Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Scottish soldiers from the Battle of Dunbar 1650: A prosopographical approach to a skeletal assemblage.

After the Battle Dunbar between English and Scottish forces in 1650, captured Scottish soldiers were imprisoned in Durham and many hundreds died there within a few weeks. The partial skeletal remains of 28 of these men were discovered in 2013. Building on previous osteological work, here we report wide-ranging scientific studies of the remains to address the following questions: Did they have comparable diet, health and disease throughout their lives? Did they have common histories of movement (or lack of movement) during their childhoods? Can we create a collective biography of these men? Strontium and oxygen isotope analysis of tooth enamel investigated childhood movement. Carbon and nitrogen isotope analysis of incrementally sampled dentine addressed childhood diet and nutrition. Metaproteomic analysis of dental calculus investigated oral microbiomes and food residues; this was complemented by microscopic analysis of debris in calculus from ingested materials. Selected individuals were examined for dental microwear. The extent of hydroxylation of proline in collagen was examined as a potential biomarker for scurvy. An osteobiography for each man was created using the full range of data generated about him, and these were synthesised using an approach based on the historical method for a collective biography or prosopography. The childhood residences of the men were primarily within the Midland Valley of Scotland, though some spent parts of their childhood outside the British Isles. This is concordant with the known recruitment areas of the Scottish army in 1650. Their diets included oats, brassicas and milk but little seafood, as expected for lowland rather than highland diets of the period. Childhood periods of starvation or illness were almost ubiquitous, but not simultaneous, suggesting regionally variable food shortages in the 1620s and 1630s. It is likely there was widespread low-level scurvy, ameliorating in later years of life, which suggests historically unrecorded shortages of fruit and vegetables in the early 1640s. Almost all men were exposed to burnt plant matter, probably as inhaled soot, and this may relate to the high proportion of them with of sinusitis. Interpersonal violence causing skeletal trauma was rare. Based on commonalities in their osteobiographies, we argue that these men were drawn from the same stratum of society. This study is perhaps the most extensive to date of individuals from 17th century Scotland. Combined with a precise historical context it allows the lives of these men to be investigated and compared to the historical record with unprecedented precision. It illustrates the power of archaeological science methods to confirm, challenge and complement historical evidence.

Spin-current-mediated rapid magnon localisation and coalescence after ultrafast optical pumping of ferrimagnetic alloys.

Sub-picosecond magnetisation manipulation via femtosecond optical pumping has attracted wide attention ever since its original discovery in 1996. However, the spatial evolution of the magnetisation is not yet well understood, in part due to the difficulty in experimentally probing such rapid dynamics. Here, we find evidence of a universal rapid magnetic order recovery in ferrimagnets with perpendicular magnetic anisotropy via nonlinear magnon processes. We identify magnon localisation and coalescence processes, whereby localised magnetic textures nucleate and subsequently interact and grow in accordance with a power law formalism. A hydrodynamic representation of the numerical simulations indicates that the appearance of noncollinear magnetisation via optical pumping establishes exchange-mediated spin currents with an equivalent 100% spin polarised charge current density of 107 A cm-2. Such large spin currents precipitate rapid recovery of magnetic order after optical pumping. The magnon processes discussed here provide new insights for the stabilization of desired meta-stable states.

Stability of dissolved and soluble Fe(II) in shelf sediment pore waters and release to an oxic water column.

Shelf sediments underlying temperate and oxic waters of the Celtic Sea (NW European Shelf) were found to have shallow oxygen penetrations depths from late spring to late summer (2.2-5.8 mm below seafloor) with the shallowest during/after the spring-bloom (mid-April to mid-May) when the organic carbon content was highest. Sediment porewater dissolved iron (dFe, <0.15 µm) mainly (>85%) consisted of Fe(II) and gradually increased from 0.4 to 15 µM at the sediment surface to ~100-170 µM at about 6 cm depth. During the late spring this Fe(II) was found to be mainly present as soluble Fe(II) (>85% sFe, <0.02 µm). Sub-surface dFe(II) maxima were enriched in light isotopes (δ56Fe -2.0 to -1.5‰), which is attributed to dissimilatory iron reduction (DIR) during the bacterial decomposition of organic matter. As porewater Fe(II) was oxidised to insoluble Fe(III) in the surface sediment layer, residual Fe(II) was further enriched in light isotopes (down to -3.0‰). Ferrozine-reactive Fe(II) was found in surface porewaters and in overlying core top waters, and was highest in the late spring period. Shipboard experiments showed that depletion of bottom water oxygen in late spring can lead to a substantial release of Fe(II). Reoxygenation of bottom water caused this Fe(II) to be rapidly lost from solution, but residual dFe(II) and dFe(III) remained (12 and 33 nM) after >7 h. Iron(II) oxidation experiments in core top and bottom waters also showed removal from solution but at rates up to 5-times slower than predicted from theoretical reaction kinetics. These data imply the presence of ligands capable of complexing Fe(II) and supressing oxidation. The lower oxidation rate allows more time for the diffusion of Fe(II) from the sediments into the overlying water column. Modelling indicates significant diffusive fluxes of Fe(II) (on the order of 23-31 µmol m-2 day-1) are possible during late spring when oxygen penetration depths are shallow, and pore water Fe(II) concentrations are highest. In the water column this stabilised Fe(II) will gradually be oxidised and become part of the dFe(III) pool. Thus oxic continental shelves can supply dFe to the water column, which is enhanced during a small period of the year after phytoplankton bloom events when organic matter is transferred to the seafloor. This input is based on conservative assumptions for solute exchange (diffusion-reaction), whereas (bio)physical advection and resuspension events are likely to accelerate these solute exchanges in shelf-seas.

All CLEAR? Preparing for IT Downtime.

Health care information technology (IT) outages pose a threat to patient safety and patient care continuity. Organizations' downtime plans must be updated regularly and staff at the work area level should have experience with implementing IT outage operations through downtime drills. This article describes the study institution's IT Outage Toolkit, based on the acronym CLEAR, which guides the development of a downtime plan as well as design, execution, and assessment of work area downtime drills. Self-report and external audits of downtime drills help identify performance gaps and gaps in downtime plans.

Elimination of X-Ray Diffraction through Stimulated X-Ray Transmission.

X-ray diffractive imaging with laterally coherent x-ray free-electron laser (XFEL) pulses is increasingly utilized to obtain ultrafast snapshots of matter. Here we report the amazing disappearance of single-shot charge and magnetic diffraction patterns recorded with resonantly tuned, narrow bandwidth XFEL pulses. Our experimental results reveal the exquisite sensitivity of single-shot charge and magnetic diffraction patterns of a magnetic film to the onset of field-induced stimulated elastic x-ray forward scattering. The loss in diffraction contrast, measured over 3 orders of magnitude in intensity, is in remarkable quantitative agreement with a recent theory that is extended to include diffraction.

Temporal constraints on hydrate-controlled methane seepage off Svalbard.

Methane hydrate is an icelike substance that is stable at high pressure and low temperature in continental margin sediments. Since the discovery of a large number of gas flares at the landward termination of the gas hydrate stability zone off Svalbard, there has been concern that warming bottom waters have started to dissociate large amounts of gas hydrate and that the resulting methane release may possibly accelerate global warming. Here, we corroborate that hydrates play a role in the observed seepage of gas, but we present evidence that seepage off Svalbard has been ongoing for at least 3000 years and that seasonal fluctuations of 1° to 2°C in the bottom-water temperature cause periodic gas hydrate formation and dissociation, which focus seepage at the observed sites.

Nanoscale spin reversal by non-local angular momentum transfer following ultrafast laser excitation in ferrimagnetic GdFeCo.

Ultrafast laser techniques have revealed extraordinary spin dynamics in magnetic materials that equilibrium descriptions of magnetism cannot explain. Particularly important for future applications is understanding non-equilibrium spin dynamics following laser excitation on the nanoscale, yet the limited spatial resolution of optical laser techniques has impeded such nanoscale studies. Here we present ultrafast diffraction experiments with an X-ray laser that probes the nanoscale spin dynamics following optical laser excitation in the ferrimagnetic alloy GdFeCo, which exhibits macroscopic all-optical switching. Our study reveals that GdFeCo displays nanoscale chemical and magnetic inhomogeneities that affect the spin dynamics. In particular, we observe Gd spin reversal in Gd-rich nanoregions within the first picosecond driven by the non-local transfer of angular momentum from larger adjacent Fe-rich nanoregions. These results suggest that a magnetic material's microstructure can be engineered to control transient laser-excited spins, potentially allowing faster (~ 1 ps) spin reversal than in present technologies.

Direct measurements of the ionization potential depression in a dense plasma.

We have used the Linac Coherent Light Source to generate solid-density aluminum plasmas at temperatures of up to 180 eV. By varying the photon energy of the x rays that both create and probe the plasma, and observing the K-α fluorescence, we can directly measure the position of the K edge of the highly charged ions within the system. The results are found to disagree with the predictions of the extensively used Stewart-Pyatt model, but are consistent with the earlier model of Ecker and Kröll, which predicts significantly greater depression of the ionization potential.

Creation and diagnosis of a solid-density plasma with an X-ray free-electron laser.

Matter with a high energy density (>10(5) joules per cm(3)) is prevalent throughout the Universe, being present in all types of stars and towards the centre of the giant planets; it is also relevant for inertial confinement fusion. Its thermodynamic and transport properties are challenging to measure, requiring the creation of sufficiently long-lived samples at homogeneous temperatures and densities. With the advent of the Linac Coherent Light Source (LCLS) X-ray laser, high-intensity radiation (>10(17) watts per cm(2), previously the domain of optical lasers) can be produced at X-ray wavelengths. The interaction of single atoms with such intense X-rays has recently been investigated. An understanding of the contrasting case of intense X-ray interaction with dense systems is important from a fundamental viewpoint and for applications. Here we report the experimental creation of a solid-density plasma at temperatures in excess of 10(6) kelvin on inertial-confinement timescales using an X-ray free-electron laser. We discuss the pertinent physics of the intense X-ray-matter interactions, and illustrate the importance of electron-ion collisions. Detailed simulations of the interaction process conducted with a radiative-collisional code show good qualitative agreement with the experimental results. We obtain insights into the evolution of the charge state distribution of the system, the electron density and temperature, and the timescales of collisional processes. Our results should inform future high-intensity X-ray experiments involving dense samples, such as X-ray diffractive imaging of biological systems, material science investigations, and the study of matter in extreme conditions.

Resonant Kα spectroscopy of solid-density aluminum plasmas.

The x-ray intensities made available by x-ray free electron lasers (FEL) open up new x-ray matter interaction channels not accessible with previous sources. We report here on the resonant generation of Kα emission, that is to say the production of copious Kα radiation by tuning the x-ray FEL pulse to photon energies below that of the K edge of a solid aluminum sample. The sequential absorption of multiple photons in the same atom during the 80 fs pulse, with photons creating L-shell holes and then one resonantly exciting a K-shell electron into one of these holes, opens up a channel for the Kα production, as well as the absorption of further photons. We demonstrate rich spectra of such channels, and investigate the emission produced by tuning the FEL energy to the K-L transitions of those highly charged ions that have transition energies below the K edge of the cold material. The spectra are sensitive to x-ray intensity dependent opacity effects, with ions containing L-shell holes readily reabsorbing the Kα radiation.

Coherence properties of individual femtosecond pulses of an x-ray free-electron laser.

Measurements of the spatial and temporal coherence of single, femtosecond x-ray pulses generated by the first hard x-ray free-electron laser, the Linac Coherent Light Source, are presented. Single-shot measurements were performed at 780 eV x-ray photon energy using apertures containing double pinholes in "diffract-and-destroy" mode. We determined a coherence length of 17 µm in the vertical direction, which is approximately the size of the focused Linac Coherent Light Source beam in the same direction. The analysis of the diffraction patterns produced by the pinholes with the largest separation yields an estimate of the temporal coherence time of 0.55 fs. We find that the total degree of transverse coherence is 56% and that the x-ray pulses are adequately described by two transverse coherent modes in each direction. This leads us to the conclusion that 78% of the total power is contained in the dominant mode.

Malignancy-induced autoimmunity to MUC1: initial antibody characterization.

Numerous reports document the existence of autoantibodies to MUC1 in the circulation of individuals with breast and other solid malignancies, with the majority of researchers utilizing MUC1 peptides in their detection. This report documents the purification, using peptide and whole molecule, and characterization of such autoantibodies from an individual with an unusual, highly MUC1-positive, myosarcoma. Purification of autoantibodies from serum was performed using affinity chromatography against either MUC1 peptide or whole molecule MUC1 [derived both from the patient (Pt-MUC1) and from a pool of sera from patients with advanced breast cancer (ABC-MUC1)]. Enzyme-linked immunosorbent assays (ELISAs) were used to compare specificity of purified autoantibodies. Peptide epitopes were determined by Ptifcan system against 7-mer peptides covering the 20 amino acid repeat of the MUC1 extracellular domain. Substantially higher amounts of autoantibodies were isolated when purifying against Pt-MUC1 rather than either ABC-MUC1 or peptide. Whole molecule purified autoantibodies demonstrated an increased specificity for tumour-derived MUC1. Pt-MUC1 autoantibodies were of both the immunoglobulin (Ig)G and IgM class, whilst autoantibodies purified against ABC-MUC1 and MUC1 peptide were IgG only. A greater range of peptide epitopes was defined by those autoantibodies purified against whole molecule. This report presents data indicating the presence of autoantibodies to MUC1 in an individual diagnosed with a MUC1 over-expressing myosarcoma. Confirmation of these autoantibodies as being specific for tumour-associated MUC1 is given. Further, it suggests that, although autoantibodies are present that recognize core protein determinants, the initial, and dominant, immunizing epitope is not purely pretentious in nature.

Two cases of uterine septum with intrauterine device.

Intrauterine devices (IUDs) have been used worldwide for contraception for decades. They are easily deployed, inexpensive and one of the most reliable contraceptive methods. Though ease of placement is such that they are frequently placed by midwives in the outpatient setting in developing countries, some complications due to its misplacement occasionally can occur. We present two cases with unknown uterine septum in which IUDs were placed without prior ultrasound examination of the pelvis. We conclude evaluation of the pelvis by ultrasound prior to placement of IUDs in women with a history of breech presentation, preterm labour, or recurrent miscarriage may be helpful in identifying uterine anomalies that make IUD placement unsuitable.

Clinical outcomes for early childhood caries: influence of aggressive dental surgery.

PURPOSE: The objective of this study was to assess the relationship between the number of stainless steel crowns (SSCs) placed, number of surfaces at risk (SAR) post dental surgery, and the risk for relapse in patients treated for Early Childhood Caries (ECC). METHODS: The study population consisted of 57 children treated for ECC under general anesthesia, ranging in age from 2.3 to 7.3 years old at the time of entry. Dental surgery utilized an aggressive approach: teeth that had necrotic pulps or were nonrestorable were extracted; decayed primary mandibular incisors that could not be treated by stripping were extracted; primary maxillary incisors with 3 or more carious surfaces were extracted; single-surface lesions of primary molars that did not compromise cusp integrity were restored with intracoronal amalgam restorations; primary maxillary, incisors and canines with smooth-surface lesions affecting 2 or less surfaces were treated with intracoronal composites; primary molars and canines requiring vital pulp therapy were restored with SSCs; primary molars with caries lesions affecting 2 or more surfaces (including smooth-surface, white-spot lesions) were restored with SSCs; primary canines with caries affecting 3 or more surfaces were restored with stainless steel crowns; topical fluoride was applied after all restorative therapy was completed. The cohort was examined for new caries lesions 6 months post dental surgery. Relapse was defined as the presence of new smooth-surface caries lesions as defined by Radike. Comparisons between relapse (R) and nonrelapse (NR) groups, with respect to the number of SSCs placed and the number of SAR, were performed using t tests and Wilcoxon tests. A 0.05 level of significance was employed in all statistical tests. RESULTS: Twenty-one of the 57 (37%) patients relapsed. No statistically significant difference for the number of SSCs placed or SAR existed between the R group (SSCs: mean = 4.57, median = 4 +/- 2.18; SAR: mean = 39.76, median = 40 +/- 13.62) and NR group (SSCs: mean=5.44, median = 5.5 +/- 2.62; SAR: mean = 39.98, median = 39.5 +/- 15.19). CONCLUSIONS: The risk for relapse in children treated for ECC is not associated with the number of SSCs placed or SAR; aggressive dental surgery for ECC does not result in acceptable clinical outcomes.

Role of estradiol-17beta on nuclear and cytoplasmic maturation of pig oocytes.

The role of estradiol-17beta on nuclear and cytoplasmic maturation of pig oocytes was investigated in the present study. To determine the estradiol effect, oocytes were cultured for 42 h in a steroid free medium composed of mTCM-199 supplemented with LH, FSH and 10% charcoal extracted follicular fluid. Estradiol receptor (ER), detected by a binding assay, were present in cumulus cells and oocytes during maturation with higher levels observed at 24 h of culture in the oocytes and at 36 h in the cumulus cells. To block estradiol action an antiestrogen (1-p-dimethylaminoethoxyphenyl-1,2-diphenyl-1-butene (tamoxifen)) was added to the maturation medium at various concentrations. The percentage of treated oocytes that underwent nuclear maturation was similar (P>0.05) to the control group. Cytoplasmic maturation, determined by the ability to form female pronucleus (FPN) and male pronucleus (MPN), was not different (P>0.05) among all groups. The presence of 4-hydroxy-4-androstene-3-17-dione (4-OHA) also did not influence nuclear (P>0.05) or cytoplasmic maturation (P>0.05). The results suggest that estradiol is not involved in maturation of pig oocytes. However, the present experiment used pronuclei formation as the endpoint, no studies were done in regard to estradiol's effects on the embryonic development.

Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products: a critical review.

Disinfection by-products (DBP) are a side effect of water chlorination. Some toxicological studies suggest an association between DBP exposure and adverse reproductive and developmental effects. This investigation considered all toxicological and epidemiological evidence for the various effects, outcome by outcome. The weight of evidence demonstrated that no association with DBP exposure exists for over a dozen outcomes including low and very low birth weight, preterm delivery, some specific congenital anomalies, and neonatal death. The analysis found inconsistent or very weak results for all congenital anomalies/birth defects, all central nervous system anomalies, neural tube defects, spontaneous abortion, and stillbirth. The weight of evidence suggested a positive association with DBP exposure for some measure of growth retardation (such as intrauterine growth retardation or small for gestational age) and for urinary tract anomalies. Having catalogued these effects, it should be noted that exposure assessment in the epidemiological studies published to date has been inadequate to definitively demonstrate an association of small magnitude. Exposure to DBP primarily has been based on routine (i.e., quarterly) monitoring of public water supplies for trihalomethanes (THM) matched to maternal residence. In order to determine whether an association exists between adverse reproductive and developmental effects and exposure to DBP, studies must consider the THM concentration and the quantity of the water actually consumed by pregnant women.