103 research outputs found
5‘-Triphosphat-RNA induziert Tumorzelltod in einer RIG-I-abhängigen priming-Phase und einer Oligoadenylatsynthetase 1 (OAS1)-RNase L-abhängigen Effektorphase
Radiotherapy for hormone-sensitive prostate cancer with synchronous low burden of distant metastases.
PURPOSE
The DEGRO Expert Commission on Prostate Cancer has revised the indication for radiation therapy of the primary prostate tumor in patients with synchronous distant metastases with low metastatic burden.
METHODS
The current literature in the PubMed database was reviewed regarding randomized evidence on radiotherapy of the primary prostate tumor with synchronous low metastatic burden.
RESULTS
In total, two randomized trials were identified. The larger study, the STAMPEDE trial, demonstrated an absolute survival benefit of 8% after 3 years for patients with low metastatic burden treated with standard of care (SOC) and additional radiotherapy (RT) (EQD2 ≤ 72 Gy) of the primary tumor. Differences in the smaller Horrad trial were not statistically significant, although risk reduction in the subgroup (< 5 bone metastases) was equal to STAMPEDE. The STOPCAP meta-analysis of both trials demonstrated the benefit of local radiotherapy for up to 4 bone lesions and an additional subanalysis of STAMPEDE also substantiated this finding in cases with M1a-only metastases.
CONCLUSION
Therefore, due to the survival benefit after 3 years, current practice is changing. New palliative SOC is radiotherapy of the primary tumor in synchronously metastasized prostate cancer with low metastatic burden (defined as ≤ 4 bone metastases, with or without distant nodes) or in case of distant nodes only detected by conventional imaging
Statement from the DEGRO working group prostate cancer
Aim: To provide an overview on the available treatments to prevent and reduce gynecomastia and/or breast pain caused by antiandrogen therapy for prostate cancer.
Methods: The German Society of Radiation Oncology (DEGRO) expert panel summarized available evidence published and assessed the validity of the information on efficacy and treatment-related toxicity.
Results: Eight randomized controlled trials and one meta-analysis were identified. Two randomized trials demonstrated that prophylactic radiation therapy (RT) using 1 × 10 Gy or 2 × 6 Gy significantly reduced the rate of gynecomastia but not breast pain, as compared to observation. A randomized dose-finding trial identified the daily dose of 20 mg tamoxifen (TMX) as the most effective prophylactic dose and another randomized trial described that daily TMX use was superior to weekly use. Another randomized trial showed that prophylactic daily TMX is more effective than TMX given at the onset of gynecomastia. Two other randomized trials described that TMX was clearly superior to anastrozole in reducing the risk for gynecomastia and/or breast pain. One comparative randomized trial between prophylactic RT using 1 × 12 Gy and TMX concluded that prophylactic TMX is more effective compared to prophylactic RT and furthermore that TMX appears to be more effective to treat gynecomastia and/or breast pain when symptoms are already present. A meta-analysis confirmed that both prophylactic RT and TMX can reduce the risk of gynecomastia and/or breast pain with TMX being more effective; however, the rate of side effects after TMX including dizziness and hot flushes might be higher than after RT and must be taken into account. Less is known regarding the comparative effectiveness of different radiation fractionation schedules and more modern RT techniques.
