Happiness is in the mouth of the beholder and fear in the eyes.

A temporal two-interval forced-choice paradigm is used to evaluate the relative strength of the visual signals conveyed by the eyes and the mouth in happy and fearful facial expressions.  Stimuli were black and white images of faces with a neutral, happy or fearful expression.  The happy and fearful visual signals were conveyed by the eyes, the mouth or by the whole face. A range of signal strengths (0-100%) were created by morphing the neutral and expressive images.  One interval contained the neutral face (0%) and the other the expressive face (varied from 0 – 100%, presented for 200ms).  Observers indicated the interval with the more expressive image.  Performance increased from chance (50%) to 100% correct as signal strength increased in all conditions.   Psychometric functions for happy expressions were shifted to the left of those for fearful expressions indicating that observers are more sensitive to happy expressions.  This suggests that the emotion signals conveyed by a happy face are more salient than those conveyed by a fearful face.   For happy expressions, psychometric functions for conditions with an expressive mouth were shifted to the left of those in which only the eyes were expressive. For fearful expressions, psychometric functions for conditions in which the eyes were expressive were shifted to the left of those in which only the mouth was expressive. This suggests that the visual signals conveyed by the mouth are more salient for happy facial expressions and the visual signals conveyed by the eyes are more salient for fearful expressions. Future research is aimed at understanding the extent to which this perceptual difference can be explained by the nature of the low level visual signal or higher cognitive function

A one-step procedure to probe the viscoelastic properties of cells by Atomic Force Microscopy

The increasingly recognised importance of viscoelastic properties of cells in pathological conditions requires rapid development of advanced cell microrheology technologies. Here, we present a novel Atomic Force Microscopy (AFM)-microrheology (AFM2) method for measuring the viscoelastic properties in living cells, over a wide range of continuous frequencies (0.005 Hz ~ 200 Hz), from a simple stress-relaxation nanoindentation. Experimental data were directly analysed without the need for pre-conceived viscoelastic models. We show the method had an excellent agreement with conventional oscillatory bulk-rheology measurements in gels, opening a new avenue for viscoelastic characterisation of soft matter using minute quantity of materials (or cells). Using this capability, we investigate the viscoelastic responses of cells in association with cancer cell invasive activity modulated by two important molecular regulators (i.e. mutation of the p53 gene and Rho kinase activity). The analysis of elastic (G′(ω)) and viscous (G″(ω)) moduli of living cells has led to the discovery of a characteristic transitions of the loss tangent (G″(ω)/G′(ω)) in the low frequency range (0.005 Hz ~ 0.1 Hz) that is indicative of the capability for cell restructuring of F-actin network. Our method is ready to be implemented in conventional AFMs, providing a simple yet powerful tool for measuring the viscoelastic properties of living cells

Pantry Suggestions.

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Permanent indwelling peritoneal catheters for palliation of refractory ascites in end-stage liver disease: a systematic review

Background and aims The incidence and mortality from end‐stage liver disease is increasing, with a minority eligible for liver transplantation. Ascites is the commonest complication of end‐stage liver disease and large volume paracentesis (LVP) the accepted management strategy where refractory to medical treatment. In malignant ascites, permanent indwelling peritoneal catheters (PIPC) are an established palliative intervention. The aims are to describe available data using permanent indwelling peritoneal catheters in refractory ascites due to end‐stage liver disease. Methods Using systematic review methodology, databases were searched (MEDLINE, EMBASE, CINAHL [The Cumulative Index to Nursing and Allied Health Literature], Google Scholar and Cochrane Database of Systematic Reviews from inception‐March 2018), for studies combining ascites and palliative care. Inclusion and exclusion criteria were applied to results. Results Following initial and updated searches, 225 studies were identified for full text review, 18 were eligible for final analysis. The studies displayed heterogeneity in design, reported on different indwelling catheters and were overall of low quality. Only one pilot randomised controlled trial was identified, of PIPC versus LVP, recruiting one patient into each arm. Technical insertion success was 100%, with low rates of non‐infectious complications (<12%), none life threatening. Rates of bacterial peritonitis were not unacceptably high (12.7%), considering this was an end‐stage liver disease population and only a minority utilising long‐term prophylactic antibiotics. Only one study attempted quality‐of‐life assessments; none addressed potential health economic benefits. Conclusions Despite lack of well‐designed studies, preliminary data suggests low significant complication rates; however safety and efficacy of permanent indwelling peritoneal catheters in end‐stage liver disease remains to be confirmed. Further prospective randomised controlled trials are warranted, potentially translating permanent indwelling peritoneal catheters into improved palliative care in end‐stage liver disease

Using linked administrative data for monitoring and evaluating the Family Nurse Partnership in England: A scoping report

This report, commissioned by the FNP National Unit and undertaken by researchers at UCL and the London School of Hygiene and Tropical Medicine, presents a scoping review of how population-based linkage between data from the Family Nurse Partnership (FNP) in England and administrative datasets from other services could be used to generate evidence for commissioning, service evaluation and research. It addresses the methodological considerations, permission pathways and technical challenges of using data from the FNP linked with routinely collected, administrative data from other public services for population-based analyses, at a national and local authority level. Our ambition, when commissioning this work, was to explore whether linking data from FNP with administrative datasets might help provide a richer view about how the FNP intervention is affecting different cohorts of clients and their child after they have graduated. The report suggests that the potential for data linkage to support ongoing evaluation of a wide range of interventions including FNP at a national level is promising and an important area to explore. It makes a significant contribution to understanding the possibilities and constraints for doing this, which include barriers to data linkage at a local level (which we know is crucial for local commissioners) and the significant investment required to realise the potential of this project. We believe this report offers valuable insights other organisations interested in the delivery of evidence based policy may want to pursue

Regulation of E2F activity by p14ARF

The p14[ARF] product of the ink4a/arf locus is induced by a variety of oncogenic signals. p14[ARF] can facilitate growth aixest through the p53 pathway by hindering the down-regulation of p53 activity through its interaction with MDM2, which interferes with formation of the complex between p53 and MDM2. Here I have explored the possibility that p14ARF may be integrated with growth regulatory pathways other than p53, and report that p14ARF can modulate the activity of the cell cycle regulating E2F transcription factor. P14ARF regulates E2F-1 activity in both SAOS2 cells and p53-1-/mdm2-1-MEFs, excluding the possibility that the effects of on E2F are influenced by MDM2. p14ARF down regulates E2F-dependent transcription, S-phase entry, apoptosis and colony formation. The mechanism responsible for this activity may be through regulation of E2F stability at the post-translational level. P14[ARF] forms a physical complex with E2F both in vitro and in cells. binds to E2F through distinct, binding domains, one of which resides in the N-terminal region and is capable of down-regulating E2F activity. These results highlight the potential interplay and cross talk between p14[ARF] and E2F-1, and establish as an antagonist of cell growth that acts by targeting two of the key pathways involved in controlling proliferation, namely E2F and p53

Apathy and Relational Changes in Huntington’s Disease: Exploring the Caregivers’ Experiences

Background: Huntington’s disease affects cognition, behaviour, and social and emotional functioning with reduction in self-initiated thoughts, activities, emotional responses or social activities, or apathy, a frequent and early consequence closely related to underlying neuropathological changes. Little is understood about how these changes impact on caregivers, despite emerging evidence that behavioural features of the disease and change in the caregiver/care recipient relationship are linked to perceptions of burden. Aim: This thesis aimed to explore the experience of caregivers and the meaning-making constructed about apathy and relational change in Huntington’s disease. Methods: Semi-structured interviews analysed with reflective thematic analysis were used to investigate caregiver experience of supporting someone with Huntington’s disease and apathy. Following which, a systematic review of qualitative research and thematic synthesis of caregiver experience of relational change in Huntington’s disease was conducted. Results: The qualitative study produced five themes: “What even is apathy?”, “It makes my life harder”, “They haven’t forgotten me but they have forgotten that they ever loved me”, “Grieving for someone who hasn’t died yet”, and “I need a safe space to say what I really feel without fear of judgement”. Narratives about the invisibility and unspoken nature of both HD and caregivers were inter-woven across themes. The systematic review identified themes of: “Loss of friendship, companionship and intimacy”, “Relationships built around fear”, “Seeing my own future played out before me”, and “HD has made us stronger”. Conclusions: This thesis portfolio highlights the emotional and interpersonal impact of Huntington’s disease on caregivers. Using the theoretical framework of anticipatory grief and ambiguous loss, it promotes the importance of a systemic view of the impact of the disease, helping to shape future research and clinical practice

