Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

Cinematic reflectometry using QIKR, the quite intense kinetics reflectometer.

The Quite Intense Kinetics Reflectometer (QIKR) will be a general-purpose, horizontal-sample-surface neutron reflectometer. Reflectometers measure the proportion of an incident probe beam reflected from a surface as a function of wavevector (momentum) transfer to infer the distribution and composition of matter near an interface. The unique scattering properties of neutrons make this technique especially useful in the study of soft matter, biomaterials, and materials used in energy storage. Exploiting the increased brilliance of the Spallation Neutron Source Second Target Station, QIKR will collect specular and off-specular reflectivity data faster than the best existing such machines. It will often be possible to collect complete specular reflectivity curves using a single instrument setting, enabling "cinematic" operation, wherein the user turns on the instrument and "films" the sample. Samples in time-dependent environments (e.g., temperature, electrochemical, or undergoing chemical alteration) will be observed in real time, in favorable cases with frame rates as fast as 1 Hz. Cinematic data acquisition promises to make time-dependent measurements routine, with time resolution specified during post-experiment data analysis. This capability will be deployed to observe such processes as in situ polymer diffusion, battery electrode charge-discharge cycles, hysteresis loops, and membrane protein insertion into lipid layers.

First Probe of Sub-GeV Dark Matter beyond the Cosmological Expectation with the COHERENT CsI Detector at the SNS.

The COHERENT Collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220 MeV/c^{2} using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9 keV_{nr}. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6 kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants α_{D}<0.64, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios.

Measurement of the Coherent Elastic Neutrino-Nucleus Scattering Cross Section on CsI by COHERENT.

We measured the cross section of coherent elastic neutrino-nucleus scattering (CEvNS) using a CsI[Na] scintillating crystal in a high flux of neutrinos produced at the Spallation Neutron Source at Oak Ridge National Laboratory. New data collected before detector decommissioning have more than doubled the dataset since the first observation of CEvNS, achieved with this detector. Systematic uncertainties have also been reduced with an updated quenching model, allowing for improved precision. With these analysis improvements, the COHERENT Collaboration determined the cross section to be (165_{-25}^{+30})×10^{-40} cm^{2}, consistent with the standard model, giving the most precise measurement of CEvNS yet. The timing structure of the neutrino beam has been exploited to compare the CEvNS cross section from scattering of different neutrino flavors. This result places leading constraints on neutrino nonstandard interactions while testing lepton flavor universality and measures the weak mixing angle as sin^{2}θ_{W}=0.220_{-0.026}^{+0.028} at Q^{2}≈(50 MeV)^{2}.

Managing pediatric psoriasis: update on treatments and challenges-a review.

BACKGROUND: Psoriasis is a chronic, immune-mediated inflammatory disease with prominent cutaneous features, although the limited number of medications approved for pediatric psoriasis makes treating this population difficult. This review provides an overview of the challenges associated with diagnosing and treating pediatric psoriasis as well as the approved and off-label treatments for children and infants with psoriasis. METHODS: Articles relevant to pediatric psoriasis were identified using a series of PubMed searches. Topics relevant to pediatric psoriasis were explored, including disease characteristics, epidemiology, treatment efficacy and safety, and access to care. Publications previously known to the authors were also included. RESULTS: Clinical features of psoriasis can be challenging to identify clinically, and patients face challenges gaining access to treatment. Most medications that have been approved for adult psoriasis lack data and labeling to support safe and effective use in pediatric patients, and therefore access is limited. A growing number of clinical trials using biologic agents for pediatric psoriasis aim to broaden available treatment options but may also raise unique concerns associated with the use of these medications in children. CONCLUSION: Pediatric psoriasis is underrecognized and often undertreated. Clinicians must balance relative risks and potential benefits when developing a treatment strategy for these patients.

Rapid Decrease in KRT14 and TP53 mRNA Expression in the Buccal Mucosa of Patients Receiving Total-Body Irradiation for Allogeneic Stem Cell Transplantation.

