Coronary heart disease and mortality following a breast cancer diagnosis

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified. METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. The receipt of potentially cardiotoxic breast cancer treatments was indicated if the patient received anthracyclines or hormone therapies. We modeled the outcomes of post-cancer diagnosis CHD and death, respectively. RESULTS: Results of these approaches indicated that the joint effect of poor CVH and receipt of cardiotoxic treatments on CHD (75.9%) and death (39.5%) was significantly higher than their independent effects [poor CVH (55.9%) and cardiotoxic treatments (43.6%) for CHD, and poor CVH (29.4%) and cardiotoxic treatments (35.8%) for death]. CONCLUSIONS: Better CVH appears to be protective against the development of CHD even among women who had received potentially cardiotoxic treatments. This study determined the extent to which attainment of ideal CVH is important not only for CHD and mortality outcomes among women diagnosed with breast cancer

Extending the Functionality of Behavioural Change-Point Analysis with k-Means Clustering: A Case Study with the Little Penguin (Eudyptula minor)

We present a simple framework for classifying mutually exclusive behavioural states within the geospatial lifelines of animals. This method involves use of three sequentially applied statistical procedures: (1) behavioural change point analysis to partition movement trajectories into discrete bouts of same-state behaviours, based on abrupt changes in the spatiotemporal autocorrelation structure of movement parameters; (2) hierarchical multivariate cluster analysis to determine the number of different behavioural states; and (3) k-means clustering to classify inferred bouts of same-state location observations into behavioural modes. We demonstrate application of the method by analysing synthetic trajectories of known ‘artificial behaviours’ comprised of different correlated random walks, as well as real foraging trajectories of little penguins (Eudyptula minor) obtained by global-positioning-system telemetry. Our results show that the modelling procedure correctly classified 92.5% of all individual location observations in the synthetic trajectories, demonstrating reasonable ability to successfully discriminate behavioural modes. Most individual little penguins were found to exhibit three unique behavioural states (resting, commuting/active searching, arearestricted foraging), with variation in the timing and locations of observations apparently related to ambient light, bathymetry, and proximity to coastlines and river mouths. Addition of k-means clustering extends the utility of behavioural change point analysis, by providing a simple means through which the behaviours inferred for the location observations comprising individual movement trajectories can be objectively classified

Clinicopathological classification of immune checkpoint inhibitor-associated myocarditis: Possible refinement by measuring macrophage abundance

BACKGROUND: Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood. METHODS: We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker. RESULTS: Only 2/17 EMBs obtained from patients with suspected ICI myocarditis satisfied the Dallas criteria. Supplemental IHC staining and quantification of CD68 CONCLUSIONS: While the Dallas criteria can identify a subset of ICI-associated myocarditis patients, quantification of macrophage abundance may expand the diagnostic role of EMB. Failure to meet the traditional Dallas Criteria should not exclude the diagnosis of myocarditis

Spin Relaxation in Single Layer Graphene with Tunable Mobility

Graphene is an attractive material for spintronics due to theoretical predictions of long spin lifetimes arising from low spin-orbit and hyperfine couplings. In experiments, however, spin lifetimes in single layer graphene (SLG) measured via Hanle effects are much shorter than expected theoretically. Thus, the origin of spin relaxation in SLG is a major issue for graphene spintronics. Despite extensive theoretical and experimental work addressing this question, there is still little clarity on the microscopic origin of spin relaxation. By using organic ligand-bound nanoparticles as charge reservoirs to tune mobility between 2700 and 12000 cm2/Vs, we successfully isolate the effect of charged impurity scattering on spin relaxation in SLG. Our results demonstrate that while charged impurities can greatly affect mobility, the spin lifetimes are not affected by charged impurity scattering.Comment: 13 pages, 5 figure

Ubistatins Inhibit Proteasome-Dependent Degradation by Binding the Ubiquitin Chain

To identify previously unknown small molecules that inhibit cell cycle machinery, we performed a chemical genetic screen in Xenopus extracts. One class of inhibitors, termed ubistatins, blocked cell cycle progression by inhibiting cyclin B proteolysis and inhibited degradation of ubiquitinated Sic1 by purified proteasomes. Ubistatins blocked the binding of ubiquitinated substrates to the proteasome by targeting the ubiquitin-ubiquitin interface of Lys^(48)-linked chains. The same interface is recognized by ubiquitin-chain receptors of the proteasome, indicating that ubistatins act by disrupting a critical protein-protein interaction in the ubiquitin-proteasome system

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73 m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73 m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria