Environmental determinants for repeatability of activity patterns in free-ranging elasmobranchs

Repeatability of behaviour is the degree of behavioural variation attributed to differences between- or within- individuals in a population and may often be conceptualised as animal personality. Behaviour is often plastic in response to environmental challenges to maximise individual survival. In ectotherms, this may be expressed as changes in behaviours due to higher environmental temperatures increasing metabolic demand. Personality is thought to constrain this behavioural plasticity as individuals express behaviours within their personality type. Most studies in this field have been conducted under controlled or semi-controlled conditions, which control for confounding factors and hence remain limited in their applicability in the face of uncertain field conditions. To date, no field studies have focused on the environmental conditions that determine how repeatability of behaviour is exhibited. Here we use biotelemetry tag derived activity data to assess environmental factors influencing the repeatability of activity patterns (i.e., repeated behaviours) in two euryhaline free-ranging elasmobranchs with differing life histories; the largetooth sawfish (Pristis pristis) and bull shark (Carcharhinus leucas) in the Fitzroy River. In response to increasing environmental temperatures and metabolism across the study period, between-individual repeatability of behaviour varied in sawfish, but not bull sharks. Overall between-individual repeatability of behaviour increased across the study period as sawfish altered their behaviours presumably to mitigate competition. Between-individual repeatability of behaviour decreased across the study period with respect to diurnal activity rhythms, indicating sawfish became less diurnal in their activity use. This may indicate active avoidance of the hottest part of the day and a loss to individuals’ ability to temporally partition the diel cycle, with more overlap in activity apparent in the population. Additionally, individuals showed consistent individual differences in their within-individual repeatability of behaviour. This further supports the hypothesis that individuals of these species exhibit personalities. Ecological pressures such as competition, predation pressure and resource constraints are potential drivers of the formation of personality, both in this system and in general. This study demonstrates that repeatability of behaviour can be studied in the field using acoustic telemetry. Additionally, this approach can be used to understand the effects of environmental change on specialisation in other aquatic ectotherms

Writing-As-Shadow-Work: An Aesthetics of Jungian Psychoanalysis

Taking a personal experience of Jungian psychoanalysis as a starting point, Writing-As-Shadow-Work: An Aesthetics of Jungian Psychoanalysis shows how I integrated the concepts and practice of Jungian psychoanalysis with creative life writing to develop fresh possibilities for writing on difficult mother-daughter relationships and related trauma. An inter-disciplinary practice-based body of creative and critical research that draws on the diverse fields of creative writing, Jungian studies and related depth psychology, trauma theory, mother-daughter relationships in feminist thought and the literary studies of autobiographical and short fiction, this thesis stages an intervention into the under-explored territories at the intersection between Jung and literary studies, and between short fiction and writing on trauma, alongside the adjacent culturally taboo subject of cruel mothers, to demonstrate how I developed the distinctive mode of writing-as-shadow-work via an inter-textual cycle of surrealist autobiographical short stories. While the challenges of representing the traumatic experience remain a dominant concern in the field of writing on trauma, Writing-As-Shadow-Work offers a literary aesthetics of Jungian psychoanalysis that views trauma as both a source of suffering and an opportunity for growth in order to expand on existing modes that explore how writing can be a container for working through. Just as physical shadows and their metaphorical counterparts are porous, permeable and shapeshifting, this thesis examples how writing-as-shadow-work is a porous, permeable and shape-shifting approach to enacting Jungian psychoanalysis on the page. It explains how, through the extensive journey entailed in this process, I synthesised the multiple resonances between the Jungian individuation process and the characteristics of the surrealist autobiographical short story to arrive at an original mode of creative life writing: ‘the shadow memoir’

Hepatic and adipose phenotype in Alström syndrome

BACKGROUND AND AIMS: Alström syndrome (AS) is a recessive monogenic syndrome characterized by obesity, extreme insulin resistance and multi-organ fibrosis. Despite phenotypically being high risk of non-alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim was to characterize the hepatic and adipose phenotype in patients with AS. METHODS: Observational cohort study with comprehensive assessment of metabolic liver phenotype including liver elastography (Fibroscan® ), serum Enhanced Liver Fibrosis (ELF) Panel and liver histology. In addition, abdominal adipose histology and gene expression was assessed. We recruited 30 patients from the UK national AS clinic. A subset of six patients underwent adipose biopsies which was compared with control tissue from nine healthy participants. RESULTS: Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m2 ). A total of 80% (24/30) were diabetic; 74% (20/27) had liver ultrasound scanning suggestive of NAFLD. As judged by the ELF panel, 96% (24/25) were categorized as having fibrosis and 10/21 (48%) had liver elastography consistent with advanced liver fibrosis/cirrhosis. In 7/8 selected cases, there was evidence of advanced NAFLD on liver histology. Adipose tissue histology showed marked fibrosis as well as disordered pro-inflammatory and fibrotic gene expression profiles. CONCLUSIONS: NAFLD and adipose dysfunction are common in patients with AS. The severity of liver disease in our cohort supports the need for screening of liver fibrosis in AS.Alström UKThis is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/liv.1316

Phenotype and Clinical Outcomes of Titin Cardiomyopathy.

BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. METHODS: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. RESULTS: Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/- groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis

Phenotype and Clinical Outcomes of Titin Cardiomyopathy

BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. METHODS: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. RESULTS: Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/- groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis

A Gamma-Herpesvirus Glycoprotein Complex Manipulates Actin to Promote Viral Spread

Viruses lack self-propulsion. To move in multi-cellular hosts they must therefore manipulate infected cells. Herpesviruses provide an archetype for many aspects of host manipulation, but only for alpha-herpesviruses in is there much information about they move. Other herpesviruses are not necessarily the same. Here we show that Murine gamma-herpesvirus-68 (MHV-68) induces the outgrowth of long, branched plasma membrane fronds to create an intercellular network for virion traffic. The fronds were actin-based and RhoA-dependent. Time-lapse imaging showed that the infected cell surface became highly motile and that virions moved on the fronds. This plasma membrane remodelling was driven by the cytoplasmic tail of gp48, a MHV-68 glycoprotein previously implicated in intercellular viral spread. The MHV-68 ORF58 was also required, but its role was simply transporting gp48 to the plasma membrane, since a gp48 mutant exported without ORF58 did not require ORF58 to form membrane fronds either. Together, gp48/ORF58 were sufficient to induce fronds in transfected cells, as were the homologous BDLF2/BMRF2 of Epstein-Barr virus. Gp48/ORF58 therefore represents a conserved module by which gamma-herpesviruses rearrange cellular actin to increase intercellular contacts and thereby promote their spread

New metrics for the Lancet Standing Commission on Liver Disease in the UK

Health Polic

Prognostic significance of nonischaemic myocardial fibrosis in patients with normal left ventricular volumes and ejection-fraction

Objectives: This study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction. Background: Nonischemic patterns of LGE with normal LV volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance, but their prognostic significance, and consequently management, is uncertain. Methods: Patients with midwall/subepicardial LGE and normal LV volumes, wall thickness, and ejection fraction on cardiovascular magnetic resonance were enrolled and compared to a control group without LGE. The primary outcome was actual or aborted sudden cardiac death (SCD). Results: Of 748 patients enrolled, 401 had LGE and 347 did not. The median age was 50 years (interquartile range: 38-61 years), LV ejection fraction 66% (interquartile range: 62%-70%), and 287 (38%) were women. Scan indications included chest pain (40%), palpitation (33%) and breathlessness (13%). No patient experienced SCD and only 1 LGE+ patient (0.13%) had an aborted SCD in the 11th follow-up year. Over a median of 4.3 years, 30 patients (4.0%) died. All-cause mortality was similar for LGE+/- patients (3.7% vs 4.3%; P = 0.71) and was associated with age (HR: 2.04 per 10 years; 95% CI: 1.46-2.79; P < 0.001). Twenty-one LGE+ and 4 LGE- patients had an unplanned cardiovascular hospital admission (HR: 7.22; 95% CI: 4.26-21.17; P < 0.0001). Conclusions: There was a low SCD risk during long-term follow-up in patients with LGE but otherwise normal LV volumes and ejection fraction. Mortality was driven by age and not LGE presence, location, or extent, although the latter was associated with greater cardiovascular hospitalization for suspected myocarditis and symptomatic ventricular tachycardia

Linking Symptom Inventories using Semantic Textual Similarity

An extensive library of symptom inventories has been developed over time to measure clinical symptoms, but this variety has led to several long standing issues. Most notably, results drawn from different settings and studies are not comparable, which limits reproducibility. Here, we present an artificial intelligence (AI) approach using semantic textual similarity (STS) to link symptoms and scores across previously incongruous symptom inventories. We tested the ability of four pre-trained STS models to screen thousands of symptom description pairs for related content - a challenging task typically requiring expert panels. Models were tasked to predict symptom severity across four different inventories for 6,607 participants drawn from 16 international data sources. The STS approach achieved 74.8% accuracy across five tasks, outperforming other models tested. This work suggests that incorporating contextual, semantic information can assist expert decision-making processes, yielding gains for both general and disease-specific clinical assessment