Analytic non-adiabatic derivative coupling terms for spin-orbit MRCI wavefunctions. II. Derivative coupling terms and coupling angle for KHeA2Π1/2⇔KHeB2Σ1/2.

A method for calculating the analytic nonadiabatic derivative coupling terms (DCTs) for spin-orbit multi-reference configuration interaction wavefunctions is reviewed. The results of a sample calculation using a Stuttgart basis for KHe are presented. Additionally, the DCTs are compared with a simple calculation based on the Nikitin's 3 × 3 description of the coupling between the Σ and Π surfaces, as well as a method based on Werner's analysis of configuration interaction coefficients. The nonadiabatic coupling angle calculated by integrating the radial analytic DCTs using these different techniques matches extremely well. The resultant nonadiabatic energy surfaces for KHe are presented.

Theoretical Cross Sections of the Inelastic Fine Structure Transition M(2P1/2) + Ng ↔ M(2P3/2) + Ng for M = K, Rb, and Cs and Ng = He, Ne, and Ar.

Scattering matrix elements of the inelastic fine structure transition M(2P1/2) + Ng ↔ M(2P3/2) + Ng are computed using the channel packet method (CPM) for alkali-metal atoms M = K, Rb, and Cs, as they collide with noble-gas atoms Ng = He, Ne, and Ar. The calculations are performed within the block Born-Oppenheimer approximation where excited state VA2Π1/2(R), VA2Π3/2(R), and VB2Σ1/2(R) adiabatic potential energy surfaces are used together with a Hund's case (c) basis to construct a 6 × 6 diabatic representation of the electronic Hamiltonian. Matrix elements of the angular kinetic energy of the nuclei incorporate Coriolis coupling and, together with the diabatic representation of the electronic Hamiltonian, yield a 6 × 6 effective potential energy matrix. This matrix is diagonal in the asymptotic limit of large internuclear separation with eigenvalues that correlate to the 2Pj alkali atomic energy levels. Scattering matrix elements are computed using the CPM by preparing reactant and product wave packets on the effective potential energy surfaces that correspond to the excited 2Pj alkali states of interest. The reactant wave packet is then propagated forward in time using the split operator method together with a unitary transformation between the adiabatic and diabatic representations. The Fourier transformation of the correlation function between the evolving reactant wave packet and stationary product wave packet yields state-to-state scattering matrix elements as a function of energy for a particular choice of total angular momentum J. Calculations are performed for energies that range from 0.0 to 0.01 hartree and values of J that start with a minimum of J = 0.5 for all M + Ng pairs up to a maximum that ranges from J = 450.5 for KAr to J = 100.5 for CsAr. A sum over J together with an average over energy is used to compute thermally averaged cross sections for a temperature range of T = 0-400 K.

Review of dietetic service provision and activity in spinal cord injury centres: a multicentre survey in the UK and Republic of Ireland.

OBJECTIVES: The present study was undertaken to review the service provision in spinal cord injury (SCI) centres (SCICs); to establish and compare how much time dietitians spend in direct and indirect contact with patients; and to document current nutritional screening practices. METHODS: All 12 SCICs in the United Kingdom and the Republic of Ireland were surveyed by a postal questionnaire in April 2014. Data collected included the number of whole-time-equivalent (WTE) staff available, whether a nutrition team was present and the use of nutrition screening tools. A work sampling tool was used to capture dietetic activity for a period of 1 week. RESULTS: Eight (66.7%) SCICs responded (390/531 of total SCI beds) and the average numbers of patients per WTE staff, including consultants, nurses, dietitians, physiotherapists, occupational therapists were recorded. Six out of eight SCICs used a validated nutritional screening tool. Thirty-two work sampling tools were analysed, revealing that spinal dietitians spend 39.1% of the working day in direct patient-related activities. Staffing levels varied and were below clinical recommendations in six out of eight SCICs. CONCLUSION: The resources allocated to nutritional care in SCICs appear to be varied and limited. This suggests malnutrition may continue to be under-recognised and under-treated. To address the complex nutritional needs of this special population group there is a clear need to establish staffing level for dietitians. Information collected from the present study could contribute to the supply analysis of a future workforce planning exercise in SCIC dietetic service.

Demonstration of an 8-dimensional modulation format with reduced inter-channel nonlinearities in a polarization multiplexed coherent system.

