First Order Phase Transition in a Two Higgs-doublet Model with Mh>MWM_{h}>M_{W}

We study the 3d effective field theory of a weakly coupled two Higgs-doublet scalar model at high temperature. Our model has three scalar quartic couplings and an $O(4)$ symmetry which is spontaneously broken by a nonzero scalar field $vev$ at zero temperature. Using high temperature perturbation theory, renormalization group arguments in $4-\epsilon$ dimensions, as well as $1/N$ expansion techniques in 3 dimensions, we argue that the transition from the high temperature symmetry restoring phase to the low temperature phase is first order for a range of scalar couplings. This result is not due to gauge couplings. We discuss the implications of our results for baryogenesis in the two Higgs-doublet electroweak model, especially when the lightest neutral Higgs is heavier than the W--bosons.Comment: 15 page

Comparison of type 5d autotransporter phospholipases demonstrates a correlation between high activity and intracellular pathogenic lifestyle

Autotransporters, or type 5 secretion systems, are widespread surface proteins of Gram-negative bacteria often associated with virulence functions. Autotransporters consist of an outer membrane β-barrel domain and an exported passenger. In the poorly studied type 5d subclass, the passenger is a patatin-like lipase. The prototype of this secretion pathway is PlpD of Pseudomonas aeruginosa , an opportunistic human pathogen. The PlpD passenger is a homodimer with phospholipase A1 (PLA1) activity. Based on sequencing data, PlpD-like proteins are present in many bacterial species. We characterized the enzymatic activity, specific lipid binding and oligomeric status of PlpD homologs from Aeromonas hydrophila (a fish pathogen), Burkholderia pseudomallei (a human pathogen) and Ralstonia solanacearum (a plant pathogen) and compared these with PlpD. We demonstrate that recombinant type 5d-secreted patatin domains have lipase activity and form dimers or higher-order oligomers. However, dimerization is not necessary for lipase activity; in fact, by making monomeric variants of PlpD, we show that enzymatic activity slightly increases while protein stability decreases. The lipases from the intracellular pathogens A. hydrophila and B. pseudomallei display PLA2 activity in addition to PLA1 activity. Although the type 5d-secreted lipases from the animal pathogens bound to intracellular lipid targets, phosphatidylserine and phosphatidylinositol phosphates, hydrolysis of these lipids could only be observed for FplA of Fusobacterium nucleatum . Yet, we noted a correlation between high lipase activity in type 5d autotransporters and intracellular lifestyle. We hypothesize that type 5d phospholipases are intracellularly active and function in modulation of host cell signaling events

Applicability of an abbreviated version of the Child-OIDP inventory among primary schoolchildren in Tanzania

Background: There is a need for studies evaluating oral health related quality of life (OHRQoL) of children in developing countries. Aim: to assess the psychometric properties, prevalence and perceived causes of the child version of oral impact on daily performance inventory (Child- OIDP) among school children in two socio-demographically different districts of Tanzania. Socio-behavioral and clinical correlates of children's OHRQoL were also investigated.Method: One thousand six hundred and one children ( mean age 13 yr, 60.5% girls) attending 16 ( urban and rural) primary schools in Kinondoni and Temeke districts completed a survey instrument in face to face interviews and participated in a full mouth clinical examination. The survey instrument was designed to measure a Kiswahili translated and culturally adapted Child-OIDP frequency score, global oral health indicators and socio-demographic factors. Results: The Kiswahili version of the Child- OIDP inventory preserved the overall concept of the original English version and revealed good reliability in terms of Cronbach's alpha coefficient of 0.77 ( Kinondoni: 0.62, Temeke: 0.76). Weighted Kappa scores from a test-retest were 1.0 and 0.8 in Kinondoni and Temeke, respectively. Validity was supported in that the OIDP scores varied systematically and in the expected direction with self-reported oral health measures and socio-behavioral indicators. Confirmatory factor analyses, CFA, confirmed three dimensions identified initially by Principle Component Analysis within the OIDP item pool. A total of 28.6% of the participants had at least one oral impact. The area specific rates for Kinondoni and Temeke were 18.5% and 45.5%. The most frequently reported impacts were problems eating and cleaning teeth, and the most frequently reported cause of impacts were toothache, ulcer in mouth and position of teeth. Conclusion: This study showed that the Kiswahili version of the Child- OIDP was applicable for use among schoolchildren in Tanzania

Dijete je gradu festival

Understanding the intra- and extracellular proteins involved in the development of the corticospinal tract (CST) may offer insights into how the pathway could be regenerated following traumatic spinal cord injury. Currently, however, little is known about the proteome of the developing corticospinal system. The present study, therefore, has used quantitative proteomics and bioinformatics to detail the protein profile of the rat CST during its formation in the spinal cord. This analysis identified increased expression of 65 proteins during the early ingrowth of corticospinal axons into the spinal cord, and 36 proteins at the period of heightened CST growth. A majority of these proteins were involved in cellular assembly and organization, with annotations being most highly associated with cytoskeletal organization, microtubule dynamics, neurite outgrowth, and the formation, polymerization and quantity of microtubules. In addition, 22 proteins were more highly expressed within the developing CST in comparison to other developing white matter tracts of the spinal cord of age-matched animals. Of these differentially expressed proteins, only one, stathmin 1 (a protein known to be involved in microtubule dynamics), was both highly enriched in the developing CST and relatively sparse in other developing descending and ascending spinal tracts. Immunohistochemical analyses of the developing rat spinal cord and fetal human brain stem confirmed the enriched pattern of stathmin expression along the developing CST, and in vitro growth assays of rat corticospinal neurons showed a reduced length of neurite processes in response to pharmacological perturbation of stathmin activity. Combined, these findings suggest that stathmin activity may modulate axonal growth during development of the corticospinal projection, and reinforces the notion that microtubule dynamics could play an important role in the generation and regeneration of the CST

A telephone survey of cancer awareness among frontline staff: informing training needs

Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors

Identification of ABC Transporter Interaction of a Novel Cyanoquinoline Radiotracer and Implications for Tumour Imaging by Positron Emission Tomography.

