Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry

PURPOSE Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. MATERIALS AND METHODS The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. RESULTS A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. CONCLUSIONS In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.

Reporting quality of randomised controlled trials published in prosthodontic and implantology journals

The purpose of this study was to examine the reporting quality of randomised controlled trials (RCTs) published in prosthodontic and implantology journals. Thirty issues of nine journals in prosthodontics and implant dentistry were searched for RCTs, covering the years 2005-2012: The Journal of Prosthetic Dentistry, Journal of Oral Rehabilitation, The International Journal of Prosthodontics, The International Journal of Periodontics & Restorative Dentistry, Clinical Oral Implants Research, Clinical Implant Dentistry & Related Research, The International Journal of Oral & Maxillofacial Implants, Implant Dentistry and Journal of Dentistry. The reporting quality was assessed using a modified Consolidated Standards of Reporting Trials (CONSORT) statement checklist. Data were analysed using descriptive statistics followed by univariable and multivariable examination of statistical associations (α = 0·05). A total of 147 RCTs were identified with a mean CONSORT score of 69·4 (s.d. = 9·7). Significant differences were found among journals with the Journal of Oral Rehabilitation achieving the highest score (80·6, s.d. = 5·5) followed by Clinical Oral Implants Research (73·7, s.d. = 8·3). Involvement of a statistician/methodologist was significantly associated with increased CONSORT scores. Overall, the reporting quality of RCTs in major prosthodontic and implantology journals requires improvement. This is of paramount importance considering that optimal reporting of RCTs is an important prerequisite for clinical decision-making.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance.

UNLABELLED Patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (IRAK4), a critical signaling mediator in Toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2, L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll-like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction. CONCLUSION Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity.

What drives European beech (Fagus sylvatica L.) mortality after forest fires of varying severity?

Predicting the timing and amount of tree mortality after a forest fire is of paramount importance for post-fire management decisions, such as salvage logging or reforestation. Such knowledge is particularly needed in mountainous regions where forest stands often serve as protection against natural hazards (e.g., snow avalanches, rockfalls, landslides). In this paper, we focus on the drivers and timing of mortality in fire-injured beech trees (Fagus sylvatica L.) in mountain regions. We studied beech forests in the southwestern European Alps, which burned between 1970 and 2012. The results show that beech trees, which lack fire-resistance traits, experience increased mortality within the first two decades post-fire with a timing and amount strongly related to the burn severity. Beech mortality is fast and ubiquitous in high severity sites, whereas small- (DBH <12 cm) and intermediate-diameter (DBH 12–36 cm) trees face a higher risk to die in moderate-severity sites. Large-diameter trees mostly survive, representing a crucial ecological legacy for beech regeneration. Mortality remains low and at a level similar to unburnt beech forests for low burn severity sites. Beech trees diameter, the presence of fungal infestation and elevation are the most significant drivers of mortality. The risk of beech to die increases toward higher elevation and is higher for small-diameter than for large-diameter trees. In case of secondary fungi infestation beech faces generally a higher risk to die. Interestingly, fungi that initiate post-fire tree mortality differ from fungi occurring after mechanical injury. From a management point of view, the insights about the controls of post-fire mortality provided by this study should help in planning post-fire silvicultural measures in montane beech forests.

Cataract surgery in cancer patients and its impact on quality of life as measured by the National Eye Institute Visual Functioning Questionnaire - 25 (NEI-VFQ-25)

Purpose. The measurement of quality of life has become an important topic in healthcare and in the allocation of limited healthcare resources. Improving the quality of life (QOL) in cancer patients is paramount. Cataract removal and lens implantation appears to improve patient well-being of cancer patients, though a formal measurement has never been published in the US literature. In this current study, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), a validated vision quality of life metric, was used to study the change in vision-related quality of life in cancer patients who underwent cataract extraction with intraocular lens implantation. ^ Methods. Under an IRB approved protocol, cancer patients who underwent cataract surgery with intraocular lens implantation (by a single surgeon) from December 2008 to March 2011, and who had completed a pre- and postoperative NEI-VFQ-25 were retrospectively reviewed. Post-operative data was collected at their routine 4-6 week post-op visit. Patients' demographics, cancer history, their pre and postoperative ocular examinations, visual acuities, and NEI-VFQ-25 with twelve components were included in the evaluation. The responses were evaluated using the Student t test, Spearman correlation and Wilcoxon signed rank test. ^ Results. 63 cases of cataract surgery (from 54 patients) from the MD Anderson Cancer Center were included in the study. Cancer patients had a significant improvement in the visual acuity (P<0.0001) postoperatively, along with a significant increase in vision-related quality of life (P<0.0001). Patients also had a statistically significant improvement in ten of the twelve subcategories which are addressed in the NEI-VFQ-25. ^ Conclusions. In our study, cataract extraction and intraocular implantation showed a significant impact on the vision-related quality of life in cancer patients. Although this study includes a small sample size, it serves as a positive pilot study to evaluate and quantify the impact of a surgical intervention on QOL in cancer patients and may help to design a larger study to measure vision related QOL per dollar spent for health care cost in cancer patients.^

