Evaluation of Niobium as Candidate Electrode Material for DC High Voltage Photoelectron Guns

The field emission characteristics of niobium electrodes were compared to those of stainless steel electrodes using a DC high voltage field emission test apparatus. A total of eight electrodes were evaluated: two 304 stainless steel electrodes polished to mirror-like finish with diamond grit and six niobium electrodes (two single-crystal, two large-grain, and two fine-grain) that were chemically polished using a buffered-chemical acid solution. Upon the first application of high voltage, the best large-grain and single-crystal niobium electrodes performed better than the best stainless steel electrodes, exhibiting less field emission at comparable voltage and field strength. In all cases, field emission from electrodes (stainless steel and/or niobium) could be significantly reduced and sometimes completely eliminated, by introducing krypton gas into the vacuum chamber while the electrode was biased at high voltage. Of all the electrodes tested, a large-grain niobium electrode performed the best, exhibiting no measurable field emission (< 10 pA) at 225 kV with 20 mm cathode/anode gap, corresponding to a field strength of 18:7 MV/m

Identification of cytosolic phosphodiesterases in the erythrocyte: A possible role for PDE5

Background Within erythrocytes (RBCs), cAMP levels are regulated by phosphodiesterases (PDEs). Increases in cAMP and ATP release associated with activation of β-adrenergic receptors (βARs) and prostacyclin receptors (IPRs) are regulated by PDEs 2, 4 and PDE 3, respectively. Here we establish the presence of cytosolic PDEs in RBCs and determine a role for PDE5 in regulating levels of cGMP. Material/Methods Purified cytosolic proteins were obtained from isolated human RBCs and western analysis was performed using antibodies against PDEs 3A, 4 and 5. Rabbit RBCs were incubated with dbcGMP, a cGMP analog, to determine the effect of cGMP on cAMP levels. To determine if cGMP affects receptor-mediated increases in cAMP, rabbit RBCs were incubated with dbcGMP prior to addition of isoproterenol (ISO), a βAR receptor agonist. To demonstrate that endogenous cGMP produces the same effect, rabbit and human RBCs were incubated with SpNONOate (SpNO), a nitric oxide donor, and YC1, a direct activator of soluble guanylyl cyclase (sGC), in the absence and presence of a selective PDE5 inhibitor, zaprinast (ZAP). Results Western analysis identified PDEs 3A, 4D and 5A. dbcGMP produced a concentration dependent increase in cAMP and ISO-induced increases in cAMP were potentiated by dbcGMP. In addition, incubation with YC1 and SpNO in the presence of ZAP potentiated βAR-induced increases in cAMP. Conclusions PDEs 2, 3A and 5 are present in the cytosol of human RBCs. PDE5 activity in RBCs regulates cGMP levels. Increases in intracellular cGMP augment cAMP levels. These studies suggest a novel role for PDE5 in erythrocytes

Production of highly-polarized positrons using polarized electrons at MeV energies

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-$Z$ target. Positron polarization up to 82\% have been measured for an initial electron beam momentum of 8.19~MeV/$c$, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.Comment: 5 pages, 4 figure

Wound care in older adults

Wound care in older adults is complex. A logical, structured approach should be taken, using a nursing process such as assessing, planning, implementing and evaluating. This clinical focus paper outlines the nursing process to support wound care in this patient group. It recommends considering dressing selection as a cost-effective, prescribing decision because of the risks and comorbidities associated with these patient

Developing CCS in the UK and beyond: insights from the UK CCS Research Centre

The UK Carbon Capture and Storage Research Centre co-ordinates a programme of research covering all aspects of CCS in support of basic science and UK government efforts on energy and climate change. This paper will present progress and ‘lessons learned’ from the Centre’s activities, with a particular focus on the development and use of pilot scale facilities and encouraging industrial and other stakeholder engagement in research. It will also highlight key features of an extensive programme of international engagement activities undertaken by the Centre, identifying added value for both the UK CCS community and global development of CCS

Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare salivary cancer. The highest rates of disease recurrence are in patients with NOTCH pathway activation, reported in up to 20%. Novel drugs targeting NOTCH signaling are under investigation in the recurrent/metastatic (R/M) setting. To understand their clinical utility, there is an urgent need to better characterize the disease course and outcomes following current standard of care treatment. METHODS: 120 patients with R/M ACC underwent clinical review at a single UK Cancer Centre. Patients were retrospectively assessed for tumor NOTCH pathway activation using next generation sequencing (NGS) targeting NOTCH1/2/3 genes and/or NOTCH1 intra-cellular domain (NICD1) immunohistochemistry. Demographic and treatment data were extracted from the clinical notes. Kaplan-Meier survival analysis was performed using log rank test. RESULTS: NOTCH pathway activation was identified in 13/120 patients (11 %). In 12/101 patients analyzed by NGS, NOTCH1/3 activating somatic mutations were identified, and a further patient was identified with NICD1 diffuse nuclear staining in whom NGS testing was not possible. Patients with NOTCH pathway activation had shorter median RFS (1.1 vs 3.4 years, p = 0.2032) and significantly reduced median OS from diagnosis (4.0 vs 16.3 years, p < 0.0001). There was significantly reduced median OS from time of disease recurrence/metastasis (1.9 vs 9.6 years, p < 0.0001). CONCLUSION: This study clearly demonstrates a reduction in OS from time of first confirmed disease recurrence/metastasis for patients with NOTCH pathway activated ACC. This provides support for developing new drugs for this sub-group of patients, for whom clinical outcomes are significantly worse and effective treatments are lacking

Photoinjector improvements at CEBAF in support of parity violation experiments

Three photoinjector modifications were undertaken at CEBAF to help ensure successful completion of the PREx and Qweak parity violation experiments: the development of a pockels cell high voltage switch that provides stable voltages at 960 Hz helicity flip rate with 60 μs rise/fall time, the installation of a two-Wien-filter spin flipper for slow spin reversal, and the installation of a new photogun with inverted insulator geometry that operates at higher bias voltage

A decomposition of Fisher's information to inform sample size for developing fair and precise clinical prediction models -- Part 2:time-to-event outcomes

Background: When developing a clinical prediction model using time-to-event data, previous research focuses on the sample size to minimise overfitting and precisely estimate the overall risk. However, instability of individual-level risk estimates may still be large. Methods: We propose a decomposition of Fisher's information matrix to examine and calculate the sample size required for developing a model that aims for precise and fair risk estimates. We propose a six-step process which can be used before data collection or when an existing dataset is available. Steps (1) to (5) require researchers to specify the overall risk in the target population at a key time-point of interest; an assumed pragmatic 'core model' in the form of an exponential regression model; the (anticipated) joint distribution of core predictors included in that model; and the distribution of any censoring. Results: We derive closed-form solutions that decompose the variance of an individual's estimated event rate into Fisher's unit information matrix, predictor values and total sample size; this allows researchers to calculate and examine uncertainty distributions around individual risk estimates and misclassification probabilities for specified sample sizes. We provide an illustrative example in breast cancer and emphasise the importance of clinical context, including risk thresholds for decision making, and examine fairness concerns for pre- and post-menopausal women. Lastly, in two empirical evaluations, we provide reassurance that uncertainty interval widths based on our approach are close to using more flexible models. Conclusions: Our approach allows users to identify the (target) sample size required to develop a prediction model for time-to-event outcomes, via the pmstabilityss module. It aims to facilitate models with improved trust, reliability and fairness in individual-level predictions

A decomposition of Fisher's information to inform sample size for developing fair and precise clinical prediction models -- Part 2:time-to-event outcomes

Background: When developing a clinical prediction model using time-to-event data, previous research focuses on the sample size to minimise overfitting and precisely estimate the overall risk. However, instability of individual-level risk estimates may still be large. Methods: We propose a decomposition of Fisher's information matrix to examine and calculate the sample size required for developing a model that aims for precise and fair risk estimates. We propose a six-step process which can be used before data collection or when an existing dataset is available. Steps (1) to (5) require researchers to specify the overall risk in the target population at a key time-point of interest; an assumed pragmatic 'core model' in the form of an exponential regression model; the (anticipated) joint distribution of core predictors included in that model; and the distribution of any censoring. Results: We derive closed-form solutions that decompose the variance of an individual's estimated event rate into Fisher's unit information matrix, predictor values and total sample size; this allows researchers to calculate and examine uncertainty distributions around individual risk estimates and misclassification probabilities for specified sample sizes. We provide an illustrative example in breast cancer and emphasise the importance of clinical context, including risk thresholds for decision making, and examine fairness concerns for pre- and post-menopausal women. Lastly, in two empirical evaluations, we provide reassurance that uncertainty interval widths based on our approach are close to using more flexible models. Conclusions: Our approach allows users to identify the (target) sample size required to develop a prediction model for time-to-event outcomes, via the pmstabilityss module. It aims to facilitate models with improved trust, reliability and fairness in individual-level predictions