Local Dose Effects for Late Gastrointestinal Toxicity After Hypofractionated and Conventionally Fractionated Modern Radiotherapy for Prostate Cancer in the HYPRO Trial

Purpose: Late gastrointestinal (GI) toxicity after radiotherapy for prostate cancer may have significant impact on the cancer survivor's quality of life. To da

The Accidental Terrorist: Okhrana Connections to the Extreme-Right and the Attempt to Assassinate Sergei Witte in 1907

This article represents a case study in the relationship between the tsarist secret police (commonly known as the Okhrana in the West and okhranka in Russia) and acts of political terror perpetrated by the extreme-right in late imperial Russia. This specific case concerns the tangled web of conspiracy, propaganda and controversy that surrounded the attempted assassination of former-Chairman of the Council of Ministers, Sergei Witte, in 1907

The generalized non-conservative model of a 1-planet system - revisited

We study the long-term dynamics of a planetary system composed of a star and a planet. Both bodies are considered as extended, non-spherical, rotating objects. There are no assumptions made on the relative angles between the orbital angular momentum and the spin vectors of the bodies. Thus, we analyze full, spatial model of the planetary system. Both objects are assumed to be deformed due to their own rotations, as well as due to the mutual tidal interactions. The general relativity corrections are considered in terms of the post-Newtonian approximation. Besides the conservative contributions to the perturbing forces, there are also taken into account non-conservative effects, i.e., the dissipation of the mechanical energy. This dissipation is a result of the tidal perturbation on the velocity field in the internal zones with non-zero turbulent viscosity (convective zones). Our main goal is to derive the equations of the orbital motion as well as the equations governing time-evolution of the spin vectors (angular velocities). We derive the Lagrangian equations of the second kind for systems which do not conserve the mechanical energy. Next, the equations of motion are averaged out over all fast angles with respect to time-scales characteristic for conservative perturbations. The final equations of motion are then used to study the dynamics of the non-conservative model over time scales of the order of the age of the star. We analyze the final state of the system as a function of the initial conditions. Equilibria states of the averaged system are finally discussed.Comment: 37 pages, 13 figures, accepted to Celestial Mechanics and Dynamical Astronom

Association between incidental dose outside the prostate and tumor control after modern image-guided radiotherapy

Background and purpose: External beam radiotherapy for prostate cancer deposits incidental dose to a region surrounding the target volume. Previously, an association was identified between tumor control and incidental dose for patients treated with conventional radiotherapy. We investigated whether such an association exists for patients treated using intensity modulated radiotherapy (IMRT) and tighter margins. Materials and methods: Computed tomography scans and three-dimensional treatment planning dose distributions were available from the Dutch randomized HYPRO trial for 397 patients in the standard fractionation arm (39 × 2 Gy) and 407 patients in the hypofractionation arm (19 × 3.4 Gy), mainly delivered using online image-guided IMRT. Endpoint was any treatment failure within 5 years. A mapping of 3D dose distributions between anatomies was performed based on distance to the surface of the prostate delineation. Mean mapped dose distributions were computed for patient groups with and without failure, obtaining dose difference distributions. Random patient permutations were performed to derive p values and to identify relevant regions. Results: For high-risk patients treated in the conventional arm, higher incidental dose was significantly associated with a higher probability of tumor control in both univariate and multivariate analysis. The locations of the excess dose mainly o

Feasibility of a mobile and web-based intervention to support self-management in outpatients with cancer pain

Purpose: Cancer pain is a prevalent and distressing symptom. To enhance self-management in outpatients, a multi-component intervention was developed, integrating patient self-management and professional care through healthcare technology. This article describes feasibility of the intervention in everyday practice. Method: Patients with moderate to severe cancer pain (n = 11) and registered nurses specialized in pain and palliative care (n = 3) participated in a four-week study. The intervention involved daily monitoring, graphical feedback, education, and advice by means of a mobile application for patients and a web application for nurses. Learnability, usability and desirability were measured in patients with a 20-item questionnaire (1–5 scale), higher scores indicating better feasibility. Patients' adherence was based on completion rates from server logs. Single semi-structured interviews with patients and a focus group interview with nurses provided insight into experiences. Results: Questionnaire findings confirmed learnability (4.8), usability (4.8) and desirability (4.6) of the application for patients. Average completion rates were 76.8% for pain monitoring, 50.4% for medication monitoring and 100% for education sessions. Interviews revealed that patients were pleased with the simplicity of the mobile application and appreciated different components. Nurses agreed upon the added value and were mostly positive about the possibilities of the web application. Patients and nurses provided ideas for improvements relating to the content and technical performance of the intervention. Conclusions: Study results demonstrate feasibility of the intervention in everyday practice. Provided that content-related and technical adjustments are made, the intervention enables patients with cancer pain to practice self-management and nurses to remotely support these patients

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters

Microbial Biotechnolog

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC