Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial.

Purpose/Objectives: To analyze the long term efficacy and safety of an ultra-hypofractionated (UHF) radiation therapy prostate treatment regimen with HDR brachytherapy boost (BB) and compare it to moderate-hypofractionated regimens (MHF). Materials/Methods: In this single arm, prospective monocentric study, 28 patients with intermediate risk prostate cancer were recruited in an experimental treatment arm of 25 Gy in 5 fractions plus a 15 Gy HDR BB. They were then compared to two historical control groups, treated with either 36 Gy in 12 fractions or 37.5 Gy in 15 fractions with a similar HDR BB. The control groups included 151 and 311 patients respectively. Patient outcomes were reported using the International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC-26) questionnaires at baseline and at each follow-up visit. Results: Median follow-up for the experimental arm was 48.5 months compared to 47 months and 60 months compared to the 36/12 and 37,5/15 groups respectively. The IPSS and EPIC scores did not demonstrate any significant differences in the gastrointestinal or genitourinary domains between the three groups over time. No biochemical recurrence occurred in the UHF arm as defined by the Phoenix criterion. Conclusion: The UHF treatment scheme with HDR BB seems equivalent to standard treatment arms in terms of toxicities and local control. Randomized control trials with larger cohorts are ongoing and needed to further confirm our findings.

Experimental Observation of Classical Dynamical Monodromy.

A Hamiltonian system is said to have nontrivial monodromy if its fundamental action-angle loops do not return to their initial topological state at the end of a closed circuit in angular momentum-energy space. This process has been predicted to have consequences which can be seen in dynamical systems, called dynamical monodromy. Using an apparatus consisting of a spherical pendulum subject to magnetic potentials and torques, we observe nontrivial monodromy by the associated topological change in the evolution of a loop of trajectories.

Melatonin and cortisol profiles in the absence of light perception.

As light plays an important role in the synchronisation of the internal biological clock to the environmental day/night schedule, we compared the 24-h profiles of biological circadian markers in blind and normal sighted individuals. Salivary melatonin and cortisol concentrations were collected every two hours in eleven blind subjects, reporting no conscious light perception, and eleven age- and sex-matched normal sighted controls. Timing of melatonin onset and associated cortisol quiescence period confirm an increased incidence of abnormal circadian patterns in blindness. Additionally, blind subjects showed a greater overall melatonin concentration throughout the 24-h period. Cortisol profiles, including concentration and morning cortisol peaks, on the other hand, did not differ between blind and sighted individuals. These findings support previous reports of an increase in abnormal circadian rhythms and the absence of the entrainment properties of light in blindness.

Altered sleep-wake patterns in blindness: a combined actigraphy and psychometric study.

OBJECTIVE: Light plays an important role in the synchronization of the internal biological clock and the environmental day/night pattern. Thus, absence of vision is often associated with both increases in reported sleep disturbances and incidence of free-running circadian rhythms. In this study we discuss variability in the sleep-wake pattern between blind and normal-sighted individuals. METHODS: Thirty-day actigraphy recordings were collected from 11 blind individuals without residual light perception and 11 age- and sex-matched normal-sighted controls. From these recordings, we extracted parameters of sleep and wake, including episodes of rest, day-time and night-time sleep periods, and the number of awakenings throughout sleep. A measure of sleep efficiency was derived from these measures for each night-time sleep episode. We also examined complementary measures of sleep quality, using the Pittsburgh Sleep Quality Index, and chronotype, using the Morningness-Eveningness Questionnaire. RESULTS: Although no group differences were found when averaging over the entire recording period, we found a greater variability throughout the 30-days in both sleep efficiency and timing of the night-time sleep episode in blind participants as compared to sighted control participants. We also confirm previous reports of reduced sleep quality in blind individuals. Notably, the variability in sleep efficiency and in the timing of sleep correlated with the severity of sleep disturbances. CONCLUSION: The timing and physiology of sleep are strongly dependent on the endogenous circadian phase; therefore, observed findings support the hypothesis of free-running circadian rhythms as a dominant factor for the sleep disturbances experienced in blindness.

Adolescent and young adult cancer: principles of care.