The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis. In this study, we obtained miRNAs and mRNAs from daily buccal swabs collected from patients undergoing allogeneic stem cell transplantation. Unexpectedly, there was no prominent p53-induced mRNA or miRNA response in these samples, despite the fact that the p53 pathway is a well-characterized radiation-inducible response. Instead, the expression of mRNAs encoding p53 and cytokeratin 14 (TP53 and KRT14, respectively) decreased precipitously within hours of the first radiation treatment. These patients went on to develop oral mucositis, however, it is unclear whether TP53 and/or KRT14 expression are predictive of this adverse event. Larger scale analysis of buccal epithelial samples from patients undergoing allogeneic stem cell transplantation appears to be warranted.

Evaluating the solid electrolyte interphase formed on silicon electrodes: a comparison of ex situ X-ray photoelectron spectroscopy and in situ neutron reflectometry.

This work details the in situ characterization of the interface between a silicon electrode and an electrolyte using a linear fluorinated solvent molecule, 0.1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in deuterated dimethyl perfluoroglutarate (d6-PF5M2) (1.87 × 10(-2) mS cm(-1)). The solid electrolyte interphase (SEI) composition and thickness determined via in situ neutron reflectometry (NR) and ex situ X-ray photoelectron spectroscopy (XPS) were compared. The data show that SEI expansion and contraction (breathing) during electrochemical cycling were observed via both techniques; however, ex situ XPS suggests that the SEI thickness increases during Si lithiation and decreases during delithiation, while in situ NR suggests the opposite. The most likely cause of this discrepancy is the selective removal of SEI components (top 20 nm of the SEI) during the electrode rinse process, which is required to remove the electrolyte residue prior to ex situ analysis, demonstrating the necessity of performing SEI characterization in situ.

Marked retroperitoneal lymphadenopathy in hairy cell leukemia: a case report.

Hairy cell leukemia (HCL) is uncommonly associated with lymphadenopathy, while retroperitoneal lymphadenopathy is extremely uncommon. We report on a patient with a 12-year history of HCL who developed painless jaundice and ascites, accompanied by positional discomfort with persistent nausea. Computed tomography examination revealed 2 large retroperitoneal masses, which at autopsy consisted of HCL with focally intermixed pancreatic and peripancreatic tissue. Lymphadenopathy was not identified above the diaphragm or below the aortic bifurcation. No vasculitis or an unusual HCL histology was identified. As previous reports, our findings suggest that HCL with massive lymphadenopathy has a specific site predilection, but it is not necessarily accompanied by vasculitis or an unusual histology.

A non-electrolyte haemolysis assay for diagnosis and prognosis of sickle cell disease.

Abstract Red blood cells (RBCs) from patients with sickle cell disease (SCD) lyse in deoxygenated isosmotic non-electrolyte solutions. Haemolysis has features which suggest that it is linked to activation of the pathway termed Psickle. This pathway is usually described as a non-specific cationic conductance activated by deoxygenation, HbS polymerisation and RBC sickling. The current work addresses the hypothesis that this haemolysis will provide a novel diagnostic and prognostic test for SCD, dependent on the altered properties of the RBC membrane resulting from HbS polymerisation. A simple test represented by this haemolysis assay would be useful especially in less affluent deprived areas of the world where SCD is most prevalent. RBCs from HbSS and most HbSC individuals showed progressive lysis in deoxygenated isosmotic sucrose solution at pH 7.4 to a level greater than that observed with RBCs from HbAS or HbAA individuals. Cytochalasin B prevented haemolysis. Haemolysis was temperature- and pH-dependent. It required near physiological temperatures to occur in deoxygenated sucrose solutions at pH 7.4. At pH 6, haemolysis occurred even in oxygenated samples. Haemolysis was reduced in patients on long-term (>5 months) hydroxyurea treatment. Several manoeuvres which stabilise soluble HbS (aromatic aldehydes o-vanillin or 5-hydroxymethyl, and urea) reduced haemolysis, an effect not due to increased oxygen affinity. Conditions designed to elicit HbS polymerisation in cells from sickle trait patients (deoxygenated hyperosmotic sucrose solutions at pH 6) supported their haemolysis. These findings are consistent with haemolysis requiring HbS polymerisation and support the hypothesis that this may be used as a test for SCD.

The miscibility and depth profile of PCBM in P3HT: thermodynamic information to improve organic photovoltaics.

Recent work has shown that poly(3-hexylthiophene) (P3HT) and the surface-functionalized fullerene 1-(3-methyloxycarbonyl)propyl(1-phenyl[6,6])C(61) (PCBM) are much more miscible than originally thought, and the evidence of this miscibility requires a return to understanding the optimal morphology and structure of organic photovoltaic active layers. This manuscript describes the results of experiments that were designed to provide quantitative thermodynamic information on the miscibility, interdiffusion, and depth profile of P3HT : PCBM thin films that are formed by thermally annealing initial bilayers. It is found that the resultant thin films consist of a 'bulk' layer that is not influenced by the air or substrate surface. The composition of PCBM in this 'bulk' layer increases with increased PCBM loading in the original bilayer until the 'bulk' layer contains 22 vol% PCBM. The introduction of additional PCBM into the sample does not increase the amount of PCBM dispersed in this 'bulk' layer. This observation is interpreted to indicate that the miscibility limit of PCBM in P3HT is 22 vol%, while the precise characterization of the depth profiles in these films shows that the PCBM selectively segregates to the silicon and near air surface. The selective segregation of the PCBM near the air surface is ascribed to an entropic driving force.

Lymphotoxin and the amazing technicolor circus of intestinal homeostasis.

Recently a new lymphocyte subset called innate lymphoid cells has emerged and it includes key producers of interleukin (IL)-17 and IL-22 in the mucosal environment. Using Citrobacter rodentium infection to deliver a pathogenic insult to the colon, two studies have revealed an underlying role for lymphotoxin-ß receptor signaling in the generation of IL-22 by these cells. This observation links a system well known for its ability to organize lymphoid microenvironments into a basic mucosal response.

Expression of cancer-testis antigens (MAGE-A1, MAGE-A3/6, MAGE-A4, MAGE-C1 and NY-ESO-1) in primary human uveal and conjunctival melanoma.

AIM: Metastatic disease in ocular melanoma remains untreatable, is associated with late detection and is resistant to conventional systemic therapies. Many tumours including cutaneous melanoma express specific cancer-testis (CT) antigens and vaccines targeting these antigens can induce T-cell-mediated and humoural immune responses. The authors examined primary uveal and conjunctival melanomas for expression of CT antigens to assess their potential as targets for ocular melanoma immunotherapy. METHODS: Paraffin-embedded uveal (n=32) and conjunctival (n=15) melanomas were assessed by immunohistochemistry for melanocyte differentiation antigens (gp100, Melan-A/MART-1 and tyrosinase), and CT antigens (MAGE-A1, MAGE-A3/6, MAGE-A4, MAGE-C1 and NY-ESO-1). RESULTS: Melanoma differentiation antigens, gp100, Melan-A/MART1 and tyrosinase, were expressed in >75% of tumour cells in all uveal and conjunctival melanomas tested. Expression of all five CT antigens tested was low in uveal melanomas, and when present, stained <25% of the tumour cells. MAGE-A1, MAGE-A4 and NY-ESO-1 were expressed in <10% of tumour cells in conjunctival melanomas, while MAGE-C1 and MAGE-A3/6 were expressed in ∼20% and ∼35% of tumour cells in this malignancy, respectively, with variable expression levels. CONCLUSIONS: Uveal and conjunctival melanomas consistently expressed high levels of the differentiation antigens (gp100, Melan-A/MART1 and tyrosinase). However, compared with other tumours, including cutaneous melanoma, only low levels of CT antigens were found in ocular melanomas. These observations suggest that immunotherapy directly targeting the CT antigens studied may not be effective for ocular melanoma.

Bedside testing for myasthenia gravis: the ice-test.