Background The epidermal growth factor receptor (EGFR) is overexpressed in many cancers including lung, ovarian, breast, head and neck and brain. Mutation of this receptor has been shown to play a crucial role in the response of non-small cell lung carcinoma (NSCLC) to EGFR-targeted therapies. It is envisaged that imaging of EGFR using positron emission tomography (PET) could aid in selection of patients for treatment with novel inhibitors. We recognised multi-drug resistant phenotype as a threat to development of successful imaging agents. In this report, we describe discovery of a novel cyanoquinoline radiotracer that lacks ABC transporter activity.Methods Cellular retention of the prototype cyanoquinoline [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxyquinolin-6-yl}-4-({[1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl]methyl}amino)-but-2-enamide ([18F]FED6) and [18F](2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxyquinolin-6-yl}-4-[({1-[(2R,5S)-3-fluoro-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]-1H-1,2,3-triazol-4-yl}methyl)amino]but-2-enamide ([18F]FED20) were evaluated to establish potential for imaging specificity. The substrate specificity of a number of cyanoquinolines towards ABC transporters was investigated in cell lines proficient or deficient in ABCB1 or ABCG2.Results FED6 demonstrated substrate specificity for both ABCG2 and ABCB1, a property that was not observed for all cyanoquinolines tested, suggesting scope for designing novel probes. ABC transporter activity was confirmed by attenuating the activity of transporters with drug inhibitors or siRNA. We synthesized a more hydrophilic compound [18F]FED20 to overcome ABC transporter activity. FED20 lacked substrate specificity for both ABCB1 and ABCG2, and maintained a strong affinity for EGFR. Furthermore, FED20 showed higher inhibitory affinity for active mutant EGFR versus wild-type or resistant mutant EGFR; this property resulted in higher [18F]FED20 cellular retention in active mutant EGFR expressing NSCLC.Conclusion [18F]FED20 binds EGFR but is devoid of ABC transporter activity, thus, has potential for EGFR imaging

WELLFOCUS PPT – modified positive psychotherapy to improve well-being in psychosis: study protocol for a pilot randomised controlled trial

BACKGROUND: The promotion of well-being is an important goal of recovery oriented mental health services. No structured, evidence-based intervention exists that aims to increase the well-being in people with severe mental illness such as psychosis. Positive psychotherapy (PPT) is a promising intervention for this goal. Standard PPT was adapted for use with people with psychosis in the UK following the Medical Research Council framework for developing and testing complex interventions, resulting in the WELLFOCUS Model describing the intended impact of WELLFOCUS PPT. This study aims to test the WELLFOCUS Model, by piloting the intervention, trial processes, and evaluation strategy. METHODS/DESIGN: This study is a non-blinded pragmatic pilot RCT comparing WELLFOCUS PPT provided as an 11-session group therapy in addition to treatment as usual to treatment as usual alone. Inclusion criteria are adults (aged 18–65 years) with a main diagnosis of psychosis who use mental health services. A target sample of 80 service users with psychosis are recruited from mental health services across the South London and Maudsley NHS Foundation Trust. Participants are randomised in blocks to the intervention and control group. WELLFOCUS PPT is provided to groups by specifically trained and supervised local therapists and members of the research team. Assessments are conducted before randomisation and after the group intervention. The primary outcome measure is well-being assessed by the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes include good feelings, symptom relief, connectedness, hope, self-worth, empowerment, and meaning. Process evaluation using data collected during the group intervention, post-intervention individual interviews and focus groups with participants, and interviews with trial therapists will complement quantitative outcome data. DISCUSSION: This study will provide data on the feasibility of the intervention and identify necessary adaptations. It will allow optimisation of trial processes and inform the evaluation strategy, including sample size calculation, for a future definitive RCT. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04199273 – WELLFOCUS study: an intervention to improve well-being in people with psychosis, Date registered: 27 March 2013, first participant randomised on 26 April 2013

'It was as if the dots hadn't been joined up': bereaved families experiences of end of life care on an acute stroke ward: a qualitative investigation

Background and Aims: Despite significant improvements in survival, severe stroke remains a major cause of mortality. Acute stroke settings have a key role at the end of people’s lives following a severe stroke. Ensuring appropriate, timely, high quality, person-centred, safe and effective end-of-life care in these settings is a professional priority. This study aimed to illuminate bereaved family members’ experiences of end-of-life care in an acute stroke setting following implementation of an end-of-life care training intervention. Methods: A qualitative exploratory study using in-depth, semi-structured, face to face, digitally recorded interviews was conducted. Nine bereaved (> three months) family members, all women, participated. Interviews were fully transcribed and analysed using thematic analysis. Results: The analysis identified three major themes: the variable nature and quality of interaction with healthcare staff; doing care at the end of life and toward the realisation of a certain manner of good death. Findings illuminated some positive end-of-life care practices following a severe stroke in terms of recognising dying and family members’ support, care and engagement in decision-making. However, a pressing need for improved, timely, proactive and regular interaction with family members of people dying imminently in the acute stroke care setting was identified. Conclusions: End-of-life stroke care in the busy, noisy, fast paced acute hospital environments is not without challenge for many reasons. Furthermore, interacting with the family members of imminently dying people is delicate, difficult territory. Yet these are places where people die and the manner of a person’s dying casts an indelible mark on those who live on