Disease coverage of human genome-wide association studies and pharmaceutical research and development.

Background: Despite the growing interest in the use of human genomic data for drug target identification and validation, the extent to which the spectrum of human disease has been addressed by genome-wide association studies (GWAS), or by drug development, and the degree to which these efforts overlap remain unclear.

Methods: In this study we harmonize and integrate different data sources to create a sample space of all the human drug targets and diseases and identify points of convergence or divergence of GWAS and drug development efforts.

Results: We show that only 612 of 11,158 diseases listed in Human Disease Ontology have an approved drug treatment in at least one region of the world.

Improving outcomes in carcinoid heart disease - learning from a single centre.

Introduction: A significant proportion of patients with carcinoid syndrome develop carcinoid heart disease (CHD). Valve degeneration can lead to right heart failure, and worsening prognosis. Replacement of affected valves is an effective therapy.

Clinical and pathogenic significance of S100A4 overexpression in systemic sclerosis.

Objectives: We have studied the damage-associated molecular pattern protein S100A4 as a driver of fibroblast activation in systemic sclerosis (SSc).

Methods: S100A4 protein concentration was measured by ELISA in serum of SSc (n=94) and healthy controls (n=15). Protein expression in skin fibroblast cultures from diffuse cutaneous SSc (SScF, n=6) and healthy controls (normal fibroblasts (NF), n=6) was assessed.

Clinician perception of pathological narcissism in females: a vignette-based study.

The DSM-5 reports that up to 75% of those diagnosed with Narcissistic Personality Disorder (NPD) are males, which denotes that narcissism is a clinical phenomenon that operates differently in men and women. Vulnerable narcissism, which tends to be more prevalent in females and is currently under-appreciated in the DSM-5, may be diagnosed as other "vulnerable" disorders (e.g.

A Phenome-Wide Association Study of Drugs and Comorbidities Associated With Gastrointestinal Dysfunction in Systemic Sclerosis.

Objective: To explore the causes of and contributors to gastrointestinal (GI) dysfunction in systemic sclerosis (SSc) in a phenome-wide association study (PheWAS), using real-world clinical records data.

Methods: Twelve thousand five hundred thirty-five documented clinical assessments of 2058 consenting individuals with SSc at the Royal Free Hospital (UK) were available for detailed phenotyping. Diagnoses and drugs were mapped to structured dictionaries of terms (Disease Ontology project and DrugBank Open Data, respectively).

Distinct cardiovascular phenotypes are associated with prognosis in systemic sclerosis: a cardiovascular magnetic resonance study.

Aims: Cardiovascular involvement in systemic sclerosis (SSc) is heterogeneous and ill-defined. This study aimed to: (i) discover cardiac phenotypes in SSc by cardiovascular magnetic resonance (CMR); (ii) provide a CMR-based algorithm for phenotypic classification; and (iii) examine for associations between phenotypes and mortality.

Methods And Results: A retrospective, single-centre, observational study of 260 SSc patients who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2019 was performed.

Characteristics of adults with type 1 diabetes and treatment-resistant problematic hypoglycaemia: a baseline analysis from the HARPdoc RCT.

Aims/hypothesis: Problematic hypoglycaemia still complicates insulin therapy for some with type 1 diabetes. This study describes baseline emotional, cognitive and behavioural characteristics in participants in the HARPdoc trial, which evaluates a novel intervention for treatment-resistant problematic hypoglycaemia.

Methods: We documented a cross-sectional baseline description of 99 adults with type 1 diabetes and problematic hypoglycaemia despite structured education in flexible insulin therapy.

Hypoglycemia Subtypes in Type 1 Diabetes: An Exploration of the Hypoglycemia Fear Survey-II.

Objective: The Hypoglycemia Fear Survey-II (HFS-II) is a well-validated measure of fear of hypoglycemia in people with type 1 diabetes. The aim of this study was to explore the relationships between hypoglycemia worries, behaviors, and cognitive barriers to hypoglycemia avoidance and hypoglycemia awareness status, severe hypoglycemia, and HbA1c.

Research Design And Methods: Participants with type 1 diabetes (n = 178), with the study population enriched for people at risk for severe hypoglycemia (49%), completed questionnaires for assessing hypoglycemia fear (HFS-II), hyperglycemia avoidance (Hyperglycemia Avoidance Scale [HAS]), diabetes distress (Problem Areas In Diabetes [PAID]), and cognitive barriers to hypoglycemia avoidance (Attitudes to Awareness of Hypoglycemia [A2A]).

Female Narcissism: Assessment, Aetiology, and Behavioural Manifestations.

Despite putative gender differences in the expression of narcissism, prominent theories have virtually dismissed the role of females in the development and manifestation of narcissism. The contention that narcissism is a pathology of the self that may partly differ in males and females is further evident in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The DSM-5 reports that up to 75% of those diagnosed with Narcissistic Personality Disorder (NPD) are men.

Verdict spotting: investigating the effects of juror bias, evidence anchors and verdict system in jurors.

The Scottish verdict of represents a second acquittal verdict which is not legally defined. Existing research into the influence of the verdict on jury decision making is modest. The main aim of the current study was therefore to investigate the influence of verdict systems (two vs three) on juror decision making.

Autoantibody predictors of gastrointestinal symptoms in systemic sclerosis.

Objectives: To assess the prevalence and burden of SSc-related gastrointestinal dysfunction (SSc-GI) and to evaluate associations with demographic, clinical and serological characteristics.

Methods: Patients completed the UCLA SCTC GIT 2.0 questionnaire for SSc-GI disease to assess the burden of GI disease across multiple functional and psychological domains.

Trialstreamer: A living, automatically updated database of clinical trial reports.

Objective: Randomized controlled trials (RCTs) are the gold standard method for evaluating whether a treatment works in health care but can be difficult to find and make use of. We describe the development and evaluation of a system to automatically find and categorize all new RCT reports.

Materials And Methods: Trialstreamer continuously monitors PubMed and the World Health Organization International Clinical Trials Registry Platform, looking for new RCTs in humans using a validated classifier.

Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes' toxicity.

Background: Aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of aliphatic aldehydes, including acetaldehyde. About 45% of Han Chinese (East Asians), accounting for 8% of humans, carry a single point mutation in ALDH2*2 (E504K) that leads to accumulation of toxic reactive aldehydes.

Methods: Sequencing of a small Mexican cohort and a search in the ExAC genomic database for additional ALDH2 variants common in various ethnic groups was set to identify missense variants.

Threshold point utilisation in juror decision-making.

This study aims to identify whether a model of juror decision-making (i.e. the threshold point model) that encompasses both rational and intuitive decision-making exists.

Assessing Cognitive Bias in Forensic Decisions: A Review and Outlook.

In recent years, a number of studies have demonstrated that forensic examiners can be biased by task-irrelevant contextual information. However, concerns relating to methodological flaws and ecological validity attenuate how much the current body of knowledge can be applied to real-life operational settings. The current review takes a narrative approach to synthesizing the literature across forensic science.

The bastard verdict and its influence on jurors.

The Scottish legal system is a unique jurisdiction, as jurors are able to give not proven verdicts in addition to the well-known Anglo-American verdicts (guilty and not guilty). The not proven verdict has never been legally defined, meaning that currently legal practitioners can only estimate why a not proven verdict has been given. The main aim of this study was to investigate if jurors violate the regularity principle, which is commonly incorporated in many rational choice models, by testing if the introduction of the not proven verdict has an impact on the outcomes given by jurors.

Faith in thy threshold.

The current study focussed on the decision-making processes of jurors. The study investigated how jurors make a decision, if they integrate information within their decision-making process and if cue utilisation thresholds promote confirmation bias. To do this, 108 participants listened to one of nine cases.

Are consistent juror decisions related to fast and frugal decision making? Investigating the relationship between juror consistency, decision speed and cue utilisation.

The aim of this study was to establish whether more consistent/accurate juror decision making is related to faster decision-making processes which use fewer cues - that is, fast and frugal heuristic processes. A correlational design was implemented with the co-variables: consistency of verdict decisions (participant decisions compared to the actual court verdicts), decision speed, and cue utilisation (the number of cues used to make a final verdict decision). Sixty participants read information about six murder trials which were based on real cases and whose outcome verdicts were deemed to be correct by the Scottish legal institution.

Functional evolution of IGF2:IGF2R domain 11 binding generates novel structural interactions and a specific IGF2 antagonist.

Among the 15 extracellular domains of the mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R), domain 11 has evolved a binding site for IGF2 to negatively regulate ligand bioavailability and mammalian growth. Despite the highly evolved structural loops of the IGF2:domain 11 binding site, affinity-enhancing AB loop mutations suggest that binding is modifiable. Here we examine the extent to which IGF2:domain 11 affinity, and its specificity over IGF1, can be enhanced, and we examine the structural basis of the mechanistic and functional consequences.

Life satisfaction in people with post-traumatic stress disorder.

Background/aims: There is limited research on the association between post-traumatic stress disorder (PTSD) and life satisfaction in community samples. We set out to investigate levels of life satisfaction and its demographic, trauma related and clinical predictors in a sample of people with PTSD (n = 46).

Methods: Participants completed a battery of standardised self-report measures including Satisfaction with Life Scale, the PTSD Checklist and The Hospital Anxiety and Depression Scale.

Age and the understanding of emotions: neuropsychological and sociocognitive perspectives.

Sociocognitive approaches suggest that the ability to understand emotions should be well maintained in adult aging. However, neuropsychological evidence suggests potential impairments in processing emotions in older adults. In the current study, 30 young adults (aged 20-40 years) and 30 older adults (aged 60-80 years) were tested on a range of emotional ability measures.