We demonstrate a polarization-managed 8-dimensional modulation format that is time domain coded to reduce inter-channel nonlinearity. Simulation results show a 2.3 dB improvement in maximum net system margin (NSM) relative to polarization multiplexed (PM)-BPSK, and a 1.0 dB improvement relative to time interleaved return-to-zero (RZ)-PM-BPSK, for five WDM channels propagating over 1600 km ELEAF with 90% inline optical dispersion compensation. In contrast to the other modulations considered, the new 8-dimensional format has negligible sensitivity to the polarization states of the neighboring WDM channels. High-density WDM (HD-WDM) measurements on a 5000 km dispersion-managed link show a 1.0 dB improvement in net system margin relative to PM-BPSK.

Current and Future Advanced Imaging Modalities for the Diagnosis of Early Osteoarthritis of the Hip.

Hip osteoarthritis (OA) can be idiopathic or develop secondary to structural joint abnormalities of the hip joint (alteration of normal anatomy) and/or due to a systemic condition with joint involvement. Early osteoarthritic changes to the hip can be completely asymptomatic or may cause the development hip symptomatology without evidence of OA on radiographs. Delaying the progression of hip OA is critical due to the significant impact of this condition on the patient's quality of life. Pre-OA of the hip is a newly established term that is often described as the development of signs and symptoms of degenerative hip disease but no radiographic evidence of OA. Advanced imaging methods can help to diagnose pre-OA of the hip in patients with hip pain and normal radiographs or aid in the surveillance of asymptomatic patients with an underlying hip diagnosis that is known to increase the risk of early OA of the hip. These methods include the delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC), quantitative magnetic resonance imaging (qMRI- T1rho, T2, and T2* relaxation time mapping), 7-Tesla MRI, computed tomography (CT), and optical coherence tomography (OCT). dGEMRIC proved to be a reliable and accurate modality though it is limited by the significant time necessary for contrast washout between scans. This disadvantage is potentially overcome by T2 weighted MRIs, which do not require contrast. 7-Tesla MRI is a promising development for enhanced imaging resolution compared to 1.5 and 3T MRIs. This technique does require additional optimization and development prior to widespread clinical use. The purpose of this review was to summarize the results of translational and clinical studies investigating the utilization of the above-mentioned imaging modalities to diagnose hip pre-OA, with special focus on recent research evaluating their implementation into clinical practice.

The Auger effect in physical and biological research.

PURPOSE: The paper reports on progress in physics of radiationless transitions and new Auger spectra of (125)I and (124)I. We report progress in Monte Carlo track structure simulation of low energy electrons comprising majority electrons released in decay most Auger emitters. MATERIALS AND METHODS: The input data for electron capture (EC) and internal conversion(IC) were obtained from various physics data libraries. Monte Carlo technique was used for the simulation of Auger electron spectra. Similarly, electron tracks were generated using Monte Carlo track structure methods. RESULTS: Data are presented for the EC, IC and binding energy (BE) of radionuclides (124)I and (125)I. For each of the radionuclides (125)I and (124)I some examples of electron spectra of individual decays are given. Because most Auger electrons are low energy and short range, data and a short discussion are presented on recent Monte Carlo track structure development in condensed media and their accuracy. CONCLUSIONS: Accuracy of electron spectra calculated in the decay of electron shower by Auger emitting radionuclides depends on availability of accurate physics data. There are many gaps in these libraries and there is a need for detailed comparison between analytical method and Monte Carlo calculations to refine the method of calculations. On simulation of electron tracks, although improved models for sub-keV electron interaction cross sections for liquid water are now available, more experimental data are needed for benchmarking. In addition, it is desirable to make data and programs for calculations of Auger spectra available online for use by students and researchers.

Auger electrons--a nanoprobe for structural, molecular and cellular processes.

This paper provides a brief review of recently published work on biophysical and biological aspects of Auger processes. Three specific questions have been considered. (1) Does charge neutralisation contribute to molecular damage such as DNA strand breaks? (2) How many DNA double strand breaks are produced by a single decay of DNA bound (125)I? (3) What is the correlation between number of gammaH2AX foci and number of double strand breaks (DSB)? The paper also gives preliminary reports on two new calculations: (a) calculation of the spectrum of Auger electrons released during decay of (124)I and (b) the use of Auger electrons in the decay of (125)I as a probing agent of novel DNA structures.

Response of LNCaP spheroids after treatment with an alpha-particle emitter (213Bi)-labeled anti-prostate-specific membrane antigen antibody (J591).

