Decoding the Notch signal.

Notch signalling controls many key cellular processes which differ according to the context where the pathway is deployed due to the transcriptional activation of specific sets of genes. The pathway is unusual in its lack of amplification, also raising the question of how it can efficiently activate transcription with limited amounts of nuclear activity. Here, we focus on mechanisms that enable Notch to produce appropriate transcriptional responses and speculate on models that could explain the current gaps in knowledge

Bar-Halo Friction in Galaxies II: Metastability

It is well-established that strong bars rotating in dense halos generally slow down as they lose angular momentum to the halo through dynamical friction. Angular momentum exchanges between the bar and halo particles take place at resonances. While some particles gain and others lose, friction arises when there is an excess of gainers over losers. This imbalance results from the generally decreasing numbers of particles with increasing angular momentum, and friction can therefore be avoided if there is no gradient in the density of particles across the major resonances. Here we show that anomalously weak friction can occur for this reason if the pattern speed of the bar fluctuates upwards. After such an event, the density of resonant halo particles has a local inflexion created by the earlier exchanges, and bar slowdown can be delayed for a long period; we describe this as a metastable state. We show that this behavior in purely collisionless N-body simulations is far more likely to occur in methods with adaptive resolution. We also show that the phenomenon could arise in nature, since bar-driven gas inflow could easily raise the bar pattern speed enough to reach the metastable state. Finally, we demonstrate that mild external, or internal, perturbations quickly restore the usual frictional drag, and it is unlikely therefore that a strong bar in a galaxy having a dense halo could rotate for a long period without friction.Comment: 13 pages, 11 figures, to appear in Ap

The significance of seniority for women managers’ interpretations of organizational restructuring

This paper examines the impact of restructuring within the transport and logistics sector on women managers working at senior and less senior (middle/junior management) levels of the organization. The majority of women experienced increased performance pressures and heavier workloads as well as an increase in working hours. At the same time, there were pressures to work at home (i.e. week-ends and evenings) and reduced opportunities to work from home (i.e. during normal office hours). Management level emerged as an important factor in how these changes were interpreted. Senior managers perceived more positive outcomes in terms of increased motivation and loyalty. Despite a longer working week, they were less likely to report low morale as an outcome from long hours. In fact, irrespective of management level, women working shorter hours were more likely to report low morale as an outcome. Results are discussed in relation to literature on restructuring and careers, in terms of perceptual framing and in relation to different levels of investment in the organization

Anomalous lifetime distributions and topological traps in ordering dynamics

We address the role of community structure of an interaction network in ordering dynamics, as well as associated forms of metastability. We consider the voter and AB model dynamics in a network model which mimics social interactions. The AB model includes an intermediate state between the two excluding options of the voter model. For the voter model we find dynamical metastable disordered states with a characteristic mean lifetime. However, for the AB dynamics we find a power law distribution of the lifetime of metastable states, so that the mean lifetime is not representative of the dynamics. These trapped metastable states, which can order at all time scales, originate in the mesoscopic network structure.Comment: 7 pages; 6 figure

Percolation on the average and spontaneous magnetization for q-states Potts model on graph

We prove that the q-states Potts model on graph is spontaneously magnetized at finite temperature if and only if the graph presents percolation on the average. Percolation on the average is a combinatorial problem defined by averaging over all the sites of the graph the probability of belonging to a cluster of a given size. In the paper we obtain an inequality between this average probability and the average magnetization, which is a typical extensive function describing the thermodynamic behaviour of the model

Mental health service user experiences of targeted violence and hostility and help-seeking in the UK: a scoping review

The aim of this research scoping review was to assemble an evidence base for the UK on mental health service user experiences and perspectives on mental health-related targeted violence and hostility ('disability hate crime'). It also aims to address some of the gaps in the knowledge on risk management, help-seeking and prevention from the perspectives of those who experienced targeted violence and hostility because of their mental health problems or psychiatric status. Seven key mental health and social care bibliographic databases were searched for relevant UK research studies from 1990 until 2016. Grey literature was identified through online searches. A scoping review charting approach and thematic analysis methodology were used to analyse the studies. In total 13 studies were finally included, over half of which used survey methods. All studies included people with experiences of mental health problems. The studies provide information on: the types of potential hate crime; indicate where incidents take place; give some insight into the victims' relationship with the perpetrators; the location of incidents as well as the psychological, social, financial and physical impacts on the victim; the types of help-seeking behaviours adopted by the victims; a range coping strategies that people with mental health problems adopted in response to experiences of targeted violence or abuse. This scoping review provides a UK-based overview of mental health service user concepts and experiences of mental health-related targeted violence and hostility ('disability hate crime'). It reveals some specific issues relating to mental health and disability hate crime. Further investigation into disability hate crime with a specific focus on mental health is required. This is a UK-based overview, which offers a useful comparator for researchers, practitioners and policy-makers internationally

Block Ionomer Complexes Consisting of siRNA and \u3ci\u3ea\u3c/i\u3eRAFT-Synthesized Hydrophilic-\u3ci\u3eBlock\u3c/i\u3e-Cationic Copolymers II: The Influence of Cationic Block Charge Density on Gene Suppression

Block ionomer complex (BIC)–siRNA interactions and effectiveness in cell transfection are reported. Aqueous RAFT polymerization was used to prepare a series of hydrophilic-block-cationic copolymers in which the cationic block statistically incorporates increasing amounts of neutral, hydrophilic monomer such that the number of cationic groups remains unchanged but the cationic charge density is diluted along the polymer backbone. Reduced charge density decreases the electrostatic binding strength between copolymers and siRNA with the goal of improving siRNA release after targeted cellular delivery. However, lower binding strength resulted in decreased transfection and RNA interference pathway activation, leading to reduced gene knockdown. Enzymatic siRNA degradation studies with BICs indicated lowered binding strength increases susceptibility to RNases, which is the likely cause for poor gene knockdown

"Keeping Control": a user‐led exploratory study of mental health service user experiences of targeted violence and abuse in the context of adult safeguarding in England

The situation for people with mental health problems as a group of disabled people who experience targeted violence and abuse is a complex one. Disabled people, particularly those with mental health problems, are at higher risk of targeted violence and hostility with few effective evidence‐based prevention and protection strategies. Achieving effective safeguarding for adults with mental health problems is characterised by differential attitudes to and understandings of abuse by safeguarding practitioners, as well as systemic issues arising from multi‐agency working. “Keeping Control” was a 16‐month user‐led, co‐produced exploratory qualitative study into service user experiences of targeted violence and abuse that was examined in the context of Care Act 2014 adult safeguarding reforms in England. User‐controlled interviews of mental health service users (N = 23) explored their experiences and concepts of targeted violence and abuse, prevention and protection. Preliminary findings from these interviews were discussed in adult safeguarding and mental health stakeholder and practitioner focus groups (N = 46). The data were also discussed via two facilitated Twitter chats (responses N = 585 and N = 139). Mental health service users’ experiences and concepts of risk from others, vulnerability and neglect can be different to those of practitioners but should be central to adult safeguarding. Histories of trauma, multi‐factorial abuse; living with fear and stigma as well as mental distress; the effects of “psychiatric disqualification” and individual blaming should be addressed in adult safeguarding in mental health. Fragmented responses from services can mean a person becomes “lost in the process”. Staff can feel disempowered, afraid or lacking in confidence to “speak up” for individuals in complex service systems with poor communication and lines of accountability. Adult safeguarding practitioners and stakeholders need to be confident, accessible and respond quickly to service users reporting incidents of targeted violence and abuse particularly in closed environments such as wards or supported housing

‘Dignity and respect’: An example of service user leadership and co‐production in mental health research

This paper explores the methodological aspects of a user‐led study investigating mental health service user experiences of targeted violence and abuse (often called 'hate crime'). 'Keeping Control' was a 16‐month qualitative study, undertaken in the context of adult safeguarding reforms in England. By collecting data on service user concepts and experiences, the research sought to address a gap in research and practice knowledge relating to targeted violence, abuse and hostility against people with mental health problems. In this paper, we discuss the significance of the design and methodology used for this study, with a particular focus on the interviews with service users. The research was both user‐led and carried out in collaboration with practitioners and academics, a form of research co‐production. Our aim is to inform researchers, practitioners and policymakers about the value of user leadership in co‐productive research with practitioners, particularly for a highly sensitive and potentially distressing topic

Detailed assessment of benefits and risks of retrievable inferior vena cava filters on patients with complicated injuries: the da Vinci multicentre randomised controlled trial study protocol

Introduction Retrievable inferior vena cava (IVC) filters have been increasingly used in patients with major trauma who have contraindications to anticoagulant prophylaxis as a primary prophylactic measure against venous thromboembolism (VTE). The benefits, risks and cost-effectiveness of such strategy are uncertain. Methods and analysis Patients with major trauma, defined by an estimated Injury Severity Score >15, who have contraindications to anticoagulant VTE prophylaxis within 72 hours of hospitalisation to the study centre will be eligible for this randomised multicentre controlled trial. After obtaining consent from patients, or the persons responsible for the patients, study patients are randomly allocated to either control or IVC filter, within 72 hours of trauma admission, in a 1:1 ratio by permuted blocks stratified by study centre. The primary outcomes are (1) the composite endpoint of (A) pulmonary embolism (PE) as demonstrated by CT pulmonary angiography, high probability ventilation/perfusion scan, transoesophageal echocardiography (by showing clots within pulmonary arterial trunk), pulmonary angiography or postmortem examination during the same hospitalisation or 90-day after trauma whichever is earlier and (B) hospital mortality; and (2) the total cost of treatment including the costs of an IVC filter, total number of CT and ultrasound scans required, length of intensive care unit and hospital stay, procedures and drugs required to treat PE or complications related to the IVC filters. The study started in June 2015 and the final enrolment target is 240 patients. No interim analysis is planned; incidence of fatal PE is used as safety stopping rule for the trial. Ethics and dissemination Ethics approval was obtained in all four participating centres in Australia. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal. Trial registration number ACTRN12614000963628; Pre-results