In vitro studies of PDR brachytherapy

BACKGROUND: Calculations on the basis of the LQ-model have been focussed on the possible radiobiological equivalence between common continuous low dose rate irradiation (CLDR) and a superfractionated irradiation (PDR = pulsed dose rate) provided that the same total dose will be prescribed in the same overall time as with the low doserate. A clinically usable fractionation scheme for brachytherapy was recommended by Brenner and Hall and should replace the classical CLDR brachytherapy with line sources with an afterloading technique using a stepping source. The hypothes is that LDR equivalency can be achieved by superfractionation was tested by means of in vitro experiments on V79 cells in monolayer and spheroid cultures as well as on HeLa monolayers. MATERIALS AND METHODS: Simulating the clinical situation in PDR brachytherapy, fractionation experiments were carried out in the dose rate gradient of afterloading sources. Different dose levels were produced with the same number of fractions in the same overall incubation time. The fractionation schedules which were to be compared with a CLDR reference curve were: 40 x 0.47 Gy, 20 x 0.94 Gy, 10 x 1.88 Gy, 5 x 3.76 Gy, 2 x 9.4 Gy given in a period of 20 h and 1 x 18.8 Gy as a "single dose" exposition. As measured by flow cytometry, the influence of the dose rate in the pulse on cell survival and on cell cycle distribution under superfractionation was examined on V79 cells. RESULTS: V79 spheroids as a model for a slowly growing tumor, reacted according to the radiobiological calculations, as a CLDR equivalency was achieved with increasing fractionation. Rapidly growing V79 monolayer cells showed an inverse fractionation effect. A superfractionated irradiation with pulses of 0.94 Gy/h respectively 0.47 Gy/0.5 h was significantly more effective than the CLDR irradiation. This inverse fractionation effect in log-phase V79 cells could be attributed to the accumulation of cycling cells in the radiosensitive G2/M phase (G2 block) during protected exposure which was drastically more pronounced for the pulsed scheme. HeLa cells were rather insensitive to changes of fractionation. Superfractionation as well as hypofractionation yielded CLDR equivalent survival curves. CONCLUSIONS: The fractionation scheme, derived from the PDR theory to achieve CLDR equivalent effects, is valid for many cell lines, however not for all. Proliferation and dose rate dependend cell cycle effects modify predictions derived from the sublethal damage recovery model and can influence acute irradiation effects significantly. Dose rate sensitivity and rapid proliferation favour cell cycle effects and substantiate, applied to the clinical situation, the possibility of a higher effectiveness of the pulsed irradiation on rapidly growing tumors.     

Differences between completers and early dropouts from 2 HIV intervention trials: a health belief approach to understanding prevention program attrition

OBJECTIVES: The purpose of this study was to identify factors predicting program attrition among participants in human immunodeficiency virus (HIV) risk reduction trials. METHODS: Participants were gay/bisexual men and severely mentally ill adults recruited to take part in HIV risk reduction small-group interventions. Program completers were compared with participants who were assessed at baseline but then failed to attend any sessions. The health belief model provided a framework for selection of possible predictors of program attrition. RESULTS: Younger age was associated with early dropout in both samples. Other predictors among gay/bisexual men included involvement in an exclusive sexual relationship, minority ethnicity, injection drug use, and higher perceived severity of AIDS. Severely mentally ill dropouts were less knowledgeable about safer sex methods and more likely to hold positive outcome expectancies for condom use. CONCLUSIONS: Evaluation of intervention effectiveness among vulnerable population segments is threatened if there is selective attrition. Better methods are needed to attract and maintain participation in HIV prevention programs. Alternatively, wider application of "intention to treat" analysis of intervention outcomes is recommended to minimize selection bias due to program dropout.     

A nonlinear geometric approach to power system excitation control and stabilization

In this paper, a unified approach to the design of a nonlinear excitation controller/power system stabilizer for a synchronous generator/infinite bus power system is presented. The approach is based on a form of state feedback linearization, known as input–output feedback linearization, which provides an exact semi-global state transformation that is valid for a large class of operating points of the power system. With this transformation, the terminal voltage becomes a linear function of the control input. The excitation controller/power system stabilizer is then synthesized by using linear controller design techniques. The controller is proven to provide small signal stability and to provide local asymptotic tracking of admissible constant reference signals for a large class of operating points. A procedure is given to tune the controller gains to provide significant damping of the power angle oscillations.     

The chicken beta-globin gene promoter forms a novel "cinched" tetrahelical structure

We have previously shown that the G-rich sequence G16CG(GGT)2GG in the promoter region of the chicken beta-globin gene poses a formidable barrier to DNA synthesis in vitro (Woodford et al., 1994, J. Biol. Chem. 269, 27029-27035). The K+ requirement, template-strand specificity, template concentration independence, and involvement of Hoogsteen bonding suggested that the underlying basis of this new type of DNA synthesis arrest site might be an intrastrand tetrahelical structure. However, the arrest site lacks the four G-rich repeats that are a hallmark of previously described intramolecular tetraplexes and contains a number of noncanonical bases that would be expected to greatly destabilize such a structure. Here we report evidence for an unusual K+-dependent intrastrand "cinched" tetraplex. This structure has several unique features including the incorporation of bases other than guanine into the stem of the tetraplex, interaction between loop bases and bases in the flanking region, and base pairing between bases 3 and 5 of the tetrahelix-forming region to form a molecular "cinch." This finding extends the range of sequences capable of tetraplex formation as well as our appreciation of the conformational complexity of the chicken beta-globin promoter.     

