Perspectives in linear accelerator for FLASH VHEE: Study of a compact C-band system.

PURPOSE: In order to translate the FLASH effect in clinical use and to treat deep tumors, Very High Electron Energy irradiations could represent a valid technique. Here, we address the main issues in the design of a VHEE FLASH machine. We present preliminary results for a compact C-band system aiming to reach a high accelerating gradient and high current necessary to deliver a Ultra High Dose Rate with a beam pulse duration of 3µs. METHODS: The proposed system is composed by low energy high current injector linac followed by a high acceleration gradient structure able to reach 60-160 MeV energy range. To obtain the maximum energy, an energy pulse compressor options is considered. CST code was used to define the specifications RF parameters of the linac. To optimize the accelerated current and therefore the delivered dose, beam dynamics simulations was performed using TSTEP and ASTRA codes. RESULTS: The VHEE parameters Linac suitable to satisfy FLASH criteria were simulated. Preliminary results allow to obtain a maximum energy of 160 MeV, with a peak current of 200 mA, which corresponds to a charge of 600 nC. CONCLUSIONS: A promising preliminary design of VHEE linac for FLASH RT has been performed. Supplementary studies are on going to complete the characterization of the machine and to manufacture and test the RF prototypes.

Compact X-Band Electron Linac for Radiotherapy and Security Applications.

RadiaBeam has developed a 6 MeV accelerator that is compact and light enough to be placed on a robotic arm or light truck. The main drivers of size and weight in conventional accelerators are the power source and the shielding. Small dimensions are enabled by operation at 9.3 GHz frequency (X-band), which allows reducing the size and weight of all accelerator components. Thanks to the robust design of the accelerating structure, the accelerator can be used as a source for novel cargo inspection and radiotherapy techniques. In this paper, we present the linac design and its components, as well the results of the experimental demonstration of beam acceleration.

Novel radio-frequency gun structures for ultrafast relativistic electron diffraction.

Radio-frequency (RF) photoinjector-based relativistic ultrafast electron diffraction (UED) is a promising new technique that has the potential to probe structural changes at the atomic scale with sub-100 fs temporal resolution in a single shot. We analyze the limitations on the temporal and spatial resolution of this technique considering the operating parameters of a standard 1.6 cell RF gun (which is the RF photoinjector used for the first experimental tests of relativistic UED at Stanford Linear Accelerator Center; University of California, Los Angeles; Brookhaven National Laboratory), and study the possibility of employing novel RF structures to circumvent some of these limits.

Evidence that Meishan and large-white hybrid preovulatory follicles may differentially affect oocyte in vitro maturation and fertilization.

Two experiments were carried out to test the hypothesis that follicles recovered from Meishan animals may provide a more favourable environment for oocyte maturation in vitro than follicles recovered from Large-White hybrid animals. In Experiment 1, all follicles > or = 4 mm were recovered from six Meishan and seven Large-White hybrid gilts in the late follicular phase and healthy oocyte cumulus complexes recovered. Cumulus oocyte complexes were randomly divided into two groups, and each group cultured for 27 or 34 h (62 and 64; 56 and 56 for Meishan and Large-White hybrid, respectively) in defined medium in the presence of either of the two largest follicle shells per animal. Subsequent examination of oocyte nuclear maturation showed that although maturation did not differ significantly between the breeds after 27 h, more (P < 0.01) Meishan oocytes co-cultured with Meishan follicles developed to metaphase II stage than Large-White hybrid oocytes co-cultured with Large-White hybrid follicles after 34 h. The next eight largest follicles per animal were cultured for 34 h to produce conditioned media. In Experiment 2, oocytes recovered from the slaughterhouse were matured for 46 h in the presence of conditioned media from Meishan (612 oocytes) or Large-White hybrid (731 oocytes) follicles, or in fresh medium in the presence of a follicle shell from slaughterhouse ovaries. Oocytes were then inseminated and 12 h later examined for penetration and male pronuclear formation. A higher (P < 0.05) percentage of oocytes cultured in Meishan follicle conditioned medium underwent sperm penetration and male pronuclear formation than oocytes cultured in conditioned media from Large-White hybrid animals. Concentration of oestradiol and progesterone in the conditioned media did not differ between the breeds (P > 0.1). In conclusion, these results suggest that (1) Meishan oocytes have advanced maturational capacity when cultured with Meishan preovulatory follicle shells and (2) differences in follicle maturation in the Meishan compared to the Large-White hybrid pig may result in an improved ability of the follicles, via conditioned media, to support oocyte maturation and fertilization in vitro.

