Phase Space Reconstruction from Accelerator Beam Measurements Using Neural Networks and Differentiable Simulations.

Characterizing the phase space distribution of particle beams in accelerators is a central part of understanding beam dynamics and improving accelerator performance. However, conventional analysis methods either use simplifying assumptions or require specialized diagnostics to infer high-dimensional (>2D) beam properties. In this Letter, we introduce a general-purpose algorithm that combines neural networks with differentiable particle tracking to efficiently reconstruct high-dimensional phase space distributions without using specialized beam diagnostics or beam manipulations. We demonstrate that our algorithm accurately reconstructs detailed 4D phase space distributions with corresponding confidence intervals in both simulation and experiment using a limited number of measurements from a single focusing quadrupole and diagnostic screen. This technique allows for the measurement of multiple correlated phase spaces simultaneously, which will enable simplified 6D phase space distribution reconstructions in the future.

A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers.

BACKGROUND: Two carotenoids, lutein and zeaxanthin are found in the retinal pigment epithelium of the eye where they are believed to protect it against oxidative and light damage. The amounts of these carotenoids consumed by premature infants are not known. OBJECTIVE: The objective of the investigation was to measure these carotenoids in human and formulae milks. DESIGN: In all, 28 human milk samples were obtained at various times between days 1 and 41 of lactation from 13 mothers. Six formula milks commonly used in hospitals were also analysed. SETTING: Mothers who provided the milk samples had infants in the neonatal ward at the Royal Maternity Hospital, Belfast. RESULTS: Median lutein and zeaxanthin concentrations in human milk were 4.79 (range 0.42-9.98) nmol/g fat and 0.55 (0.00-1.70) nmol/g fat, respectively. Five of the six formula milks also contained lutein and zeaxanthin with concentrations that varied over a wide range (0.7-9.7 and 0.1-1.2 nmol/g fat, respectively). CONCLUSIONS: Carotenoid concentrations usually decreased with the duration of lactation. Some formula milks that were specially formulated for premature infants contained high concentrations of the lutein and zeaxanthin and the source may be egg yolk. SPONSORSHIP: These studies were supported by the University of Ulster and the Northern Ireland Mother and Baby Appeal.

Sonographically guided thrombin injection of iatrogenic femoral pseudoaneurysms: further experience of a single institution.

OBJECTIVE: In September 1998, we began to treat iatrogenic femoral pseudoaneurysms with direct thrombin injection under sonographic guidance. Our purpose was to determine the success and complication rate of this technique. SUBJECTS AND METHODS: We treated 114 consecutive patients who had iatrogenic femoral pseudoaneurysms using direct thrombin injection. A 22-gauge spinal needle was placed into the pseudoaneurysm lumen with sonographic guidance, and bovine or human thrombin (mean dose, 306 U; range, 50--1600 U) was injected under continuous color Doppler sonographic visualization. Distal pulses were monitored. Patient demographics, clinical variables, and pseudoaneurysm characteristics were collected. RESULTS: One hundred three (90%) of 114 patients had pseudoaneurysm thrombosis after the first procedure. Of the remaining 11 patients who required a second procedure 1 day later, thrombosis occurred in seven (64%) of 11. Thus, the overall success rate was 96% (110/114). Of the patients who required one injection, the mean thrombosis time was 12 sec (range, 3--90 sec). Three (3%) of 114 patients required conscious sedation. Of the patients with successful thrombosis, 24-hr follow-up sonograms showed no recurrent pseudoaneurysm. Four patients (4%) had potential complications: a "blue toe" 15 hr after the thrombin injection that resolved spontaneously, a groin abscess, leg ischemia that resolved spontaneously after 4 hr, and crampy buttock pain that resolved spontaneously. CONCLUSION: For the treatment of iatrogenic femoral pseudoaneurysms, thrombin injection under sonographic guidance is a quick and effective method of therapy. Failures and complications are infrequent. At our institution, sonographically guided thrombin injection has replaced compression repair.

Low-dose hypersensitivity after fractionated low-dose irradiation in vitro.

PURPOSE: It was demonstrated previously that some radioresistant tumour cell lines respond to decreasing single, low radiation doses by becoming increasingly radiosensitive. This paper reports the response of four radioresistant human glioma cell lines to multiple low-dose radiation exposures given at various intervals. Three of the cell lines (T98G, U87, A7) were proven already to show low-dose hyper-radiosensitivity (HRS) after single low doses; the fourth, U373, does not show HRS after acute doses. MATERIALS AND METHODS: Clonogenic cell-survival measurements were made in vitro using the Dynamic Microscopic Image Processing Scanner (DMIPS) or Cell Sorter (CS) following exposure to 240kVp X-rays one or more times. RESULTS: A consistent, time-dependent hypersensitive response to a second, or subsequent, dose was observed in the cell lines that demonstrated HRS. This time-dependent change in radiosensitivity did not occur in the radioresistant cell line that did not show HRS (U373). In one cell line that demonstrated strong HRS, T98G, a similar time-dependent hypersensitive response was also seen when the cells were irradiated whilst held in the G1-phase of the cell cycle. In this same cell line, significantly increased cell kill was demonstrated when three very low doses (0.4 Gy) were given per day, 4 h apart, for 5 days, compared with the same total dose given as once-daily 1.2Gy fractions. CONCLUSIONS: These data demonstrate the possibility that a multipledose per day, low-dose per fraction regimen, termed 'ultrafractionation', could produce increased tumour cell kill in radioresistant tumours compared with the same total dose given as conventional-sized 2 Gy fractions.

A purpose-built iodine-125 irradiation plaque for low dose rate low energy irradiation of cell lines in vitro.

The phenomenon of hyper-radiosensitivity (HRS) to very low acute single doses of radiation has been demonstrated in several cell lines in vitro and in vivo, and has been studied in theory and in practice. The theory suggests a similar hypersensitivity when cells are continuously exposed to radiation at very low dose rates. These low dose rates are used when radioactive seed (iodine-125 or palladium-103) implants of the prostate are used as an alternative to surgery or external beam radiotherapy. To investigate the radiobiology of hypersensitivity of this type on various cell lines in vitro, an iodine-125 seed irradiator has been designed and built for safe use in the Gray Laboratory. In practice, the calculated dose rate has been used for consistency. Discrepancies between calculated and measured dose rates are discussed.

Automated counting of mammalian cell colonies.

Investigating the effect of low-dose radiation exposure on cells using assays of colony-forming ability requires large cell samples to maintain statistical accuracy. Manually counting the resulting colonies is a laborious task in which consistent objectivity is hard to achieve. This is true especially with some mammalian cell lines which form poorly defined or 'fuzzy' colonies, typified by glioma or fibroblast cell lines. A computer-vision-based automated colony counter is presented in this paper. It utilizes novel imaging and image-processing methods involving a modified form of the Hough transform. The automated counter is able to identify less-discrete cell colonies typical of these cell lines. The results of automated colony counting are compared with those from four manual (human) colony counts for the cell lines HT29, A172, U118 and IN1265. The results from the automated counts fall well within the distribution of the manual counts for all four cell lines with respect to surviving fraction (SF) versus dose curves, SF values at 2 Gy (SF2) and total area under the SF curve (Dbar). From the variation in the counts, it is shown that the automated counts are generally more consistent than the manual counts.

Archeological evidence of parasitic infection from the 19th century company town of Fayette, Michigan.

Archeological deposits from the 19th century company town of Fayette, Michigan were analyzed for evidence of endoparasitic infection in the human population residing in the town between 1867 and 1891. Three privies were associated with upper-income and middle-income neighborhoods; 2 household refuse disposal areas were found in a predominately lower-income immigrant working class neighborhood. Sediment samples from 2 privies associated with dwellings in the middle-income neighborhood were positive for eggs of the human whipworm Trichuris trichiura. The parasite was probably also present among residents of the lower income neighborhood, but the shallow nature of the refuse deposits in that locality precluded preservation of the eggs. Contemporary epidemiologic studies of helminth infections support the belief that T. trichiura may have been a common parasite of 19th century school-age children given the natural inclination of young children to defecate indiscriminately, play freely in the dirt, and eat without washing their hands.

Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in ras- and Rho-mediated signaling.

The small GTPase Ras plays an important role in many cellular signaling processes. Ras activity is negatively regulated by GTPase activating proteins (GAPs). It has been proposed that RasGAP may also function as an effector of Ras activity. We have identified and characterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin). rin mutants are viable and display defects in photoreceptor recruitment and ommatidial polarity in the eye. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/MAPK pathway components. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. The ommatidial polarity phenotypes of rin are similar to those of RhoA and the polarity genes, e.g. fz and dsh. Although rin/G3BP interacts genetically with RhoA, affecting both photoreceptor differentiation and polarity, it does not interact with the gain-of-function genotypes of fz and dsh. These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways.