A 67-year-old man presented to the acute medical take with a history of droopy eyelids and difficulty swallowing. A diagnosis of myasthenia gravis was suspected from the clinical history. The patient's symptoms were progressive, raising concerns of aspiration pneumonia or respiratory compromise if untreated. Definitive diagnosis of myasthenia gravis relies upon a combination of serological and electrophysiological investigations, the results of which are not immediately available in an acute situation. Bedside tests are therefore of practical clinical importance to enable prompt and effective initiation of treatment, particularly where critical symptoms are present. The ice-test is a straightforward and non-invasive investigation with a high sensitivity for myasthenia gravis and is a useful alternative to edrophonium testing. It is especially helpful in patients with cardiac and respiratory co-morbidities for whom acetylcholinesterase inhibitors are contraindicated. We describe a case where this simple bedside test successfully expedited the correct treatment and improved patient care.

Novel permeability characteristics of red blood cells from sickle cell patients heterozygous for HbS and HbC (HbSC genotype).

Individuals heterozygous for HbS and HbC (HbSC) represent about 1/3(rd) of sickle cell disease (SCD) patients. Whilst HbSC disease is generally milder, there is considerable overlap in symptoms with HbSS disease. HbSC patients, as well as HbSS ones, present with the chronic anaemia and panoply of acute vaso-occlusive complications that characterize SCD. However, there are important clinical and haematological differences. Certain complications occur with greater frequency in HbSC patients (like proliferative retinopathy and osteonecrosis) whilst intravascular haemolysis is reduced. Patients with HbSC disease can be considered as a discrete subset of SCD cases. Although much work has been carried out on understanding the pathogenesis of SCD in HbSS homozygotes, including the contribution of altered red blood cell permeability, relatively little pertains directly to HbSC individuals. Results reported in the literature suggest that HbSC cells, and particularly certain subpopulations, present with similar permeability to HbSS cells but there are also important differences - these have not been well characterized. We hypothesise that their unique cell transport properties accounts for the different pattern of disease in HbSC patients and represents a potential chemotherapeutic target not shared in red blood cells from HbSS patients. The distinct pattern of clinical haematology in HbSC disease is emphasised here. We analyse some of the electrophysiological properties of single red blood cells from HbSC patients, comparing them with those from HbSS patients and normal HbAA individuals. We also use the isosmotic haemolysis technique to investigate the behaviour of total red blood cell populations. Whilst both HbSS and HbSC cells show increased monovalent and divalent (Ca(2+)) cation conductance further elevated upon deoxygenation, the distribution of current magnitudes differs, and outward rectification is greatest for HbSC cells. In addition, although Gd(3+) largely abolishes the cation conductance of both HbSS and HbSC cells, only in HbSS ones are currents inhibited by the aminoglycosides like streptomycin. This distinction is retained in isosmotic lysis experiments where both HbSS and HbSC cells undergo haemolysis in sucrose solutions but streptomycin significantly inhibits lysis only in HbSS cells. These findings emphasise similarities but also differences in the permeability properties of HbSS and HbSC cells, which may be important in pathogenesis.

Bedside testing for myasthenia gravis: the ice-test.

A 67-year-old man presented to the acute medical take with a history of droopy eyelids and difficulty swallowing. A diagnosis of myasthenia gravis was suspected from the clinical history. The patient's symptoms were progressive, raising concerns of aspiration pneumonia or respiratory compromise if untreated. Definitive diagnosis of myasthenia gravis relies upon a combination of serological and electrophysiological investigations, the results of which are not immediately available in an acute situation. Bedside tests are therefore of practical clinical importance to enable prompt and effective initiation of treatment, particularly where critical symptoms are present. The ice-test is a straightforward and non-invasive investigation with a high sensitivity for myasthenia gravis and is a useful alternative to edrophonium testing. It is especially helpful in patients with cardiac and respiratory co-morbidities for whom acetylcholinesterase inhibitors are contraindicated. We describe a case where this simple bedside test successfully expedited the correct treatment and improved patient care.

Imaging paediatric blunt abdominal trauma in the emergency department: ultrasound versus computed tomography.