Follicle development and oocyte maturation during the immediate preovulatory period in Meishan and white hybrid gilts.

A study was carried out to compare preovulatory ovarian events in prolific Meishan gilts (which have high levels of embryo survival) with contemporary white hybrid control gilts. Gilts of similar reproductive ages (second or third oestrous cycle) were observed three times a day for oestrous behaviour and ovaries recovered at a time estimated as within 7 h of ovulation (white hybrid, n = 13; Meishan, n = 16). Preovulatory follicles were recovered (n = 195, white hybrid; n = 252, Meishan), and oocytes were aspirated and fixed for later identification of meiotic stage, and follicular fluid was frozen for subsequent determination of progesterone. The number of presumed ovulatory follicles recovered per animal was similar to the expected ovulation rate (15.0, white hybrid; 15.75, Meishan; P > 0.1); however, follicles from Meishan gilts were smaller (8.1 versus 9.0 mm, P < 0.001) and contained less follicular fluid (139.9 versus 187.6 microliters, P < 0.02) than did white hybrid gilts. Total follicular progesterone (88.7 ng per follicle, white hybrid; 77.4 ng per follicle, Meishan) and concentration of progesterone in follicular fluid (526 ng ml-1, white hybrid; 640 ng ml-1, Meishan) did not differ between the two breeds (P > 0.1). There were no breed differences in the extent of heterogeneity in follicular diameter, volume of follicular fluid, and total follicular progesterone and progesterone concentration (P > 0.1). However, classification of recovered oocytes into seven discrete meiotic stages revealed that more oocytes recovered from Meishan preovulatory follicles were in the more advanced stages of meiosis than were those recovered from white hybrid gilts (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Differences in follicular aromatase activity between Meishan and large-white hybrid gilts.

Two experiments were carried out in which follicular aromatase activity was compared between Meishan and Large-White hybrid gilts. In Expt 1, preovulatory follicles (n = 10 largest per animal) were recovered from Meishan and Large-White hybrid gilts (n = 5 per breed) on the day before predicted onset of behavioural oestrus, and the granulosa cells and theca tissue incubated to determine aromatase activity. Follicles recovered from Meishan pigs were smaller (P < 0.01) and contained fewer granulosa cells (P < 0.05), but follicular oestradiol content of the breeds was similar (P > 0.1). Aromatase activity was higher in the theca tissue (P < 0.05) and tended to be higher in the granulosa cells recovered from Meishan follicles (P = 0.065). In Expt 2, granulosa cell aromatase activity was investigated during the early follicular phase (estimated day 16 of cycle) in Meishan and Large-White hybrid gilts (n = 6 and 5, respectively). The number of follicles > or = 1 mm diameter recovered per animal was 171 for both breeds (P > 0.1), whereas the number of follicles > or = 2 mm diameter was 65 and 101 (P < 0.05) from Meishan and Large-White hybrid gilts, respectively. The mean diameter of all follicles recovered was smaller in the Meishan gilts (P < 0.001). Overall, neither the number of granulosa cells per follicle, as indicated by DNA estimation, nor the oestradiol content differed between the breeds at this time (P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting the age at onset of puberty, ovulation rate and time of ovulation in Chinese Meishan gilts.

Experiments were carried out to study: the effects of season on age at puberty, the influence of reproductive age on ovulation rate, and the time interval from the onset of oestrus to ovulation in Chinese Meishan gilts. Gilts approaching puberty either in the spring (n = 88) or in the autumn (n = 40) were housed indoors under natural daylight conditions and observed daily for oestrous behaviour. Gilts approaching puberty in the spring were younger (P < 0.001) and more likely to reach puberty by 100 days of age (P < 0.01) than were those approaching puberty in the autumn. Ovulation rate was estimated in gilts at second (n = 22), third (n = 24), fourth (n = 18), fifth to ninth (n = 9) and tenth to twenty-first (n = 17) oestrous cycle and in primiparous Meishan sows (n = 12) by counting the number of corpora lutea or corpora albicantia at laparoscopy, laparotomy or at ovarian recovery following slaughter. Ovulation rate increased (P < 0.001) with reproductive age and approached that of primiparous sows only when gilts had experienced > or = 10 oestrous cycles (19.2 versus 21.0). The time interval between the onset of oestrus and ovulation was studied in six naturally cyclic Meishan gilts and nine Meishan gilts administered hCG at the onset of oestrus. All glits were observed six times a day for the commencement of oestrous behaviour and were subsequently examined by laparoscopy at 32 h following onset of oestrous and every 8 h till ovulation, which was a maximum of 56 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrauterine and peripheral steroid concentrations and conceptus development in Meishan and Large White hybrid gilts.

Six Meishan and five Large White hybrid gilts were naturally mated to boars of the same breed during their tenth or third oestrous cycle respectively. Maternal serum progesterone and total oestrone were monitored throughout the pregnancy period. On Day 30 of gestation, all gilts were slaughtered and ovulation rate, embryonic survival, conceptus development and intrauterine steroidogenesis were evaluated. The results of the study confirm previous reports that Meishan pigs have a higher number of live conceptuses (P < 0.03), a higher rate of embryonic survival (92.1% v. 78.6% for Large White hybrids) and a higher ovulation rate (P < 0.02) than Large White hybrid gilts. Embryos from Large White hybrid gilts were heavier (P < 0.001) than Meishan embryos and placental lengths (P < 0.001) and weights (P < 0.001) were greater. The volume of allantoic fluid per conceptus was greater (P < 0.03) in Large White hybrid gilts. The oestradiol concentration in the allantoic fluid was greater in Large White hybrid gilts (P < 0.002), but the progesterone concentration in allantoic fluid did not differ (P > 0.15) between the breeds. More oestradiol was synthesized in vitro on a wet weight basis from placental tissue in Large White hybrid gilts than in Meishan gilts (P < 0.001); however, a positive linear relationship existed in both breeds between oestradiol synthesis and placental length (P < 0.005). Progesterone concentrations in maternal serum tended to be higher overall (P < 0.1) in Meishan gilts than in Large White hybrid gilts throughout the 30-day period of study and were significantly higher (P < 0.02) from Day 13 to Day 30.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in alcohol expectancies and drinking behavior among treated problem drinkers.

Research on alcohol expectancies among clinical populations has not focused on the extent to which changes in alcohol expectancies correspond to changes in drinking. In this investigation, male and female problem drinkers participating in an outpatient treatment focused on drinking reduction techniques provided data on drinking behavior and alcohol expectancies at pretreatment, posttreatment and at an 18-month follow-up. Results showed a significant relationship between decreases in alcohol expectancies and decreased drinking. Decreases in alcohol expectancies were not found over the course of the 8-week treatment, but instead at the 18-month follow-up. Implications and future research needs are discussed.

Endocrine and follicular studies in Meishan pigs.

The enhanced early embryonic survival in Chinese Meishan compared with Large-White gilts may be due, in part, to differences in ovarian and endocrine function, particularly during the periovulatory period. The overall patterns of oestradiol, LH and FSH secretion were not different between Meishan and Large-White hybrid controls during this period, although circulating inhibin concentrations were higher in Meishan gilts. Thus, there appeared to be a decreased sensitivity to inhibin feedback on FSH secretion in Meishan gilts. Behavioural oestrus was exhibited earlier relative to the LH surge in Meishan gilts than in Large-White hybrid gilts, but the time interval from the oestradiol peak until the LH surge was similar in both breeds. This finding suggests that Meishan gilts are more sensitive in terms of initiating a behavioural response, but not in terms of positive feedback. Although preovulatory follicular characteristics were as variable in Meishan as in Large-White hybrid gilts, follicles from Meishan gilts were smaller, but contained a higher concentration of oestradiol in the follicular fluid. This was probably due to increased aromatase activity in both granulosa and theca cells of Meishan follicles. The enhanced maturation of the intrafollicular environment in Meishan gilts was reflected in the oocyte population which was at a more advanced stage of development in the period preceding ovulation. In addition to decreasing the time between onset of oestrus and ovulation, advancing the LH surge to coincide with onset of oestrus (via hCG administration) decreased embryo survival at day 30 of gestation. It is concluded that both endocrine and follicular mechanisms have a role in ensuring the prolificacy in the Meishan breed.

Current concepts of folliculogenesis in monovular and polyovular farm species.

Follicular growth in sheep and pigs is under both endocrine and paracrine control, and the local factors involved include steroids, growth factors and other regulatory peptides such as the putative follicle regulatory protein. These factors can act either directly on ovarian cells, or by modulating the response to circulating gonadotrophins. It is suggested that during the early stages of development in sheep and pigs, follicles pass through a stage at which they are modulated by growth factors, after which endocrine control mechanisms become more important. There is evidence that interactions between follicle-stimulating hormone, insulin-like growth factor-1 and oestradiol further enhance development and steroidogenesis. Interfollicular relationships in polyovular pigs may differ from those in sheep, in that the more mature follicles may act to enhance development of the less mature in the selected population. Although it is unclear whether similar mechanisms operate in both hyperprolific pigs and prolific breeds of sheep, Meishan pigs and Booroola ewes do exhibit similar follicular characteristics compared with those of nonprolific breeds. The significance of this in relation to prolificacy requires further investigation.

Trans-cranial electrical stimulation attenuates abrupt morphine withdrawal in rats assayed by remote computerized quantification of multiple motor behavior indices.

The goal of the present study was to assess the effects of trans-cranial electrical stimulation on the behavioral signs of the abrupt withdrawal syndrome of rats. However, this goal also necessitated the introduction of an experimental model measuring animal behavior for prolonged periods of time using a computerized animal activity monitoring system to quantify spontaneous motor activities associated with abstinence behavior. Comparable withdrawal severity was obtained by both the activity monitoring system and investigator observation of motor signs of abstinence behavior. Moreover, using this system we demonstrate a time-dependent effect of electrical stimulation in reducing the severity of various indices of motor hyperactivity associated with abrupt morphine withdrawal in rats.

Freshman and senior medical students' attitudes toward the elderly.

The authors' purpose in the present study was to examine attitudes toward the elderly among medical students and the impact of medical education on such attitudes. Questionnaires first used in a similar study in the 1960s were administered to freshman and senior medical students in 1981 and 1984 at one medical school. Comparison of these two groups indicated that the seniors viewed the elderly more positively than did the freshmen in certain areas, namely the productivity, social significance, and sexuality of the aged. To control for potentially confounding shifts in cultural values in society as a whole and in medical school selection variables, the two freshman groups were compared, and the two senior groups were compared. Results of these analyses indicated few, if any, differences between the freshman classes of 1981 and 1984 or between the senior classes of the same years. Finally, a longitudinal analysis was performed to contrast the attitudes of the students first sampled as freshmen in 1981 to their perceptions as seniors in 1984. Further, the results of the present study were compared with those of a similar study in the 1960s. Taken together, these results indicate that attitudes toward the elderly are becoming more favorable in society in general and in medical schools in particular and that the medical education process was responsible for the more favorable attitudes expressed by the senior medical students.

Computer-based monitoring of clinical care in a public psychiatric hospital unit.

A computer-based clinical monitoring system on a 40-bed university hospital psychiatric unit provides documentation to justify clinicians' diagnosis and choice of treatment and facilitates evaluation of patients' progress at scheduled intervals. The microcomputer system was developed to meet state guidelines for monitoring patients receiving neuroleptic drug treatment. A weekly status report generated for each patient alerts the treating physician to cases in which data do not justify clinical decisions, identifies potential problems, and suggests considering for discharge patients whose symptoms have sufficiently abated. The system is also useful in supervision and research.

Implications of restrictive diagnosis for compliance to antidepressant drug therapy: alprazolam versus imipramine.

Early dropouts from a double-blind comparison of the therapeutic efficacy of alprazolam and imipramine were examined. The dropout rate across the total sample of 99 analyzable outpatients with major depression was 3 times higher in the imipramine treatment group. Although essentially all patients met DSM-III criteria for major depressive episode, only two thirds of the total sample met the restrictive Feighner criteria for primary depressive disorder. Early termination in the imipramine group was concentrated in the group of depressed outpatients who failed to satisfy the Feighner criteria. Implications of these and other recently reported results for choice of drug treatment for depressed psychiatric outpatients are discussed.

Mechanisms of host defense in well nourished patients with chronic alcoholism.

Tests of immune function were performed on five recently abstinent, well nourished,and disease-free patients with chronic alcoholism. No significant defects in adherence, metabolic, or bactericidal activity of polymorphonuclear leukocytes were found when compared to sex-matched controls. Antibody-dependent and natural killer cellular cytotoxicity of monocyte-macrophages and lymphocytes also were normal. These data support the concept that immunity might be intact in the group of patients with chronic alcoholism who are recently sober, well nourished, and free of underlying disease.