Diabetes mellitus does not alter mortality or hospitalisation risk in patients with newly diagnosed heart failure with preserved ejection fraction: Time to rethink pathophysiological models of disease progression.

Introduction: Type 2 diabetes is a common and adverse prognostic co-morbidity for patients with heart failure with reduced ejection fraction (HFrEF). The effect of diabetes on long-term outcomes for heart failure with preserved ejection fraction (HFpEF) is less established.

Methods: Prospective cohort study of patients referred to a regional HF clinic with newly diagnosed with HFrEF and HFpEF according to the 2016 European Society of Cardiology guidelines.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

Background: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established.

Purpose: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation.

Atrial secondary mitral regurgitation: prevalence, characteristics, management, and long-term outcomes.

Background: The prevalence, clinical characteristics, management and long-term outcomes of patients with atrial secondary mitral regurgitation (ASMR) are not well described.

Methods: We performed a retrospective, observational study of consecutive patients with grade III/IV MR determined by transthoracic echocardiography. The aetiology of MR was grouped as being either primary (due to degenerative mitral valve disease), ventricular SMR (VSMR: due to left ventricular dilatation/dysfunction), ASMR (due to LA dilatation), or other.

Atrial fibrillation and risk of progressive heart failure in patients with preserved ejection fraction heart failure.

Aims: Understanding of the pathophysiology of progressive heart failure (HF) in patients with heart failure with preserved ejection fraction (HFpEF) is incomplete. We sought to identify factors differentially associated with risk of progressive HF death and hospitalization in patients with HFpEF compared with patients with HF and reduced ejection fraction (HFrEF).

Methods And Results: Prospective cohort study of patients newly referred to secondary care with suspicion of HF, based on symptoms and signs of HF and elevated natriuretic peptides (NP), followed up for a minimum of 6 years.

Guideline-directed medical therapy is similarly effective in heart failure with mildly reduced ejection fraction.

Aims: Current guidelines recommend that disease-modifying pharmacological therapies may be considered for patients who have heart failure with mildly reduced ejection fraction (HFmrEF). We aimed to describe the characteristics, outcomes, provision of pharmacological therapies and dose-related associations with mortality risk in HFmrEF.

Methods And Results: We explored data from two prospective observational studies, which permitted the examination of the effects of pharmacological therapies across a broad spectrum of left ventricular ejection fraction (LVEF).

Personalised reprogramming to prevent progressive pacemaker-related left ventricular dysfunction: A phase II randomised, controlled clinical trial.

Background: Pacemakers are widely utilised to treat bradycardia, but right ventricular (RV) pacing is associated with heightened risk of left ventricular (LV) systolic dysfunction and heart failure. We aimed to compare personalised pacemaker reprogramming to avoid RV pacing with usual care on echocardiographic and patient-orientated outcomes.

Methods: A prospective phase II randomised, double-blind, parallel-group trial in 100 patients with a pacemaker implanted for indications other than third degree heart block for ≥2 years.

Impact of QRS duration on left ventricular remodelling and survival in patients with heart failure.

Aims: In patients with chronic heart failure, QRS duration is a consistent predictor of poor outcomes. It has been suggested that for indicated patients, cardiac resynchronization therapy (CRT) could come sooner in the treatment algorithm, perhaps in parallel with the attainment of optimal guideline-directed medical therapy (GDMT). We aimed to investigate differences in left ventricular (LV) remodelling in those with narrow QRS (NQRS) compared with wide QRS (WQRS) in the absence of CRT, whether an early CRT strategy resulted in unnecessary implants and the effect of early CRT on outcomes.

Diabetes, gender and deterioration in estimated glomerular filtration rate in patients with chronic heart failure: Ten-year prospective cohort study.

Introduction: We aimed to evaluate the relationship between temporal changes in renal function and long-term mortality in patients with heart failure with reduced ejection fraction (HFrEF) and identify correlates of deteriorating renal function.

Methods: A total of 381 patients with HFrEF enrolled in a prospective cohort study between 2006-2014 had eGFR measured at initial visit and at 1 year. Baseline characteristics were used in a multivariate analysis to establish variables that predict deterioration in eGFR.

Effect of disease-modifying agents and their association with mortality in multi-morbid patients with heart failure with reduced ejection fraction.

Aims: An increasing proportion of patients with heart failure with reduced ejection fraction (HFrEF) have co-morbidities. The effect of these co-morbidities on modes of death and the effect of disease-modifying agents in multi-morbid patients is unknown.

Methods And Results: We performed a prospective cohort study of ambulatory patients with HFrEF to assess predictors of outcomes.

Long-term performance of left ventricular leads in cardiac resynchronisation therapy.

Background: Cardiac resynchronisation therapy (CRT) confers symptomatic and survival benefits in chronic heart failure with reduced ejection fraction (HFrEF). There remains a paucity of data on long-term performance of left ventricular (LV) leads, particularly with newer quadripolar lead designs.

Methods: This single-centre study utilised an electronic, outpatient HFrEF database to identify CRT recipients (2008-2014).

Personalized Rate-Response Programming Improves Exercise Tolerance After 6 Months in People With Cardiac Implantable Electronic Devices and Heart Failure: A Phase II Study.

Background: Heart failure with reduced ejection fraction (HFrEF) is characterized by blunting of the positive relationship between heart rate and left ventricular (LV) contractility known as the force-frequency relationship (FFR). We have previously described that tailoring the rate-response programming of cardiac implantable electronic devices in patients with HFrEF on the basis of individual noninvasive FFR data acutely improves exercise capacity. We aimed to examine whether using FFR data to tailor heart rate response in patients with HFrEF with cardiac implantable electronic devices favorably influences exercise capacity and LV function 6 months later.

COSMIC: the Catalogue Of Somatic Mutations In Cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.

The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers.

The Catalogue of Somatic Mutations in Cancer (COSMIC) Cancer Gene Census (CGC) is an expert-curated description of the genes driving human cancer that is used as a standard in cancer genetics across basic research, medical reporting and pharmaceutical development. After a major expansion and complete re-evaluation, the 2018 CGC describes in detail the effect of 719 cancer-driving genes. The recent expansion includes functional and mechanistic descriptions of how each gene contributes to disease generation in terms of the key cancer hallmarks and the impact of mutations on gene and protein function.

Seven Essential Elements for Creating Effective Children's Media to Promote Peacebuilding: Lessons from International Coproductions of Sesame Street and Other Children's Media Programs.

Children's media have the capacity to prepare young learners to develop the knowledge, attitudes, and skills they need to contribute to a more peaceful world. Research suggests international coproductions of Sesame Street and other children's media efforts are linked to positive impact on how viewers perceive themselves and their own cultures, as well as how they perceive others. Creating such media, however, relies on a commitment to a complex development process where the educational needs of children are considered alongside intra- and intergroup dynamics and political realities.

COSMIC: somatic cancer genetics at high-resolution.

COSMIC, the Catalogue of Somatic Mutations in Cancer (http://cancer.sanger.ac.

COSMIC: exploring the world's knowledge of somatic mutations in human cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer (http://cancer.sanger.ac.

Understanding the role of mHealth and other media interventions for behavior change to enhance child survival and development in low- and middle-income countries: an evidence review.

Given the high morbidity and mortality among children in low- and middle-income countries as a result of preventable causes, the U.S. government and the United Nations Children's Fund convened an Evidence Summit on Enhancing Child Survival and Development in Lower- and Middle-Income Countries by Achieving Population-Level Behavior Change on June 3-4, 2013, in Washington, D.

Data mining using the Catalogue of Somatic Mutations in Cancer BioMart.

Catalogue of Somatic Mutations in Cancer (COSMIC) (http://www.sanger.ac.

COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer.

COSMIC (http://www.sanger.ac.

COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer.

The catalogue of Somatic Mutations in Cancer (COSMIC) (http://www.sanger.ac.

Finishing the finished human chromosome 22 sequence.

Background: Although the human genome sequence was declared complete in 2004, the sequence was interrupted by 341 gaps of which 308 lay in an estimated approximately 28 Mb of euchromatin. While these gaps constitute only approximately 1% of the sequence, knowledge of the full complement of human genes and regulatory elements is incomplete without their sequences.

Results: We have used a combination of conventional chromosome walking (aided by the availability of end sequences) in fosmid and bacterial artificial chromosome (BAC) libraries, whole chromosome shotgun sequencing, comparative genome analysis and long PCR to finish 8 of the 11 gaps in the initial chromosome 22 sequence.

The DNA sequence of the human X chromosome.

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome.

A genome annotation-driven approach to cloning the human ORFeome.

We have developed a systematic approach to generating cDNA clones containing full-length open reading frames (ORFs), exploiting knowledge of gene structure from genomic sequence. Each ORF was amplified by PCR from a pool of primary cDNAs, cloned and confirmed by sequencing. We obtained clones representing 70% of genes on human chromosome 22, whereas searching available cDNA clone collections found at best 48% from a single collection and 60% for all collections combined.