Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications.

The increasing number of patients with sequenced prostate cancer genomes enables us to study not only individual oncogenic mutations, but also capture the global burden of genomic alterations. Here we review the extent of tumor genome mutations and chromosomal structural variants in various clinical states of prostate cancer, and the related prognostic information. Next, we discuss the underlying mutational processes that give rise to these various alterations, and their relationship to the various molecular subtypes of prostate cancer. Finally, we examine the relationships between the tumor mutation burden of castration-resistant prostate cancer, DNA repair defects, and response to immune checkpoint inhibitor therapy

An Analytical Link Loss Model for On-Body Propagation Around the Body Based on Elliptical Approximation of the Torso with Arms' Influence Included

An analytical model for estimating the link loss for the on-body wave propagation around the torso is presented. The model is based on the attenuation of the creeping waves over an elliptical approximation of the human torso and includes the influence of the arms. The importance of including the arms' effect for a proper estimation of the link loss is discussed. The model is validated by the full-wave electromagnetic simulations on a numerical phantom

A Link Loss Model for the On-body Propagation Channel for Binaural Hearing Aids

Binaural hearing aids communicate with each other through a wireless link for synchronization. A propagation model is needed to estimate the ear-to-ear link loss for such binaural hearing aids. The link loss is a critical parameter in a link budget to decide the sensitivity of the transceiver. In this paper, we have presented a model for the deterministic component of the ear-to-ear link loss. The model takes into account the dominant paths having most of the power of the creeping wave from the transceiver in one ear to the transceiver in other ear and the effect of the protruding part of the outer ear called pinna. Simulations are done to validate the model using in-the-ear (ITE) placement of antennas at 2.45 GHz on two heterogeneous phantoms of different age-group and body size. The model agrees with the simulations. The ear-to-ear link loss between the antennas for the binaural hearing aids in the homogeneous SAM phantom is compared with a heterogeneous phantom. It is found that the absence of the pinna and the lossless shell in the SAM phantom underestimate the link loss. This is verified by the measurements on a phantom where we have included the pinnas fabricated by 3D-printing

Near Infrared Spectroscopic Monitoring During Cardiopulmonary Exercise Testing Detects Anaerobic Threshold

Cardiopulmonary exercise testing (CPET) provides assessment of the integrative responses involving the pulmonary, cardiovascular, and skeletal muscle systems. Application of exercise testing remains limited to children who are able to understand and cooperate with the exercise protocol. Near-infrared spectroscopy (NIRS) provides a noninvasive, continuous method to monitor regional tissue oxygenation (rSO2). Our specific aim was to predict anaerobic threshold (AT) during CPET noninvasively using two-site NIRS monitoring. Achievement of a practical noninvasive technology for estimating AT will increase the compatibility of CPET. Patients without structural or acquired heart disease were eligible for inclusion if they were ordered to undergo CPET by a cardiologist. Data from 51 subjects was analyzed. The ventilatory anaerobic threshold (VAT) was computed on VCO2 and respiratory quotient post hoc using the standard V-slope method. The inflection points of the regional rSO2 time-series were identified as the noninvasive regional NIRS AT for each of the two monitored regions (cerebral and kidney). AT calculation made using an average of kidney and brain NIRS matched the calculation made by VAT for the same patient. Two-site NIRS monitoring of visceral organs is a predictor of AT

Near Infrared Spectroscopy Describes Physiologic Payback Associated With Excess Postexercise Oxygen Consumption in Healthy Controls and Children With Complex Congenital Heart Disease

Exercise creates a physiologic burden with recovery from such effort crucial to adaptation. Excess postexercise oxygen consumption (EPOC) refers to the body’s increased metabolic need after work. This investigation was designed to determine the role of near infrared spectroscopy (NIRS) in the description of exercise recovery in healthy controls (NL) and children with congenital heart disease (CHD). Subjects were recruited with exercise testing performed to exhaustion. Exercise time (EXT), heart rate (HR), and oxygen consumption (VO2) were measured. Four-site NIRS (brain, kidney, deltoid, and vastus lateralis) were measured during exercise and into recovery to establish trends. Fifty individuals were recruited for each group (NL = 26 boys and 24 girls; CHD = 33 boys and 17 girls). Significant differences existed between EXT, VO2, and peak HR (P \u3c 0.01). NIRS values were examined at four distinct intervals: rest, peak work, and 2 and 5 min after exercise. Significant cerebral hyperemia was seen in children with CHD post exercise when compared to normal individuals in whom redistribution patterns were directed to somatic muscles. These identified trends support an immediate compensation of organ systems to re-establish homeostasis in peripheral beds through enhanced perfusion. Noninvasive NIRS monitoring helps delineate patterns of redistribution associated with EPOC in healthy adolescents and children with CHD

Unsupervised grammar induction of clinical report sublanguage

BACKGROUND: Clinical reports are written using a subset of natural language while employing many domain-specific terms; such a language is also known as a sublanguage for a scientific or a technical domain. Different genres of clinical reports use different sublaguages, and in addition, different medical facilities use different medical language conventions. This makes supervised training of a parser for clinical sentences very difficult as it would require expensive annotation effort to adapt to every type of clinical text. METHODS: In this paper, we present an unsupervised method which automatically induces a grammar and a parser for the sublanguage of a given genre of clinical reports from a corpus with no annotations. In order to capture sentence structures specific to clinical domains, the grammar is induced in terms of semantic classes of clinical terms in addition to part-of-speech tags. Our method induces grammar by minimizing the combined encoding cost of the grammar and the corresponding sentence derivations. The probabilities for the productions of the induced grammar are then learned from the unannotated corpus using an instance of the expectation-maximization algorithm. RESULTS: Our experiments show that the induced grammar is able to parse novel sentences. Using a dataset of discharge summary sentences with no annotations, our method obtains 60.5% F-measure for parse-bracketing on sentences of maximum length 10. By varying a parameter, the method can induce a range of grammars, from very specific to very general, and obtains the best performance in between the two extremes