A theoretical drawback to alpha-particle therapy with 213Bi is the short range of the particle track coupled with the short half-life of the radionuclide, thereby potentially limiting effective cytotoxicity to rapidly accessible, disseminated individual tumor cells (e.g., as in leukemia). In this work, a prostate carcinoma spheroid model was used to evaluate the feasibility of targeting micrometastatic clusters of tumor cells using 213Bi-labeled anti-prostate-specific membrane antigen (PSMA) antibody, J591. In prostate cancer, vascular dissemination of tumor cells or tumor cell clusters to the marrow constitutes an important step in the progression of this disease to widespread skeletal involvement, an incurable state. Such prevascularized clusters are ideal targets for radiolabeled antibodies because the barriers to antibody penetration that are associated with the capillary basal lamina have not yet formed. Beta- and gamma-emitting radionuclides such as 131I, which are widely used in radioimmunotherapy, are not expected to be effective when targeting single cells or small cell clusters. This is because the range of the emissions is one to two orders of magnitude greater than the target size, and the energy deposited per traversal is insufficient to produce any significant radiobiological effect. Spheroids of the prostate cancer cell line, LNCaP-LN3, were used as a model of prevascularized micrometastases; their response to an anti-PSMA antibody, J591, radiolabeled with the alpha-particle emitter 213Bi (T(1/2), 45.6 min.) has been measured. The time course of spheroid volume reductions was found to be sensitive to the initial spheroid volume. J591 labeled with 0.9 MBq/ml 213Bi resulted in a 3-log reduction in spheroid volume on day 33, relative to control, for spheroids with an initial diameter of 130 microm; 1.8 MBq/ml were required to achieve a similar response for spheroids with an initial diameter of 180 microm. Equivalent spheroid responses were observed after 12 Gy of acute external beam photon irradiation. Monte Carlo-based microdosimetric analyses of the 213Bi decay distribution in individual spheroids of 130-microm diameter yielded an average alpha-particle dose of 3.7 Gy to the spheroids, resulting in a relative biological effectiveness factor of 3.2 over photon irradiation. The activity concentrations used in the experiments were clinically relevant, and this work supports the possibility of using 213Bi-labeled antibodies not only for disseminated single tumor cells, as found in patients with leukemia, but also for micrometastatic tumor deposits up to 180 microm in diameter (1200 cells).

Pre-existent adenovirus antibody inhibits systemic toxicity and antitumor activity of CN706 in the nude mouse LNCaP xenograft model: implications and proposals for human therapy.

Pre-existent humoral antibody to adenovirus potentially confounds human clinical trials involving intravascular administration of adenovirus. Using the LNCaP prostate cancer xenograft model in BALB/c nu/nu mice and the prostate-specific attenuated replication-competent adenovirus (ARCATM) CN706, we developed an animal model that systematically controls both the dose of intravascularly administered adenovirus and the titer of the pre-existent anti-Ad5 antibody, and then measures the virus-induced toxicity as well as antitumor activity. We prepared hyperimmune sera to adenovirus in rabbits, passively injected the purified rabbit anti-Ad5 antibody into tumor-bearing mice, and established measurable humoral anti-Ad5 antibody titers. CN706 was intravenously injected into the tail vein of animals 24 hr after passive anti-Ad5 antibody administration. In the absence of pre-existent antibody, the lethal dose (LD100) for BALB/c nu/nu mice was 2.5x10(11) CN706 particles, whereas 1x10(11) CN706 particles was not lethal. However, in the presence of a 1:80 pre-existent titer of Ad5 neutralizing antibody (NAb), intravenous injection of 5x10(11) CN706 particles was no longer lethal. In addition, pre-existent antibody also prevented antitumor activity in a dose-dependent manner: 1x 10(11) CN706 particles prevented LNCaP xenograft tumor progression, but antitumor activity was eliminated by a pre-existent 1:80 NAb titer. These results led us to propose transient removal of pre-existent adenovirus antibody by immunoapheresis. An affinity column of cloned virus capsid proteins was constructed that was able to specifically remove adenovirus antibody from human clinical serum samples. A 5-min disposable immunoassay was also developed to monitor the level of pre-existent antibody in sera before and after immunoapheresis. Clinically, this approach may enable controlled clinical studies of intravenously administered adenovirus in patients with pre-existent anti-adenovirus antibody.

