Bioimpedance-Based Heart Failure Deterioration Prediction Using a Prototype Fluid Accumulation Vest-Mobile Phone Dyad: An Observational Study

BACKGROUND: Recurrent heart failure (HF) events are common in patients discharged after acute decompensated heart failure (ADHF). New patient-centered technologies are needed to aid in detecting HF decompensation. Transthoracic bioimpedance noninvasively measures pulmonary fluid retention. OBJECTIVE: The objectives of our study were to (1) determine whether transthoracic bioimpedance can be measured daily with a novel, noninvasive, wearable fluid accumulation vest (FAV) and transmitted using a mobile phone and (2) establish whether an automated algorithm analyzing daily thoracic bioimpedance values would predict recurrent HF events. METHODS: We prospectively enrolled patients admitted for ADHF. Participants were trained to use a FAV-mobile phone dyad and asked to transmit bioimpedance measurements for 45 consecutive days. We examined the performance of an algorithm analyzing changes in transthoracic bioimpedance as a predictor of HF events (HF readmission, diuretic uptitration) over a 75-day follow-up. RESULTS: We observed 64 HF events (18 HF readmissions and 46 diuretic uptitrations) in the 106 participants (67 years; 63.2%, 67/106, male; 48.1%, 51/106, with prior HF) who completed follow-up. History of HF was the only clinical or laboratory factor related to recurrent HF events (P=.04). Among study participants with sufficient FAV data (n=57), an algorithm analyzing thoracic bioimpedance showed 87% sensitivity (95% CI 82-92), 70% specificity (95% CI 68-72), and 72% accuracy (95% CI 70-74) for identifying recurrent HF events. CONCLUSIONS: Patients discharged after ADHF can measure and transmit daily transthoracic bioimpedance using a FAV-mobile phone dyad. Algorithms analyzing thoracic bioimpedance may help identify patients at risk for recurrent HF events after hospital discharge. Sert Kuniyoshi, Joseph Rock, Theo E Meyer, David D McManus. Originally published in JMIR Cardio (http://cardio.jmir.org), 13.03.2017

Detecting Heart Failure Decompensation by Measuring Transthoracic Bioimpedance in the Outpatient Setting: Rationale and Design of the SENTINEL-HF Study

BACKGROUND: Recurrent hospital admissions are common among patients admitted for acute decompensated heart failure (ADHF), but identification of patients at risk for rehospitalization remains challenging. Contemporary heart failure (HF) management programs have shown modest ability to reduce readmissions, partly because they monitor signs or symptoms of HF worsening that appear late during decompensation. Detecting early stages of HF decompensation might allow for immediate application of effective HF therapies, thereby potentially reducing HF readmissions. One of the earliest indicators of HF decompensation is intrathoracic fluid accumulation, which can be assessed using transthoracic bioimpedance. OBJECTIVE: The SENTINEL-HF study is a prospective observational study designed to test a novel, wearable HF monitoring system as a predictor of HF decompensation among patients discharged after hospitalization for ADHF. METHODS: SENTINEL-HF tests the hypothesis that a decline in transthoracic bioimpedance, as assessed daily with the Philips fluid accumulation vest (FAV) and transmitted using a mobile phone, is associated with HF worsening and rehospitalization. According to pre-specified power calculations, 180 patients admitted with ADHF are enrolled. Participants transmit daily self-assessments using the FAV-mobile phone dyad for 45 days post-discharge. The primary predictor is the deviation of transthoracic bioimpedance for 3 consecutive days from a patient-specific normal variability range. The ADHF detection algorithm is evaluated in relation with a composite outcome of HF readmission, diuretic up-titration, and self-reported HF worsening (Kansas City Cardiomyopathy Questionnaire) during a 90-day follow-up period. Here, we provide the details and rationale of SENTINEL-HF. RESULTS: Enrollment in the SENTINEL-HF study is complete and the 90-days follow-up is currently under way. Once data collection is complete, the study dataset will be used to evaluate our ADHF detection algorithm and the results submitted for publication. CONCLUSION: SENTINEL-HF emerged from our long-term vision that advanced home monitoring technology can improve the management of chronic HF by extending clinical care into patients\u27 homes. Monitoring transthoracic bioimpedance with the FAV may identify patients at risk of recurrent HF decompensation and enable timely preventive measures. TRIAL REGISTRATION: Clinicaltrials.gov NCT01877369: https://clinicaltrials.gov/ct2/show/NCT01877369 (Archived by WebCite at http://www.webcitation.org/6bDYl0dGy)

Adiabatic processes need not correspond to optimal work

The minimum work principle states that work done on a thermally isolated equilibrium system is minimal for the adiabatically slow (reversible) realization of a given process. This principle, one of the formulations of the second law, is studied here for finite (possibly large) quantum systems interacting with macroscopic sources of work. It is shown to be valid as long as the adiabatic energy levels do not cross. If level crossing does occur, counter examples are discussed, showing that the minimum work principle can be violated and that optimal processes are neither adiabatically slow nor reversible.Comment: 5 pages, 1 figure, revtex

Transthoracic Bioimpedance Monitoring Predicts Heart Failure Decompensation and Early Readmission after Heart Failure Hospitalization: Preliminary Data from SENTINEL-HF

Background: Patients, providers, and health systems are focused on reducing readmissions for patients with acute decompensated heart failure (ADHF). Readmission after hospitalization is common and often secondary to HF decompensation, but it remains challenging to identify patients at-risk. Bioimpedance is a validated marker of thoracic fluid accumulation. We examined whether transthoracic bioimpedance, measured using a Fluid Accumulation Vest (FAV), predicted HF decompensation in advance of a clinical event in patients discharged after ADHF. Methods: Participants included 42 patients hospitalized for ADHF. Participants were trained on the use of a FAV-smartphone dyad to obtain and transmit a 5-minute bioimpedance measurement once daily for 45-days after discharge. Readmission and diuretic dosing adjustments were identified using participant report and causes adjudicated using medical records. Receiver operating characteristic (ROC) curves and C-statistics were calculated to describe the characteristics of a bioimpedance based algorithm as a predictor of HF decompensation 3 or 7-days in advance of the clinical event. Results: Participants (mean age 69 ± 12 years, 43% female, 88% white, 11% cognitively impaired, 12% depressed) had a mean ejection fraction of 50 ± 18%. HF-related rehospitalization occurred in 10% (n=4) and 10% (n=4) reported diuretic up-titration during the 45-day follow-up. An algorithm analyzing bioimpedance up to 3 or 7 days prior to an event was related to HF readmission (C statistics for 3 and 7 days = 0.83, 0.94, respectively) and the combined outcome of HF hospitalization or diuretic up-titration (C statistics for 3 and 7 days = 0.76, 0.80, respectively). Conclusions: Early readmission after hospitalization for ADHF was common and predicted up to 7 days in advance by an algorithm analyzing transthoracic bioimpedance. Despite their advanced age and high burden of comorbid diseases, study participants with ADHF were able to make daily bioimpedance measurements using a FAV and transmit them using a smartphone. Transthoracic bioimpedance monitoring may offer possibilities for reducing HF readmissions by enabling identification and treatment of outpatients with early HF decompensation

A liquid crystalline copper phthalocyanine derivative for high performance organic thin film transistors

This journal is © The Royal Society of Chemistry 2012Bottom-gate, bottom-contact organic thin film transistors (OTFTs) were fabricated using solvent soluble copper 1,4,8,11,15,18,22,25-octakis(hexyl)phthalocyanine as the active semiconductor layer. The compound was deposited as 70 nm thick spin-coated films onto gold source–drain electrodes supported on octadecyltrichlorosilane treated 250 nm thick SiO2 gate insulators. The performance of the OTFTs was optimised by investigating the effects of vacuum annealing of the films at temperatures between 50 0C and 200 0C, a range that included the thermotropic mesophase of the bulk material. These effects were monitored by ultraviolet-visible absorption spectroscopy, atomic force microscopy and XRD measurements. Device performance was shown to be dependent upon the annealing temperature due to structural changes of the film. Devices heat treated at 100 0C under vacuum (≥10-7 mbar) were found to exhibit the highest field-effect mobility, 0.7 cm2 V^-1 s^-1, with an on–off current modulation ratio of~107, a reduced threshold voltage of 2.0 V and a sub-threshold swing of 1.11 V per decade.UK Technology Strategy Board (Project no: TP/6/EPH/6/S/K2536J) and UK National Measurement System (Project IRD C02 ‘‘Plastic Electronics’’, 2008–2011)

The numerical renormalization group method for quantum impurity systems

In the beginning of the 1970's, Wilson developed the concept of a fully non-perturbative renormalization group transformation. Applied to the Kondo problem, this numerical renormalization group method (NRG) gave for the first time the full crossover from the high-temperature phase of a free spin to the low-temperature phase of a completely screened spin. The NRG has been later generalized to a variety of quantum impurity problems. The purpose of this review is to give a brief introduction to the NRG method including some guidelines of how to calculate physical quantities, and to survey the development of the NRG method and its various applications over the last 30 years. These applications include variants of the original Kondo problem such as the non-Fermi liquid behavior in the two-channel Kondo model, dissipative quantum systems such as the spin-boson model, and lattice systems in the framework of the dynamical mean field theory.Comment: 55 pages, 27 figures, submitted to Rev. Mod. Phy

Analytical Investigations of Toxic p-Phenylenediamine (PPD) Levels in Clinical Urine Samples with Special Focus on MALDI-MS/MS

Para-phenylenediamine (PPD) is a common chromophoric ingredient in oxidative hair-dyes. In some African countries like Sudan, Egypt and Morocco but also in India this chemical is used alone or in combination with colouring extracts like Henna for dyeing of the hair or the skin. Excessive dermal exposure to PPD mainly leads to the N-mono- and N,N′-diacetylated products (MAPPD, DAPPD) by N-acetyltransferase 1 and 2 (NAT1 and 2) catalyzed reactions. Metabolites and PPD are mainly excreted via renal clearance. Despite a low risk of intoxication when used in due form, there are numerous cases of acute intoxication in those countries every year. At the ENT Hospital - Khartoum (Sudan) alone more than 300 cases are reported every year (∼10% fatal), mostly caused by either an accidental or intended (suicidal) high systemic exposure to pure PPD. Intoxication leads to a severe clinical syndrome including laryngeal edema, rhabdomyolysis and subsequent renal failure, neurotoxicity and acute toxic hepatitis. To date, there is no defined clinical treatment or antidote available and treatment is largely supportive. Herein, we show the development of a quick on-site identification assay to facilitate differential diagnosis in the clinic and, more importantly, the implementation of an advanced analytical platform for future in-depth investigations of PPD intoxication and metabolism is described. The current work shows a sensitive (∼25 µM) wet chemistry assay, a validated MALDI-MS/MS and HPLC-UV assay for the determination of PPD and its metabolites in human urine. We show the feasibility of the methods for measuring PPD over a range of 50–1000 µM. The validation criteria included linearity, lower limit of quantification (LLOQ), accuracy and precision, recovery and stability. Finally, PPD concentrations were determined in clinical urine samples of cases of acute intoxication and the applied technique was expanded to identify MAPPD and DAPPD in the identical samples

High Log-Scale Expansion of Functional Human Natural Killer Cells from Umbilical Cord Blood CD34-Positive Cells for Adoptive Cancer Immunotherapy

Immunotherapy based on natural killer (NK) cell infusions is a potential adjuvant treatment for many cancers. Such therapeutic application in humans requires large numbers of functional NK cells that have been selected and expanded using clinical grade protocols. We established an extremely efficient cytokine-based culture system for ex vivo expansion of NK cells from hematopoietic stem and progenitor cells from umbilical cord blood (UCB). Systematic refinement of this two-step system using a novel clinical grade medium resulted in a therapeutically applicable cell culture protocol. CD56+CD3− NK cell products could be routinely generated from freshly selected CD34+ UCB cells with a mean expansion of >15,000 fold and a nearly 100% purity. Moreover, our protocol has the capacity to produce more than 3-log NK cell expansion from frozen CD34+ UCB cells. These ex vivo-generated cell products contain NK cell subsets differentially expressing NKG2A and killer immunoglobulin-like receptors. Furthermore, UCB-derived CD56+ NK cells generated by our protocol uniformly express high levels of activating NKG2D and natural cytotoxicity receptors. Functional analysis showed that these ex vivo-generated NK cells efficiently target myeloid leukemia and melanoma tumor cell lines, and mediate cytolysis of primary leukemia cells at low NK-target ratios. Our culture system exemplifies a major breakthrough in producing pure NK cell products from limited numbers of CD34+ cells for cancer immunotherapy

Interpretation and Visualization of Non-Linear Data Fusion in Kernel Space: Study on Metabolomic Characterization of Progression of Multiple Sclerosis

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