Adolescents and young adults (ayas) with cancer in active treatment face a number of barriers to optimal care. In the present article, we focus on the 3 critical domains of care for ayas-medical, psychosocial, and research-and how changes to the system could overcome barriers. We summarize the current literature, outline recommended principles of care, raise awareness of barriers to optimal care, and suggest specific changes to the system to overcome those barriers in the Canadian context. Many of the recommendations can nevertheless be applied universally. These recommendations are endorsed by the Canadian Task Force on Adolescents and Young Adults with Cancer and build on outcomes from two international workshops held by that group.

Hyperfine Anomalies in Fr: Boundaries of the Spherical Single Particle Model.

We have measured the hyperfine splitting of the 7P_{1/2} state at the 100 ppm level in Fr isotopes (^{206g,206m,207,209,213,221}Fr) near the closed neutron shell (N=126 in ^{213}Fr). The measurements in five isotopes and a nuclear isomeric state of francium, combined with previous determinations of the 7S_{1/2} splittings, reveal the spatial distribution of the nuclear magnetization, i.e., the Bohr-Weisskopf effect. We compare our results with a simple shell model consisting of unpaired single valence nucleons orbiting a spherical nucleus, and find good agreement over a range of neutron-deficient isotopes (^{207-213}Fr). Also, we find near-constant proton anomalies for several even-N isotopes. This identifies a set of Fr isotopes whose nuclear structure can be understood well enough for the extraction of weak interaction parameters from parity nonconservation studies.

Atom chip apparatus for experiments with ultracold rubidium and potassium gases.

We present a dual chamber atom chip apparatus for generating ultracold (87)Rb and (39)K atomic gases. The apparatus produces quasi-pure Bose-Einstein condensates of 10(4) (87)Rb atoms in an atom chip trap that features a dimple and good optical access. We have also demonstrated production of ultracold (39)K and subsequent loading into the chip trap. We describe the details of the dual chamber vacuum system, the cooling lasers, the magnetic trap, the multicoil magnetic transport system, the atom chip, and two optical dipole traps. Due in part to the use of light-induced atom desorption, the laser cooling chamber features a sufficiently good vacuum to also support optical dipole trap-based experiments. The apparatus is well suited for studies of atom-surface forces, quantum pumping and transport experiments, atom interferometry, novel chip-based traps, and studies of one-dimensional many-body systems.

Dynamical monodromy.

Integrable Hamiltonian systems are said to display nontrivial monodromy if fundamental action-angle loops defined on phase-space tori change their topological structure when the system is carried around a circuit. In an earlier paper it was shown that this topological change can occur as a result of time evolution under certain rather abstract flows in phase space. In the present paper, we show that the same topological change can occur as a result of application of ordinary forces. We also show how this dynamical phenomenon could be observed experimentally in classical or in quantum systems.

Note: fast, small, and low vibration mechanical laser shutters.

We present three novel mechanical laser shutter designs based, respectively, on a stepper motor, a relay, and a piezoelectric actuator. Each shutter type is ideally suited to a specific shuttering application. The stepper motor is well suited for applications requiring low vibrations, the relay is compact and capable of rapid bursts, and the piezoelectric is 2 orders of magnitude faster than other available mechanical shutters.

Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer.

PURPOSE: Men with prostate-specific antigen (PSA)-only relapse of prostate cancer after primary therapy are generally fully functional and asymptomatic with a life expectancy of up to 10 or more years. Androgen deprivation therapy (ADT) is a common treatment option. This study examined mood and cognitive changes in otherwise healthy men with prostate cancer prior to, during and after ADT. EXPERIMENTAL DESIGN: Twenty hormone naïve, eugonadal prostate cancer patients without evidence of metastases and with a rising PSA were treated with intermittent ADT consisting of 9 months of complete androgen blockade (CAB) achieved with combined leuprolide and flutamide followed by an 'off treatment' period. Cognitive function tests and mood measures were administered at baseline, after 3 and 9 months of ADT and after 3 months of no treatment. Twenty healthy control patients without prostate cancer range matched for age and education were tested at the same time intervals. RESULTS: ADT patients evidenced a significant decline in spatial reasoning, spatial abilities and working memory during treatment compared with baseline. No changes were noted for measures of verbal or spatial memory, selective attention or language. Significant changes in self-rated mood such as increased depression, tension, anxiety, fatigue and irritability were evident during treatment compared with baseline for ADT patients. No significant changes in either cognitive tests or mood measures were noted for the healthy control group. CONCLUSIONS: These findings, suggest that 9 months of combined androgen blockade may result in some adverse changes in cognition and mood. However, many but not all of these changes can return to baseline after cessation of ADT.

