Peripartum cardiomyopathy: diagnosis and management

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Late gadolinium enhancement and adverse outcomes in a contemporary cohort of adult survivors of tetralogy of Fallot

Objective: Myocardial fibrosis has been associated with poorer outcomes in tetralogy of Fallot, however only a handful of studies have assessed its significance in the current era. Our aim was to quantify the amount of late gadolinium enhancement in both the LV and RV in a contemporary cohort of adults with surgically repaired tetralogy of Fallot, and assess the relationship with adverse clinical outcomes. Design: Single centre cohort study Setting: National tertiary referral center Patients: One hundred fourteen patients with surgically repaired tetralogy of Fallot with median age 29.5 years (range 17.5-64.2). Prospective follow-up for mean 2.4 years (SD 1.29). Interventions: Cardiovascular magnetic resonance was performed, and late gadolinium enhancement mass was estimated for the LV using the 5-SD remote myocardium method, and for the RV using a segmental scoring system. Cohort characterization was determined through the use of a computerized database. Outcome measures: Survival analysis from time of scan to first adverse event, defined as an episode of atrial arrhythmia, sustained ventricular arrhythmia, hospitalization with heart failure, or implantable cardioverter-defibrillator insertion. Results: Eleven patients experienced an adverse outcome in the follow-up period, although there were no deaths. LV late gadolinium enhancement was associated with adverse outcomes in a univariate model (P = .027). However, when adjusted for age at scan the significant variables included NYHA class (P = .006), peak oxygen uptake (P = .028), number of prior sternotomies (P = .044), and higher indexed RV and LV end diastolic volumes (P = .002 and P < .001), but not RV or LV late gadolinium enhancement. Conclusions: Formal quantification of late gadolinium enhancement is not currently as helpful in ascertaining prognosis compared to other, more easily assessed parameters in a contemporary cohort of tetralogy of Fallot survivors, however assessment particularly of the LV holds promise for the future

The design, launch and assessment of a new volunteer-based plant monitoring scheme for the United Kingdom

Volunteer-based plant monitoring in the UK has focused mainly on distribution mapping; there has been less emphasis on the collection of data on plant communities and habitats. Abundance data provide different insights into ecological pattern and allow for more powerful inference when considering environmental change. Abundance monitoring for other groups of organisms is well-established in the UK, e.g. for birds and butterflies, and conservation agencies have long desired comparable schemes for plants. We describe a new citizen science scheme for the UK (the ‘National Plant Monitoring Scheme’; NPMS), with the primary aim of monitoring the abundance of plants at small scales. Scheme development emphasised volunteer flexibility through scheme co-creation and feedback, whilst retaining a rigorous approach to design. Sampling frameworks, target habitats and species, field methods and power are all described. We also evaluate several outcomes of the scheme design process, including: (i) landscape-context bias in the first two years of the scheme; (ii) the ability of different sets of indicator species to capture the main ecological gradients of UK vegetation; and, (iii) species richness bias in returns relative to a professional survey. Survey rates have been promising (over 60% of squares released have been surveyed), although upland squares are under-represented. Ecological gradients present in an ordination of an independent, unbiased, national survey were well-represented by NPMS indicator species, although further filtering to an entry-level set of easily identifiable species degraded signal in an ordination axis representing succession and disturbance. Comparison with another professional survey indicated that different biases might be present at different levels of participation within the scheme. Understanding the strengths and limitations of the NPMS will guide development, increase trust in outputs, and direct efforts for maintaining volunteer interest, as well as providing a set of ideas for other countries to experiment with

Bleeding and thrombotic risk in pregnant women with Fontan physiology

Background/objectives Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan.  Methods We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors.  Results We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33 +/- 5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). Conclusions Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy

Soil carbon loss in warmed subarctic grasslands is rapid and restricted to topsoil

Global warming may lead to carbon transfers from soils to the atmosphere, yet this positive feedback to the climate system remains highly uncertain, especially in subsoils (Ilyina and Friedlingstein, 2016; Shi et al., 2018). Using natural geothermal soil warming gradients of up to +6.4 degrees C in subarctic grasslands (Sigurdsson et al., 2016), we show that soil organic carbon (SOC) stocks decline strongly and linearly with warming (-2.8 t ha(-1) degrees C-1). Comparison of SOC stock changes following medium-term (5 and 10 years) and long-term (> 50 years) warming revealed that all SOC stock reduction occurred within the first 5 years of warming, after which continued warming no longer reduced SOC stocks. This rapid equilibration of SOC observed in Andosol suggests a critical role for ecosystem adaptations to warming and could imply short-lived soil carbon-climate feedbacks. Our data further revealed that the soil C loss occurred in all aggregate size fractions and that SOC stock reduction was only visible in topsoil (0-10 cm). SOC stocks in subsoil (10-30 cm), where plant roots were absent, showed apparent conservation after > 50 years of warming. The observed depth-dependent warming responses indicate that explicit vertical resolution is a prerequisite for global models to accurately project future SOC stocks for this soil type and should be investigated for soils with other mineralogies

Life Beyond the Solar System: Remotely Detectable Biosignatures

For the first time in human history, we will soon be able to apply to the scientific method to the question "Are We Alone?" The rapid advance of exoplanet discovery, planetary systems science, and telescope technology will soon allow scientists to search for life beyond our Solar System through direct observation of extrasolar planets. This endeavor will occur alongside searches for habitable environments and signs of life within our Solar System. While these searches are thematically related and will inform each other, they will require separate observational techniques. The search for life on exoplanets holds potential through the great diversity of worlds to be explored beyond our Solar System. However, there are also unique challenges related to the relatively limited data this search will obtain on any individual world

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead