The twisted fourth moment of the Riemann zeta function

We compute the asymptotics of the fourth moment of the Riemann zeta function times an arbitrary Dirichlet polynomial of length $T^{{1/11} - \epsilon}$Comment: 28 pages. v2: added reference

Mechanical properties of α-tricalcium phosphate-based bone cements incorporating regenerative biomaterials for filling bone defects exposed to low mechanical loads

Calcium phosphate-based cements with enhanced regenerative potential are promising biomaterials for the healing of bone defects. With a view to the use of such cements for low load bearing applications such as sinus augmentation or filling extraction sites, we have prepared α-tricalcium phosphate (α-TCP)-based bone cements including materials that we would expect to improve their regenerative potential, and describe the mechanical properities of the resulting formulations herein. Formulations incorporated α-TCP, hydroxyapatite, biopolymer-thickened wetting agents, sutures, and platelet poor plasma. The mechanical properties of the composites were composition dependent, and optimized formulations had clinically relevant mechanical properties. Such calcium phosphate-based cements have potential as replacements for cements such as those based on polymethylmethacrylate (PMMA)

The U&I study: study protocol for a feasibility randomised controlled trial of a pre-cognitive behavioural therapy digital ‘informed choice’ intervention to improve attitudes towards uptake and implementation of CBT for psychosis

Background: At least 40% of people with psychosis have persistent distressing symptoms despite optimal medication treatment. Cognitive Behaviour Therapy for psychosis (CBTp) is the only NICE recommended individual therapy for psychosis, with effects on symptoms, distress and quality of life. Yet fewer than 20% of service-users receive it and 94% of trusts struggle to provide it. Of those offered it, 22-43% refuse or do not attend. We have developed a new pre-CBTp informed choice intervention to address knowledge and attitudes that influence uptake and implementation and now want to test it in a feasibility trial. Methods: The design is a 2-arm, feasibility RCT, with 1:1 randomisation, stratified by participant group and site. Participants are 40 psychosis patients and 40 clinicians, who are ambivalent towards uptake or implementation of CBTp. Sites are community and inpatient services in Sussex and London. The intervention is a pre-CBT digital psychoeducation intervention designed to address identified knowledge and attitudinal barriers to uptake and implementation of CBTp, incorporating behaviour change mechanisms, and supported by animated introductory, patient and clinician stories. The comparator is the NHS choices website for CBT. The primary aim is to assess clinical feasibility (recruitment, randomization, acceptability, use, delivery, outcome measurement, retention). A secondary aim is a preliminary evaluation of efficacy. Outcomes will be assessed at baseline, post-intervention, and one-month follow up (blind to treatment arm). The primary efficacy outcome is likelihood of offering/taking up CBTp. Secondary outcomes include knowledge and attitudes towards CBTp; illness perceptions; empowerment; psychological wellbeing (patients only); CBTp implementation (clinicians only). Use of the intervention and CBT behaviours during the follow-up period will be recorded, and captured in a feedback questionnaire. Use, acceptability and experience of outcome assessment will be explored in qualitative interviews with participants (n = 6 per group). The efficacy evaluation will report descriptive data, key model parameters and 95% Highest Probability Density intervals in a Bayesian growth model. Discussion: This is the first feasibility trial of a digital ‘informed choice’ decision aid for the implementation of CBTp. If the trial proves feasible and demonstrates preliminary evidence of efficacy, a large multi-site trial will be warranted

A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations

Exposure to carbon monoxide (CO) causes early afterdepolarization arrhythmias. Previous studies in rats indicated arrhythmias arose due to augmentation of the late Na+ current. The purpose of the present study was to examine the basis of CO-induced arrhythmias in guinea pig myocytes in which action potentials more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes and also from HEK293 cells expressing wild-type or a C723S mutant form of Kv11.1 (ERG). We also monitored formation of peroxynitrite (ONOO-) in HEK293 cells fluorimetrically. CO, applied as the CO releasing molecule, CORM-2, prolonged action potentials and induced early after-depolarizations (EADs) in guinea pig myocytes. In HEK293 cells CO inhibited wild-type but not C723S mutant Kv11.1 K+ currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors or inhibition of nitric oxide formation. CO also raised ONOO- levels, an effect reversed by the ONOO- scavenger, FeTPPS which also prevented CO inhibition of Kv11.1 currents, and abolished the effects of CO on Kv11.1 tail currents and action potentials in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes via ONOO--mediated inhibition of Kv11.1 K+ channel

The Uniqueness Theorem for Entanglement Measures

We explore and develop the mathematics of the theory of entanglement measures. After a careful review and analysis of definitions, of preliminary results, and of connections between conditions on entanglement measures, we prove a sharpened version of a uniqueness theorem which gives necessary and sufficient conditions for an entanglement measure to coincide with the reduced von Neumann entropy on pure states. We also prove several versions of a theorem on extreme entanglement measures in the case of mixed states. We analyse properties of the asymptotic regularization of entanglement measures proving, for example, convexity for the entanglement cost and for the regularized relative entropy of entanglement.Comment: 22 pages, LaTeX, version accepted by J. Math. Phy

Among friends:A qualitative exploration of the role of peers in young people's alcohol use using Bourdieu’s concepts of habitus, field and capital

Drinking is viewed by young people as a predominantly social activity which provides an opportunity for entertainment and bonding with friends. Using Bourdieu's concepts of habitus, field and capital, this article explores young people's attitudes and beliefs around alcohol use, influences on behaviour, and the role of peers, with a view to informing the development of preventive interventions. Semi-structured interviews were conducted with 28 young people aged 18–20 in the south west of England. We describe how friends were integral in drinking experiences, and drinking with friends was equated with fun and enjoyment. In this way, the desire for social and symbolic capital appeared to be a key motivator for adolescent drinking. Critically, however, wider cultural norms played the predominant role in shaping behaviour, via the internalisation of widely accepted practice and the subsequent externalisation of norms through the habitus. Applying Bourdieu's theory suggests that population-level interventions that regulate alcohol consumption, and thus disrupt the field, are likely to facilitate behaviour change among young people by driving a response in habitus

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Leadership and decision-making practices in public versus private universities in Pakistan

The goal of this study is to examine differences in leadership and decision-making practices in public and private universities in Pakistan, with a focus on transformational leadership (TL) and participative decision-making (PDM). We conducted semi-structured interviews with 46 deans and heads of department from two public and two private universities in Pakistan. Our findings indicate that leadership and decision-making practices are different in public and private universities. While differences were observed in all six types of TL-behaviour, the following three approaches emerged to be crucial in both public and private universities: (1) articulating a vision, (2) fostering the acceptance of group goals, and (3) high-performance expectations. In terms of PDM, deans and heads of department in public and private universities adopt a collaborative approach. However, on a practical level this approach is limited to teacher- and student-related matters. Overall, our findings suggest that the leadership and decision-making practices in Pakistani public and private universities are transformational and participative in nature