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The Kalman filter is a well-established approach to get information on the time-dependent state of a system from noisy observations. It was developed in the context of the Apollo project to see the deviation of the true trajectory of a rocket from the desired trajectory. Afterwards it was applied to many different systems with small numbers of components of the respective state vector (typically about 10). In all cases the equation of motion for the state vector was known exactly. The fast dissipative magnetization dynamics is often investigated by x-ray magnetic circular dichroism movies (XMCD movies), which are often very noisy. In this situation the number of components of the state vector is extremely large (about 10(5)), and the equation of motion for the dissipative magnetization dynamics (especially the values of the material parameters of this equation) is not well known. In the present paper it is shown by theoretical considerations that - nevertheless - there is no principle problem for the use of the Kalman filter to denoise XMCD movies of fast dissipative magnetization dynamics.

Purpose To determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer. Patients and methods Forty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1 and infusional 5-fluorouracil 750 mg/m2/day on days 1–5 followed by radiotherapy plus C at 250 mg/m2/week (after an initial loading dose of 400 mg/m2). Results After completion of ICT 44 of 49 patients received radiotherapy plus C. Three months after therapy completion tumour response was observed in 33 patients and after two years, 25 patients were in complete remission (CR). The most common grade 4 toxicity during the whole treatment period was dermatitis (30%), followed by mucositis (27%) and neutropenia (17%) without fever. One toxic related death was observed during ICT. Two-year progression-free survival (PFS) rate was 59% and two-year overall survival (OS) rate was 63%, respectively. Conclusion Concurrent radiotherapy plus C after three courses of ICT was feasible and was associated with promising CR, PFS and OS rates. Further optimisation of dose and sequence is warranted.

We study a two-locus model of a quantitative trait with a continuum-of alleles and multilinear epistasis that evolves under mutation, selection, and genetic drift. We derive analytical results based on the so-called House of Gauss approximation for the genetic variance, the mean phenotype, and the mutational variance in the balance of the evolutionary forces. The analytical work is complemented by extensive individual-based computer simulations. We find that (1) analytical results are accurate in a large parameter space; (2) epistasis always reduces the equilibrium genetic variance, as predicted in earlier studies that exclude drift; (3) large-scale stochastic fluctuations and non-equilibrium phenomena like adaptive inertia can strongly influence the evolution of the genetic architecture of the trait.

We investigate the dynamic effects of an inducible prey defense in the Nicholson-Bailey predator-prey model. We assume that the defense is of all-or-nothing type but that the probability for a prey individual to express the defended phenotype increases gradually with predator density. Compared to a defense that is independent of predation risk, an inducible defense facilitates persistence of the predator-prey system. In particular, inducibility reduces the minimal strength of the defense required for persistence. It also promotes stability by damping predator-prey cycles, but there are exceptions to this result: first, a strong inducible defense leads to the existence of multiple equilibria, and sometimes, to the destruction of stable equilibria. Second, a fast increase in the proportion of defended prey can create predator-prey cycles as the result of an over-compensating negative feedback. Non-equilibrium dynamics of the model are extremely complex.

Purpose Neointimal hyperplasia is one of the limiting factors in infrainguinal prosthetic vascular grafting. We conducted a pilot study to assess the possible role of radiotherapy for the prevention of this proliferating cellular process. Methods and materials Ten patients (7 men, 3 women; median age: 73 years) suffering from critical leg ischemia were treated by infrainguinal revascularization using 6-mm polytetrafluoroethylene. Postoperative radiation therapy of the anastomotic sites started within 24 h. A dose of 20.4 Gy was delivered in 12 fractions in 2.5 weeks by external beam radiation with electrons. The target volume was defined as the clip-marked anastomotic region plus a 1.5-cm safety margin in each direction. Results Radiation therapy was technically feasible in all cases without radiation-related side effects. In one patient, radiotherapy had to be terminated prematurely, because of a hematoma at the distal anastomotic site with consequent skin necrosis. One patient developed an occlusion of a suprainguinal graft without anastomotic stenosis after 9 months; 2 other grafts occluded at 12-month intervals. At a median follow-up of 16 months, the remaining 6 patients had no signs of restenosis. Conclusions The restenosis rate of peripheral vascular grafts after external beam radiation was lower than expected without additional treatment. The value of this approach will now be determined in a randomized prospective trial.

The mammalian hypothalamic suprachiasmatic nucleus (SCN) is an endogenous pacemaker generating circadian rhythms. SCN activity is synchronized with environmental light/dark cycles by photic information primarily transmitted via the retinohypothalamic tract (RHT). The SCN controls synthesis and release of melatonin, the hormone of the pineal gland. Melatonin itself feeds back to the SCN. Using brain slice technique and immunocytochemistry we demonstrate that (1) pituitary adenylate cyclase-activating polypeptide (PACAP) induces the phosphorylation of the transcription factor cAMP response element binding protein (CREB) in the SCN during late subjective day and (2) melatonin inhibits this PACAP-induced phosphorylation. Our data suggest that PACAP is a neurotransmitter which affects gene expression in the SCN probably via the cAMP signaling pathway and that the antagonistic effect of melatonin mirrors a feed-back loop within the circadian system.

Jayant Vaidya and colleagues (July 10, p 91) suggest that a single dose of targeted intraoperative radiotherapy (TARGIT) should be considered as an alternative to external-beam radiotherapy delivered over several weeks for selected patients with breast cancer. We consider the results of this trial preliminary and immature since the follow-up is much too short to draw any conclusions about local recurrence rates. The fi nding in this trial that most local recurrences occur in years 2 and 3 do not imply that local recurrences after this time will not occur. When using an orthovoltage technique with a very low-dose penetration to a depth of 1 cm, the rate of in-breast recurrences has to be observed extremely carefully in the long term. The median time to true local recurrences is somewhere between 40 months and 65 months, and out-quadrant relapses occur later than that. Furthermore, the Kaplan-Meier plots in fi gure 4 show that, of 2232 patients at risk, only 420 (19%) completed 4-year follow-up (212 in the TARGIT group). Of these 212 patients, only 86% received intra operative radio therapy alone, meaning that about 14% received external-beam radiotherapy as well. 65% of patients also received endocrine treatment, which is known to be associated with a signifi cant decrease or at least delay in the rate of local recurrences, which become apparent after more than 5 years’ follow-up. Another area of concern is the postpathology stratum: 672 patients had a postpathology entry to the trial, meaning that about 336 patients allocated to TARGIT (most of the Danish and the Australian patients) were referred for a second surgical procedure. In those cases, targeted intraoperative radiotherapy was not an intraoperative treatment in the classic sense—a second surgical procedure had to be done for no reason other than the application of the radiation therapy. Overall, we advise against the use of targeted intraoperative radiotherapy as a single shot outside a clinical trial until the long-term follow-up data for non-inferiority are available.