Statistical Learning for Structured Models: Tree Based Methods and Neural Networks

In this thesis, estimation in regression and classification problems which include low dimensional structures are considered. The underlying question is the following. How well do statistical learn- ing methods perform for models with low dimensional structures? We approach this question using various algorithms in various settings. For our first main contribution, we prove optimal convergence rates in a classification setting using neural networks. While non-optimal rates ex- isted for this problem, we are the first to prove optimal ones. Secondly, we introduce a new tree based algorithm we named random planted forest. It adapts particularly well to models which consist of low dimensional structures. We examine its performance in simulation studies and include some theoretical backing by proving optimal convergence rates in certain settings for a modification of the algorithm. Additionally, a generalized version of the algorithm is included, which can be used in classification settings. In a further contribution, we prove optimal con- vergence rates for the local linear smooth backfitting algorithm. While such rates have already been established, we bring a new simpler perspective to the problem which leads to better understanding and easier interpretation. Additionally, given an estimator in a regression setting, we propose a constraint which leads to a unique decomposition. This decomposition is useful for visualising and interpreting the estimator, in particular if it consits of low dimenional structures

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

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Heart failure in the oldest old : clinical and echocardiographic insights

While the incidence and prevalence of heart failure (HF) increase markedly with age, few studies have included data on a large series of patients aged 85 years and older. Clinical and echocardiographic data from 533 patients admitted to a tertiary care hospital for acute HF were obtained. Data from the oldest old (\u3eor=85 years; n=252; mean age, 91.9+/-3.6 years) were compared with data from those aged 65 to 74 years (n=123; mean age, 70.1+/-2.8 years) and 75 to 84 years (n=158; mean age, 79.4+/-2.9 years). Echocardiographic data were consistent with hypertensive remodeling. The proportion of patients with HF and a preserved left ventricular ejection fraction was greatest in the oldest patients (61%) in comparison to patients aged 65 to 74 years (48%) and 75 to 84 years (48%). Approximately three-fourths of the oldest patients were women, and two-thirds of women had a left ventricular ejection fraction \u3eor=50%

Prevalence and clinical characteristics of right ventricular dysfunction in transient stress cardiomyopathy

Transient stress cardiomyopathy (TSC) is a cause of reversible left ventricular (LV) dysfunction that is increasingly recognized. Reports to date have focused primarily on LV involvement, with little attention paid to associated right ventricular (RV) dysfunction. With other forms of LV dysfunction, RV involvement has been shown to confer an adverse prognosis. Prevalence, clinical characteristics, and short-term prognosis of RV dysfunction in TSC remain ill-defined. Presenting echocardiograms of 40 patients with TSC were reviewed. RV function was assessed by evaluating regional wall motion and calculating a wall motion score index (WMSI). RV dysfunction was defined as a WMSI \u3e1.0. Clinical and demographic characteristics of patients with and without RV dysfunction were compared. RV dysfunction was identified in 27% of patients (11 of 40). RV WMSI was 1.20 +/- 0.30 for the entire cohort compared with 1.72 +/- 0.30 for those with RV dysfunction (p 1/4 of cases of TSC. Although associated with higher B-type natriuretic peptide levels, higher pulmonary artery systolic pressures, and longer hospital stays, RV dysfunction was not associated with significant differences in short-term cardiac morbidity or increased early mortality