Impact of effective intravesical therapies on quality of life in patients with non-muscle invasive bladder cancer: a systematic review

Background: Conventional and newly emerged intravesical modalities have demonstrated prophylactic effectiveness that may improve quality of life (QoL) in non-muscle invasive bladder cancer. The purpose of this study is to analyze existing QoL evidence in patients receiving any form of intravesical therapy. Methods: A PubMed search without time restriction was conducted to identify all relevant studies in accordance with the PICOT question. Additionally, a search was also performed in the Cochrane library database, Internet, and citation. The CONSORT 2010 checklist and STROBE statement checklist were used to evaluate the risk of bias of the included studies. Results: A total of 24 eligible articles were included, which consisted of 11 interventional and 13 observational studies. Intravesical therapy with Bacillus Calmette–Guérin (BCG) or certain chemotherapeutic agents worsens symptom burdens and functional performance during the initial induction phase while continuous improved is observed throughout the maintenance treatment and beyond. Hyperthermia has shown a positive trend in enhancing QoL of patients receiving intravesical chemotherapy, which requires more investigations. However, QoL data were unavailable for other forms of immunotherapy, immune checkpoint inhibitors, electromotive drug administration, and photodynamic therapy. Conclusions: Limited studies suggested the long-term positive impact of intravesical BCG immunotherapy and chemotherapy. However, existing evidence was lacking to clarify the impact of many emerging intravesical therapies that have suggested to be effective and safe, which demands treatment-specific QoL studies

Dynamics of precipitation pattern formation at geothermal hot springs

We formulate and model the dynamics of spatial patterns arising during the precipitation of calcium carbonate from a supersaturated shallow water flow. The model describes the formation of travertine deposits at geothermal hot springs and rimstone dams of calcite in caves. We find explicit solutions for travertine domes at low flow rates, identify the linear instabilities which generate dam and pond formation on sloped substrates, and present simulations of statistical landscape evolution

Hawaii Geothermal Project : quarterly progress report no. 3 (December 1, 1973 through February 28, 1974)

Discussion of early exploration research conducted under the Hawaii Geothermal Project.Support for project provided by National Science Foundation, State of Hawaii, County of Hawai

Influenza H5N1 and H1N1 Virus Replication and Innate Immune Responses in Bronchial Epithelial Cells Are Influenced by the State of Differentiation

Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE) cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004) and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998), the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of α2-6-linked sialic acid receptors and human airway trypsin-like (HAT) protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the epithelium regeneration, the data generated from the undifferentiated NHBE cultures may also be relevant to disease pathogenesis

Optimal Universal and State-Dependent Quantum Cloning

We establish the best possible approximation to a perfect quantum cloning machine which produces two clones out of a single input. We analyze both universal and state-dependent cloners. The maximal fidelity of cloning is shown to be 5/6 for universal cloners. It can be achieved either by a special unitary evolution or by a novel teleportation scheme. We construct the optimal state-dependent cloners operating on any prescribed two non-orthogonal states, discuss their fidelities and the use of auxiliary physical resources in the process of cloning. The optimal universal cloners permit us to derive a new upper bound on the quantum capacity of the depolarizing quantum channel.Comment: 30 pages (RevTeX), 2 figures (epsf), further results and further authors added, to appear in Physical Review

The elastic constants of MgSiO3 perovskite at pressures and temperatures of the Earth's mantle

The temperature anomalies in the Earth's mantle associated with thermal convection1 can be inferred from seismic tomography, provided that the elastic properties of mantle minerals are known as a function of temperature at mantle pressures. At present, however, such information is difficult to obtain directly through laboratory experiments. We have therefore taken advantage of recent advances in computer technology, and have performed finite-temperature ab initio molecular dynamics simulations of the elastic properties of MgSiO3 perovskite, the major mineral of the lower mantle, at relevant thermodynamic conditions. When combined with the results from tomographic images of the mantle, our results indicate that the lower mantle is either significantly anelastic or compositionally heterogeneous on large scales. We found the temperature contrast between the coldest and hottest regions of the mantle, at a given depth, to be about 800K at 1000 km, 1500K at 2000 km, and possibly over 2000K at the core-mantle boundary.Comment: Published in: Nature 411, 934-937 (2001

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

The European Plate Observing System and the Arctic

The European Plate Observing System (EPOS) aims to integrate existing infrastructures in the solid earth sciences into a single infrastructure, enabling earth scientists across Europe to combine, model, and interpret multidisciplinary datasets at different time and length scales. In particular, a primary objective is to integrate existing research infrastructures within the fields of seismology, geodesy, geophysics, geology, rock physics, and volcanology at a pan-European level. The added value of such integration is not visible through individual analyses of data from each research infrastructure; it needs to be understood in a long-term perspective that includes the time when changes implied by current scientific research results are fully realized and their societal impacts have become clear. EPOS is now entering its implementation phase following a four-year preparatory phase during which 18 member countries in Europe contributed more than 250 research infrastructures to the building of this pan-European vision. The Arctic covers a significant portion of the European plate and therefore plays an important part in research on the solid earth in Europe. However, the work environment in the Arctic is challenging. First, most of the European Plate boundary in the Arctic is offshore, and hence, sub-sea networks must be built for solid earth observation. Second, ice covers the Arctic Ocean where the European Plate boundary crosses through the Gakkel Ridge, so innovative technologies are needed to monitor solid earth deformation. Therefore, research collaboration with other disciplines such as physical oceanography, marine acoustics, and geo-biology is necessary. The establishment of efficient research infrastructures suitable for these challenging conditions is essential both to reduce costs and to stimulate multidisciplinary research.Le système European Plate Observing System (EPOS) vise l’intégration des infrastructures actuelles en sciences de la croûte terrestre afin de ne former qu’une seule infrastructure pour que les spécialistes des sciences de la Terre des quatre coins de l’Europe puissent combiner, modéliser et interpréter des ensembles de données multidisciplinaires moyennant diverses échelles de temps et de longueur. Un des principaux objectifs consiste plus particulièrement à intégrer les infrastructures de recherche existantes se rapportant aux domaines de la sismologie, de la géodésie, de la géophysique, de la géologie, de la physique des roches et de la volcanologie à l’échelle paneuropéenne. La valeur ajoutée de cette intégration n’est pas visible au moyen des analyses individuelles des données émanant de chaque infrastructure de recherche. Elle doit plutôt être considérée à la lumière d’une perspective à long terme, lorsque les changements qu’impliquent les résultats de recherche scientifique actuels auront été entièrement réalisés et que les incidences sur la société seront claires. Le système EPOS est en train d’amorcer sa phase de mise en oeuvre. Cette phase succède à la phase préparatoire de quatre ans pendant laquelle 18 pays membres de l’Europe ont soumis plus de 250 infrastructures de recherche en vue de l’édification de cette vision paneuropéenne. L’Arctique couvre une grande partie de la plaque européenne et par conséquent, il joue un rôle important dans les travaux de recherche portant sur la croûte terrestre en Europe. Cependant, le milieu de travail de l’Arctique n’est pas sans défis. Premièrement, la majorité de la limite de la plaque européenne se trouvant dans l’Arctique est située au large, ce qui signifie que des réseaux marins doivent être aménagés pour permettre l’observation de la croûte terrestre. Deuxièmement, de la glace recouvre l’océan Arctique, là où la limite de la plaque européenne traverse la dorsale de Gakkel, ce qui signifie qu’il faut recourir à des technologies innovatrices pour surveiller la déformation de la croûte terrestre. C’est pourquoi les travaux de recherche doivent nécessairement se faire en collaboration avec d’autres disciplines comme l’océanographie physique, l’acoustique marine et la géobiologie. L’établissement d’infrastructures de recherche efficaces capables de faire face à ces conditions rigoureuses s’avère essentiel, tant pour réduire les coûts que pour stimuler la recherche multidisciplinaire

TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.

The neuroblastoma cell line SH-SY5Y is widely used to study retinoic acid (RA)-induced gene expression and differentiation and as a tool to study neurodegenerative disorders. SH-SY5Y cells predominantly exhibit adrenergic neuronal properties, but they can also exist in an epigenetically interconvertible alternative state with more mesenchymal characteristics; as a result, these cells can be used to study gene regulation circuitry controlling neuroblastoma phenotype. Using a combination of pharmacological inhibition and targeted gene inactivation, we have probed the requirement for DNA topoisomerase IIB (TOP2B) in RA-induced gene expression and differentiation and in the balance between adrenergic neuronal versus mesenchymal transcription programmes. We found that expression of many, but not all genes that are rapidly induced by ATRA in SH-SY5Y cells was significantly reduced in the TOP2B null cells; these genes include BCL2, CYP26A1, CRABP2, and NTRK2. Comparing gene expression profiles in wild-type versus TOP2B null cells, we found that long genes and genes expressed at a high level in WT SH-SY5Y cells were disproportionately dependent on TOP2B. Notably, TOP2B null SH-SY5Y cells upregulated mesenchymal markers vimentin (VIM) and fibronectin (FN1) and components of the NOTCH signalling pathway. Enrichment analysis and comparison with the transcription profiles of other neuroblastoma-derived cell lines supported the conclusion that TOP2B is required to fully maintain the adrenergic neural-like transcriptional signature of SH-SY5Y cells and to suppress the alternative mesenchymal epithelial-like epigenetic state