Paediatric renal transplantation in Northern Ireland (1984-1998).

Over the last 20 years a comprehensive paediatric nephrology service has been developed in Northern Ireland, based in the academic medical unit at the Royal Belfast Hospital for Sick Children (RBHSC). In the 15 years 1984-1998 a total of 77 renal transplants have taken place in patients aged 18 years and under. Initially transplants were only considered in children over five years of age but in the past eight years children as young as two years have successfully received kidneys. Aggressive nutritional support combined with peritoneal dialysis has enabled survival to a size when transplantation is feasible. The 5 year graft survival was 64%, with two children dying following transplantation. The complexity of managing this age group is reflected by the fact that a total of 10 transplants (13%) failed in the first 30 days. These figures compare favourably with statistics reported by similar paediatric centres from across the United Kingdom and Republic of Ireland, and with local results in adult patients. This demonstrates that a successful end stage renal replacement programme for children is achievable in a relatively small population, which is geographically isolated.

Percutaneous mitral balloon valvuloplasty.

Almost all mitral stenosis (MS) is rheumatic in etiology. The patient with MS who is symptomatic despite medical therapy should undergo percutaneous mitral balloon valvuloplasty or mitral valvular surgery (commissurotomy or replacement). The choice of procedure is determined by patient preference and the echocardiographic morphologic features of the valvular and subvalvular apparati. With balloon valvuloplasty, the rate of success is > 90%. At institutions where operators are experienced with balloon valvuloplasty and open surgical commissurotomy, their acute and long-term results are comparable. Balloon valvuloplasty occasionally is associated with complications, including death in 0 to 1%, moderate or severe valvular regurgitation in 3 to 5%, and systemic embolization in 1 to 3%.

Low dose hypersensitivity in the T98G human glioblastoma cell line.

PURPOSE: To examine the low dose-response of a human radioresistant glioblastoma cell line (T98G) using two different methods to measure surviving fraction and to define the influence of cell cycle phase on this response. MATERIALS AND METHODS: The survival of cells following exposure to single very low doses of X-rays in vitro was measured using either the Dynamic Microscopic Image Processing Scanner (DMIPS) or a Cell Sorter (CS). The DMIPS was also used to measure the low dose survival response of T98G cells following manipulation of their progression through the cell cycle. RESULTS: With both methods, T98G demonstrated marked low dose hyper-radiosensitivity (HRS) and the two methods produced very similar data in the low dose region of the survival curve. However, the CS protocol produced less variable results and was the more efficient method of generating low dose data. HRS was also demonstrated when these cells were irradiated while held in reversible arrest in the G1 phase of the cell cycle, but the effect was less marked than in the asynchronous population. CONCLUSIONS: T98G glioblastoma cells demonstrate marked HRS, which is a characteristic of the whole population rather than being due to the influence of a small subpopulation of hyper-radiosensitive cells within a particular phase of the cell cycle.

Linking cell-fate specification to planar polarity: determination of the R3/R4 photoreceptors is a prerequisite for the interpretation of the Frizzled mediated polarity signal.

The adult eye of Drosophila is a highly ordered structure composed of about 800 ommatidia, each displaying precise polarity. The planar polarity is reflected in the mirror-symmetric arrangement of ommatidia relative to the dorso-ventral midline, the equator. This arrangement is generated when ommatidia rotate towards the equator and the photoreceptor R3 displaces R4 creating different chiral forms in each half. Analysis of ommatidia mosaic for the tissue polarity gene frizzled (fz) has shown that the presence of a single Fz+ photoreceptor cell within the R3/ R4 pair is critical for the direction of rotation and chirality. By analysing clones mutant for seven-up (svp), in which R3/R4 precursors reside in their normal positions and become photoreceptor neurones but fail to adopt the normal R3/R4 fate, we find that the R3/R4 photoreceptor subtype specification is a prerequisite for planar polarisation in the eye. Moreover, in mosaic R3/R4 pairs we find that the svp- cell always adopts the R4 position. This bias is reminiscent of what happens in fz mosaic R3/R4 pairs, where the fz- cell also almost always adopts the R4 position. In addition, we find that in genotypes where too many cells adopt the R3/R4 fate, ommatidial polarity is also disturbed. Taken together, these data imply that correct specification of a single R3 cell per ommatidium is essential for the normal interpretation of the Fz-mediated polarity signal.

A scoring system for the prediction of successful delivery in low-risk birthing units.

OBJECTIVE: To establish and test the effectiveness of a low-risk scoring system to predict obstetric outcome for the selection of women suitable for confinement in low-intervention units. METHODS: Retrospective analyses were performed on data from 2900 women enrolled in the Western Australian Pregnancy Cohort Study and 1353 women managed at a midwifery-based birth center. A combination of the principal predictors of obstetric outcome, incorporating a previously published scoring system and various clinical features, was used to exclude high-risk cases at 18 weeks' and 36 weeks' gestation. Stepwise multivariate logistic regression analyses of the remaining pregnancies then produced a low-risk scoring system. RESULTS: This system predicted a 55% chance of an uncomplicated delivery in a midwifery-based setting after allocating 54% of women to the low-risk category. It predicted an 82% chance of an uncomplicated delivery in a primary medical care setting with the allocation of 84% of women as low risk. CONCLUSION: The results of this study suggest that adding induction and augmentation of labor, together with low pelvic instrumental delivery, to the treatment options in a low-intervention unit would raise the rate of successful confinement within the unit from 55% to 82%. Our scoring system now requires prospective evaluation to further assess its clinical value.

Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet-derived growth factor and transforming growth factor beta.

The healing responses of the anterior cruciate ligament and the patellar tendon differ markedly. The anterior cruciate ligament fails to heal, whereas the patellar tendon heals slowly. The basis of these differences is unknown. Since cellular proliferation is a critical element of healing, we investigated the response to explants of anterior cruciate ligament and patellar tendon from sheep knees to platelet-derived growth factor-AB and transforming growth factor beta 1 as a function of time and dose. Explants cultured for 48, 72, and 96 hours with transforming growth factor beta 1 (0-100 ng/ml) or platelet-derived growth factor-AB (0-200 ng/ml) were radiolabeled for the final 24 hours with [3H]thymidine, and DNA synthesis was quantified as trichloroacetic acid-precipitable radioactivity normalized to dry tissue weight. Statistical analyses (analysis of variance) showed that transforming growth factor beta 1 induced a significant proliferative response in the anterior cruciate ligament at 96 hours with equivalent responses at 10, 50, and 100 ng/ml, whereas the patellar tendon only responded to one condition, 10 ng/ml at 96 hours. Conversely, the patellar tendon had a significant dose-dependent response to platelet-derived growth factor-AB at 72 and 96 hours, whereas the anterior cruciate ligament showed no proliferative response to platelet-derived growth factor-AB. The minimal response of anterior cruciate ligament to platelet-derived growth factor-AB could explain, at least in part, the poor repair capacity of this tissue. The response of the anterior cruciate ligament to transforming growth factor beta suggests that exogenous transforming growth factor beta may promote initial healing. Although growth factors have the potential to modulate soft-tissue repair, tissue responses in tendons and ligaments may vary at different anatomic sites.

Regional mitogenic response of the meniscus to platelet-derived growth factor (PDGF-AB).

Since meniscal healing is region-specific, we studied the regional (peripheral compared with central) response of meniscal explants to human, recombinant platelet-derived growth factor-AB. Meniscal explants from the hindlimbs of both knees of mature sheep were sectioned and were cultured with variable doses of human, recombinant platelet-derived growth factor-AB, and incorporation of [3H]-thymidine was measured. The mitogenic response was measured at different times in culture (48 or 96 hours) and by location (lateral or medial). In the absence of the growth factor, the peripheral third of both menisci incorporated 10-fold more [3H]-thymidine on a weight basis than did the central two-thirds. Cellularity was equivalent in the two regions. Doses of less than 100 ng/ml of growth factor produced either no stimulation or a variable response. A dose of 100 ng/ml resulted in consistent, significant (p < 0.05) stimulation in all groups in the peripheral region, and a dose of 200 ng/ml provided more than a 2.5-fold increase. Multiple-factor analysis of variance demonstrated that there were no significant differences between experiments, times in culture, or menisci. The central region did not respond to stimulation with the growth factor at any of the doses tested. These data suggest that regional differences (peripheral compared with central) in responsiveness to human, recombinant platelet-derived growth factor-AB may reflect a different level of signal transduction machinery for growth factor receptors and distinct fibrobchondrocyte populations. These findings are consistent with the variable healing capacity of the meniscal regions in vivo and suggest a pharmacological means to promote the repair of the peripheral meniscal region.