Psychosexual development of women with congenital adrenal hyperplasia

Women with congenital adrenal hyperplasia (CAH) (N = 31) and their unaffected sisters or female cousins (N = 15) participated in a study of psychosexual development. All participants were > or = 18 years of age (mean age, 25 years; range, 18-40). Comparisons were also made between the CAH women with the salt-wasting (SW) form of the disorder and those with simple virilization (SV). A psychosexual assessment protocol examined six variables: (1) sex assignment at birth (probands only); (2) recalled sex-typed behavior during childhood; (3) gender identity and gender role identification in adulthood; (4) relationship status; (5) sexual orientation in fantasy; and (6) sexual orientation in behavior. Salt-wasting status and sex assignment at birth were also ascertained for the CAH women who either refused to participate in the study (N = 10) or could not be traced (N = 13). Compared to the controls, the women with CAH recalled more cross-gender role behavior and less comfort with their sense of "femininity" during childhood. The two groups did not differ in degree of gender dysphoria in adulthood, although the probands showed more cross-gender role identification. Three of the nonparticipant probands were living, as adults, in the male social role (2 reared from birth as boys and 1 who changed from the female to the male social role during adolescence). The CAH women and the controls did not differ in relationship status (married/cohabiting vs. single). The CAH women had lower rates of exclusive heterosexual fantasy and fewer sexual experiences with men than the controls; however, the CAH women did not have more sexual experiences with women than the controls. Comparisons between the SW and SV revealed several differences: the SW were less likely to be assigned to the female sex at birth, recalled more cross-gender role behavior during childhood, were less likely to be married or cohabiting, and had lower rates of sexual experiences with men. The results were discussed in relation to the effects of prenatal androgens on psychosexual differentiation.     

Analogues of capsaicin with agonist activity as novel analgesic agents: structure-activity studies. 4. Potent, orally active analgesics

Structural features of three regions of the capsaicin molecule necessary for agonist properties were delineated by a previously reported modular approach. These in vitro agonist effects were shown to correlate with analgesic potency in rodent models. Combination of optimal structural features from each of these regions of the capsaicin molecule have led to highly potent agonists (eg., 1b). Evaluation in vivo established that 1b had analgesic properties but poor oral activity, short duration of action, and excitatory side effects which precluded further development of this compound. Preliminary metabolism studies had shown that the phenol moiety of 1b was rapidly glucuronidated in vivo, providing a possible explanation for the poor pharmacokinetic profile. Subsequent specific modification of the phenol group led to compounds 2a-j, which retained in vitro potency. The in vivo profiles of two representatives of this series, 2a,h, were much improved over the "parent" phenol series, and they are candidates for development as analgesic agents.     

Postural instability induced by virtual reality exposure: development of a certification protocol

Exposure to virtual environments often causes users to experience symptoms of motion sickness. An accessory manifestation of motion sickness symptoms is postural disequilibrium. If the postural disequilibrium that occurs persists beyond the time an individual is within the confines of the laboratory or system site, user safety could be compromised and products liability issues could be forthcoming. In this study, a portable, automated postural assessment system is developed that can be employed before and after exposure to a virtual reality (VR) system in order to certify that a user's balance on exiting the system is at least demonstrably as good as it was on entering. It is argued that if the "coming out" balance performance is sufficiently poorer than the "going in" balance, then the user should be retained until the pretest balance performance is regained. The results from a set of normative and validation experiments on postural equilibrium identified several reliable measures of stance that could serve as a basis for certification. Furthermore, a new automated video-based measure using only head movement showed that performance over sessions is stable and reliable. The head movement changes that occur with stimuli, such as alcohol and simulator exposure, are well behaved, predictable, and significant even with small samples. The implication is that the proposed objective measure of postural stability, in conjunction with procedures for obtaining self-reports of symptoms, can afford some measure of certification that exposure to a given VR system is without harm.     

Sensitivity analysis and optimization of vehicle–bridge systems based on combined PEM–PIM strategy

This paper presents a new optimization method for coupled vehicle–bridge systems subjected to uneven road surface excitation. The vehicle system is simplified as a multiple rigid-body model and the single-span bridge is modeled as a simply supported Bernoulli–Euler beam. The pseudo-excitation method transforms the random surface roughness into the superposition of a series of deterministic pseudo-harmonic excitations, which enables convenient and accurate computation of first and second order sensitivity information. The precise integration method is used to compute the vertical random vibrations for both the vehicle and the bridge. The sensitivities are used to find the optimal solution, with vehicle ride comfort taken as the objective function. Optimization efficiency and computational accuracy are demonstrated numerically.     

Virtual rights? Property in online game objects and characters

The new industry of Massively Multi-Player Online Role-Playing Games (MMORPGs) brings together two sets of fictions: the interactive stories of shared computer games and the legal devices of intellectual property. In these virtual worlds, scarcity need not exist, but players tend to prefer the competition it creates. This leads to the development of property rights within the game world and players trading real money for virtual objects, ‘land’ and characters. This new phenomenon brings with it familiar legal problems such as theft, fraud and ownership disputes. Game creators also challenge the right of the players to claim ownership outside the game world. The volume and value of the items traded make real money trading an important area of current interest for intellectual property lawyers. Something is being traded, but does it fit neatly into existing conceptions of property rights and who owns it? Analysing the novel problems that result from various theoretical perspectives (utilitarianism, labour-desert theory and personality theory) leads to the conclusion that with time, we will see the development of property rights for players in online games. This connects with a growing understanding that the traditional conception of copyright law dealing with creative work generated by the solitary author is becoming less appropriate in the new creative spaces that information and communications technology brings, where individuals are both consumer and producer. In virtual worlds, new forms of intellectual property, and perhaps even new rights, are taking shape.