OBJECTIVE: To determine whether an abdominal ultrasound scan performed by paediatric radiologists is effective in the diagnosis of abdominal injuries in children. METHOD: A retrospective cohort study was undertaken of all children who presented with blunt abdominal trauma to a paediatric teaching hospital (RHSC) over a 5-year period between 1 January 2001 and 31 December 2005. Hospital notes and radiology computer systems were interrogated and data were collected and analysed. RESULTS: Of the 80 children with blunt abdominal trauma, 56 (70%) had abdominal imaging and 23 (30%) had no imaging. Of the 56 imaged, 48 (86%) had an USS of which 25 (52%) were positive (16 demonstrated solid organ injury, 8 free fluid and 1 suspected bladder rupture); 3 of these went on to have a CT scan. 23 had a normal USS; 2 of these children went on to have a CT scan because of a high index of suspicion for small bowel perforation due to their mechanism of injury and clinical signs. Both of these CT scans were normal. Eight children (14%) had a CT scan as the primary investigation, 6 of which (75%) were positive (5 demonstrated liver lacerations and 1 free fluid with no obvious source). All these abnormalities were demonstrated on follow-up USS. 23 children had no abdominal imaging and once their symptoms and signs had settled they were safely discharged home. CONCLUSION: Abdominal USS performed by paediatric radiologists is an accurate method of assessing abdominal injuries. However, CT scanning can assess certain abnormalities such as pancreatic or duodenal injuries and small amounts of free intraperitoneal air more accurately. The importance of serial clinical examination must not be overlooked.

Deep drilling into the Chesapeake Bay impact structure.

Samples from a 1.76-kilometer-deep corehole drilled near the center of the late Eocene Chesapeake Bay impact structure (Virginia, USA) reveal its geologic, hydrologic, and biologic history. We conducted stratigraphic and petrologic analyses of the cores to elucidate the timing and results of impact-melt creation and distribution, transient-cavity collapse, and ocean-water resurge. Comparison of post-impact sedimentary sequences inside and outside the structure indicates that compaction of the crater fill influenced long-term sedimentation patterns in the mid-Atlantic region. Salty connate water of the target remains in the crater fill today, where it poses a potential threat to the regional groundwater resource. Observed depth variations in microbial abundance indicate a complex history of impact-related thermal sterilization and habitat modification, and subsequent post-impact repopulation.

Inorganic phosphate transport in matrix vesicles from bovine articular cartilage.

AIMS: In mineralizing tissues such as growth plate cartilage extracellular organelles derived from the chondrocyte membrane are present. These matrix vesicles (MV), possess membrane transporters that accumulate Ca(2+) and inorganic phosphate (P(i)), and initiate the formation of hydroxyapatite crystals. MV are also present in articular cartilage, and hydroxyapatite crystals are believed to promote cartilage degradation in osteoarthritic joints. This study characterizes P(i) transport in MV derived from articular cartilage. METHODS: Matrix vesicles were harvested from collagenase digests of bovine articular cartilage by serial centrifugation. P(i) uptake by MV was measured using radioactive phosphate ((33)[P]HPO(4)(2-)). The Na(+) dependence, pH sensitivity and effects of P(i) analogues that inhibit P(i) transport were determined. RESULTS: P(i) uptake was temperature-sensitive and comprised Na(+)-dependent and Na(+)-independent components. The Na(+)-dependent component saturated at high extracellular P(i) concentrations, with a K(m) of 0.16 mM. In Na(+)-free solutions, uptake did not fully saturate implying that carrier-mediated uptake is supplemented by a diffusive pathway. Uptake was inhibited by phosphonoacetate and arsenate, although a fraction of Na(+)-independent P(i) uptake persisted. Total P(i) uptake was maximal at pH 6.5, and reduced at more acidic or alkaline values, representing inhibition of both components. CONCLUSION: These properties are highly similar to those of P(i) uptake by chondrocytes, suggesting that MV inherit P(i) transporters of the chondrocyte membrane from which they are derived. Na(+)-independent P(i) uptake has not previously been described in MV from growth plate cartilage and is relatively uncharacterized, but warrants further attention in articular cartilage, given its likely role in initiating inappropriate mineral formation.