Developments in CLARA accelerator design and simulations

We present recent developments in the accelerator design of CLARA (Compact Linear Accelerator for Research and Applications), the proposed UK FEL test facility at Daresbury Laboratory. Updates on the electron beam simulations and code comparisons including wakefields are described. Simulations of the effects of geometric wakefields in the small-aperture FEL undulator are shown, as well as further simulations on potential FEL experiments using chirped beams. We also present the results of simulations on post-FEL diagnostics

Natural Language Processing markers in first episode psychosis and people at clinical high-risk.

Funder: MQ: Transforming Mental Health; Grant(s): MQF17_24Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.SEM was supported by the Accelerate Programme for Scientific Discovery, funded by Schmidt Futures, a Fellowship from The Alan Turing Institute, London, and a Henslow Fellowship at Lucy Cavendish College, University of Cambridge, funded by the Cambridge Philosophical Society. PEV is supported by a fellowship from MQ: Transforming Mental Health (MQF17_24). This work was supported by The Alan Turing Institute under the EPSRC grant EP/N510129/1, the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), the UK Medical Research Council (MRC) and the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Natural Language Processing markers in first episode psychosis and people at clinical high-risk.

Funder: MQ: Transforming Mental Health; Grant(s): MQF17_24Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.SEM was supported by the Accelerate Programme for Scientific Discovery, funded by Schmidt Futures, a Fellowship from The Alan Turing Institute, London, and a Henslow Fellowship at Lucy Cavendish College, University of Cambridge, funded by the Cambridge Philosophical Society. PEV is supported by a fellowship from MQ: Transforming Mental Health (MQF17_24). This work was supported by The Alan Turing Institute under the EPSRC grant EP/N510129/1, the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), the UK Medical Research Council (MRC) and the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Observing a column-dependent zeta in dense interstellar sources: the case of the Horsehead Nebula

Context: Observations of small carbon-bearing molecules such as CCH, C4H, c-C3H2, and HCO in the Horsehead Nebula have shown these species to have higher abundances towards the edge of the source than towards the center. Aims: Given the determination of a wide range of values for zeta (s-1), the total ionization rate of hydrogen atoms, and the proposal of a column-dependent zeta(N_H), where N_H is the total column of hydrogen nuclei, we desire to determine if the effects of zeta(N_H) in a single object with spatial variation can be observable. We chose the Horsehead Nebula because of its geometry and high density. Method: We model the Horsehead Nebula as a near edge-on photon dominated region (PDR), using several choices for zeta, both constant and as a function of column. The column-dependent zeta functions are determined by a Monte Carlo model of cosmic ray penetration, using a steep power-law spectrum and accounting for ionization and magnetic field effects. We consider a case with low-metal elemental abundances as well as a sulfur-rich case. Results: We show that use of a column-dependent zeta(N_H) of 5(-15) s-1 at the surface and 7.5(-16) s-1 at Av = 10 on balance improves agreement between measured and theoretical molecular abundances, compared with constant values of zeta.Comment: 12 pages, 6 figures, 5 tables, accepted in A&

Sarcasm in written communication: emoticons are efficient markers of intention

Here we present two studies that investigate the use of emoticons in clarifying message intent. We look at sarcasm in particular, which can be especially hard to interpret correctly in written communication. In both studies, participants were required to make the intentions of their messages clear. In the first, they clarified the meaning of existing sentences without altering the wording; in the second, they produced their own sentences. Results provided clear evidence that tongue and wink emoticons are the principal indicators of sarcastic intent, and that ellipsis is associated more with criticism, rather than with sarcasm. These findings highlight the significant role emoticons play in clarifying message intention, compensating for the absence of non-verbal cues in written communicatio

Decreased nematode clearance & anti-phosphorylcholine specific IgM responses in mannose-binding lectin deficient mice

Brugia malayi is a nematode that causes human lymphatic filariasis. Previously, we showed that mannose binding lectin (MBL) ‐A is necessary for clearance of B. malayi microfilariae in mice and presence of MBL‐A is linked with maximal levels of parasite‐specific IgM. Common human MBL gene polymorphisms result in low MBL expression and lead to recurring bacterial infections. Furthermore, these low‐expressing human MBL polymorphisms result in greatly increased susceptibility to lymphatic filarial infection. Indeed, gain of new filarial infections over a 30‐year period are 10‐fold higher in people with low, compared to high, MBL‐expression phenotypes. Human MBL closely resembles mouse MBL‐C, rather than MBL‐A, therefore we examined the role of mouse MBL‐C in clearance of microfilariae. Absence of MBL‐C alone, or both MBL‐A and ‐C, resulted in delayed clearance of microfilariae and reduced parasite‐specific IgM in mice. There were few profound changes in B cell sub‐populations or in the ability of MBL‐deficient mice to respond to T‐dependent or T‐independent antigens. However, absence of MBL‐A and/or MBL‐C resulted in reduced IgM to phosphorylcholine, a constituent of filarial and bacterial antigens, suggesting that inability to form proficient antibody responses to this moiety leads to lack of microfilarial clearance and overall susceptibility to filariasis

Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.</p

Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow-up in active surveillance for prostate cancer.

OBJECTIVES: To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. PATIENTS AND METHODS: We previously developed the Cambridge Prognostics Groups (CPG) classification, a five-tiered model that uses prostate-specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate-risk classification) vs CPG1 (low-risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re-tested in an external AS cohort from Spain. RESULTS: In a UK cohort (n = 3659) the 10-year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10-year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow-up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density ≥0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. CONCLUSION: Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk-stratified management in AS