The Synthesis of Azasugars Using an I2-mediated Carbamate Annulation

The biological activity of azasugars has largely been attributed to their ability to mimic the oxocarbenium ion-like transition state formed during reactions with carbohydrate-processing enzymes and, for this reason, functional and stereochemical modifications of the azasugar scaffold have led to the development of specific and potent glycosidase inhibitors. Given the potential of azasugars as glycosidase inhibitors, we were interested in developing efficient methodology for their synthesis. This thesis highlights synthetic methodology developed to produce amino-imino-hexitols as azasugar scaffolds. Key in the synthesis of the amino-imino-hexitols was the application of a stereoselective Strecker reaction, without the need for chiral Lewis acids or catalysts, and an extension of an I2-mediated carbamate annulation to cyclise functionalised and protected alkenylamines. Sixteen amino-imino-hexitols were synthesized, including ten previously undisclosed substrates with the D-galacto, D-talo, and L-altro configurations. The novel amino-imino-hexitols were then tested for their ability to act as glycosidase inhibitors and substrates of the D-talo configuration showed promising inhibitory effects. Mechanistic considerations of the I2-mediated carbamate annulation are discussed and although the exact annulation mechanism has yet to be determined, experimental studies have revealed that an aziridine is not an intermediate in the reaction. Factors influencing the diastereoselectivity of the carbamate annulation are also explored. Furthermore, an in depth analysis of the high cis-selectivity of the carbamate annulation is investigated using density functional theory to calculate the transition states of iodocyclisations en route to the formation of carbamates. Taken as a whole, the applicability of the carbamate annulation to a variety of alkenylamines and an understanding of the factors controlling the diastereoselectivity of the reaction should make this methodology a valuable addition to the synthetic chemist’s toolbox

The Synthesis of Azasugars Using an I2-mediated Carbamate Annulation

The biological activity of azasugars has largely been attributed to their ability to mimic the oxocarbenium ion-like transition state formed during reactions with carbohydrate-processing enzymes and, for this reason, functional and stereochemical modifications of the azasugar scaffold have led to the development of specific and potent glycosidase inhibitors. Given the potential of azasugars as glycosidase inhibitors, we were interested in developing efficient methodology for their synthesis. This thesis highlights synthetic methodology developed to produce amino-imino-hexitols as azasugar scaffolds. Key in the synthesis of the amino-imino-hexitols was the application of a stereoselective Strecker reaction, without the need for chiral Lewis acids or catalysts, and an extension of an I2-mediated carbamate annulation to cyclise functionalised and protected alkenylamines. Sixteen amino-imino-hexitols were synthesized, including ten previously undisclosed substrates with the D-galacto, D-talo, and L-altro configurations. The novel amino-imino-hexitols were then tested for their ability to act as glycosidase inhibitors and substrates of the D-talo configuration showed promising inhibitory effects. Mechanistic considerations of the I2-mediated carbamate annulation are discussed and although the exact annulation mechanism has yet to be determined, experimental studies have revealed that an aziridine is not an intermediate in the reaction. Factors influencing the diastereoselectivity of the carbamate annulation are also explored. Furthermore, an in depth analysis of the high cis-selectivity of the carbamate annulation is investigated using density functional theory to calculate the transition states of iodocyclisations en route to the formation of carbamates. Taken as a whole, the applicability of the carbamate annulation to a variety of alkenylamines and an understanding of the factors controlling the diastereoselectivity of the reaction should make this methodology a valuable addition to the synthetic chemist’s toolbox