Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery

Introduction: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors’ subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia.Methods and analysis: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1?year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30?days after surgery, and the secondary outcome is all-cause death within 1?year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration.Ethics and dissemination: The METS Study has received research ethics board approval at all sites. Participant recruitment began in March 2013, and 1-year follow-up is expected to finish in 2016. Publication of the results of the METS Study is anticipated to occur in 2017.<br/

Brain Performance versus Phase Transitions

We here illustrate how a well-founded study of the brain may originate in assuming analogies with phase-transition phenomena. Analyzing to what extent a weak signal endures in noisy environments, we identify the underlying mechanisms, and it results a description of how the excitability associated to (non-equilibrium) phase changes and criticality optimizes the processing of the signal. Our setting is a network of integrate-and-fire nodes in which connections are heterogeneous with rapid time-varying intensities mimicking fatigue and potentiation. Emergence then becomes quite robust against wiring topology modification—in fact, we considered from a fully connected network to the Homo sapiens connectome—showing the essential role of synaptic flickering on computations. We also suggest how to experimentally disclose significant changes during actual brain operation.The authors acknowledge support from the Spanish Ministry of Economy and Competitiveness under the project FIS2013-43201-P

Green function techniques in the treatment of quantum transport at the molecular scale

The theoretical investigation of charge (and spin) transport at nanometer length scales requires the use of advanced and powerful techniques able to deal with the dynamical properties of the relevant physical systems, to explicitly include out-of-equilibrium situations typical for electrical/heat transport as well as to take into account interaction effects in a systematic way. Equilibrium Green function techniques and their extension to non-equilibrium situations via the Keldysh formalism build one of the pillars of current state-of-the-art approaches to quantum transport which have been implemented in both model Hamiltonian formulations and first-principle methodologies. We offer a tutorial overview of the applications of Green functions to deal with some fundamental aspects of charge transport at the nanoscale, mainly focusing on applications to model Hamiltonian formulations.Comment: Tutorial review, LaTeX, 129 pages, 41 figures, 300 references, submitted to Springer series "Lecture Notes in Physics

A methodology for parameter estimation in seaweed productivity modelling

This paper presents a combined approach for parameter estimation in models of primary production. The focus is on gross primary production and nutrient assimilation by seaweeds. A database of productivity determinations, biomass and mortality measurements and nutrient uptake rates obtained over one year for Gelidium sesquipedale in the Atlantic Ocean off Portugal has been used. Annual productivity was estimated by harvesting methods, and empirical relationships using mortality/ wave energy and respiration rates have been derived to correct for losses and to convert the estimates to gross production. In situ determinations of productivity have been combined with data on the light climate (radiation periods, intensity, mean turbidity) to give daily and annual productivity estimates. The theoretical nutrient uptake calculated using a 'Redfield ratio' approach and determinations of in situ N and P consumption by the algae during incubation periods have also been compared. The results of the biomass difference and incubation approaches are discussed in order to assess the utility of coefficients determined in situ for parameter estimation in seaweed production models

Fully-disposable multilayered phononic crystal liquid sensor with symmetry reduction and a resonant cavity

Phononic crystals are artificial structures with unique capabilities to control the transmission of acoustic waves. These novel periodic composite structures bring new possibilities for developing a fundamentally new sensor principle that combines features of both ultrasonic and resonant sensors. This paper reports the design, fabrication and evaluation of a phononic crystal sensor for biomedical applications, especially for its implementation in point of care testing technologies. The key feature of the sensor system is a fully-disposable multi-layered phononic crystal liquid sensor element with symmetry reduction and a resonant cavity. The phononic crystal structure consists of eleven layers with high acoustic impedance mismatch. A defect mode was utilized in order to generate a well-defined transmission peak inside the bandgap that can be used as a measure. The design of the structures has been optimized with simulations using a transmission line model. Experimental realizations were performed to evaluate the frequency response of the designed sensor using different liquid analytes. The frequency of the characteristic transmission peaks showed to be dependent on the properties of the analytes used in the experiments. Multi-layered phononic crystal sensors can be used in applications, like point of care testing, where the on-line measurement of small liquid samples is required

Information security: Listening to the perspective of organisational insiders

Aligned with the strategy-as-practice research tradition, this article investigates how organisational insiders understand and perceive their surrounding information security practices, how they interpret them, and how they turn such interpretations into strategic actions. The study takes a qualitative case study approach, and participants are employees at the Research & Development department of a multinational original brand manufacturer. The article makes an important contribution to organisational information security management. It addresses the behaviour of organisational insiders – a group whose role in the prevention, response and mitigation of information security incidents is critical. The article identifies a set of organisational insiders’ perceived components of effective information security practices (organisational mission statement; common understanding of information security; awareness of threats; knowledge of information security incidents, routines and policy; relationships between employees; circulation of stories; role of punishment provisions; and training), based on which more successful information security strategies can be developed

The role of input materials in shallow seismogenic slip and forearc plateau development: International Ocean Discovery Program Expedition 362 Preliminary Report Sumatra Seismogenic Zone

Drilling the input materials of the north Sumatran subduction zone, part of the 5000 km long Sunda subduction zone system and the origin of the Mw ∼9.2 earthquake and tsunami that devastated coastal communities around the Indian Ocean in 2004, was designed to groundtruth the material properties causing unexpectedly shallow seismogenic slip and a distinctive forearc prism structure. The intriguing seismogenic behavior and forearc structure are not well explained by existing models or by relationships observed at margins where seismogenic slip typically occurs farther landward. The input materials of the north Sumatran subduction zone are a distinctively thick (as thick as 4-5 km) succession of primarily Bengal-Nicobar Fan-related sediments. The correspondence between the 2004 rupture location and the overlying prism plateau, as well as evidence for a strengthened input section, suggest the input materials are key to driving the distinctive slip behavior and long-term forearc structure. During Expedition 362, two sites on the Indian oceanic plate ∼250 km southwest of the subduction zone, Sites U1480 and U1481, were drilled, cored, and logged to a maximum depth of 1500 meters below seafloor. The succession of sediment/rocks that will develop into the plate boundary detachment and will drive growth of the forearc were sampled, and their progressive mechanical, frictional, and hydrogeological property evolution will be analyzed through postcruise experimental and modeling studies. Large penetration depths with good core recovery and successful wireline logging in the challenging submarine fan materials will enable evaluation of the role of thick sedimentar y subduction zone input sections in driving shallow slip and amplifying earthquake and tsunami magnitudes, at the Sunda subduction zone and globally at other subduction zones where submarine fan-influenced sections are being subducted

Somatic mutation and gain of copy number of PIK3CA in human breast cancer

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified. METHODS: Fifteen breast cancer cell lines and 92 primary breast tumors (33 with matched normal tissue) were used to check somatic mutation and gene copy number of PIK3CA. For the somatic mutation study, we specifically checked exons 1, 9, and 20, which have been reported to be hot spots in colon cancer. For the analysis of the gene copy number, we used quantitative real-time PCR and fluorescence in situ hybridization. We also treated several breast cancer cells with the PIK3CA inhibitor LY294002 and compared the apoptosis status in cells with and without PIK3CA mutation. RESULTS: We identified a 20.6% (19 of 92) and 33.3% (5 of 15) PIK3CA somatic mutation frequency in primary breast tumors and cell lines, respectively. We also found that 8.7% (8 of 92) of the tumors harbored a gain of PIK3CA gene copy number. Only four cases in this study contained both an increase in the gene copy number and a somatic mutation. In addition, mutation of PIK3CA correlated with the status of Akt phosphorylation in some breast cancer cells and inhibition of PIK3CA-induced increased apoptosis in breast cancer cells with PIK3CA mutation. CONCLUSION: Somatic mutation rather than a gain of gene copy number of PIK3CA is the frequent genetic alteration that contributes to human breast cancer progression. The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer