Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction After a Recent Worsening Heart Failure Event

Background Contemporary trials of patients with heart failure with reduced ejection fraction (HFrEF) required a recent worsening heart failure (WHF) event for inclusion. We aimed to describe characteristics and outcomes of patients with HFrEF and a recent WHF event at a large tertiary referral center. Methods and Results We identified adult patients with chronic symptomatic HFrEF (ejection fraction ≤35%) treated at Duke University between January 1, 2009, and December 31, 2018, and applied a set of exclusion criteria to generate a cohort similar to those enrolled in contemporary heart failure trials. Patients were stratified by presence or absence of a recent WHF event, defined as an emergency department visit for heart failure or hospitalization for heart failure in the prior 12 months. Characteristics and outcomes including death and hospitalization were assessed. Of 3867 patients with HFrEF meeting study criteria, 2823 (73.0%) had a WHF event in the prior 12 months. Compared with patients without a WHF event, those with a WHF event were more likely to be under‐represented racial and ethnic groups and had lower ejection fraction, a greater burden of comorbidities, and more echocardiographic evidence of cardiac dysfunction. Despite higher use of guideline‐directed therapies, patients with a WHF event had higher rates of death (hazard ratio, 2.30; 95% CI, 2.01–2.63), all‐cause hospitalization (hazard ratio, 1.56; 95% CI, 1.42–1.71), and heart failure hospitalization (hazard ratio, 1.59; 95% CI, 1.44–1.75) through 5 years compared with those without a recent WHF event. Conclusions WHF events are common in patients with HFrEF and are associated with more advanced disease. Patients with recent WHF have high rates of death and hospitalization, underscoring the need for novel therapies in this large subgroup of patients with HFrEF.

Norton Algebras of the Hamming Graphs via Linear Characters

The Norton product is defined on each eigenspace of a distance regular graph by the orthogonal projection of the entry-wise product. The resulting algebra, known as the Norton algebra, is a commutative nonassociative algebra that is useful in group theory due to its interesting automorphism group. We provide a formula for the Norton product on each eigenspace of a Hamming graph using linear characters. We construct a large subgroup of automorphisms of the Norton algebra of a Hamming graph and completely describe the automorphism group in some cases. We also show that the Norton product on each eigenspace of a Hamming graph is as nonassociative as possible, except for some special cases in which it is either associative or equally as nonassociative as the so-called double minus operation previously studied by the author, Mickey, and Xu. Our results restrict to the hypercubes and extend to the halved and/or folded cubes, the bilinear forms graphs, and more generally, all Cayley graphs of finite abelian groups.

Patterns of spinal cord malformation in cloacal exstrophy

OBJECTIVE The objective of this study was to assess the prevalence and spectrum of spinal dysraphism in a cohort of children with cloacal exstrophy (CEX) using MRI. METHODS Children with CEX presenting between 1999 and 2019 with baseline spinal MRI were included. The images were reviewed in consensus to assess the type of dysraphism. The dysraphisms were initially reviewed and described based on their descriptive anatomy, and then classified according to anomalies of gastrulation, primary neurulation, or secondary neurulation. RESULTS Thirty-four children were included. Thirty-three of these children had closed spinal dysraphism, and 1 had a normal spine. Of the 33 cases of closed spinal dysraphism, the conus and/or filum terminale were involved in all cases. The most common malformations were spinal lipoma (n = 20) and terminal myelocystocele (n = 11). The lipomas were heterogeneous: 4 dorsal, 9 transitional, 4 chaotic, and 3 terminal. A large subgroup (10/20, 50%) within the lipomas had an unusual morphology of noncontiguous double lipomas, the proximal fat related to the conus and the distal fat within the filum. These were difficult to characterize using existing classifications. In 2 cases, only a thickened filum was noted. The majority of these malformations were compatible with a disorder of secondary neurulation. CONCLUSIONS Complex spinal dysraphisms are consistently associated with CEX. The unusual dysraphism patterns found in this group of patients highlight the limitations of current embryological classifications. Given the propensity for neurological deterioration in this group of patients, spinal MRI should be routinely performed. The type and distribution of malformations seen have implications for the wider understanding of the pathogenesis and classification of lumbosacral lipomas.

Primary decomposition in the smooth concordance group of topologically slice knots

We address primary decomposition conjectures for knot concordance groups, which predict direct sum decompositions into primary parts. We show that the smooth concordance group of topologically slice knots has a large subgroup for which the conjectures are true and there are infinitely many primary parts, each of which has infinite rank. This supports the conjectures for topologically slice knots. We also prove analogues for the associated graded groups of the bipolar filtration of topologically slice knots. Among ingredients of the proof, we use amenable $L^2$ -signatures, Ozsváth-Szabó d-invariants and Némethi’s result on Heegaard Floer homology of Seifert 3-manifolds. In an appendix, we present a general formulation of the notion of primary decomposition.

‘When I asked for help and support it was not there’: current NHS employment practice and its impact on people with systemic lupus erythematosus

Objectives The aim was to investigate whether National Health Service (NHS) employees with SLE, for whom work disability and early retirement are high, are supported effectively in at work. Methods An online survey of 393 people with lupus was completed through the LUPUS UK website, investigating participants’ experiences in maintaining employment. Quantitative and qualitative data were collected. Disease fluctuation, invisibility and fatigue were identified as having substantial negative impacts on employment. This study examined data from a large subgroup (n = 72, 18.74%) of current/previous NHS employees. Descriptive statistics and thematic analysis were used to explore and characterize the demography and experiences of participants. Results The NHS subgroup (n = 72) represented 18.74% of the whole cohort; 100% were female and of working age (18–64 years). Fifty-one were currently (70.8%) and 21 previously (29.2%) NHS employees. Forty-nine (60%) were clinicians. Twenty-one (29.16%) of this working-age subgroup had left any employment. Negative effects of SLE on employment were universal (including an impact on career choices, work disability, enforced part-time working, lower income and early retirement). NHS support for participants to maintain employment was inconsistent, with more negative experiences than positive. The impact of SLE on employment seemed to be poorly understood. Conclusion A punitive approach to NHS employees with SLE was more common than a proactive, flexible, problem-solving one despite inclusive rhetoric, resulting in the loss of skills and experience to the service. Characterizing conditions such as SLE and long coronavirus disease 2019 as fluctuating, invisible conditions with constitutional symptoms highlights features with negative employment impact, potentially facilitating much-needed change in NHS organizations, with greater use of occupational health, vocational rehabilitation, redeployment and retraining opportunities, highlighting the need for evidence-based employment interventions and improved management of fatigue.

Natural Polypropionates in 1999–2020: An Overview of Chemical and Biological Diversity

Natural polypropionates (PPs) are a large subgroup of polyketides with diverse structural features and bioactivities. Most of the PPs are discovered from marine organisms including mollusks, fungi and actinomycetes, while some of them are also isolated from terrestrial resources. An increasing number of studies about PPs have been carried out in the past two decades and an updated review is needed. In this current review, we summarize the chemical structures and biological activities of 164 natural PPs reported in 67 research papers from 1999 to 2020. The isolation, structural features and bioactivities of these PPs are discussed in detail. The chemical diversity, bioactive diversity, biodiversity and the relationship between chemical classes and the bioactivities are also concluded.

Iron islands in the Amazon: investigating plant beta diversity of canga outcrops

The world’s largest mineral iron province, Serra dos Carajás, is home to an open vegetation known as canga, found on top of isolated outcrops rising out of the Amazon rainforest. Over one thousand vascular plants species have been recorded in these canga sites, including 38 edaphic endemics. A new survey adds to our investigation of biogeographic relationships between sixteen canga outcrops and the effect of the distance between site pairs on the number of shared species, regional species turnover and species distribution patterns. Plant collecting expeditions to the westernmost site, the Serra de Campos of São Félix do Xingu (SFX), were carried out followed by the identification of all collected specimens and the creation of a species database, built to perform biogeographical analyses. Floristic relationships among the sites were investigated regarding their similarity, using multivariate analyses. The correlation between canga areas and species richness was tested, as well as the geographical distance between pairs of outcrops and their shared species. Vascular plants at SFX total 254 species including 17 edaphic endemics. All canga sites are grouped with 25% of minimum similarity, and the SFX falls within a large subgroup of outcrops. The total species number shared between site pairs does not change significantly with geographical distance but is positively correlated with the area of each outcrop. Meanwhile, shared endemic species numbers between site pairs decline when geographical distance increases, possibly imposed by the barrier of the rainforest. Our data suggest higher shared similarity between the largest and species-richest sites as opposed to geographically nearby sites, and provide useful insight for drafting conservation and compensation measures for canga locations. The size of the canga outcrops is associated to higher floristic diversity but connectivity among islands also plays a role in their similarity.

Equidistribution Among Cosets of Elliptic Curve Points in Intervals

In a recent paper devoted to fault analysis of elliptic curve-based signature schemes, Takahashi et al. (TCHES 2018) described several attacks, one of which assumed an equidistribution property that can be informally stated as follows: given an elliptic curve E over 𝔽q in Weierstrass form and a large subgroup H ⊂ E(𝔽q) generated by G(xG, yG), the points in E(𝔽q) whose x-coordinates are obtained from xG by randomly flipping a fixed, sufficiently long substring of bits (and rejecting cases when the resulting value does not correspond to a point in E(𝔽q)) are close to uniformly distributed among the cosets modulo H. The goal of this note is to formally state, prove and quantify (a variant of) that property, and in particular establish sufficient bounds on the size of the subgroup and on the length of the substring of bits for it to hold. The proof relies on bounds for character sums on elliptic curves established by Kohel and Shparlinski (ANTS–IV).

GROUPS WITH NORMALITY CONDITIONS FOR UNCOUNTABLE SUBGROUPS

This paper continues the investigation of the structure of uncountable groups whose large subgroups are normal. Moreover, we describe the behaviour of uncountable groups in which every large subgroup is close to normal with the only obstruction of a finite section.

Imaginal Retraining Reduces Cigarette Smoking: A Randomized Controlled Study

<b><i>Objectives:</i></b> Smoking is a highly prevalent addictive behavior with severe and life-shortening health consequences. This is the first study to evaluate the efficacy of a newly developed imaginal variant of approach bias modification (ABM) (i.e., imaginal retraining) for the reduction of craving for tobacco and actual smoking behavior. <b><i>Methods:</i></b> We randomized 345 smokers to imaginal retraining (self-help manual) or a control group (either active control or wait-list control). Assessments were carried out online. The treatment interval was 6 weeks. Craving for tobacco represented the primary outcome. The study was registered as DRKS00016860. <b><i>Results:</i></b> Retention was 79.7% with no difference between groups. The intention-to-treat (ITT) analyses were significant for the primary outcome (Visual Analogue Scale on craving for tobacco) as well as subjective reduction of smoking (45.5 vs. 26.4%) in favor of imaginal retraining. In the treatment group, 47.6% performed the exercises at least once. This subgroup (per-protocol [PP] sample) showed a significant reduction in tobacco dependency as measured with the Cigarette Dependence Scale (short and long forms) and the Fagerström Test for Nicotine Dependence relative to controls. Number of daily cigarettes declined to a greater extent in imaginal retraining in the PP but not ITT analysis. A small dose-effect relationship emerged between craving and frequency of performance of the technique. <b><i>Conclusion:</i></b> When used regularly, imaginal retraining may reduce craving for tobacco and actual smoking behavior in a subgroup of smokers. In view of the large subgroup that did not read the manual or did not perform the exercises, alternative ways of conveying the imaginal retraining technique should be sought (e.g., demonstration via video clips). To conclude, imaginal retraining may represent a simple low-threshold technique to reduce smoking and assist current evidence-based treatment programs targeted at abstinence. It needs to be tested whether its mechanism of action deviates from standard ABM.