Relative survival in early-stage cancers in the Netherlands: a population-based study

In this nationwide, population-based study, we assessed 10-year relative survival among 225,305 patients with ten early-stage cancers diagnosed in the Netherlands during 2004-2015. This study aimed to ascertain which early-stage cancer is associated with minimal or no excess mortality and likely to be diagnosed in individuals who are otherwise more healthy or health-conscious than their counterparts in the general population. Ten-year relative survival marginally exceeded 100% in patients with early-stage prostate cancer, while it was close to 100% for patients with ductal carcinoma in situ (DCIS) and stage I cancers of the breast, skin (melanoma), testis, and thyroid. In contrast, patients with early-stage oral/pharyngeal, bladder, lung, and pancreatic cancers experienced considerable excess mortality, reflected by a 10-year relative survival of 74.9%, 69.4%, 45.5%, and 33.9%, respectively. Collectively, the life expectancy of patients with DCIS and early-stage cancers of the prostate, breast, skin (melanoma), testis, and thyroid parallels the expected survival of an age-, sex-, and calendar year-matched group from the general population. Our study findings add to the controversy surrounding overdiagnosis of particular early-stage cancers that are generally not destined to metastasis or cause excess mortality

Waiting Time from Diagnosis to Treatment has no Impact on Survival in Patients with Esophageal Cancer

Background Waiting time from diagnosis to treatment has emerged as an important quality indicator in cancer care. This study was designed to determine the impact of waiting time on long-term outcome of patients with esophageal cancer who are treated with neoadjuvant therapy followed by surgery or primary surgery. Methods Patients who underwent esophagectomy for esophageal cancer at the University Medical Center Utrecht between 2003 and 2014 were included. Patients treated with neoadjuvant therapy followed by surgery and treated with primary surgery were separately analyzed. The influence of waiting time on survival was analyzed using Cox proportional hazard analyses. Kaplan–Meier curves for short (<8 weeks) and long (≥8 weeks) waiting times were constructed. Results A total of 351 patients were included; 214 received neoadjuvant treatment, and 137 underwent primary surgery. In the neoadjuvant group, the waiting time had no impact on disease-free survival (DFS) [hazard ratio (HR) 0.96, 95 % confidence interval (CI) 0.88–1.04; p = 0.312] or overall survival (OS) (HR 0.96, 95 % CI 0.88–1.05; p = 0.372). Accordingly, no differences were found between neoadjuvantly treated patients with waiting times of <8 and ≥8 weeks in terms of DFS (p = 0.506) and OS (p = 0.693). In the primary surgery group, the waiting time had no impact on DFS (HR 1.03, 95 % CI 0.95–1.12; p = 0.443) or OS (HR 1.06, 95 % CI 0.99–1.13; p = 0.108). Waiting times of <8 weeks versus ≥8 weeks did not result in differences regarding DFS (p = 0.884) or OS (p = 0.374). Conclusions In esophageal cancer patients treated with curative intent by either neoadjuvant therapy followed by surgery or primary surgery, waiting time from diagnosis to treatment has no impact on long-term outcom

The risk of overanticoagulation in patients with heart failure on coumarin anticoagulants

Heart failure has been identified as a risk factor for increased coumarin anticoagulant responsiveness in several small-scale experiments. Epidemiological studies quantifying the risk of overanticoagulation by heart failure in a non-selected population on coumarins are scarce. Therefore, we investigated whether patients with heart failure have an increased risk of overanticoagulation and determined the effect of incidental heart failure on coumarin dose requirements. A cohort study of all patients was performed from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon between 1 January 1990 and 1 January 2000. All cohort members were followed until the first occurrence of an international normalized ratio (INR) ≥6.0, the last INR assessment, death, loss to follow-up, or end of the study period. Of the 1077 patients in the cohort, 396 developed an INR ≥6.0. The risk of overanticoag

Model of hopping dc conductivity via nearest neighbor boron atoms in moderately compensated diamond crystals

Expressions for dependences of the pre-exponential factor \sigma_3 and the thermal activation energy \epsilon_3 of hopping electric conductivity of holes via boron atoms on the boron atom concentration N and the compensation ratio K are obtained in the quasiclassical approximation. It is assumed that the acceptors (boron atoms) in charge states (0) and (-1) and the donors that compensate them in the charge state (+1) form a nonstoichiometric simple cubic lattice with translational period R_h = [(1 + K)N]^{-1/3} within the crystalline matrix. A hopping event occurs only over the distance R_h at a thermally activated accidental coincidence of the acceptor levels in charge states (0) and (-1). Donors block the fraction K/(1 - K) of impurity lattice sites. The hole hopping conductivity is averaged over all possible orientations of the lattice with respect to the external electric field direction. It is supposed that an acceptor band is formed by Gaussian fluctuations of the potential energy of boron atoms in charge state (-1) due to Coulomb interaction only between the ions at distance R_h. The shift of the acceptor band towards the top of the valence band with increasing N due to screening (in the Debye--H\"uckel approximation) of the impurity ions by holes hopping via acceptor states was taken into account. The calculated values of \sigma_3(N) and \epsilon_3(N) for K \approx 0.25 agree well with known experimental data at the insulator side of the insulator--metal phase transition. The calculation is carried out at a temperature two times lower than the transition temperature from hole transport in v-band of diamond to hopping conductance via boron atoms.Comment: 6 pages, 2 figure