G -rich oligodeoxyribonucleotides: Triplexes and transcription

Formation of a triple helix resulting from oligonucleotide binding to the DNA double helix offers new possibilities to control gene expression at the transcriptional level. Purine-motif triplexes can be formed under physiological pH. Nevertheless, this formation was inhibited by certain monovalent cations during the association but not during dissociation. Since triplexes are very stable, it was possible to assemble them in the absence of KCl and have them survive throughout the course of an in vitro transcription reaction. As for the design of a better triplex-forming oligonucleotide, 12 nucleotides in length afforded the highest binding affinity. G/T-rich oligonucleotides can be very polymorphic in solution. The conditions for forming purine-motif triplexes, duplexes or G-quartets were determined. Understanding these parameters will be important for the practical use of G-rich oligonucleotides in the development of DNA aptamers where the structure of the oligonucleotide is paramount in dictating its function. Finally, purine-motif triplexes were demonstrated to significantly inhibit gene transcription in vitro. The optimal effect on this process was dependent on the location of triplexes within the promoter, i.e., whether upstream or proximally downstream of the transcription start site. The mechanism for the inhibition of transcription appeared to be interference with initiation through preventing engagement by RNA polymerase. This finding is revolutionary when compared to the conventional model where triplexes inhibit transcription only by occluding binding by trans-acting proteins. Our findings broaden the utility of triplexes and support a strategy for antigene therapy by triplexes. ^

Influencia del clima en bayas y mostos de las variedades Bonarda y Syrah : Mendoza (Argentina)

En la elaboración de los vinos tintos, el estado de maduración de las uvas es de importancia capital pues del contenido de azúcares y ácidos dependerá el desarrollo adecuado de la fermentación y del contenido polifenólico, el color y la capacidad de crianza. Considerando que el clima es un aspecto relevante que debe considerarse para evaluar el impacto de las condiciones ambientales en el contenido fenólico de las uvas, en el presente trabajo se estudió su influencia en las variedades Bonarda y Syrah de la provincia de Mendoza, Argentina. El muestreo se realizó en el momento de cosecha. Se observó un leve determinismo climático en la variedad Syrah para el contenido de antocianos y polifenoles. Las diferencias de temperaturas nocturnas no se vincularon con una variación de contenido de antocianos y polifenoles. El contenido de azúcares reductores de la variedad Bonarda fue significativamente menor al de la variedad Syrah en el momento de cosecha. La zona Este resulta particularmente propicia para el cultivo de Bonarda diferenciándose de Syrah en el contenido de antocianos en dicha zona. La menor relación semilla/pulpa de la variedad Syrah podría incidir en algunas características sensoriales de sus vinos, tal como la astringencia.

Hidden realities: What women do when they want to terminate an unwanted pregnancy in Bolivia

OBJECTIVE: To explore women's experience of unwanted pregnancy and induced abortion in Bolivia, where nearly all induced abortions are carried out in clandestine, unregulated, and unsafe conditions. METHODS: Qualitative and quantitative research methods, including focus group discussions, in-depth interviews and a structured survey of women of reproductive age, were used to explore the experience of unwanted pregnancy and induced abortion in poor urban areas of 5 Bolivian cities. RESULTS: Of the 1175 sexually experienced women surveyed, 13% reported having had an induced abortion. The methods they tried included surgical abortion, taking misoprostol, drinking herbal and chemical preparations, and inflicting physical trauma on themselves. Many women made multiple attempts before successfully terminating a pregnancy. Lack of knowledge and confusion about how to use misoprostol may have contributed to the complications that resulted in seeking postabortion care. CONCLUSION: Increased access to accurate information and counseling about abortion options are paramount if women are to make informed decisions and minimize health risks.

La enseñanza de las Ciencias Sociales en los profesorados de educación primaria de la provincia de Buenos Aires : La Geografía, gran ausente : Análisis de situación y aporte superador

Alejandro Kaufman (2008) señala que grandes transformaciones se están produciendo desde una perspectiva histórico - cultural en la relación que se establece entre la educación y la sociedad. Y que muchas de las tensiones entre ambas son el producto de lo que denomina "novedades" culturales. Sostiene que la educación se ha sustentado en una cierta previsibilidad y que, en cuanto que la modernidad representa progreso, el cual estaría asociado a la desaparición o transformación de muchas de esas certidumbres, la escuela estaría sufriendo ciertas modificaciones que involucran los propios cimientos de la institución escolar. La formación de los futuros maestros en el área de Ciencias Sociales debe ser ajustada a los requerimientos de esta nueva sociedad. El abordaje de la Didáctica de las Ciencias Sociales debe considerar las nuevas aproximaciones epistemológicas y temáticas relevantes en las propuestas pedagógicas. Es indispensable que, así como existen contenidos de Geografía en los planes de estudio de los profesorados y profusas indicaciones para su tratamiento en los diseños curriculares de Primero y Segundo ciclo, se verifique el desarrollo de los mismos desde una mirada crítica que permita tanto a docentes como alumnos un compromiso con el mundo en el que la escuela está inserta

La enseñanza de las Ciencias Sociales en los profesorados de educación primaria de la provincia de Buenos Aires : La Geografía, gran ausente : Análisis de situación y aporte superador

Alejandro Kaufman (2008) señala que grandes transformaciones se están produciendo desde una perspectiva histórico - cultural en la relación que se establece entre la educación y la sociedad. Y que muchas de las tensiones entre ambas son el producto de lo que denomina "novedades" culturales. Sostiene que la educación se ha sustentado en una cierta previsibilidad y que, en cuanto que la modernidad representa progreso, el cual estaría asociado a la desaparición o transformación de muchas de esas certidumbres, la escuela estaría sufriendo ciertas modificaciones que involucran los propios cimientos de la institución escolar. La formación de los futuros maestros en el área de Ciencias Sociales debe ser ajustada a los requerimientos de esta nueva sociedad. El abordaje de la Didáctica de las Ciencias Sociales debe considerar las nuevas aproximaciones epistemológicas y temáticas relevantes en las propuestas pedagógicas. Es indispensable que, así como existen contenidos de Geografía en los planes de estudio de los profesorados y profusas indicaciones para su tratamiento en los diseños curriculares de Primero y Segundo ciclo, se verifique el desarrollo de los mismos desde una mirada crítica que permita tanto a docentes como alumnos un compromiso con el mundo en el que la escuela está inserta

La enseñanza de las Ciencias Sociales en los profesorados de educación primaria de la provincia de Buenos Aires : La Geografía, gran ausente : Análisis de situación y aporte superador

Alejandro Kaufman (2008) señala que grandes transformaciones se están produciendo desde una perspectiva histórico - cultural en la relación que se establece entre la educación y la sociedad. Y que muchas de las tensiones entre ambas son el producto de lo que denomina "novedades" culturales. Sostiene que la educación se ha sustentado en una cierta previsibilidad y que, en cuanto que la modernidad representa progreso, el cual estaría asociado a la desaparición o transformación de muchas de esas certidumbres, la escuela estaría sufriendo ciertas modificaciones que involucran los propios cimientos de la institución escolar. La formación de los futuros maestros en el área de Ciencias Sociales debe ser ajustada a los requerimientos de esta nueva sociedad. El abordaje de la Didáctica de las Ciencias Sociales debe considerar las nuevas aproximaciones epistemológicas y temáticas relevantes en las propuestas pedagógicas. Es indispensable que, así como existen contenidos de Geografía en los planes de estudio de los profesorados y profusas indicaciones para su tratamiento en los diseños curriculares de Primero y Segundo ciclo, se verifique el desarrollo de los mismos desde una mirada crítica que permita tanto a docentes como alumnos un compromiso con el mundo en el que la escuela está inserta

Shear experiments from IODP Expedition 322 and 333 samples

The mechanical behavior of the plate boundary fault zone is of paramount importance in subduction zones, because it controls megathrust earthquake nucleation and propagation as well as the structural style of the forearc. In the Nankai area along the NanTroSEIZE (Kumano) drilling transect offshore SW Japan, a heterogeneous sedimentary sequence overlying the oceanic crust enters the subduction zone. In order to predict how variations in lithology, and thus mechanical properties, affect the formation and evolution of the plate boundary fault, we conducted laboratory tests measuring the shear strengths of sediments approaching the trench covering each major lithological sedimentary unit. We observe that shear strength increases nonlinearly with depth, such that the (apparent) coefficient of friction decreases. In combination with a critical taper analysis, the results imply that the plate boundary position is located on the main frontal thrust. Further landward, the plate boundary is expected to step down into progressively lower stratigraphic units, assisted by moderately elevated pore pressures. As seismogenic depths are approached, the décollement may further step down to lower volcaniclastic or pelagic strata but this requires specific overpressure conditions. High-taper angle and elevated strengths in the toe region may be local features restricted to the Kumano transect.