Conclusions: Prophylactic RT as well as daily TMX can significantly reduce the incidence of gynecomastia and/or breast pain. TMX appears to be an effective alternative to RT also as a therapeutic treatment in the presence of gynecomastia but its side effects and off-label use must be considered
Dynamics of the frustrated Ising lattice gas
The dynamical properties of a three dimensional model glass, the frustrated
Ising lattice gas (FILG) are studied by Monte Carlo simulations. We present
results of compression experiments, where the chemical potential is either
slowly or abruptly changed, as well as simulations at constant density. One
time quantities like density and two time ones like correlations, responses and
mean square displacements are measured, and the departure from equilibrium
clearly characterized. The aging scenario, particularly in the case of density
autocorrelations is reminiscent of spin glass phenomenology with violations of
the Fluctuation-dissipation theorem, typical of systems with one replica
symmetry breaking. The FILG, as a valid on-lattice model of structural glasses
can be described with tools developed in spin glass theory and, being a finite
dimensional model, can open the way for a systematic study of activated
processes in glasses.Comment: to appear in Phys. Rev. E, november (2000
Septation of Infectious Hyphae Is Critical for Appressoria Formation and Virulence in the Smut Fungus Ustilago Maydis
Differentiation of hyphae into specialized infection structures, known as appressoria, is a common feature of plant pathogenic fungi that penetrate the plant cuticle. Appressorium formation in U. maydis is triggered by environmental signals but the molecular mechanism of this hyphal differentiation is largely unknown. Infectious hyphae grow on the leaf surface by inserting regularly spaced retraction septa at the distal end of the tip cell leaving empty sections of collapsed hyphae behind. Here we show that formation of retraction septa is critical for appressorium formation and virulence in U. maydis. We demonstrate that the diaphanous-related formin Drf1 is necessary for actomyosin ring formation during septation of infectious hyphae. Drf1 acts as an effector of a Cdc42 GTPase signaling module, which also consists of the Cdc42-specific guanine nucleotide exchange factor Don1 and the Ste20-like kinase Don3. Deletion of drf1, don1 or don3 abolished formation of retraction septa resulting in reduced virulence. Appressorium formation in these mutants was not completely blocked but infection structures were found only at the tip of short filaments indicating that retraction septa are necessary for appressorium formation in extended infectious hyphae. In addition, appressoria of drf1 mutants penetrated the plant tissue less frequently
Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene
Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The
most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO,
respectively). Although genetic components play an important role in nsCLP, the genetic
factors that predispose to palate involvement are largely unknown. In this study, we carried
out a meta-analysis on genetic and clinical data from three large cohorts and identified
strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for
rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not
nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps
downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4
pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip
and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations
between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold
increase in risk was observed in patients displaying clefts of both the lip and soft palate but
who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip
or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed
divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The
present study identified a non-coding region at 15q13 as the second, genome-wide significant
locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely
located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically
involves abnormalities of the lip and soft palate, which develop at different time-points and
in separate anatomical regions.Clefts of the lip and palate are common birth defects, and require long-term multidisciplinary
management. Their etiology involves genetic factors and environmental influences
and/or a combination of both, however, these interactions are poorly defined. Moreover,
although clefts of the lip may or may not involve the palate, the determinants predisposing
to specific subphenotypes are largely unknown. Here we demonstrate that variations in
the non-coding region near the GREM1 gene show a highly significant association with a
particular phenotype in which cleft lip and cleft palate co-occ
Goltsov phenomenon as a natural-technogenic electromagnetic discharge of the lithosphere
The article presents data on an unusual natural phenomenon that occurred on November 30, 1984 in the village of Goltsovka, Zmeinogorsky District, Altai Territory. It manifested itself in the passage above the village of a luminous ball, which was accompanied by an impact on the surface of the earth and led to some damage to structures and buildings. A detailed description of this unusual phenomenon in the published scientific literature, as far as we know, is practically absent. The article describes this phenomenon, based on data collected soon after the event, with the addition of upto-date clarifying information. A comparison is made with several known cases of ball lightning and a whirlwind. The conclusion is made about an unusually large energy release in the Goltsovka event
Electrophysiological measurements of peripheral vestibular function—A review of electrovestibulography
Electrocochleography (EcochG), incorporating the Cochlear Microphonic (CM), the Summating Potential (SP), and the cochlear Compound Action Potential (CAP), has been used to study cochlear function in humans and experimental animals since the 1930s, providing a simple objective tool to assess both hair cell (HC) and nerve sensitivity. The vestibular equivalent of ECochG, termed here Electrovestibulography (EVestG), incorporates responses of the vestibular HCs and nerve. Few research groups have utilized EVestG to study vestibular function. Arguably, this is because stimulating the cochlea in isolation with sound is a trivial matter, whereas stimulating the vestibular system in isolation requires significantly more technical effort. That is, the vestibular system is sensitive to both high-level sound and bone-conducted vibrations, but so is the cochlea, and gross electrical responses of the inner ear to such stimuli can be difficult to interpret. Fortunately, several simple techniques can be employed to isolate vestibular electrical responses. Here, we review the literature underpinning gross vestibular nerve and HC responses, and we discuss the nomenclature used in this field. We also discuss techniques for recording EVestG in experimental animals and humans and highlight how EVestG is furthering our understanding of the vestibular system
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene
Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic
factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for
rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant
locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically
involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions
- …