High-precision prostate cancer irradiation by clinical application of an offline patient setup verification procedure, using portal imaging

Purpose: To investigate in three institutions, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis [AvL]), Dr. Daniel den Hoed Cancer Center (DDHC), and Dr. Bernard Verbeeten Institute (BVI), how much the patient setup accuracy for irradiation of prostate cancer can be improved by an offline setup verification and correction procedure, using portal imaging. Methods and Materials: The verification procedure consisted of two stages. During the first stage, setup deviations were measured during a number (N(max)) of consecutive initial treatment sessions. The length of the average three dimensional (3D) setup deviation vector was compared with an action level for corrections, which shrunk with the number of setup measurements. After a correction was applied, N(max) measurements had to be performed again. Each institution chose different values for the initial action level (6, 9, and 10 mm) and N(max) (2 and 4). The choice of these parameters was based on a simulation of the procedure, using as input preestimated values of random and systematic deviations in each institution. During the second stage of the procedure, with weekly setup measurements, the AvL used a different criterion ('outlier detection') for corrective actions than the DDHC and the BVI ('sliding average'). After each correction the first stage of the procedure was restarted. The procedure was tested for 151 patients (62 in AvL, 47 in DDHC, and 42 in BVI) treated for prostate carcinoma. Treatment techniques and portal image acquisition and analysis were different in each institution. Results: The actual distributions of random and systematic deviations without corrections were estimated by eliminating the effect of the corrections. The percentage of mean (systematic) 3D deviations larger than 5 mm was 26% for the AvL and the DDHC, and 36% for the BVI. The setup accuracy after application of the procedure was considerably improved (percentage of mean 3D deviations larger than 5 mm was 1.6% in the AvL and 0% in the DDHC and BVI), in agreement with the results of the simulation. The number of corrections (about 0.7 on the average per patient) was not larger than predicted. Conclusion: The verification procedure appeared to be feasible in the three institutions and enabled a significant reduction of mean 3D setup deviations. The computer simulation of the procedure proved to be a useful tool, because it enabled an accurate prediction of the setup accuracy and the required number of corrections

High-Redshift Cosmography

We constrain the parameters describing the kinematical state of the universe using a cosmographic approach, which is fundamental in that it requires a very minimal set of assumptions (namely to specify a metric) and does not rely on the dynamical equations for gravity. On the data side, we consider the most recent compilations of Supernovae and Gamma Ray Bursts catalogues. This allows to further extend the cosmographic fit up to $z = 6.6$, i.e. up to redshift for which one could start to resolve the low z degeneracy among competing cosmological models. In order to reliably control the cosmographic approach at high redshifts, we adopt the expansion in the improved parameter $y = z/(1+z)$. This series has the great advantage to hold also for $z > 1$ and hence it is the appropriate tool for handling data including non-nearby distance indicators. We find that Gamma Ray Bursts, probing higher redshifts than Supernovae, have constraining power and do require (and statistically allow) a cosmographic expansion at higher order than Supernovae alone. Exploiting the set of data from Union and GRBs catalogues, we show (for the first time in a purely cosmographic approach parametrized by deceleration $q_0$, jerk $j_0$, snap $s_0$) a definitively negative deceleration parameter $q_0$ up to the 3$\sigma$ confidence level. We present also forecasts for realistic data sets that are likely to be obtained in the next few years.Comment: 16 pages, 6 figures, 3 tables. Improved version matching the published one, additional comments and reference

Stability of Circular Orbits in General Relativity: A Phase Space Analysis

Phase space method provides a novel way for deducing qualitative features of nonlinear differential equations without actually solving them. The method is applied here for analyzing stability of circular orbits of test particles in various physically interesting environments. The approach is shown to work in a revealing way in Schwarzschild spacetime. All relevant conclusions about circular orbits in the Schwarzschild-de Sitter spacetime are shown to be remarkably encoded in a single parameter. The analysis in the rotating Kerr black hole readily exposes information as to how stability depends on the ratio of source rotation to particle angular momentum. As a wider application, it is exemplified how the analysis reveals useful information when applied to motion in a refractive medium, for instance, that of optical black holes.Comment: 20 pages. Accepted for publication in Int. J. theor. Phy

BPS Domain Wall Junctions in Infinitely Large Extra Dimensions

We consider models of scalar fields coupled to gravity which are higher-dimensional generalizations of four dimensional supergravity. We use these models to describe domain wall junctions in an anti-de Sitter background. We derive Bogomolnyi equations for the scalar fields from which the walls are constructed and for the metric. From these equations a BPS-like formula for the junction energy can be derived. We demonstrate that such junctions localize gravity in the presence of more than one uncompactified extra dimension.Comment: 17 pages, uses RevTeX, new references adde

Bosonic Fields in the String-like Defect Model

We study localization of bosonic bulk fields on a string-like defect with codimension 2 in a general space-time dimension in detail. We show that in cases of spin 0 scalar and spin 1 vector fields there are an infinite number of massless Kaluza-Klein (KK) states which are degenerate with respect to the radial quantum number, but only the massless zero mode state among them is coupled to fermion on the string-like defect. It is also commented on interesting extensions of the model at hand to various directions such as 'little' superstring theory, conformal field theory and a supersymmetric construction.Comment: 17 pages, LaTex 2e, revised version (to appear in Phys. Rev. D