Limits of the Southern Ocean

The knowledge about processes concerning perception and understanding is of paramount importance for designing means of communication like maps and charts. This is especially the case, if one does not want to lose sight of the map-user and if map-design is to be orientated along the map-users needs and preferences in order to improve the cartographic product's usability. A scientific approach to visualization can help to achieve useable results. The insights achieved by such an approach can lead to modes of visualization that are superior to those, which have seemingly proved their value in praxis - so-called "bestpractices" -, concerning their utility and efficiency. This thesis shows this by using the example of visualizing the limits of bodies of waters in the Southern Ocean. After making some introductorily remarks on the chosen mode of problem-solution in chapter one, which simultaneously illustrate the flow of work while working on the problem, in chapter two the relevant information concerning the drawing of limits in the Southern Ocean is outlined. Chapter 3 builds the theoretical framework, which is a multidisciplinary approach to representation. This theoretical framework is based on "How Maps Work" by the American Cartographer MacEachren (1995/2004). His "scientific approach to visualization" is amended and adjusted by the knowledge gained from recent findings of the social sciences where necessary. So, the approach suggested in this thesis represents a synergy of psychology, sociology, semiotics, linguistics, communication theory and cartography. It follows the tradition of interdisciplinary research getting over the boundaries of a single scientific subject. The achieved holistic approach can help to improve the usability of cartographic products. It illustrates on the one hand those processes taking place while perceiving and recognizing cartographic information - so-called bottom-up-processes. On the other hand it illuminates the processes which happen during understanding this information in so-called top-down-processes. Bottom-up- and top-down-processes are interdependent and inseparably interrelated and therefore cannot be understood without each other. Regarding aspects of usability the approach suggested in this thesis strongly focuses on the map-user. This is the reason why the phenomenon of communication gains more weight than in MacEachren's map-centered approach. Because of this, in chapter 4 a holistic approach to communication is developed. This approach makes clear that only the map-user can evaluate the usability of a cartographic product. Only if he can extract the information relevant for him from the cartographical product, it is really useable. The concept of communication is well suited to conceive that. In case of the visualization of limits of bodies of water in the Southern Ocean, which is not complex enough to illustrate all results of the theoretical considerations, it is suggested to visualize the limits with red lines. This suggestion deviates from the commonly used mode of visualization. So, this thesis shows how theory is able to ameliorate praxis. Chapter 5 leads back to the task of fixing limits of the bodies of water in the area of concern. A convention by the International Hydrographic Organization (IHO) states that those limits should be drawn by using meridians, parallels, rhumb lines and bathymetric data. Based on the available bathymetric data both a representation and a process model are calculated, which should support the drawing of the limits. The quality of both models, which depends on the quality of the bathymetric data at hand, leads to the decision that the representation model is better suited to support the drawing of limits.

Essays on Inequality and Integration

Inequality and integration have been sociology’s two key paradigms since the classics, associated with the names of Marx and Durkheim and Europe’s current economic crisis has forcefully reinvigorated their joint relevance. Above all, the debt crisis has fueled the wheel of social inequality: cash-starved states are further forced to cut back on public expenditures, to minimize the margin for redistribution and to raise new challenges for the integration policies addressing the emerging disparities. At the same time, global environmental and demographic problems, intertwined with escalating migration pressure, tear at the texture of European and all Western societies, in particular, the unequal impact of climate change and the unequal distribution of population growth make migration and integration paramount public policy issues and a soaring source of social conflict. In principle, the inequalities engendered by these cascading processes are also an opportunity. They increase the diversity of society and can bring about innovation and growth. Our desire and ability for social integration depends, above all, on the ultimate balance between these advantages and disadvantages. The chapters in the volume concentrate on the opportunities as well as the risks associated with these social changes from various angles. They are a handpicked set of outstanding contributions from the Congress of the Swiss Sociological Association that took place at the University of Bern, June 26–28, 2013.