of the hypothesis for a Neotropical origin of the Leishmania is also considered. The classification of Galati (1995 is proposed to be most consistent with the hypothesis of a Neotropical origin of the Leishmania, whilst classifications which place the New and Old World species in separate taxa are inconsistent with this hypothesis.

  10. Do perceptual consequences of spontaneous otoacoustic emissions reflect a central plasticity effect?

    DEFF Research Database (Denmark)

    Hansen, Rói; Santurette, Sébastien; Verhulst, Sarah

    Frequency difference limens (FDLs) have been found to improve in the vicinity of spontaneous otoacoustic emissions (SOAEs). This effect has been observed ipsilaterally and contralaterally to the emission ear, suggesting that prolonged ongoing stimulation of nerve cells tuned to the SOAE frequency...... by continuous ipsilateral presentation of a pure tone aimed at emulating an SOAE. These findings suggest a peripheral rather than central plasticity origin for perceptual consequences of SOAEs....

  11. Vitamin D and Cancer (United States)

    Vuolo, Laura; Di Somma, Carolina; Faggiano, Antongiulio; Colao, Annamaria


    Vitamin D system is a complex pathway that includes precursors, active metabolites, enzymes, and receptors. This complex system actives several molecular pathways and mediates a multitude of functions. In addition to the classical role in calcium and bone homeostasis, vitamin D plays “non-calcemic” effects in host defense, inflammation, immunity, and cancer processes as recognized in vitro and in vivo studies. The aim of this review is to highlight the relationship between vitamin D and cancer, summarizing several mechanisms proposed to explain the potential protective effect of vitamin D against the development and progression of cancer. Vitamin D acts like a transcription factor that influences central mechanisms of tumorigenesis: growth, cell differentiation, and apoptosis. In addition to cellular and molecular studies, epidemiological surveys have shown that sunlight exposure and consequent increased circulating levels of vitamin D are associated with reduced reduced occurrence and a reduced mortality in different histological types of cancer. Another recent field of interest concerns polymorphisms of vitamin D receptor (VDR); in this context, preliminary data suggest that VDR polymorphisms more frequently associated with tumorigenesis are Fok1, Bsm1, Taq1, Apa1, EcoRV, Cdx2; although further studies are needed to clarify their role in the cancer. In this review, the relationship between vitamin D and cancer is discussed. PMID:22649423

  12. Testicular microlithiasis and testicular cancer

    DEFF Research Database (Denmark)

    Pedersen, Malene Roland; Rafaelsen, Søren Rafael; Møller, Henrik


    PURPOSE: To perform a systematic literature review to assess whether the occurrence of testicular microlithiasis (TML) in conjunction with other risk factors is associated with testicular cancer. METHODS: A systematic literature search was performed of original articles in English published 1998......: In total, 282 abstracts in were identified. Based on title and abstract the eligibility was assessed and 31 studies were included. Five conditions in relation to TML and testicular cancer emerged: Down syndrome, McCune-Albright syndrome, cryptorchidism, infertility and familial disposition of testicular...... cancer. CONCLUSION: Data support the conclusion that TML is not an independent risk factor for testicular cancer but associated with testicular cancer through other conditions. In male infertility, TML appears to be related to an increased risk of testicular cancer possibly as part of a testicular...

  13. Consequence Identification for Maloperation in Batch Process

    Institute of Scientific and Technical Information of China (English)

    张玉良; 张贝克; 马昕; 曹柳林; 吴重光


    Batch processes are important in chemical industry, in which operators usually play a major role and hazards may arise by their inadvertent acts. In this paper, based on hazard and operability study and concept of qualitative simulation, an automatic method for adverse consequence identification for potential maloperation is proposed. The qualitative model for production process is expressed by a novel directed graph. Possible operation deviations from normal operating procedure are identified systematically by using a group of guidewords. The pro-posed algorithm is used for qualitative simulation of batch processes to identify the effects of maloperations. The method is illustrated with a simple batch process and a batch reaction process. The results show that batch processes can be simulated qualitatively and hazards can be identified for operating procedures including maloperations. After analysis for possible plant maloperations, some measures can be taken to avoid maloperations or reduce losses re-sulted from maloperations.

  14. False confessions: causes, consequences, and implications. (United States)

    Leo, Richard A


    In the past two decades, hundreds of convicted prisoners have been exonerated by DNA and non-DNA evidence, revealing that police-induced false confessions are a leading cause of wrongful conviction of the innocent. In this article, empirical research on the causes and correlates of false confessions is reviewed. After a description of the three sequential processes that are responsible for the elicitation of false confessions--misclassification, coercion, and contamination--the three psychologically distinct types of false confession (voluntary, compliant, and persuaded) are discussed along with the consequences of introducing false-confession evidence in the criminal justice system. The article concludes with a brief discussion of the implications of empirical research for reducing the number of false confessions and improving the accuracy of confession evidence that is introduced against a defendant at trial.

  15. Catastrophic Consequences of Kicking the Chameleon

    CERN Document Server

    Erickcek, Adrienne L; Burrage, Clare; Huang, Zhiqi


    The physics of the "dark energy" that drives the current cosmological acceleration remains mysterious, and the dark sector may involve new light dynamical fields. If these light scalars couple to matter, a screening mechanism must prevent them from mediating an unacceptably strong fifth force locally. Here we consider a concrete example: the chameleon mechanism. We show that the same coupling between the chameleon field and matter employed by the screening mechanism also has catastrophic consequences for the chameleon during the Universe's first minutes. The chameleon couples to the trace of the stress-energy tensor, which is temporarily non-zero in a radiation-dominated universe whenever a particle species becomes non-relativistic. These "kicks" impart a significant velocity to the chameleon field, causing its effective mass to vary non-adiabatically and resulting in the copious production of quantum fluctuations. Dissipative effects strongly modify the background evolution of the chameleon field, invalidati...

  16. Wham: Identifying Structural Variants of Biological Consequence.

    Directory of Open Access Journals (Sweden)

    Zev N Kronenberg


    Full Text Available Existing methods for identifying structural variants (SVs from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (, with documentation on a wiki ( For community support please post questions to

  17. Cosmological Consequences of Initial State Entanglement

    CERN Document Server

    Albrecht, Andreas; Holman, R


    We explore the cosmological consequences of having the fluctuations of the inflaton field entangled with those of another scalar, within the context of a toy model consisting of non-interacting, minimally coupled scalars in a fixed de Sitter background. We find that despite the lack of interactions in the Lagrangian, the initial state entanglement modifies the mode equation for the inflaton fluctuations and thus can induce changes in cosmological observables. These effects are examined for a variety of choices of masses and we find that they can be consistent with the requirement that the back reaction of the modified state not affect the inflationary phase while still giving rise to observable effects in the power spectrum. Our results suggest that more realistic extensions of the ideas explored here beyond the simple toy model may lead to interesting observable effects.

  18. Community-level consequences of cannibalism. (United States)

    Ohlberger, Jan; Langangen, Oystein; Stenseth, Nils C; Vøllestad, L Asbjørn


    Ecological interactions determine the structure and dynamics of communities and their responses to the environment. Understanding the community-level effects of ecological interactions, such as intra- and interspecifc competition, predation, and cannibalism, is therefore central to ecological theory and ecosystem management. Here, we investigate the community-level consequences of cannibalism in populations with density-dependent maturation and reproduction. We model a stage-structured consumer population with an ontogenetic diet shift to analyze how cannibalism alters the conditions for the invasion and persistence of stage-specific predators and competitors. Our results demonstrate that cannibalistic interactions can facilitate coexistence with other species at both trophic levels. This effect of cannibalism critically depends on the food dependence of the demographic processes. The underlying mechanism is a cannibalism-induced shift in the biomass distribution between the consumer life stages. These findings suggest that cannibalism may alter the structure of ecological communities through its effects on species coexistence.

  19. Unexpected consequences of midwifery in the NHS. (United States)

    Pollock, Jane


    This article presents information from the Caring for the carers conference held at George Eliot Hospital in July 2015. For many midwives, feelings of stress are an unexpected consequence of rising birth rates, low staffing levels and negative organisational cultures, so our aim was that delegates would take away skills for 'surviving' in maternity services. The conference was the catalyst to a project at George Eliot NHS Trust to improve the wellbeing of staff so that they can develop a positive outlook towards the care which they offer. As part of the project, a toolkit for survival was produced which helps to prompt maternity workers to remember their own wellbeing. This project is continuing to grow and the results will be available next year.

  20. Wham: Identifying Structural Variants of Biological Consequence. (United States)

    Kronenberg, Zev N; Osborne, Edward J; Cone, Kelsey R; Kennedy, Brett J; Domyan, Eric T; Shapiro, Michael D; Elde, Nels C; Yandell, Mark


    Existing methods for identifying structural variants (SVs) from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics) to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (, with documentation on a wiki ( For community support please post questions to

  1. The consequences of the heterosexual norm

    Directory of Open Access Journals (Sweden)

    Anna Johansson


    Full Text Available Librarians may exclude people accidentally. This is so because there is a widespread use of classifications and subject headings reflecting the heterosexual norm. Critical classification theory tackles this norm for the reason that it affects the retrieval of gay literature. In order to allow a reconsideration of this exclusive practice in the LIS community I challenge two main questions: Firstly, how does the heterosexual norm appear in classification systems and subject headings lists? And secondly, what are the consequences of that practice for the retrieval of gay literature?This paper focuses on the professional practise in Swedish public libraries. If subject cataloguing prevents Lesbians, Gays, Bisexuals and Transgender (LGBT finding their literatures, then Swedish public libraries are upholders of the exclusive heterosexual norm in society.

  2. Environmental consequences of energy production: Proceedings

    Energy Technology Data Exchange (ETDEWEB)



    The Seventeenth Annual Illinois Energy conference entitled Environmental consequences of Energy Production was held in Chicago, Illinois on October 19-20, 1989. The purpose of the meeting was to provide a forum for exchange of information on the technical, economic and institutional issues surrounding energy production and related environmental problems. The conference program was developed by a planning committee which included Illinois energy and environmental specialists from the major sectors including energy industries, environmental organizations, research universities, utility companies, federal, state and local government agencies, and public interest groups. The conference included presentations on four major topic areas. The issue areas were: urban pollution: where are we now and what needs to be done in the future; the acid rain problem: implications of proposed federal legislation on the Midwest; global warming: an update on the scientific debate; and strategies to minimize environmental damage. Separate abstracts have been prepared for the individual presentations. (FL)

  3. General consequences of the violated Feynman scaling (United States)

    Kamberov, G.; Popova, L.


    The problem of scaling of the hadronic production cross sections represents an outstanding question in high energy physics especially for interpretation of cosmic ray data. A comprehensive analysis of the accelerator data leads to the conclusion of the existence of breaked Feynman scaling. It was proposed that the Lorentz invariant inclusive cross sections for secondaries of a given type approaches constant in respect to a breaked scaling variable x sub s. Thus, the differential cross sections measured in accelerator energy can be extrapolated to higher cosmic ray energies. This assumption leads to some important consequences. The distribution of secondary multiplicity that follows from the violated Feynman scaling using a similar method of Koba et al is discussed.

  4. Deep Impact: Unintended consequences of journal rank

    CERN Document Server

    Brembs, Björn


    Much has been said about the increasing bureaucracy in science, stifling innovation, hampering the creativity of researchers and incentivizing misconduct, even outright fraud. Many anecdotes have been recounted, observations described and conclusions drawn about the negative impact of impact assessment on scientists and science. However, few of these accounts have drawn their conclusions from data, and those that have typically relied on a few studies. In this review, we present the most recent and pertinent data on the consequences that our current scholarly communication system has had on various measures of scientific quality (such as utility/citations, methodological soundness, expert ratings and retractions). These data confirm previous suspicions: using journal rank as an assessment tool is bad scientific practice. Moreover, the data lead us to argue that any journal rank (not only the currently-favored Impact Factor) would have this negative impact. Therefore, we suggest that abandoning journals altoge...


    Directory of Open Access Journals (Sweden)

    Romanowska-Tołłoczko Anna


    Full Text Available The need to adapt to the ever-increasing socio-professional requirements carries many risks to human health, both in somatic and psychological aspects. Strong stress associated with work leads to the occurrence of burnout syndrome. Persons performing so called aid professions, where teachers belong to a special group, are usually vulnerable to this syndrome. The aim of this paper is to present the causes, course and consequences of teacher burnout and to highlight the multidimensional nature of the phenomenon, indicating possible corrective and preventive actions. Among the that contribute to burnout important are environmental , organizational and subjective factors. Subjective factors like professional training and personality dispositions, are treated as the primary determinants of resistance or susceptibility of individuals to stress. They can intensify or protect against burning out. The lack of ability to counter stress is considered crucial in the formation and accumulation of burnout symptoms.

  6. Gene transfer approaches in cancer immunotherapy. (United States)

    Larin, S S; Georgiev, G P; Kiselev, S L


    The idea of enhancing or establishing effective immune response against endogenously developed tumor cells is not novel. More than a hundred years ago, bacterial components were used to develop antitumor immune response. Later, when a number of immune system-effecting cytokines had been discovered, they were used for systemic treatment of cancer patients. However, systemic treatment often resulted in even negative outcome. Recent developments of genetic approaches of cell modifications allowed developing of modern techniques of targeted tumor cell elimination. In the present paper, we review modern trends of the antitumor response enhancement based on immunoregulatory gene transfer into different cell types both in vivo and in vitro. Almost all these approaches are based on the activation of the adaptive arm of the immune system in response to tumor cells. However, recent studies indicate that the innate arm of the immune system, as well as adaptive arm, is involved in tumor suppression. The innate immune system uses nonrearranging germline receptors, which could trigger cellular effector responses that are conditional (or instructive) to the subsequent adaptive immune response. Last years' viewpoints on 'self' and 'non-self' recognition and primary induction of the immune response have changed. The key role of lymphocytes is pathogen recognition and, following immune response induction, switched on the central role of dendritic cells in 'non-self' recognition and induction of both innate and adaptive responses. Moreover, innate response is supposed to be an essential starting point in induction of successful and effective acquired response. Most cancer vaccines do not have 'non-self' marks presentation due to their endogenous origin, thus lacking their effectiveness in the induction of the specific long-lasting immune response. Taking this point into consideration, we can conclude that to make cancer vaccine more effective we have to present tumor antigens

  7. Environment and Health: Not Only Cancer

    Directory of Open Access Journals (Sweden)

    Annamaria Colao


    Full Text Available The Hippocratic tradition emphasized environmental causes of diseases and the need for harmony between the individual and the natural environment as the right philosophy to maintain a good health status. Public awareness and scientific attention concerning environmental pollution is usually focused on the consequent increased risk of developing cancer. Air pollution has been recognized by the World Health Organization (WHO to cause cardiovascular and respiratroy diseases, as well as lung cancer, after acute/chronic exposure to fine particulates (PM2.5 and PM10 even at concentrations which are 50% lower than those accepted as legal limits in many developed countries. An increase of 10 µg/m3 of PM2.5 produces a +4%–6% of overall mortality, a +10% of cardiovascular disease prevalence (arithmyas, acute myocardial infarctions, and heart failure and a +22% of lung cancer prevalence. In addition to these chronic effects, acute hospitalizations are also affected, especially among susceptible populations such as children and diabetic patients. Water and soil contamination also have an additional detrimental effect on people’s health. Other issues concerning environment contamination and human health include male/female fertility, metabolic and thyroid conditions, but also professional exposures resulting in occupational diseases. Moreover, in the perspective of “gender medicine”, different acute or chronic effects of environmental pollution should be specifically assessed both in men and in women. This special issue on “Environmental Diseases” is aimed at providing a global overview about different threats to human health possibily originating from environmental contamination.

  8. Path Distribution Energy and Possible Consequences

    Directory of Open Access Journals (Sweden)

    Špringer J.


    Full Text Available Previously (Progress in Physics, 2013, v. 4, 83–84 one investigated the geometric distribution of the frequencies of the path of the electron in the ground state of Hydrogen atom. In this paper one shows that the resulting difference detected on the fifth decimal of the inverse fine structure constant is accompanied by the difference in the quantized energy up to 0.04 eV. The difference in charge as well as energy of the distributed and non-distributed electrons could explain the origin of van der Waals intermolecular interactions.


    Directory of Open Access Journals (Sweden)



    Full Text Available Return migration is probably the aspect of the migration cycle, which was granted the lowest attention, perhaps because most research resources are located in highly developed countries, while most of the returning most returnees return to developing countries. This is especially unfortunate because perceptions about the process of returning to the country of origin and attitudes towards returning migrants have a significant impact on migrants and their host communities. Rollback, sometimes called remigration, is considered by some authors as the final stage of the migration process, which further comprises the step preparation / decision to migrate and actual migration phase or installation of migrant destination country selected.

  10. Mental health consequences of the Chernobyl disaster. (United States)

    Bromet, Evelyn J


    The psychosocial consequences of disasters have been studied for more than 100 years. The most common mental health consequences are depression, anxiety, post-traumatic stress disorder, medically unexplained somatic symptoms, and stigma. The excess morbidity rate of psychiatric disorders in the first year after a disaster is in the order of 20%. Disasters involving radiation are particularly pernicious because the exposure is invisible and universally dreaded, and can pose a long-term threat to health. After the Chernobyl disaster, studies of clean-up workers (liquidators) and adults from contaminated areas found a two-fold increase in post-traumatic stress and other mood and anxiety disorders and significantly poorer subjective ratings of health. Among liquidators, the most important risk factor was severity of exposure. In general population samples, the major risk factor was perceived exposure to harmful levels of radiation. These findings are consistent with results from A-bomb survivors and populations studied after the Three Mile Island nuclear power plant accident. With regard to children, apart from findings from ecological studies that lack direct data on radiation or other teratologic exposures and local studies in Kiev, the epidemiologic evidence suggests that neither radiation exposure nor the stress of growing up in the shadow of the accident was associated with emotional disorders, cognitive dysfunction, or impaired academic performance. Thus, based on the studies of adults, the Chernobyl Forum concluded that mental health was the largest public health problem unleashed by the accident. Since mental health is a leading cause of disability, physical morbidity, and mortality, health monitoring after radiation accidents like Fukushima should include standard measures of well-being. Moreover, given the comorbidity of mental and physical health, the findings support the value of training non-psychiatrist physicians in recognizing and treating common mental

  11. Dynamical Origins of the Kepler Dichotomy (United States)

    Spalding, Christopher; Batygin, Konstantin


    An overabundance of single-transiting planetary systems relative to those with multiple transits within the Kepler dataset, has been interpreted as evidence for mutual inclinations between planetary orbits. The physical origins of this so-called "Kepler Dichotomy," however, remain elusive. Here we show that the observed prevalence of single-planet systems is a direct consequence of the secular evolution of initially co-planar multi-planet systems that orbit stars whose spin-axes are inclined with respect to the protoplanetary disks they host. Such primordial misalignments arise naturally within the disk-hosting stage by way of gravitational torques from stellar companions, and have been previously invoked as explanations for the commonness of spin-orbit misalignments in hot Jupiter systems. Accordingly, our model places the early dynamical evolution of hot super-Earths and hot Jupiters into a unified theoretical framework.