A solid phase micro-radioimmunoassay to detect minute amounts of Ig class specific anti-viral antibody in a mouse model system.

A simple and rapid micro-radioimmunoassay was developed to detect and quantitate class specific mouse anti-Sendai virus antibodies. Two different 125I-labelled indicator systems were studied. After incubation of test serum with antigen one system used 125I-rabbit anti-mouse IgG (RIA 1) and the second employed rabbit anti-mouse IgG, IgA or IgM followed by 125I-sheep anti-rabbit immunoglobulin reagent (RIA 2). The RIA 2 method was adopted for routine use as it was more sensitive, gave better discrimination between sample and background counts and eliminated the need for several labelled rabbit anti-mouse Ig class specific antisera. The technique was found to be about 100 times more sensitive than conventional HI tests, specific, reliable and economical of reagents and time.

A new calculational method to assess the therapeutic potential of Auger electron emission.

This paper discusses a new computer code to estimate the efficacy of Auger electron sources in cancer therapy. Auger electron emission accompanies the decay of many radionuclides already commonly used in nuclear medicine, for example; 99mTc and 201Tl. The range of these electrons is in general sub-cellular, therefore, the toxicity of the source depends on the site of decay relative to the genetic material of the cell. Electron track structure methods have been used which enable the study of energy deposition from Auger sources down to the Angstrom level. A figure for the minimum energy required per single strand break is obtained by fitting our energy deposition calculations for 125I decays in a model of the DNA to experimental data on break lengths from 125I labeled plasmid fragments. This method is used to investigate the efficiency of double strand break production by other Auger sources which have potential value for therapy. The high RBE of Auger sources depends critically on the distance between the source and target material. The application of Auger emitters for therapy may necessitate a carrier molecule that can append the source to the DNA. Many DNA localizing agents are known in the field of chemotherapy, some of which could be carrier molecules for Auger sources; the halogenated thymidine precursors are under scrutiny in this field. The activation of Auger cascades in situ by high energy, collimated X ray and neutron beams is also assessed.

Comments on strand breaks calculated from average doses to the DNA from incorporated isotopes.

The techniques used to calculate DNA strand breakage from average doses to small segments of DNA are examined. It is shown that the methods of calculation contain serious flaws and lead to invalid results.

The range of high LET effects from 125I decays.

Track structure techniques are applied to calculate energy depositions in cylindrical targets 20 A in diameter (simulating the DNA duplex) containing, or near, 125I decays. Two problems are examined: (1) The possible effects of incorporated versus nonincorporated 125I are evaluated; (2) the extent of the radiological damage along the DNA is described and discussed for individual decays taking place in the DNA. The results of three different calculations are presented: (1) The distribution of the total energy deposited in the target per decay: Here it is shown that the 125I decays deposit considerably more energy than 5-MeV alpha particles when the decay occurs on the central axis of the cylinder. When the decay occurs at 40 A from the axis, the energy depositions are small and infrequent, showing that the iodine decay must occur within this distance to produce a high LET-like effect. (2) The distribution of average energy depositions around a curved cylinder simulating the DNA duplex encircling the nucleosome: There is a rapid decrease in the energy deposited in elements (of size resembling a base pair) away from the location of the decay. At approximately 17 A (approximately 5 bp) from the decay the mean energy deposited in an element is reduced by a factor of 10. (3) The energy deposited in individual elements of the cylinder is presented for single decays: The smooth decrease in average energy depositions with distance from the decay ((2) above) is not reflected in individual decays.

The minimum Do for cell killing for alpha-particle emitters uniformly distributed in an extended medium.

For cells irradiated by alpha particles in suspension, there is presently no simple test to show that the cell killing can be attributed to alpha-particle passages through the nuclei. In this communication, for a uniform distribution of alpha-particle sources and spherical nuclei, a D0 is calculated such that at least 63% of the cell nuclei have at least one alpha-particle passage. For a uniform distribution of alpha-particle sources and spherical nuclei, it is shown that the average dose for 63% of the cell nuclei to be hit (37% not hit) is equal to the average dose per hit. For this condition an energy deposition of any size would result in cell death and the average dose is the minimum D0 possible. Minimum D0 values are calculated using a Monte Carlo treatment for nuclear diameters from 4 to 10 microm and initial alpha-particle energies between 3.18 and 8.38 MeV.

The survival of monolayers of cells growing in clusters irradiated by 211At appended to the cell surfaces.

A model of cell survival is described for the case of closely packed clusters of cells growing in monolayers. For alpha-particle decays on the cell surfaces, it is shown that cross-firing between cells produces nonuniform dose distributions within the cluster and that cells in larger clusters are exposed on average to greater doses. The model is used to simulate the survival of SK-MEL-28 human melanoma cells labeled with different radiolabeled monoclonal antibodies. The survival data suggest that this cell line is more sensitive to high-LET radiation than previously thought.

A Monte Carlo simulation of Auger cascades.

The energy imparted to biological tissue after the decay of incorporated Auger emitters stems from two sources: (a) energy deposition by the Auger and Coster-Kronig electrons and (b) the charge potential which remains on the multiple ionized atom after the end of the cascade. For the numerical assessment of both the kinetic energy of the released electrons and the charge potential, a new and--for purposes of microdosimetry--precise method is presented. Based on relativistic Dirac-Fock calculations and a rigorous bookkeeping, this method provides a perfect energy balance of the considered atomic system when applied to Monte Carlo simulations of Auger cascades. By comparing the results for charge distribution for krypton and iodine with experimental data and the electron spectrum of 125I with theoretical data, it can be shown that the approach followed in this work is reasonable and appropriate for the determination of the energy deposited by incorporated Auger emitters in small volumes of condensed matter. The total energy deposited by 125I in a volume of 20-nm diameter is 2.03 keV which is made up by multiple ionization (1.07 keV) and energy deposition by the emitted Auger electrons (0.96 keV).

Some consequences of the Auger effect: fluorescence yield, charge potential, and energy imparted.

The potential energy produced by the Auger cascade due to the charging of atoms is evaluated and incorporated into conventional treatment of energy deposition. A straightforward method for calculating this energy is presented. For the photoelectric interaction the potential energy is shown to be at least as important as L-shell fluorescence in calculating the electron kerma. For radioactive decay by electron capture or internal conversion, it is shown that, for small (less than 100 nm) targets containing the decay, the atomic charging can be the dominant contribution to the total energy deposited in the target.

Monte Carlo modeling of the effects of injected short-, medium- and longer-range alpha-particle emitters on human marrow at various ages.

The effects of injected short-, medium- and longer-range alpha-particle emitters ((149)Tb, (211)At/(211)Po and (213)Bi/(213)Po, respectively) on the total hemopoietic stem cell population of active normal bone marrow in humans of various ages has been estimated using Monte Carlo modeling. The fraction of the normal hemopoietic stem cells that are hit and survive has been calculated as a first step toward estimating the risk of development of therapy-induced leukemia. The fraction was lowest for the shorter-range alpha-particle emitter ((149)Tb) and highest for the longer-range alpha-particle emitter ((213)Bi/(213)Po), with the value for the medium-range alpha-particle emitter (211)At/(211)Po being intermediate between these. There was little variation in the data with the age of the subject within each alpha-particle emitter. This lack of age dependence provides reassurance that the fraction of cells hit in any subject of any age with normal marrow can be estimated by modeling newborn marrow (which requires little computing time) despite age-related differences in microarchitecture.

The paradoxical nature of DNA damage and cell death induced by 125I decay.

Chinese hamster ovary cells were synchronized at the G1/S-phase boundary of the cell cycle and pulse-labeled for 10 min with 125I-iododeoxyuridine 30 min after entering the S phase. Cell samples were harvested for freezing and 125I-decay accumulation at intervals ranging from 15 to 480 min after termination of labeling. The survival data showed a marked shift from cell killing characteristic of low-LET radiation to that more characteristic of killing by high-LET radiation with increasing intervals between DNA pulse-labeling and decay accumulation. Cells harvested and frozen within 1 h after pulse-labeling yielded a low-LET radiation survival response with a pronounced shoulder and a large D0 of up to 0.9 Gy. With longer chase periods the shoulder and the D0 decreased progressively, and cells harvested 5 h after pulse-labeling or later exhibited a high-LET survival response (D0: 0.13 Gy). Two interpretations for these findings are discussed. (1) If DNA is the sole target for radiation death, the results indicate that DNA maturation increases radiation damage to DNA or reduces damage repair. (2) If radiation cell death involves damage to higher-order structures in the cell nucleus, the findings suggest that newly replicated DNA is not attached to these structures during the initial low-LET period, but 125I starts to induce high-LET radiation effects as labeled DNA segments become associated with the target structure(s). On balance, or data favor the latter interpretation.