Recovery time of a plasma-wakefield accelerator.

The interaction of intense particle bunches with plasma can give rise to plasma wakes1,2 capable of sustaining gigavolt-per-metre electric fields3,4, which are orders of magnitude higher than provided by state-of-the-art radio-frequency technology5. Plasma wakefields can, therefore, strongly accelerate charged particles and offer the opportunity to reach higher particle energies with smaller and hence more widely available accelerator facilities. However, the luminosity and brilliance demands of high-energy physics and photon science require particle bunches to be accelerated at repetition rates of thousands or even millions per second, which are orders of magnitude higher than demonstrated with plasma-wakefield technology6,7. Here we investigate the upper limit on repetition rates of beam-driven plasma accelerators by measuring the time it takes for the plasma to recover to its initial state after perturbation by a wakefield. The many-nanosecond-level recovery time measured establishes the in-principle attainability of megahertz rates of acceleration in plasmas. The experimental signatures of the perturbation are well described by simulations of a temporally evolving parabolic ion channel, transferring energy from the collapsing wake to the surrounding media. This result establishes that plasma-wakefield modules could be developed as feasible high-repetition-rate energy boosters at current and future particle-physics and photon-science facilities.

High-resolution sampling of beam-driven plasma wakefields.

Plasma-wakefield accelerators driven by intense particle beams promise to significantly reduce the size of future high-energy facilities. Such applications require particle beams with a well-controlled energy spectrum, which necessitates detailed tailoring of the plasma wakefield. Precise measurements of the effective wakefield structure are therefore essential for optimising the acceleration process. Here we propose and demonstrate such a measurement technique that enables femtosecond-level (15 fs) sampling of longitudinal electric fields of order gigavolts-per-meter (0.8 GV m-1). This method-based on energy collimation of the incoming bunch-made it possible to investigate the effect of beam and plasma parameters on the beam-loaded longitudinally integrated plasma wakefield, showing good agreement with particle-in-cell simulations. These results open the door to high-quality operation of future plasma accelerators through precise control of the acceleration process.

FLASHForward: plasma wakefield accelerator science for high-average-power applications.

The FLASHForward experimental facility is a high-performance test-bed for precision plasma wakefield research, aiming to accelerate high-quality electron beams to GeV-levels in a few centimetres of ionized gas. The plasma is created by ionizing gas in a gas cell either by a high-voltage discharge or a high-intensity laser pulse. The electrons to be accelerated will either be injected internally from the plasma background or externally from the FLASH superconducting RF front end. In both cases, the wakefield will be driven by electron beams provided by the FLASH gun and linac modules operating with a 10 Hz macro-pulse structure, generating 1.25 GeV, 1 nC electron bunches at up to 3 MHz micro-pulse repetition rates. At full capacity, this FLASH bunch-train structure corresponds to 30 kW of average power, orders of magnitude higher than drivers available to other state-of-the-art LWFA and PWFA experiments. This high-power functionality means FLASHForward is the only plasma wakefield facility in the world with the immediate capability to develop, explore and benchmark high-average-power plasma wakefield research essential for next-generation facilities. The operational parameters and technical highlights of the experiment are discussed, as well as the scientific goals and high-average-power outlook. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Tunable Plasma-Based Energy Dechirper.

A tunable plasma-based energy dechirper has been developed at FLASHForward to remove the correlated energy spread of a 681 MeV electron bunch. Through the interaction of the bunch with wakefields excited in plasma the projected energy spread was reduced from a FWHM of 1.31% to 0.33% without reducing the stability of the incoming beam. The experimental results for variable plasma density are in good agreement with analytic predictions and three-dimensional simulations. The proof-of-principle dechirping strength of 1.8 GeV/mm/m significantly exceeds those demonstrated for competing state-of-the-art techniques and may be key to future plasma wakefield-based free-electron lasers and high energy physics facilities, where large intrinsic chirps need to be removed.

Lipids and polyunsaturated fatty acid levels in deliberate self-harm: a 10-year follow-up study.