  12. Penile cancer (United States)

    Cancer - penis; Squamous cell cancer - penis; Glansectomy; Partial penectomy ... Cancer of the penis is rare. Its exact cause is unknown. However, certain risk factors include: Uncircumcised men who don't keep the ...

  13. Cancer Chemotherapy (United States)

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  14. Skin Cancer (United States)

    ... the head, face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ... cancer is found early. If not treated, some types of skin cancer cells can spread to other tissues and organs. ...

  15. Testicular cancer (United States)

    Testicular cancer is cancer that starts in the testicles, the male reproductive glands located in the scrotum. ... developing testicular cancer increases if he has: Abnormal testicle development Exposure to certain chemicals Family history of ...

  16. Ovarian Cancer (United States)

    ... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

  17. Cancer Moonshot (United States)

    The Cancer Moonshot, led by Vice President Joe Biden, will marshal resources across the federal government to speed progress in cancer research and lead to improved cancer prevention, detection, and treatment.

  18. Uterine Cancer (United States)

    ... is pregnant. There are different types of uterine cancer. The most common type starts in the endometrium, ... the uterus. This type is also called endometrial cancer. The symptoms of uterine cancer include Abnormal vaginal ...

  19. Thyroid Cancer (United States)

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  20. Stomach Cancer (United States)

    ... with stomach acid and helps digest protein. Stomach cancer mostly affects older people - two-thirds of people ... Smoke cigarettes Have a family history of stomach cancer It is hard to diagnose stomach cancer in ...

  1. Bone Cancer (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  2. Cancer Immunotherapy (United States)

    Immunotherapy is a cancer treatment that helps your immune system fight cancer. It is a type of biological therapy. Biological therapy uses substances ... t yet use immunotherapy as often as other cancer treatments, such as surgery, chemotherapy, and radiation therapy. ...

  3. Throat Cancer (United States)

    ... food. Surgery to remove cancerous lymph nodes (neck dissection). If throat cancer has spread deep within your ... neck cancers. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2015. Freedman ND, et al. Fruit ...

  4. Unemployment among breast cancer survivors

    DEFF Research Database (Denmark)

    Carlsen, Kathrine; Ewertz, Marianne; Dalton, Susanne Oksbjerg


    AIM: Though about 20% of working age breast cancer survivors do not return to work after treatment, few studies have addressed risk factors for unemployment. The majority of studies on occupational consequences of breast cancer focus on non-employment, which is a mixture of sickness absence......, unemployment, retirement pensions and other reasons for not working. Unemployment in combination with breast cancer may represent a particular challenge for these women. The aim of the present study is therefore to analyze the risk for unemployment in the years following diagnosis and treatment for breast...... cancer. METHOD: This study included 14,750 women diagnosed with breast cancer in Denmark 2001-2009 identified through a population-based clinical database and linked with information from Danish administrative population based registers for information on labour market affiliation, socio...

  5. Escaping growth arrest in cancer

    NARCIS (Netherlands)

    Kortlever, R.M.


    We now have a general idea of which genes and cellular pathways are central in cancer development: uncontrolled growth governs establishment and spread of the disease. Nevertheless, to fully appreciate the consequences of the interplay of driver mutations in this genetic disease it is imperative we

  6. Igneous rock from Severnyi Kolchim (H3) chondrite: Nebular origin (United States)

    Nazarov, M. A.; Brandstaetter, F.; Kurat, G.


    The discovery of lithic fragments with compositions and textures similar to igneous differentiates in unequilibrated ordinary chondrites (UOC's) and carbonaceous chondrites (CC's) has been interpreted as to suggest that planetary bodies existed before chondrites were formed. As a consequence, chondrites (except, perhaps CI chondrites) cannot be considered primitive assemblages of unprocessed nebular matter. We report about our study of an igneous clast from the Severnyi Kolchim (H3) chondrite. The results of the study are incompatible with an igneous origin of the clast but are in favor of a nebular origin similar to that of chondrules.

  7. Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

    Institute of Scientific and Technical Information of China (English)

    Guanghui Li; Donglin Wang


    Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.

  8. Stresses on women physicians: consequences and coping techniques. (United States)

    Robinson, Gail Erlick


    We review current data on types of stressors acting on women physicians, the consequences of these stressors and methods of coping with them. We undertook a systematic review of original articles published in the last 15 years and registered mainly on Medline and on the internet websites focusing on these issues. In addition to the pressures acting on all physicians, women physicians face specific stressors related to discrimination, lack of role models and support, role strain, and overload. The depression rate in women physicians does not vary from that of the general public but the rates of successful suicide and divorce are much higher. Women in academic settings are promoted more slowly, have lower salaries, receive fewer resources, and suffer from a range of micro-inequities. They often lack mentors to provide advice and guidance. They must cope with the pressures of choosing when to have a child and conflicts between being a wife and mother and having a career. Despite these pressures, they report a high degree of career satisfaction. Although women physicians suffer from a variety of stressors that can lead to career impediments, stress reactions, and psychiatric problems, generally they are satisfied with their careers. Personal coping techniques can help women deal with these stressors. Pressures will continue until attitudes and practices change in institutional settings. Some institutions are initiating changes to end discrimination against women faculty.

  9. Fair use versus fair return: copyright legislation and its consequences. (United States)

    Horowitz, I L; Curtis, M E


    The purpose of this article is to examine the ramifications of legislative recognition of the concept of fair use in the Copyright Act of 1976. The fair use concept, while of small consequence in its normative origins, has turned out to be the foundation of the most perplexing and divisive issues in the new legislative guidelines governing copyright. Legislative recognition of the concept of fair use, coupled with enormous growth of a new technology--extending from xerography to on-line database systems--creates de facto exemptions to both the intent and content of new copyright guidelines. The issue is not one of limiting use or suppressing information, but of mechanisms for safeguarding the rights of copyright holders, be they authors or publishers, and insuring the free flow of information by providing a proper return on both intellectual creativity and capital expenditures. The authors argue that the elimination, or at least curtailment of fair use doctrine, coupled with an increase in technological approaches to reporting of secondary use of copyrighted material, will benefit all sections of the knowledge industry. Authors will receive proper royalties on use; publishers will be able to sell more books and journals at lower prices; and librarians will be liberated from extensive chores such as monitoring usage or determining fee schedules and transferences. The issue is one of fair return--an issue obscured and ultimately subverted by fair use.

  10. The Chernobyl Catastrophe. Consequences on Human Health

    Energy Technology Data Exchange (ETDEWEB)

    Yablokov, A.; Labunska, I.; Blokov, I. (eds.)


    Twenty years after the Chernobyl disaster, the need for continued study of its far-reaching consequences remains as great as ever. Several million people (by various estimates, from 5 to 8 million) still reside in areas that will remain highly contaminated by Chernobyl's radioactive pollution for many years to come. Since the half-life of the major (though far from the only) radioactive element released, caesium-137 (137Cs), is a little over 30 years, the radiological (and hence health) consequences of this nuclear accident will continue to be experienced for centuries to come. This event had its greatest impacts on three neighbouring former Soviet republics: Ukraine, Belarus, and Russia. The impacts, however, extended far more widely. More than half of the caesium-137 emitted as a result of the explosion was carried in the atmosphere to other European countries. At least fourteen other countries in Europe (Austria, Sweden, Finland, Norway, Slovenia, Poland, Romania, Hungary, Switzerland, Czech Republic, Italy, Bulgaria, Republic of Moldova and Greece) were contaminated by radiation levels above the 1 Ci/km{sup 2} (or 37 kBq/m{sup 2}), limit used to define areas as 'contaminated'. Lower, but nonetheless substantial quantities of radioactivity linked to the Chernobyl accident were detected all over the European continent, from Scandinavia to the Mediterranean, and in Asia. Despite the documented geographical extent and seriousness of the contamination caused by the accident, the totality of impacts on ecosystems, human health, economic performance and social structures remains unknown. In all cases, however, such impacts are likely to be extensive and long lasting. Drawing together contributions from numerous research scientists and health professionals, including many from the Ukraine, Belarus and the Russian Federation, this report addresses one of these aspects, namely the nature and scope of the long-term consequences for human health. The range

  11. Tumour markers in gastrointestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lamerz, R.


    For non-endocrine gastrointestinal tumours the following tumour markers are of clinical interest: For esophageal cancer CEA (sensitivity, s: 40-60%) and SCC (squamous cell carcinoma antigen, x: 20-50%); for gastric cancer CEA (s: 30-40%) as well as CA 19-9 (s: 30-40%) because of complementary results (additive s: 50-60); for hepatocellular cancer AFP (first choice, s: 70-90%; second choice CA 19-9, s: 50-70%); for cholangiocellular cancer CA 19-9 (s: 40-70%); for secondary liver cancer in general CEA; for biliary tract cancer CA 19-9 (s: 40-70%) as well as for excretory pancreatic cancer (s: 70-90%); for colorectal cancer CEA (s: 40-70%) as a first choice marker, and CA 19-9 (s: 20-60%) as a second choice marker, and for anal cancer SCC. The frequency of tumour marker determinations depends on follow-up care recommendations for different tumour diseases (e.g. 1-3 monthly during the 1st and 2nd postoperative year, following chemotherapy courses, on change of therapy, on restaging and at unclear alteration of the clinical state). Tumour markers are only valuable adjuncts to the medical care of tumour patients and therefore useless as solitary findings or on missing therapeutic consequence.

  12. [Fertility transition in Brazil. Causes and consequences]. (United States)

    Carvalho, J A; Wong, L R


    This work examines the determinants and most important consequences of the Brazilian fertility decline. Brazil's total fertility rate declined from 6.2 in 1940 to around 3.5 in 1985. the decline began in the 1960s and amounted to 45% in about 20 years. The most rapid drop began in the late 1970s, with much of it concentrated in 2 specific periods: 1970-75 and 1980-85. The early period coincided with Brazil's so-called "Economic Miracle", a period of rapid growth accompanied however by deteriorating living conditions for the poorest population sectors. The second period coincided with the international economic crisis of the early 1980s, which was felt more strongly in Brazil than elsewhere in Latin America because of Brazil's greater degree of industrialization and closer integration into the world economy. Most of the fertility decline has been accomplished by use of just two contraceptive methods, oral contraceptives and sterilization, which together account for around 85% of contraceptive usage throughout Brazil. The third most common method, rhythm, accounts for just 6%. No reliable data on abortion are available, but it appears to be a common practice equally accessible to all socioeconomic strata despite greater associated health risks for poorer women. Brazil's fertility transition appears to have been a response to the process of proletarianization and urbanization underway in the country as well as to particular circumstances in the country. The most evident and immediate consequence of the continuous fertility decline over more than 20 years is the change in the age structure of the population. The proportions of children under 5 will decline from 14.4% in 1980 to 9.2% in 2010. The proportion aged 5-14 will decline from 24.5% to 17.4%, while the proportion aged 65 and over will increase from 4.0% to 5.6%. Brazil's recent demographic changes are scarcely reflected in development plans and political and social projects. There is almost no mention of the new

  13. The origins of life: old problems, new chemistries. (United States)

    Mann, Stephen


    Synthetic life: the origin of life on the early Earth, and the ex novo transition of non-living matter to artificial living systems are deep scientific challenges that provide a context for the development of new chemistries with unknown technological consequences. This Essay attempts to re-frame some of the epistemological difficulties associated with these questions into an integrative framework of proto-life science. Chemistry is at the heart of this endeavour.

  14. Glossary for Testicular Cancer and Related Conditions (United States)

    ... differentiated tumors closely resemble normal tissue. Disseminated disease - Disease in which the cancerous cells have spread from the tissue of origin to other organs. (AKA: Metastasis ) Ejaculate - The semen ...

  15. Oxidation of pyrite: Consequences and significance

    Directory of Open Access Journals (Sweden)

    Dimitrijević Mile D.


    Full Text Available This paper presents the most important studies on the oxidation of pyrite particularly in aqueous solutions. The consequences of pyrite oxidation was examined, as well as its importance, from both the technical-technological and environmental points of view. The oxidation of pyrite was considered in two parts. The spontaneous oxidation of pyrite in nature was described in the first part, with this part comprising pyrite oxidation in deposits depots and mines. It is explained how way natural electrochemical processes lead to the decomposition of pyrite and other minerals associated with pyrite. The oxidation of pyrite occurring during technological processes such as grinding, flotation and leaching, was shown in the second part. Particular emphasis was placed on the oxidation of pyrite during leaching. This part includes the leaching of sulphide and oxide ores, the leaching of pyrite coal and the leaching of refractory gold-bearing ores (pressure oxidation, bacterial oxidation, oxidation by means of strong oxidants and the electrolysis of pyrite suspensions. Various mechanisms of pyrite oxidation and of the galvanic interaction of pyrite with other sulphide minerals are shown.

  16. Anticipating the unintended consequences of security dynamics.

    Energy Technology Data Exchange (ETDEWEB)

    Backus, George A.; Overfelt, James Robert; Malczynski, Leonard A.; Saltiel, David H.; Simon Paul Moulton


    In a globalized world, dramatic changes within any one nation causes ripple or even tsunamic effects within neighbor nations and nations geographically far removed. Multinational interventions to prevent or mitigate detrimental changes can easily cause secondary unintended consequences more detrimental and enduring than the feared change instigating the intervention. This LDRD research developed the foundations for a flexible geopolitical and socioeconomic simulation capability that focuses on the dynamic national security implications of natural and man-made trauma for a nation-state and the states linked to it through trade or treaty. The model developed contains a database for simulating all 229 recognized nation-states and sovereignties with the detail of 30 economic sectors including consumers and natural resources. The model explicitly simulates the interactions among the countries and their governments. Decisions among governments and populations is based on expectation formation. In the simulation model, failed expectations are used as a key metric for tension across states, among ethnic groups, and between population factions. This document provides the foundational documentation for the model.

  17. Insomnia causes, consequences, and therapeutics: an overview. (United States)

    Drake, Christopher L; Roehrs, Timothy; Roth, Thomas


    There is growing interest in insomnia both from the perspective of recent advances in clinical management as well as research aimed at elucidating its pathophysiology. This theoretical overview of insomnia describes the negative impact, etiological considerations, and pharmacological and behavioral treatments for the disorder, with an emphasis on areas receiving increased research attention. Insomnia, the most prevalent sleep disorder, affects 10-15% of the general population. In population-based studies severe insomnia has been shown to last for a median of 4 years. In addition, insomnia has a significant negative impact on an individual's work, physical, and social performance as well as overall quality of life. Furthermore, the economic cost of insomnia related to lost productivity, work-related accidents, absenteeism, and health-care costs are enormous. There is increasing evidence linking the precipitation of insomnia to stress, and converging evidence from cognitive, endocrine, neurological, and behavioral domains provide clear evidence for hyper-arousal in insomnia. However, there remains no consensus regarding the specific etiological mechanisms of this disorder. Although the pathophysiology of primary insomnia remains an enigma, numerous treatments both pharmacological and behavioral have been developed and found to be efficacious in controlled studies. Despite the wide availability of pharmacological treatments and increased knowledge of behavioral interventions, the vast majority of individuals with insomnia do not appear to be receiving adequate treatment. The inadequate treatment of insomnia leads to several important and under-recognized consequences including subsequent development of psychiatric disease and increased substance use.

  18. Intrauterine hypoxia: clinical consequences and therapeutic perspectives

    Directory of Open Access Journals (Sweden)

    Thompson LP


    Full Text Available Loren P Thompson,1 Sarah Crimmins,1 Bhanu P Telugu,2 Shifa Turan1 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; 2Department of Animal Sciences, University of Maryland, College Park, MD, USA Abstract: Intrauterine hypoxia is a significant clinical challenge in obstetrics that affects both the pregnant mother and fetus. Intrauterine hypoxia can occur in pregnant women living at high altitude and/or with cardiovascular disease. In addition, placental hypoxia can be generated by altered placental development and spiral artery remodeling leading to placental insufficiency and dysfunction. Both conditions can impact normal maternal cardiovascular homeostasis leading to preeclampsia and/or impair transfer of O2/nutrient supply resulting in fetal growth restriction. This review discusses the mechanisms underlying altered placental vessel remodeling, maternal and fetal consequences, patient management, and potential future therapies for improving these conditions. Keywords: fetal growth restriction, oxidative stress, extravillous trophoblast invasion, Doppler ultrasound, pulsatility index, preeclampsia 

  19. Internet piracy and consequences for victims

    Directory of Open Access Journals (Sweden)

    Savić Miljan


    Full Text Available After the evolution of technology made it possible to perform actions via the Internet that constitute copyright violations, the analysis of the effects of internet piracy on social welfare became the subject of academic polemics. The main and the biggest victims of Internet piracy are the holders of copyright and related rights, however, the damage that piracy causes them comes from multiple sources, is difficult to quantify and is only a part of the total social cost of piracy. However, there are other categories of victims, such as those whose honor was besmirched as a result of piracy, and who suffer the consequences in the form of negative emotional reactions, loss of job as well as those who subsequently commit suicide. The object of this paper is to describe the effects of internet piracy on the victims of this phenomenon, and the goal is the analysis of the various direct and indirect effects of piracy on victims and their motivation for future creation, as well as analysis of prevention measures, with special emphasis on the Republic of Serbia.

  20. Corporate personhood: Lay perceptions and ethical consequences. (United States)

    Jago, Arthur S; Laurin, Kristin


    Modern conceptions of corporate personhood have spurred considerable debate about the rights that society should afford business organizations. Across eight experiments, we compare lay perceptions of how corporations and people use rights, and also explore the consequences of these judgments. We find that people believe corporations, compared to humans, are similarly likely to use rights in protective ways that prevent harm but more likely to use rights in nonprotective ways that appear independent from-or even create-harm (Experiments 1a through 1c and Experiment 2). Because of these beliefs, people support corporate rights to a lesser extent than human rights (Experiment 3). However, people are more supportive of specific corporate rights when we framed them as serving protective functions (Experiment 4). Also as a result of these beliefs, people attribute greater ethical responsibility to corporations, but not to humans, that gain access to rights (Experiments 5a and 5b). Despite their equitability in many domains, people believe corporations and humans use rights in different ways, ultimately producing different reactions to their behaviors as well as asymmetric moral evaluations. (PsycINFO Database Record

  1. Tetrodotoxin, an Extremely Potent Marine Neurotoxin: Distribution, Toxicity, Origin and Therapeutical Uses

    Directory of Open Access Journals (Sweden)

    Jorge Lago


    Full Text Available Tetrodotoxin (TTX is a potent neurotoxin responsible for many human intoxications and fatalities each year. The origin of TTX is unknown, but in the pufferfish, it seems to be produced by endosymbiotic bacteria that often seem to be passed down the food chain. The ingestion of contaminated pufferfish, considered the most delicious fish in Japan, is the usual route of toxicity. This neurotoxin, reported as a threat to human health in Asian countries, has spread to the Pacific and Mediterranean, due to the increase of temperature waters worldwide. TTX, for which there is no known antidote, inhibits sodium channel producing heart failure in many cases and consequently death. In Japan, a regulatory limit of 2 mg eq TTX/kg was established, although the restaurant preparation of “fugu” is strictly controlled by law and only chefs qualified are allowed to prepare the fish. Due to its paralysis effect, this neurotoxin could be used in the medical field as an analgesic to treat some cancer pains.

  2. An Original Approach for Quantification of Blood Vessels on the Whole Tumour Section

    Directory of Open Access Journals (Sweden)

    Nga Tran Kim


    Full Text Available Relative abundance of tumour angiogenesis has been shown to be of clinical relevance in cancers of various locations such as the ovary. Nevertheless, several problems are encountered when quantifying tumour microvessels: (i as many other tumour markers, vascularity pattern is often heterogeneous within the tumour mass and even within the same histological section. As a consequence, an adequate acquisition method must be developed for accurate field sampling. (ii Manual microvessel counting is long, tedious and subject to poor reproducibility. Introduction in routine practice requires a fast, reproducible and reliable automatic image processing. In this study we present an original procedure combining a slide scanner image acquisition and a fully automatic image analysis sequence. The slide scanner offers the advantage of recording an image of the whole histological section for subsequent automatic blood vessel detection and hot spot area location. Microvessel density and surface fraction were measured for the whole section as well as within hot spots. Different immunostaining methods were tested in order to optimise the procedure. Moreover, the method proposed was submitted to a quality control procedure, with reference to interactive identification of microvessels at scanner level. This experiment showed that 93 to 97% of blood vessels were detected, according to the staining protocol used. Colour figures can be viewed on‐2/kim.htm.

  3. Origins of narcissism in children

    NARCIS (Netherlands)

    Brummelman, E.; Thomaes, S.; Nelemans, S.A.; Orobio de Castro, B.; Overbeek, G.; Bushman, B.J.


    Narcissism levels have been increasing among Western youth, and contribute to societal problems such as aggression and violence. The origins of narcissism, however, are not well understood. Here, we report, to our knowledge, the first prospective longitudinal evidence on the origins of narcissism in

  4. The Origins of Soviet Sociolinguistics. (United States)

    Brandist, Craig


    Discusses the origins of Soviet sociolinguistics and suggests that the historical significance of the reception and reinterpretation of these ideas is considerable, leading to a reconsideration of the origins of sociolinguistics and the relationship between Marxism and the language sciences in the early years of the Soviet Union. (Author/VWL)

  5. HCSD: the human cancer secretome database (United States)

    Feizi, Amir; Banaei-Esfahani, Amir; Nielsen, Jens


    The human cancer secretome database (HCSD) is a comprehensive database for human cancer secretome data. The cancer secretome describes proteins secreted by cancer cells and structuring information about the cancer secretome will enable further analysis of how this is related with tumor biology. The secreted proteins from cancer cells are believed to play a deterministic role in cancer progression and therefore may be the key to find novel therapeutic targets and biomarkers for many cancers. Consequently, huge data on cancer secretome have been generated in recent years and the lack of a coherent database is limiting the ability to query the increasing community knowledge. We therefore developed the Human Cancer Secretome Database (HCSD) to fulfil this gap. HCSD contains >80 000 measurements for about 7000 nonredundant human proteins collected from up to 35 high-throughput studies on 17 cancer types. It has a simple and user friendly query system for basic and advanced search based on gene name, cancer type and data type as the three main query options. The results are visualized in an explicit and interactive manner. An example of a result page includes annotations, cross references, cancer secretome data and secretory features for each identified protein. Database URL: PMID:26078477

  6. Characterizing genomic alterations in cancer by complementary functional associations | Office of Cancer Genomics (United States)

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment.

  7. College students' evaluations of alcohol consequences as positive and negative. (United States)

    Patrick, Megan E; Maggs, Jennifer L


    Alcohol expectancy, motivation, and consequences measures assume a known valence of 'positive' and 'negative' outcomes. However, different individuals may rate the same consequences of alcohol use as good or bad. The current study examines the extent to which: (a) college students rate researcher-defined positive consequences as good and researcher-defined negative consequences as bad, and (b) these evaluations predict alcohol use and problems after controlling for previous use. In longitudinal self-reports via web-surveys across the first three semesters of college, students (N=600; 54% women) reported their alcohol use and problems, experienced consequences, and evaluations of those consequences. Contrary to the generally-accepted valence of positive consequences, Fun/Social consequences were viewed as neutral or negative by 22% (having more fun) to 73% (relieving boredom) of participants. Over half of participants evaluated each of the Relaxation, Sex, and Image consequences items as neutral or negative. Consistent with the generally-accepted valence of negative consequences, Physical/Behavioral consequences were viewed by the majority as negative, although 11% (getting in trouble with police/authorities) to 34% (doing/saying something embarrassing) of students rated these consequences as neutral or positive. Independent of levels of previous drinking, more positive evaluations of Fun/Social consequences prospectively predicted frequency, quantity, and maximum drinks. Less negative evaluations of Physical/Behavioral consequences predicted more alcohol problems. There is variation in the evaluations of consequences among college students, and understanding characteristics of those who view consequences as positive or negative may have implications for future alcohol-related behaviors and problems.

