Absolute calibration of Fujifilm BAS-TR image plate response to laser driven protons up to 40 MeV.

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

Relationships among gastrointestinal symptoms, sleep problems, challenging behaviour, comorbid psychopathology and autism spectrum disorder symptoms in children and adolescents with 15q duplication syndrome.

BACKGROUND: Comorbidity is the presence of at least two disorders in one person at one time. This study examined the frequency of gastrointestinal (GI) symptoms, sleep problems, comorbid psychopathology, challenging behaviour and autism spectrum disorder (ASD) symptoms in children and adolescents with duplication 15q syndrome (Dup15q), aged 3-17 years. This study also examined whether challenging behaviour in Dup15q is predicted by age, gender, presence of an intellectual disability, sleep problems, GI symptoms and comorbid psychopathology. METHOD: Parental measures were completed by 101 parents of children and adolescents with Dup15q. Questionnaires were composed of the Children's Sleep Habits Questionnaire, Behavior Problems Inventory - Short Form, GI Symptom Inventory, Social Communication Questionnaire and the Child Behavior Checklist. RESULTS: Sleep problems (94%), GI symptoms (87%) and challenging behaviour (100%) were common comorbidities represented in the sample in this study. Significant relationships were found between challenging behaviour and the presence of co-occurring sleep problems, GI symptoms, comorbid psychopathology and ASD symptoms. Further analysis revealed that these comorbidities also predicted challenging behaviour. CONCLUSION: This research demonstrated the importance of studying the relationships between GI symptoms, sleep problems, comorbid psychopathology, ASD symptoms and challenging behaviour in Dup15q and how these conditions can shape the Dup15q phenotype.

DNA DSB Repair Dynamics following Irradiation with Laser-Driven Protons at Ultra-High Dose Rates.

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 109 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered.

Polarization Dependence of Bulk Ion Acceleration from Ultrathin Foils Irradiated by High-Intensity Ultrashort Laser Pulses.

The acceleration of ions from ultrathin (10-100 nm) carbon foils has been investigated using intense (∼6×10^{20} W cm^{-2}) ultrashort (45 fs) laser pulses, highlighting a strong dependence of the ion beam parameters on the laser polarization, with circularly polarized (CP) pulses producing the highest energies for both protons and carbons (25-30 MeV/nucleon); in particular, carbon ion energies obtained employing CP pulses were significantly higher (∼2.5 times) than for irradiations employing linearly polarized pulses. Particle-in-cell simulations indicate that radiation pressure acceleration becomes the dominant mechanism for the thinnest targets and CP pulses.

Efficient post-acceleration of protons in helical coil targets driven by sub-ps laser pulses.

The characteristics of laser driven proton beams can be efficiently controlled and optimised by employing a recently developed helical coil technique, which exploits the transient self-charging of solid targets irradiated by intense laser pulses. Here we demonstrate a well collimated (<1° divergence) and narrow bandwidth (~10% energy spread) proton beamlet of ~107 particles at 10 ± 0.5 MeV obtained by irradiating helical coil targets with a few joules, sub-ps laser pulses at an intensity of ~2 × 1019 W cm-2. The experimental data are in good agreement with particle tracing simulations suggesting post-acceleration of protons inside the coil at a rate ~0.7 MeV/mm, which is comparable to the results obtained from a similar coil target irradiated by a fs class laser at an order of magnitude higher intensity, as reported in S. Kar et al., Nat. Commun, 7, 10792 (2016). The dynamics of hot electron escape from the laser irradiated target was studied numerically for these two irradiation regimes, which shows that the target self-charging can be optimised at a pulse duration of few hundreds of fs. This information is highly beneficial for maximising the post-acceleration gradient in future experiments.

Enhancement of Quasistationary Shocks and Heating via Temporal Staging in a Magnetized Laser-Plasma Jet.

We investigate the formation of a laser-produced magnetized jet under conditions of a varying mass ejection rate and a varying divergence of the ejected plasma flow. This is done by irradiating a solid target placed in a 20 T magnetic field with, first, a collinear precursor laser pulse (10^{12} W/cm^{2}) and, then, a main pulse (10^{13} W/cm^{2}) arriving 9-19 ns later. Varying the time delay between the two pulses is found to control the divergence of the expanding plasma, which is shown to increase the strength of and heating in the conical shock that is responsible for jet collimation. These results show that plasma collimation due to shocks against a strong magnetic field can lead to stable, astrophysically relevant jets that are sustained over time scales 100 times the laser pulse duration (i.e., >70 ns), even in the case of strong variability at the source.

Laboratory formation of a scaled protostellar jet by coaligned poloidal magnetic field.

Although bipolar jets are seen emerging from a wide variety of astrophysical systems, the issue of their formation and morphology beyond their launching is still under study. Our scaled laboratory experiments, representative of young stellar object outflows, reveal that stable and narrow collimation of the entire flow can result from the presence of a poloidal magnetic field whose strength is consistent with observations. The laboratory plasma becomes focused with an interior cavity. This gives rise to a standing conical shock from which the jet emerges. Following simulations of the process at the full astrophysical scale, we conclude that it can also explain recently discovered x-ray emission features observed in low-density regions at the base of protostellar jets, such as the well-studied jet HH 154.

Antitropical distributions and species delimitation in a group of ophiocomid brittle stars (Echinodermata: Ophiuroidea: Ophiocomidae).

In this paper we examine the phylogeny and biogeography of the temperate genera of the Ophiocomidae (Echinodermata: Ophiuroidea) which have an interesting asymmetrical anti-tropical distribution, with two genera (Ophiocomina and Ophiopteris) previously considered to have a separate species in both the North and South hemispheres, and the third (Clarkcoma) diversifying in the southern Australian/New Zealand region. Our phylogeny, generated from one mitochondrial and two nuclear markers, revealed that Ophiopteris is sister to a mixed Ophiocomina/Clarkcoma clade. Ophiocomina was polyphyletic, with O. nigra and an undescribed species from the South Atlantic Ocean sister to a clade including Clarkcoma species and O. australis. The phylogeny also revealed a number of recently diverged lineages occurring within Clarkcoma, some of which are considered to be cryptic species due to the similarity in morphology combined with the apparent absence of interbreeding in a sympatric distribution, while the status of others is less certain. The phylogeny provides support for two transequatorial events in the group under study. A molecular clock analysis places both events in the middle to late Miocene. The analysis excludes a tectonic vicariance hypothesis for the antitropical distribution associated with the breakup of Pangaea and also excludes the hypothesis of more recent gene flow associated with Plio/Pleistocene glacial cycling.

Sympatric cryptic species in the crinoid genus Cenolia (Echinodermata: Crinoidea: Comasteridae) delineated by sequence and microsatellite markers.

The marine species of the southern coast of Australia have not been well studied with regard to molecular connectivity. Cryptic species are expected to be prevalent on this coastline. Here, we investigate the crinoid genus Cenolia (Echinodermata: Crinoidea: Comasteridae) using molecular methods to elucidate cryptic species and phylogenetic relationships. The genus Cenolia dominates the southern Australian crinoid fauna in shallow waters. Few studies have examined crinoids for cryptic species at a molecular level and these have been predominantly based on mitochondrial data. We employ the nuclear markers 28S rRNA and ITS-2 in addition to the mitochondrial COI. Six divergent mitochondrial clades were identified. Gene flow between confirmed clades was subsequently examined by the use of six novel microsatellite markers, showing that sympatric taxa with low mtDNA divergences (1.7% K2P) were not interbreeding in the wild. The type specimens of Cenolia benhami and C. spanoschistum were examined, as well as all six divergent clades. Morphological characters dividing taxa were refined. Due to comb pinnule morphology, the New Zealand species benhami was determined to belong to the genus Oxycomanthus (nov. comb.). Three new species of Cenolia (including the Australian "benhami") require description.

A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis.

AIMS/HYPOTHESIS: Insulin-requiring diabetes affects 25-50% of young adults with cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent heritability studies in CF twins and siblings indicate that genetic modifiers play a substantial role. We sought to assess whether genes conferring risk for diabetes in the general population may play a risk modifying role in CF. METHODS: We tested whether a family history of type 2 diabetes affected diabetes risk in CF patients in 539 families in the CF Twin and Sibling family-based study. A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 unrelated CF patients in an independent case-control study. RESULTS: Family history of type 2 diabetes increased the risk of diabetes in CF (OR 3.1; p = 0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T allele at rs7903146) was associated with diabetes in CF in the family study (p = 0.004) and in the case-control study (p = 0.02; combined p = 0.0002). In the family-based study, variation in TCF7L2 increased the risk of diabetes about three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p = 0.0006), and decreased the mean age at diabetes diagnosis by 7 years. In CF patients not treated with systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per allele, 95% CI 1.7-4.9, p = 0.00011). CONCLUSIONS/INTERPRETATION: A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.

Combined daily therapy with intravenous ganciclovir and foscarnet for patients with recurrent cytomegalovirus retinitis.

We treated seven patients (nine eyes) who had cytomegalovirus retinitis with daily intravenous ganciclovir plus foscarnet. All patients had demonstrated multiple progressions of retinitis on single-drug therapy, and some were intolerant to induction doses of one or both medications. Before combination therapy, the median number of progressions was five per patient. The mean interval between progressions was 11 weeks, and the mean interval before the final progression was four weeks. While taking combination therapy, two patients showed progression after 14 and 34 weeks. Two patients showed no progression after 17 and 36 weeks of follow-up. Three patients died after five, 14, and 23 weeks, respectively, without progression of retinitis. In every patient, the progression-free interval was longer during combination therapy than the previous progression-free interval during single-drug therapy. In no case was combination therapy stopped because of toxicity. Combination therapy was fairly well tolerated and appeared to prolong the interval to progression and to preserve vision in our patients.

Concurrent use of ganciclovir and foscarnet to treat cytomegalovirus infection in AIDS patients.

Ten patients with AIDS and progressive cytomegalovirus disease were treated with ganciclovir and foscarnet concurrently. The patients had received ganciclovir and foscarnet monotherapy a median of 330 days before receiving combination therapy for a median of 80 days. Nine of the 10 patients responded to the combination. No electrolyte abnormalities were noted during combination therapy, but rates of neutropenia (relative rate, combination vs. ganciclovir, 1.99; P = .229) and thrombocytopenia (relative rate, combination vs. ganciclovir, 1.53; P = .616) were higher with combination therapy than with either drug alone. The relative rate of anemia was significantly increased with combination therapy compared with monotherapy (relative rate, combination vs. ganciclovir, 2.69; P = .025). These data suggest that combination ganciclovir and foscarnet therapy after failure of either alone appears to be as effective as standard therapy with single agents. The rate of anemia with combination therapy was significantly greater than either agent alone, but no significant difference was noted among the other parameters of toxicity studied.

Cerebral circulatory and metabolic responses to intravenously administered lorazepam.

Cerebral vascular and metabolic effects of lorazepam were evaluated in ten awake monkeys by use of a modification of the Kety-Schmidt technique. Five received ketamine, 10 mg/kg, im, five to eight hours prior to the study, but all animals were otherwise treated identically. Monkeys receiving ketamine had significantly greater (P < 0.05) cerebral blood flow (CBF) values before lorazepam was given (46 +/- 1 ml/100 g/min) than did monkeys not receiving ketamine (41 +/- 1 ml/100 g/min), but in all other respects, premedicated and unpremedicated animals did not differ. Lorazepam administration did not significantly alter systemic arterial blood pressure or blood-gas values. However, it did decrease CBF by 26 per cent and increase cerebral vascular resistance (CVR) by approximately 25 per cent (P < 0.01). The cerebral metabolic rate for glucose (CMRg) decreased 42 per cent (P < 0.05). Following lorazepam administration, the cerebral metabolic rate for oxygen (CMRO2) decreased by 21-30 per cent. When combined CMRO2 data for the two anesthetic groups are pooled, this decrease is significant (P < 0.05). This study indicates that sedative doses of lorazepam decrease cerebral blood flow and metabolism with minimal effects on blood pressure and blood-gas values. Lorazepam administration did not produce any change in cerebral metabolism indicative of brain hypoxia or ischemia.

Heterogeneity of local cerebral blood flow-PaCO2 sensitivity in neonatal dogs.

Local cerebral blood flow (1-CBF) sensitivity to changes in arterial carbon dioxide tension (PaCO2) was measured in nitrous oxide-anesthetized newborn puppies using a quantitative autoradiographic technique and [14C]antipyrine as a tracer. 1-CBF was determined in four experimental groups at PaCO2 levels of 22, 34, 48, and 65 Torr, respectively. All seven brain areas studied demonstrated 1-CBF sensitivity to altered PaCO2. There were no significant differences (P greater than 0.05) in three subcortical white matter regions (frontal, parietal, occipital) in either 1-CBF or 1-CBF-CO2 sensitivity. With the exception of the thalamus, a reciprocal relationship existed between changes in local cerebral vascular resistance and blood flow. In the thalamus, 1-CBF increased at a greater rate than the 1-CVR reduction. The results show that CBF is heterogeneous in different brain areas of the neonatal dog at normocapnia and that differences in 1-CBF-CO2 sensitivity exist.