Nuclear magnetic moment of 210Fr: a combined theoretical and experimental approach.

We measure the hyperfine splitting of the 9S_{1/2} level of 210Fr, and find a magnetic dipole hyperfine constant A=622.25(36) MHz. The theoretical value, obtained using the relativistic all-order method from the electronic wave function at the nucleus, allows us to extract a nuclear magnetic moment of 4.38(5)micro_{N} for this isotope, which represents a factor of 2 improvement in precision over previous measurements. The same method can be applied to other rare isotopes and elements.

Poster - Thurs Eve-39: Full 3D dose calculation for total body irradiation: A comparison study between treatment planning systems in homogeneous and heterogeneous conditions.

PURPOSE: To perform full 3D heterogeneous dose calculations for total body irradiation (TBI) cases and compare different treatment planning softwares (TPS). METHOD: A retrospective study was performed on 7 patients. Dose distributions obtained with Pinnacle3 v.7.9u (Philips Medical Systems) were compared with the ones calculated using our actual TBI planning system Theraplan Plus (TPP) by MDS Nordion/Nucletron. Two different Pinnacle3 models were studied: standard beam commissioning (std_Pinnacle3 ) and TBI commissioning (TBI_Pinnacle3 ). For the later case, commissioning was adapted for the special TBI conditions (extended SSD of 190cm, large field, acrylic beam spoiler, and out of field dose (OFD)). RESULTS: Significant differences are found between the TPP, std_Pinnacle3 and TBI_Pinnacle3 dose distributions. For the relative mid-line doses, differences up to 12% were observed. Systematic overestimations of 5% were found in patients extremities between TPP and TBI_Pinnacle3 . Average dose underestimation of 3% was observed between std_Pinnacle3 and TBI_Pinnacle3 . Differences in patient extremities are attributed to the OFD contribution which is not correctly computed in TPP and std_Pinnacle3 . Dose comparison outside the patient's mid-line showed greater differences (up to 20%) between models. Accurate 3D heterogeneous dose calculations with TBI_Pinnacle3 model show major differences (homogeneous versus heterogeneous) in high and low density regions. Dose overestimation of 5% was observed in bony regions and dose underestimation of 5% to 10% was observed in lung regions. CONCLUSION: Those results are of major interest since they show a strong dependence of the dose calculation outcome on both TPS and commissioning used, potentially leading to significant dose misevaluation.

Lifetime measurement of the 9s level of atomic francium.

We use two-photon resonant excitation and time-correlated single-photon counting techniques on a sample of 210Fr atoms confined and cooled in a magneto-optical trap to measure the lifetime of the 9s excited level. Direct measurement of the decay through the 7P(3/2) level at 851 nm yields a lifetime of 107.53 +/- 0.80 ns.

Robustness and precision of an automatic marker detection algorithm for online prostate daily targeting using a standard V-EPID.

An algorithm for the daily localization of the prostate using implanted markers and a standard video-based electronic portal imaging device (V-EPID) has been tested. Prior to planning, three gold markers were implanted in the prostate of seven patients. The clinical images were acquired with a BeamViewPlus 2.1 V-EPID for each field during the normal course radiotherapy treatment and are used off-line to determine the ability of the automatic marker detection algorithm to adequately and consistently detect the markers. Clinical images were obtained with various dose levels from ranging 2.5 to 75 MU. The algorithm is based on marker attenuation characterization in the portal image and spatial distribution. A total of 1182 clinical images were taken. The results show an average efficiency of 93% for the markers detected individually and 85% for the group of markers. This algorithm accomplishes the detection and validation in 0.20-0.40 s. When the center of mass of the group of implanted markers is used, then all displacements can be corrected to within 1.0 mm in 84% of the cases and within 1.5 mm in 97% of cases. The standard video-based EPID tested provides excellent marker detection capability even with low dose levels. The V-EPID can be used successfully with radiopaque markers and the automatic detection algorithm to track and correct the daily setup deviations due to organ motions.

Magnetic-field-dependent heat capacity of the single-molecule magnet [Mn(12)O(12)(O(2)CEt)(16)(H(2)O)(3)].

Accurate heat capacities of the single-molecule magnet [Mn(12)O(12)(O(2)CEt)(16)(H(2)O)(3)] were measured from 0.3 to 311 K by adiabatic calorimetry without an external magnetic field. Heat-capacity anomalies were separated by assuming several contributions including lattice vibration, magnetic anisotropy, and hyperfine splitting. Among them, a tiny thermal anomaly between 1 and 2 K is attributable to the presence of Jahn-Teller isomers. The heat capacities of the polycrystalline sample were also measured with applied magnetic fields from 0 to 9 T in the 2-20 K temperature region by the relaxation method. With an applied magnetic field of up to 2 T, a steplike heat-capacity anomaly was observed around the blocking temperature T(B) approximately 3.5 K. The magnitude of the anomaly reached a maximum at 0.7 T. With a further increase in the magnetic field, the step was decreasing, and finally it disappeared above 3 T. The step at T(B) under 0.7 T can be roughly accounted for by assuming that a conversion between the up-spin and down-spin states is allowed above T(B) by phonon-assisted quantum tunneling, while it is less effective below T(B). Excess heat capacity under a magnetic field revealed a large heat-capacity hump around 14 K and 2 T, which would be attributed to a thermal excitation from the S = 9 ground state to the spin manifold with different S values, where S is the total spin quantum number.

A randomized, controlled, single-blind trial of teaching provided by a computer-based multimedia package versus lecture.

BACKGROUND: Computer-based teaching may allow effective teaching of important psychiatric knowledge and skills. AIMS: To investigate the effectiveness and acceptability of computer-based teaching. METHOD: A single-blind, randomized, controlled study of 166 undergraduate medical students at the University of Leeds, involving an educational intervention of either a structured lecture or a computer-based teaching package (both of equal duration). RESULTS: There was no difference in knowledge between the groups at baseline or immediately after teaching. Both groups made significant gains in knowledge after teaching. Students who attended the lecture rated their subjective knowledge and skills at a statistically significantly higher level than students who had used the computers. Students who had used the computer package scored higher on an objective measure of assessment skills. Students did not perceive the computer package to be as useful as the traditional lecture format, despite finding it easy to use and recommending its use to other students. CONCLUSIONS: Medical students rate themselves subjectively as learning less from computer-based as compared with lecture-based teaching. Objective measures suggest equivalence in knowledge acquisition and significantly greater skills acquisition for computer-based teaching.

Single-molecule magnets: Jahn-Teller isomerism and the origin of two magnetization relaxation processes in Mn12 complexes.

Several single-molecule magnets with the composition [Mn12O12(O2CR)16(H2O)x] (x = 3 or 4) exhibit two out-of-phase ac magnetic susceptibility signals, one in the 4-7 K region and the other in the 2-3 K region. New Mn12 complexes were prepared and structurally characterized, and the origin of the two magnetization relaxation processes was systematically examined. Different crystallographic forms of a Mn12 complex with a given R substituent exist where the two forms have different compositions of solvent molecules of crystallization and this results in two different arrangements of bound H2O and carboxylate ligands for the two crystallographically different forms with the same R substituent. The X-ray structure of cubic crystals of [Mn12O12(O2CEt)16(H2O)3]. 4H2O (space group P1) (complex 2a) has been reported previously. The more prevalent needle-form of [Mn12O12(O2CEt)16(H2O)3] (complex 2b) crystallizes in the monoclinic space group P2(1)/c, which at -170 degrees C has a = 16.462(7) A, b = 22.401(9) A, c = 20.766(9) A, beta = 103.85(2) degrees, and Z = 4. The arrangements of H2O and carboxylate ligands on the Mn12 molecule are different in the two crystal forms. The complex [Mn12O12-(O2)CC6H4-p-Cl)16(H2O)4].8CH2Cl2 (5) crystallizes in the monoclinic space group C2/c, which at -172 degrees C has a = 29.697(9) A, b = 17.708(4) A, c = 30.204(8) A, beta = 102.12(2) degrees, and Z = 4. The ac susceptibility data for complex 5 show that it has out-of-phase signals in both the 2-3 K and the 4-7 K ranges. X-ray structures are also reported for two isomeric forms of the p-methylbenzoate complex. [Mn12O12(O2CC6H4-p-Me)16(H2O)4]. (HO2CC6H4-p-Me) (6) crystallizes in the monoclinic space group C2/c, which at 193 K has a = 40.4589(5) A, b = 18.2288(2) A, c = 26.5882(4) A, beta = 125.8359(2) degrees, and Z = 4. [Mn12O12(O2CC6H4-p-Me)16(H2O)4].3(H2O) (7) crystallizes in the monoclinic space group I2/a, which at 223 K has a = 29.2794(4) A, b = 32.2371(4) A, c = 29.8738(6) A, beta = 99.2650(10) degrees, and Z = 8. The Mn12 molecules in complexes 6 and 7 differ in their arrangements of the four bound H2O ligands. Complex 6 exhibits an out-of-phase ac peak (chi(M)' ') in the 2-3 K region, whereas the hydrate complex 7 has a chi(M)' ' signal in the 4-7 K region. In addition, however, in complex 6, one Mn(III) ion has an abnormal Jahn-Teller distortion axis oriented at an oxide ion, and thus 6 and 7 are Jahn-Teller isomers. This reduces the symmetry of the core of complex 6 compared with complex 7. Thus, complex 6 likely has a larger tunneling matrix element and this explains why this complex shows a chi(M)' ' signal in the 2-3 K region, whereas complex 7 has its chi(M)' ' peak in the 4-7 K region, i.e., the rate of tunneling of magnetization is greater in complex 6 than complex 7. Detailed 1H NMR experiments (2-D COSY and TOCSY) lead to the assignment of all proton resonances for the benzoate and p-methyl-benzoate Mn12 complexes and confirm the structural integrity of the (Mn12O12) complexes upon dissolution. In solution there is rapid ligand exchange and no evidence for the different isomeric forms of Mn12 complexes seen in the solid state.

Benzo[b]fluoranthene, a potential alternative to benzo[a]pyrene as an indicator of exposure to airborne PAHs in the vicinity of Söderberg aluminum smelters.

Benzo[b]fluoranthene (B[b]F) was used in relative abundance ratios (RARs), a parameter obtained by dividing the concentration of individual polycyclic aromatic hydrocarbons (PAHs) found in a given sample by the concentration of B[b]F in the same sample. The B[b]F RARs were derived for PAH concentrations measured at stacks and sampling stations in the vicinity of two Söderberg aluminum horizontal stud smelters (HSSs). The samples collected were analyzed by high-performance liquid chromatography using UV and fluorescence detection. A total of 15 PAHs were analyzed, but, due to the inefficiency of the sampling method used in collecting gaseous PAHs, only particulate PAHs were considered. Comparisons between the B[b]F RARs obtained simultaneously at the source (stack) and those obtained at sampling stations at the two smelters showed that B[b]F degrades more slowly than or at the same rate as most other particulate PAHs monitored. Twenty-three months of urban sampling in the vicinity of one of the aluminum HSSs are also presented, and the results indicate that B[b]F is more stable than all other particulate PAHs investigated. Sampling conducted during a smelter shutdown period confirmed that B[b]F was a much better marker of this source than was benzo[a]pyrene (B[a]P), the usual indicator. The remarkable stability of the benzo[k]fluoranthene (B[k]F)/B[b]F ratio is also discussed.

Massive isotretinoin intoxication.

We report a case of acute intoxication due to a massive overdose of isotretinoin. A 29-year-old male patient ingested 900 mg of isotretinoin corresponding to 12.5 mg (kg/day) or 30 times the prescribed dosage and 1 day later the patient experienced mild headache. Forty-eight hours later, cheilitis, diffuse cutaneous xerosis and desquamation of the forehead and of the external auditory meatus occurred; cutaneous xerosis and cheilitis resolved spontaneously, We determined the serum level of isotretinoin and of 4-oxo-isotretinoin, its natural metabolite in sera taken 4, 5, 6 and 11 days following ingestion. The side-effects were mild and represented only exacerbations of some common isotretinoin side-effects. To date, three other cases of isotretinoin overdosage have been reported. There was a low toxicity of isotretinoin overdose.