Deactivation of implantable defibrillators at the end of life- A register-based study of ICD-deactivation at home and the impact of Palliative Care

AbstractBackground: The Implantable Cardioverter-Defibrillator (ICD) is a well-established life-saving therapy for heart failure patients, but due to the risk for unnecessary shocks, deactivation of ICD:s is recommended at the end of life.We aimed to identify i) how many people with HF and an ICD who died in Sweden in 2018 received Specialized Palliative Care (SPC), ii) of those dying outside of hospital, the proportion with deactivated ICDs prior to death for the group as a whole and by SPC access.Methods and results: We analyzed data from i) the Swedish ICD and Pacemaker Registry to find all who died with an ICD in Sweden in 2018, ii) the Swedish Register of Palliative Care and, iii) the Swedish Causes of Death Certificate Register to find those who died outside of hospital. Clinical records were obtained to assess if ICDs were deactivated before death. Descriptive statistics, t-tests and chi-squared tests were applied.46/406 (11%) of those who died with an ICD in Sweden in 2018 had SPC access, of whom 50% also had cancer. 86/164 (52%) ICDs were deactivated prior to death in people dying outside of hospital; higher in those accessing SPC (36/46, (78%) SPC access versus 151/360, (42%) no SPC access; p<0.05).Conclusions: Half of those with HF and an ICD dying outside of hospital had ICD deactivation prior to death. Those accessing SPC were more likely to have their ICD deactivated but few received SPC, without a comorbid cancer diagnosis

The Santa Barbara, California, earthquake of 13 August 1978

The 5.1 M_L Santa Barbara earthquake of 13 August 1978 occurred at 22h54m 52.8s UTC. The epicenter was located 3 km southeast of Santa Barbara at 34° 23.9′N latitude and 119°40.9′W longitude with a focal depth of 12.7 km. The main shock was followed between 13 August and 30 September by 373 aftershocks that were located with the Caltech-USGS array. The aftershock zone extended 12 km WNW from the epicenter and was 6 km wide in the N-S direction, and it had a very clear temporal development. During the first 20 min of activity, all the aftershocks were located in a cluster 7 km WNW of the main shock epicenter. During the next 24 hr, the aftershock zone grew to 11 km in the WNW direction and 4 km in the N-S direction. During succeeding weeks, the zone extended to 12 by 6 km. This temporal-spatial development relative to the main shock epicenter may indicate that the initial rupture propagated 7 km unilaterally to the WNW, and the initial rupture plane may have been considerably smaller than the eventual aftershock zone. This smaller area suggests that the stress drop may have been significantly greater than that derived from the final aftershock zone. In cross section, the aftershock hypocenters outline a nearly horizontal plane (dipping 15° or less) at 13 km depth. The main shock focal mechanism indicates NNE-SSW compression and vertical extension. The preferred fault plane strikes N80°W and dips 26°NNE, indicating north-over-south thrusting with a component of left-lateral movement. Focal mechanisms for 40 aftershocks also indicate compression in the general N-S direction. For most of these events, the north-dipping nodal plane dips between 7° and 45°, with most dipping 25° or more, which is significantly steeper than the plane delineated by the hypocenters themselves. These observations are consistent with a tectonic model in which much of the slip during the Santa Barbara earthquake occurred on a nearly horizontal plane. The after shocks then might represent movement on a complex series of imbricate thrust faults that flatten into the plane of primary slip. Hence, the Santa Barbara earthquake may be taken as evidence for mid-crustal horizontal shearing in the western Transverse Ranges

Brachial Artery Constriction during Brachial Artery Reactivity Testing Predicts Major Adverse Clinical Outcomes in Women with Suspected Myocardial Ischemia: Results from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study

Background:Limited brachial artery (BA) flow-mediated dilation during brachial artery reactivity testing (BART) has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC) following hyperemia.Objectives:To determine whether BAC predicts adverse CV outcomes and/or mortality in the women's ischemic Syndrome Evaluation Study (WISE). Further, as a secondary objective we sought to determine the risk factors associated with BAC.Methods:We performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure.Results:BA diameter change ranged from -20.6% to +44.9%, and 41 (11%) women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004). In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018) when adjusting for obstructive CAD and traditional risk factors.Conclusions:BAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women. © 2013 Sedlak et al

An Elasticity Approach to Equity Risk Evaluation

This study defines and derives a measure of risk for real estate investment decisions using the concept of elasticity. Specifically, the elasticity of the after-tax equity yield with respect to the before-tax net operating cash flow growth rate is derived from a discounted cash flow equity valuation model. Also, an illustration of the use and interpretation of this elasticity measure is provided.

VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research

Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict performs amplicon aware variant calling for polymerase chain reaction (PCR)-based targeted sequencing often used in diagnostic settings, and is able to detect PCR artifacts. Finally, VarDict also detects differences in somatic and loss of heterozygosity variants between paired samples. VarDict reprocessing of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than previously published variant calls. We believe VarDict will greatly facilitate application of NGS in clinical cancer research

The Transcription Factor NURR1 Exerts Concentration-Dependent Effects on Target Genes Mediating Distinct Biological Processes

The transcription factor NURR1 plays a pivotal role in the development and maintenance of neurotransmitter phenotype in midbrain dopamine neurons. Conversely, decreased NURR1 expression is associated with a number of dopamine-related CNS disorders, including Parkinson’s disease and drug addiction. In order to better understand the nature of NURR1-responsive genes and their potential roles in dopamine neuron differentiation and survival, we used a human neural cellular background (SK-N-AS cells) in which to generate a number of stable clonal lines with graded NURR1 gene expression that approximated that seen in DA cell-rich human substantia nigra. Gene expression profiling data from these NURR1-expressing clonal lines were validated by quantitative RT-PCR and subjected to bioinformatic analyses. The present study identified a large number of NURR1-responsive genes and demonstrated the potential importance of concentration-dependent NURR1 effects in the differential regulation of distinct NURR1 target genes and biological pathways. These data support the promise of NURR1-based CNS therapeutics for the neuroprotection and/or functional restoration of DA neurons

Authors' Response

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97166/1/jfo12080.pd

Quantitative Analyses of Circadian Gene Expression in Mammalian Cell Cultures

The central circadian pacemaker is located in the hypothalamus of mammals, but essentially the same oscillating system operates in peripheral tissues and even in immortalized cell lines. Using luciferase reporters that allow automated monitoring of circadian gene expression in mammalian fibroblasts, we report the collection and analysis of precise rhythmic data from these cells. We use these methods to analyze signaling pathways of peripheral tissues by studying the responses of Rat-1 fibroblasts to ten different compounds. To quantify these rhythms, which show significant variation and large non-stationarities (damping and baseline drifting), we developed a new fast Fourier transform–nonlinear least squares analysis procedure that specifically optimizes the quantification of amplitude for circadian rhythm data. This enhanced analysis method successfully distinguishes among the ten signaling compounds for their rhythm-inducing properties. We pursued detailed analyses of the responses to two of these compounds that induced the highest amplitude rhythms in fibroblasts, forskolin (an activator of adenylyl cyclase), and dexamethasone (an agonist of glucocorticoid receptors). Our quantitative analyses clearly indicate that the synchronization mechanisms by the cAMP and glucocorticoid pathways are different, implying that actions of different genes stimulated by these pathways lead to distinctive programs of circadian synchronization

Relativistic many-body calculations of electric-dipole matrix elements, lifetimes and polarizabilities in rubidium

Electric-dipole matrix elements for ns-n'p, nd-n'p, and 6d-4f transitions in Rb are calculated using a relativistic all-order method. A third-order calculation is also carried out for these matrix elements to evaluate the importance of the high-order many-body perturbation theory contributions. The all-order matrix elements are used to evaluate lifetimes of ns and np levels with n=6, 7, 8 and nd levels with n=4, 5, 6 for comparison with experiment and to provide benchmark values for these lifetimes. The dynamic polarizabilities are calculated for ns states of rubidium. The resulting lifetime and polarizability values are compared with available theory and experiment.Comment: 8 pages, 2 figure

The effect of sample drying temperature on marine particulate organic carbon composition

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography Methods 16 (2018): 286-298, doi:10.1002/lom3.10245.Compositional changes in marine particulate organic carbon (POC) throughout the water column trace important processes that underlie the biological pump’s efficiency. While labor-intensive, particle sampling efforts offer potential to expand the empirical POC archive at different stages in the water column, provided that organic composition is sufficiently preserved between sampling and analysis. The standard procedure for preserving organic matter composition in marine samples is to immediately store particles at -80°C to -20°C until they can be freeze-dried for analysis. This report investigates the effect of warmer drying and storage temperatures on POC composition, which applies to the majority of POC samples collected in the field without intention for organic analysis. Particle samples collected off Woods Hole, MA were immediately dried at 56°C, at room temperature, or stored at -80°C until being freeze-dried. Results show that oven- and air-drying did not shift the bulk composition (i.e., carbon and nitrogen content and stable isotope composition) of POC in the samples relative to freeze-drying. Similarly, warmer drying temperatures did not affect POC thermal stability, as inferred by ramped pyrolysis/oxidation (RPO), a growing technique that uses a continuous temperature ramp to differentiate components of organic carbon by their decomposition temperature. Oven- and air-drying did depress lipid abundances relative to freeze-drying, the extent of which depended on compound size and structure. The data suggest that field samples dried at room temperatures and 56°C are appropriate for assessing bulk POC composition and thermal stability, but physical mechanisms such as molecular volatilization bias their lipid composition.This research was funded by the National Science Foundation (NSF) Graduate Research Fellowship program and the NSF Cooperative Agreement for the Operation of a National Ocean Sciences Accelerator Mass Spectrometry Facility (OCE-0753487)