Complexity and nonlinearity in short-term heart period variability: comparison of methods based on local nonlinear prediction

This paper evaluates the paradigm that proposes to quantify short-term complexity and detect nonlinear dynamics by exploiting local nonlinear prediction. Local nonlinear prediction methods are classified according to how they judge similarity among patterns of L samples (i.e., according to different definitions of the cells utilized to discretize the phase space) and examined in connection with different types of surrogate data: 1) phase-randomized or Fourier transform based, FT; 2) amplitude-adjusted FT, AAFT; 3) iteratively-refined AAFT, IAAFT, preserving distribution IAAFT-1; 4) IAAFT preserving power spectrum, IAAFT-2. The methods were applied on ad-hoc simulations and on a large database of short heart period variability series (approximately 300 cardiac beats) recorded in healthy young subjects during experimental conditions inducing a sympathetic activation (head-up tilt, infusion of nitroprusside, or handgrip), a parasympathetic activation (low dose administration of atropine or infusion of phenylephrine), a complete parasympathetic blockade (high dose administration of atropine), or during controlled respiration at different breathing rates. As to complexity analysis we found that: 1) although complexity indexes derived from different methods were different in terms of absolute values, changes due to experimental conditions were consistently detected; 2) complexity was significantly decreased by all the experimental conditions provoking a sympathetic activation and by controlled respiration at slow breathing rates. As to detection of nonlinearities we found that: 1) IAAFT-1 and IAAFT-2 surrogates performed similarly in all protocols; 2) FT and IAAFT surrogates detected about the same percentage of nonlinear dynamics in all protocols; 3) AAFT surrogates were inappropriate with all the methods and should be dismissed in future applications; 4) methods based on overlapping cells with variable size were characterized by a larger rate of false detections of nonlinear dynamics; 5) short-term heart period variability at rest was mostly linear; 6) controlled respiration at slow breathing rates increased nonlinear components, while the separate activation of the two branches of the autonomic nervous system (i.e., sympathetic or parasympathetic) was ineffective at this regard.     

The Distributed Flight Array

The Distributed Flight Array is a multi-rotor vehicle that is being developed at ETH Zurich. This vehicle consists of autonomous single-rotor modules that are able to drive, dock with its peers, and fly in a coordinated fashion. These modules are organized as distributed computational units with minimal sensory input. Experimental demonstrations in docking, driving, and flying have proven its feasibility as a research platform for investigating techniques in distributed estimation and control.     

The Role of Hormonal Replacement Therapy in BRCA Mutated Patients: Lights and Shadows

Simple SummaryAdvances in molecular genetics have radically changed all aspects of cancer prevention, screening and treatment and, today, women who are suspected of being at risk of hereditary cancer should always undergo genetic counselling. Furthermore, today there is growing attention on the tumor suppressor genes BRCA 1 and BRCA2. In addition, there is growing attention on women who carry mutations of the tumor suppressor genes BRCA 1 and BRCA2 and undergo a prophylactic risk-reducing salpingo-oophorectomy. This paper explores the pathobiology of BRCA1\2 cancer genes in a translational perspective, focusing on molecular aspects of hormonal therapy in early menopausal women as well as on the latest evidence-based guidelines for clinicians. Physicians should counsel motivated patients who ask for relief from early menopausal symptoms about the risks and benefits of hormonal therapy, as well as tailoring and appropriate treatment for selected patients. AbstractAll cancers develop as a result of mutations in genes. DNA damage induces genomic instability and subsequently increases susceptibility to tumorigenesis. Women who carry mutations of BRCA 1 and BRCA2 genes have an augmented risk of breast and ovarian cancer and a markedly augmented probability of dying because of cancer compared to the general population. As a result, international guidelines recommend that all BRCA1\2 mutation carriers be offered risk-reducing bilateral salpingo-oophorectomy at an early age to reduce the risk of cancer and decrease the mortality rate of this high-risk population. NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy in pre-menopausal women, between 35–40 years in BRCA1 mutation carriers and between 40–45 years in BRCA2 mutation carriers. Unfortunately, the well-documented reduction of cancer risk is counterbalanced by early sterility and premature ovarian failure with an early onset of secondary menopausal syndromes such as neuromotor, cardiovascular, cognitive and urogenital deficiency. Hormonal replacement therapy significantly compensates for hormonal deprivation and counteracts menopausal syndrome morbidity and mortality; however, some data suggest a possible correlation between hormonal medications and cancer risk, especially in BRCA1\2 carriers who undergo long-term regimens. Conversely, short-term treatment before the age of natural menopause does not appear to increase the cancer risk in BRCA1 mutation carriers without a personal history of breast cancer after prophylactic surgery. Few data are available on BRCA2 mutation carriers and more well-designed studies are needed. In conclusion, clinicians should propose short-term hormone replacement therapy to BRCA 1 carriers to counteract hormonal deprivation; personalized counselling should be offered to BRCA2 mutation carriers for a balance between the risks and benefits of the treatment.     

Reducing the acknowledgement frequency in IETF QUIC

Satellite networks usually use in-network methods (such as Performance Enhancing Proxies for TCP) to adapt the transport to the characteristics of the forward and return paths. QUIC is a transport protocol that prevents the use of in–network methods. This paper explores the use of the recently–standardised IETF QUIC protocol with a focus on the implications on performance when using different acknowledgement policies to reduce the number of packets and volume of bytes sent on the return path. Our analysis evaluates a set of ACK policies for three IETF QUIC implementations, examining performance over cellular, terrestrial and satellite networks. It shows that QUIC performance can be maintained even when sending fewer acknowledgements, and recommends a new QUIC acknowledgement policy that adapts QUIC's ACK Delay value based on the path RTT to ensure timely feedback. The resulting policy is shown to reduce the volume/rate of traffic sent on the return path and associated processing costs in endpoints, without sacrificing throughput.