OBJECTIVES: To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid levels are associated with episodes of self-harm or depression over a 10-year period. METHODS: We included 40 individuals who self-harmed and 40 controls. Episodes of self-harm and depression were ascertained and levels of depression, impulsivity, suicidal ideation and plasma lipid levels measured at baseline and at 10-year follow-up. RESULTS: Further episode(s) of self-harm occurred in 26% of cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm episodes. Baseline eicosapentaenoic acid levels were modestly correlated with suicidal ideation at follow-up and dihomo-γ-linolenic acid and arachidonic acid were modestly correlated with motor impulsivity at follow-up in cases. CONCLUSIONS: Despite significant negative correlations at baseline between plasma lipids, n-3 PUFAs and psychopathology, these levels were not predictive of clinical outcome over a 10-year period. Further research however is required due to the relatively low sample size and the risk of selection bias due to loss to follow-up in this study.

Loss of Dnmt3a induces CLL and PTCL with distinct methylomes and transcriptomes in mice.

Cytosine methylation of DNA is an epigenetic modification involved in the repression of genes that affect biological processes including hematopoiesis. It is catalyzed by DNA methyltransferases, one of which -DNMT3A- is frequently mutated in human hematologic malignancies. We have previously reported that Dnmt3a inactivation in hematopoietic stem cells results in chronic lymphocytic leukemia (CLL) and CD8-positive peripheral T cell lymphomas (PTCL) in EµSRα-tTA;Teto-Cre;Dnmt3afl/fl; Rosa26LOXPEGFP/EGFP (Dnmt3aΔ/Δ) mice. The extent to which molecular changes overlap between these diseases is not clear. Using high resolution global methylation and expression analysis we show that whereas patterns of methylation and transcription in normal B-1a cells and CD8-positive T cells are similar, methylomes and transcriptomes in malignant B-1a and CD8+ T cells are remarkably distinct, suggesting a cell-type specific function for Dnmt3a in cellular transformation. Promoter hypomethylation in tumors was 10 times more frequent than hypermethylation, three times more frequent in CLL than PTCL and correlated better with gene expression than hypermethylation. Cross-species molecular comparison of mouse and human CLL and PTCL reveals significant overlaps and identifies putative oncogenic drivers of disease. Thus, Dnmt3aΔ/Δ mice can serve as a new mouse model to study CLL and PTCL in relevant physiological settings.

The effect of slurry on skin permeability to methylene blue dye in dairy cows with and without a history of digital dermatitis.

This study aimed to determine whether there was a difference in skin permeability to methylene blue dye or skin morphology between dairy cows that differed in their susceptibility to digital dermatitis (DD) and to assess the effect of contact with slurry on skin permeability. Twenty nine dairy cows were monitored for DD during the winter housing period and classed as DD+ (previous DD infection, n = 17), or DD- (no recorded infection, n = 12). The animals were culled and a skin sample was taken from above the heel of each hind foot and frozen. Samples were later defrosted and one sample from each cow was tested for permeability, whereas the other was treated with slurry for 24 h before permeability testing. To test permeability, methylene blue dye was applied to the skin surface in a Franz diffusion cell. After 48 h, the amount of dye that had passed through the skin was estimated. The stratum corneum thickness and the density of hair follicles were determined from additional heel skin samples. Skin permeability to methylene blue dye was significantly greater for samples that had been treated with slurry but did not differ between DD+ and DD- animals. No difference was found in the stratum corneum thickness or density of hair follicles between DD+ and DD- animals. These findings imply that individual differences in general skin permeability are not a major factor in determining DD susceptibility and suggest that contact with slurry could contribute to DD infection by increasing the permeability of the skin, which may facilitate pathogen entry. Further work is required to clarify the role played by slurry in the pathogenesis of DD.

The inter-conversions of platinum carbonyl dianionic clusters, [Pt3(CO)6](n)2- (n = 2-5), in THF and acetonitrile. A combined in situ FTIR spectroscopic and BTEM study leading to the characterization of the new [H(4-x)Pt15(CO)19]x- (x = 2-4) clusters.

The inter-conversions of platinum carbonyl dianionic clusters, ([Pt(3)(CO)(6)](n)(2-), n = 2-5), have been studied in THF and acetonitrile using in situ FTIR spectroscopy. These inter-conversions were facilitated by the addition (or removal) of molecular hydrogen. The individual reactions, namely reductions and oxidations of [Pt(3)(CO)(6)](n)(2-) were fast and reversible. BTEM analysis of the data provided the pure component spectra of the individual species without the need for physical separation. It is shown, for the first time, that the species [Pt(3)(CO)(6)](n)(2-) (n = 2) can be formed from the reduction of [Pt(3)(CO)(6)](n)(2-) (n = 3-5) by hydrogen alone in acetonitrile. Also, detection of dissolved CO(2) in solution suggests that a room-temperature water gas shift reaction occurs. This has been shown to arise from nucleophilic attack of water on a coordinated CO of [Pt(3)(CO)(6)](n)(2-) which leads to the formation of [HPt(15)(CO)(19)](3-) and [H(2)Pt(15)(CO)(19)](2-). The parent tetraanion, [Pt(15)(CO)(19)](4-), has been isolated in high yields by reaction of [Pt(3)(CO)(6)](n)(2-) (n = 2, 3) with NaOH at 60 °C and has been structurally characterized by X-ray analysis.

Crystallographic, thermal and spectroscopic characterization of a ciprofloxacin saccharinate polymorph.

A new polymorphic form of ciprofloxacin saccharinate (CIP-SAC II) is presented, and compared with CIP-SAC I, a different polymorph which we had previously reported. The characterization techniques used were single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry analysis and infrared and (13)C solid-state nuclear magnetic resonance spectroscopy. The results obtained from these techniques are consistent. Differential scanning calorimetry and thermogravimetric analysis showed that the reaction between the precursors is completed and the crystalline forms of both salts obtained (I and II) are highly pure. Infrared spectroscopy gave clear evidence of a salt formation. Solid-state nuclear magnetic resonance spectroscopy would indicate some degree of qualitative similarity in the intermolecular interaction scheme in both polymorphs, while thermal analysis data might indicate a difference in quantitative terms. A thorough single crystal structure determination of the new form CIP-SAC II allowed disclosing the most important inter- and intramolecular interactions.

(E)-3-Ferrocenyl-1-(2-hy-droxy-phen-yl)-prop-2-en-1-one.

The mol-ecular structure of the title compound, [Fe(C(5)H(5))(C(14)H(11)O(2))] consists of a ferrocenyl and 2-hy-droxy-phenyl group linked through the prop-2-en-1-one spacer and is stabilized by an intra-molecular O-H⋯O hydrogen bond between the hydroxyl and the carbonyl groups.

(Z)-3-(4-Bromo-anilino)-1-ferrocenylbut-2-en-1-one.

In the title compound, [Fe(C(5)H(5))(C(15)H(13)BrNO)], formed from the reaction of ferrocenoylacetone and 4-bromo-aniline, the mol-ecular structure is stabilized by an intra-molecular N-H⋯O hydrogen bond between the amine and carbonyl groups.

Production of Sn-117m in the BR2 high-flux reactor.

The BR2 reactor is a 100MW(th) high-flux 'materials testing reactor', which produces a wide range of radioisotopes for various applications in nuclear medicine and industry. Tin-117m ((117m)Sn), a promising radionuclide for therapeutic applications, and its production have been validated in the BR2 reactor. In contrast to therapeutic beta emitters, (117m)Sn decays via isomeric transition with the emission of monoenergetic conversion electrons which are effective for metastatic bone pain palliation and radiosynovectomy with lesser damage to the bone marrow and the healthy tissues. Furthermore, the emitted gamma photons are ideal for imaging and dosimetry.

Synthesis of 6,19-cyclopregnanes. Constrained analogues of steroid hormones.

A procedure for the synthesis of 6,19-cyclopregnanes is described involving an intramolecular alkylation reaction of Delta(4)-3-keto steroids with a 19-mesylate in the presence of KOH in isopropanol. Three 6,19-cyclopregnanes were prepared (4, 5 ,9); in the rat, 6,19-cycloprogesterone (4) and its 21-hydroxy derivative 5 displaced [3H]-dexamethasone from glucocorticoid receptors, the former compound being more active. Both compounds did not compete with [3H]-aldosterone for kidney mineralocorticoid receptors nor with [3H]-R5020 for uterus progesterone receptors.

Phytotoxic withanolides from Jaborosa rotacea.

Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies. Compounds 4, 5, 6, and 8 showed selective phytotoxicity toward monocotyledoneous and dicotyledoneous species.

Neutron flux characterization of a peripheral target position in the High Flux Isotope Reactor.

The High Flux Isotope Reactor at the Oak Ridge National Laboratory provides the highest steady-state thermal neutron flux in the western world for a wide range of experiments and for isotope production. The highest available fluxes are located in a flux trap region created inside the nested fuel elements. The experimentally determined thermal and the empirically obtained epithermal flux values along the vertical axis of the peripheral target position were fit to cosine curves, with the thermal flux ranging from 1.1 x 10(15)ns(-1)cm(-2) at outer positions to 1.5 x 10(15)ns(-1)cm(-2) at the center. The corresponding epithermal flux ranged from 3.5 x 10(13) to 7.5 x 10(13)ns(-1)cm(-2), respectively. The fast neutron flux (En > or = 0.32 MeV in two positions and En > or = 1.5 MeV in two other positions) was approximately 6 x 10(14)ns(-1)cm(-2), corresponding to a fast to thermal ratio of approximately 0.4.

Correlates of specific childhood feeding problems.

OBJECTIVE: The correlates of specific childhood feeding problems are described to further examine possible predisposing factors for feeding problems. We report our experience with 349 participants evaluated by an interdisciplinary feeding team. METHODS: A review of records was conducted and each participant was identified as having one or more of five functionally defined feeding problems: food refusal, food selectivity by type, food selectivity by texture, oral motor delays, or dysphagia. The prevalence of predisposing factors for these feeding problems was examined. Predisposing factors included developmental disabilities, gastrointestinal problems, cardiopulmonary problems, neurological problems, renal disease and anatomical anomalies. RESULTS: The frequencies of predisposing factors varied by feeding problem. Differences were found in the prevalence of the five feeding problems among children with three different developmental disabilities: autism, Down syndrome and cerebral palsy. Gastro-oesophageal reflux was the most prevalent condition found among all children in the sample and was the factor most often associated with food refusal. Neurological conditions and anatomical anomalies were highly associated with skill deficits, such as oral motor delays and dysphagia. CONCLUSIONS: Specific medical conditions and developmental disabilities are often associated with certain feeding problems. Information concerning predisposing factors of feeding problems can help providers employ appropriate primary, secondary and tertiary prevention measures to decrease the frequency or severity of some feeding problems.

Ease of access is a principal factor in the frequency of paracetamol overdose.

BACKGROUND: In Ireland, 30% of non-fatal overdoses involve paracetamol. AIMS: To determine how and where patients obtained paracetamol, to assess awareness of toxicity and examine the relationship between dose and suicidal intent. METHODS: A prospective study of patients admitted following a paracetamol overdose recording their reasons for using paracetamol, their knowledge of its toxicity and their suicidal intent scale (SIS). RESULTS: Of 100 patients, 66% obtained paracetamol in non-pharmacy outlets, 82% cited ease of availability as the reason, 55% were aware of its toxicity, 31% of liver damage and 68% did not read the warning on packets. The mean number of tablets taken was 51.3 for males and 37.2 for females (p < 0.01). Males presented later than females for medical attention (12.5 versus seven hours [p < 0.02]) and more males than females took alcohol (p < 0.03). The mean SIS score was 14.71 for males and 12.38 for females. There was a significant correlation between the SIS and the amount of paracetamol consumed (r = 0.28; p < 0.01). CONCLUSION: The majority obtained paracetamol in local shops or at home. Knowledge of toxicity and the need for early antidote was poor. There was a significant relationship between suicidal intent and number of tablets consumed. Limiting availability could reduce number of overdoses.

Bis(2,2':6',2"-terpyridine-kappa3N)manganese(II) tetrathionate trihydrate.

The structure of the title compound, [Mn(tpy)2](S4O6)*3H2O (tpy is 2,2':6',2"-terpyridine, C15H11N3), consists of monomeric [Mn(tpy)2]2+ units embedded in a complex anionic network made up of tetrathionate ions and hydration water molecules connected via a complex hydrogen-bonding scheme.