Energy Deposition in Adjacent LHC Superconducting Magnets from Beam Loss at LHC Transfer Line Collimators

Injection intensities for the LHC are over an order of magnitude above the damage threshold. The collimation system in the two transfer lines is designed to dilute the beam sufficiently to avoid damage in case of accidental beam loss or mis-steered beam. To maximise the protection for the LHC most of the collimators are located in the last 300 m upstream of the injection point where the transfer lines approach the LHC machine. To study the issue of possible quenches following beam loss at the collimators part of the collimation section in one of the lines, TI 8, together with the adjacent part of the LHC has been modeled in FLUKA. The simulated energy deposition in the LHC for worst-case accidental losses and as well as for losses expected during a normal filling is presented

Extent and Duration of the 2003 Cascadia Slow Earthquake

Inversion of continuous GPS measurements from the Pacific Northwest show the 2003 Cascadia slow earthquake to be among the largest of ten transients recognized here. Twelve stations bracketing slow slip indicate transient slip propagated bi-directionally from initiation in the southern Puget basin, reaching 300 km along-strike over a period of seven weeks. This event produced, for the first time, resolvable vertical subsidence, and horizontal displacement reaching six mm in southern Washington State. Inverted for non-negative thrust slip, a maximum of 3.8 cm of slip is inferred, centered at 28 km depth near the sharp arch in the subducting Juan de Fuca plate. Nearly all slip lies shallower than 38 km. Inverted slip shows a total moment release equal to Mw= 6.6 and a high degree of spatial localization rather than near-uniform slip. This suggests rupture concentrated along asperities holds for slow earthquakes as well as conventional events

A discursive approach to narrative accounts of hearing voices and recovery

Substantive objective: To research the range of discursive constructions ‘recovered’ voice hearers employ to describe hearing voices and the implications for positioning and subjectivity (what can be thought and felt) using each construction. Methodological objective and method: To explore a ‘sympathetic’ application of Foucauldian discourse analysis, adapting Willig’s (2008 Willig, C. 2008. Introducing Qualitative Research in Psychology, Maidenhead: Open University Press. ) method, analysing two published accounts. Results and conclusions: Heterogeneous discursive constructions for talking about hearing voices were identified, including: ‘many-’selves’’, ‘taking-the-lead-in-your-own-recovery’, ‘voices-as-an-’imagined-world’’ and ‘voices-as-a-coping-strategy-for-dealing-with-trauma’. The discourse of the biomedical model was not prominent, suggesting alternate discursive constructions may create subjects with a greater capacity for ‘living with voices’ and create a subjectivity from which vantage point the experience holds meaning and value and can be integrated into life experiences. This research may have useful clinical applications for mental health services aiming to collaboratively explore service users’ ways of understanding hearing voices

Visual short-term memory deficits associated with GBA mutation and Parkinson's disease.

Individuals with mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene are at significantly high risk of developing Parkinson's disease with cognitive deficit. We examined whether visual short-term memory impairments, long associated with patients with Parkinson's disease, are also present in GBA-positive individuals-both with and without Parkinson's disease. Precision of visual working memory was measured using a serial order task in which participants observed four bars, each of a different colour and orientation, presented sequentially at screen centre. Afterwards, they were asked to adjust a coloured probe bar's orientation to match the orientation of the bar of the same colour in the sequence. An additional attentional 'filtering' condition tested patients' ability to selectively encode one of the four bars while ignoring the others. A sensorimotor task using the same stimuli controlled for perceptual and motor factors. There was a significant deficit in memory precision in GBA-positive individuals-with or without Parkinson's disease-as well as GBA-negative patients with Parkinson's disease, compared to healthy controls. Worst recall was observed in GBA-positive cases with Parkinson's disease. Although all groups were impaired in visual short-term memory, there was a double dissociation between sources of error associated with GBA mutation and Parkinson's disease. The deficit observed in GBA-positive individuals, regardless of whether they had Parkinson's disease, was explained by a systematic increase in interference from features of other items in memory: misbinding errors. In contrast, impairments in patients with Parkinson's disease, regardless of GBA status, was explained by increased random responses. Individuals who were GBA-positive and also had Parkinson's disease suffered from both types of error, demonstrating the worst performance. These findings provide evidence for dissociable signature deficits within the domain of visual short-term memory associated with GBA mutation and with Parkinson's disease. Identification of the specific pattern of cognitive impairment in GBA mutation versus Parkinson's disease is potentially important as it might help to identify individuals at risk of developing Parkinson's disease

Voice-selective prediction alterations in nonclinical voice hearers

Auditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but also occur in 6-13% of the general population. Voice perception is thought to engage an internal forward model that generates predictions, preparing the auditory cortex for upcoming sensory feedback. Impaired processing of sensory feedback in vocalization seems to underlie the experience of AVH in psychosis, but whether this is the case in nonclinical voice hearers remains unclear. The current study used electroencephalography (EEG) to investigate whether and how hallucination predisposition (HP) modulates the internal forward model in response to self-initiated tones and self-voices. Participants varying in HP (based on the Launay-Slade Hallucination Scale) listened to self-generated and externally generated tones or self-voices. HP did not affect responses to self vs. externally generated tones. However, HP altered the processing of the self-generated voice: increased HP was associated with increased pre-stimulus alpha power and increased N1 response to the self-generated voice. HP did not affect the P2 response to voices. These findings confirm that both prediction and comparison of predicted and perceived feedback to a self-generated voice are altered in individuals with AVH predisposition. Specific alterations in the processing of self-generated vocalizations may establish a core feature of the psychosis continuum.The Authors gratefully acknowledge all the participants who collaborated in the study, and particularly Dr. Franziska Knolle for feedback on stimulus generation, Carla Barros for help with scripts for EEG time-frequency analysis, and Dr. Celia Moreira for her advice on mixed linear models. This work was supported by the Portuguese Science National Foundation (FCT; grant numbers PTDC/PSI-PCL/116626/2010, IF/00334/2012, PTDC/MHCPCN/0101/2014) awarded to APP

Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.</p> <p>Methods</p> <p>We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.</p> <p>Results</p> <p>We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.</p> <p>Conclusion</p> <p>Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.</p

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

iDAH Research Software Engineering (RSE) Steering Group working paper

This is the final version. Available from the iDAH Research Software Engineering (RSE) Steering Group via the DOI in this record. Our purpose was to convene a broad and representative group from the UK Research Software Engineering (RSE) community to discuss opportunities for and barriers to the development of Arts & Humanities (AH) RSE capability, with a specific focus on contributing to the AHRC Infrastructure for Digital Innovation and Curation in Arts and Humanities (iDAH) project and a wider remit to consider longer term strategic priorities and opportunities for alignment with UKRI and EU initiatives. The discussion was intended to be foundational, inclusive, and broad-ranging, involving a wide stakeholder group encouraged to engage in ‘blue-sky’ thinking over short, medium, and long-term time horizons. The analysis contained in this working paper should be read in that context, as a reflection of early stage discussions intended to provide a platform for future more focused activity. Additional discussion and analysis is needed to produce substantive actionable conclusions