  8. p53 Acetylation: Regulation and Consequences

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Sara M. [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Quelle, Dawn E., E-mail: [Department of Pharmacology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Medical Scientist Training Program, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Pathology, The University of Iowa Carver College of Medicine, Iowa City, IA 52242 (United States)


    Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites) as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis) to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

  9. p53 Acetylation: Regulation and Consequences

    Directory of Open Access Journals (Sweden)

    Sara M. Reed


    Full Text Available Post-translational modifications of p53 are critical in modulating its tumor suppressive functions. Ubiquitylation, for example, plays a major role in dictating p53 stability, subcellular localization and transcriptional vs. non-transcriptional activities. Less is known about p53 acetylation. It has been shown to govern p53 transcriptional activity, selection of growth inhibitory vs. apoptotic gene targets, and biological outcomes in response to diverse cellular insults. Yet recent in vivo evidence from mouse models questions the importance of p53 acetylation (at least at certain sites as well as canonical p53 functions (cell cycle arrest, senescence and apoptosis to tumor suppression. This review discusses the cumulative findings regarding p53 acetylation, with a focus on the acetyltransferases that modify p53 and the mechanisms regulating their activity. We also evaluate what is known regarding the influence of other post-translational modifications of p53 on its acetylation, and conclude with the current outlook on how p53 acetylation affects tumor suppression. Due to redundancies in p53 control and growing understanding that individual modifications largely fine-tune p53 activity rather than switch it on or off, many questions still remain about the physiological importance of p53 acetylation to its role in preventing cancer.

  10. Cancer and environment

    Energy Technology Data Exchange (ETDEWEB)

    Meerkamp van Embden, I.C.


    The author comes to the following conclusions: cancerous diseases, if occurring as a result of chemical-dependent expositions at work, are diminished by continual improvements of medical-technical industrial safety measures. An increasing cancer risk by chemical products must be denied. The statements on a generally excessive content of carcinogeneous residues in food do not bear a critical examination either. The former endangering rate of men by carcinogens, partly of natural, partly of anthropogeneous origin, had been at least as high and frequently also much higher than it is today. Within the past 15 years comprehensive measures of technical-hygienic pollution protection have relieved the emission of pollutants. Now as before the general life expectance is increasing. While the age-adjusted cancer mortality rate has remained practically unchanged during the past decades the number deaths caused by heart and circulation diseases shows an alarming rise, also when age-adjusted. The way of living plays an important part as to cancer, apart from the status of immunity and age-dependent processes. An environmental factor for cancer risks which is frequently underestimated is excessive insolation. The importance of psychosocial risk factors has not yet been investigated sufficiently although it may be just them which could be important for the assessment of cancer hazards.

  11. The gastric cancer

    Directory of Open Access Journals (Sweden)

    Pelayo Correa


    Full Text Available Gastric cancer ranks fourth in incidence and second in mortality among all cancers worldwide. Despite the decrease in incidencein some regions of the world, gastric cancer continues to present a major clinical challenge due to most cases beingdiagnosed in advanced stages with poor prognosis and limited treatment options. The development of gastric cancer is acomplex and multi-factored process involving a number of etiological factors and multiple genetic and epigenetic alterations.Among the predisposing factors are: Helicobacter pylori infection, high salt intake, smoking, and, in a small percentage ofpatients, a family genetic component. More than 90% of stomach cancers are adenocarcinomas, which are classified intotwo major histological groups: intestinal and diffuse. Intestinal adenocarcinoma is preceded by a sequence of gastric lesionsknown as Correa´s cascade. According to the anatomical position, adenocarcinomas are classified as proximal (originatingin the cardia and distal (originating in the body and antrum. This is a classification that recognizes two different clinicalentities. In general, the only possible cure for the disease is resection of the tumor in an early stage for which the identificationand monitoring of at-risk patients play a significant role. With the exception of Japan, no effective early detection programsexist. Anti-H. pylori has been shown to be an effective measure in the prevention of gastric cancer.

  12. Targeting tumor suppressor genes for cancer therapy. (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin


    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

  13. Mitochondrial dysfunction and risk of cancer

    DEFF Research Database (Denmark)

    Lund, M; Melbye, M; Diaz, L J


    -years of follow-up, 19 subjects developed a primary cancer. The corresponding SIR for any primary cancer was 1.06 (95% confidence interval 0.68-1.63). Subgroup analyses according to mutational subtype yielded similar results, for example, a SIR of 0.94 (95% CI 0.53 to 1.67) for the m.3243A>G maternally inherited......BACKGROUND: Mitochondrial mutations are commonly reported in tumours, but it is unclear whether impaired mitochondrial function per se is a cause or consequence of cancer. To elucidate this, we examined the risk of cancer in a nationwide cohort of patients with mitochondrial dysfunction. METHODS...... matrilineal relatives to a cohort member with a genetically confirmed maternally inherited mDNA mutation. Information on cancer was obtained by linkage to the Danish Cancer Register. Standardised incidence ratios (SIRs) were used to assess the relative risk of cancer. RESULTS: During 7334 person...

  14. Vaginal Cancer (United States)

    Vaginal cancer is a rare type of cancer. It is more common in women 60 and older. You are also more likely to get it if you have had a human ... test can find abnormal cells that may be cancer. Vaginal cancer can often be cured in its ...

  15. Lung Cancer (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Talking about Advanced Cancer Coping with Your Feelings Planning for Advanced Cancer Advanced Cancer and Caregivers Questions ... Talking About Advanced Cancer Coping With Your Feelings Planning for Advanced Cancer Advanced Cancer & Caregivers Managing Cancer ...

  17. What Is Thyroid Cancer? (United States)

    ... Treatment? Thyroid Cancer About Thyroid Cancer What Is Thyroid Cancer? Cancer starts when cells in the body begin ... cell) Medullary Anaplastic (an aggressive undifferentiated tumor) Differentiated thyroid cancers Most thyroid cancers are differentiated cancers. The cells ...

  18. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Lung Cancer Lymphoma Pancreatic Cancer ... grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ...

  19. Diet and cancer (United States)

    Fiber and cancer; Cancer and fiber; Nitrates and cancer; Cancer and nitrates ... DIET AND BREAST CANCER The link between nutrition and breast cancer has been well studied. To reduce risk of breast cancer the American ...

  20. Breast Cancer Overview (United States)

    ... Cancer > Breast Cancer > Breast Cancer: Overview Request Permissions Breast Cancer: Overview Approved by the Cancer.Net Editorial Board , ... bean-shaped organs that help fight infection. About breast cancer Cancer begins when healthy cells in the breast ...