Resilience of Hierarchical Critical Infrastructure Networks

Concern over the resilience of critical infrastructure networks has increased dramatically over the last decade due to a number of well documented failures and the significant disruption associated with these. This has led to a large body of research that has adopted graph-theoretic based analysis in order to try and improve our understanding of infrastructure network resilience. Many studies have asserted that infrastructure networks possess a scale-free topology which is robust to random failures but sensitive to targeted attacks at highly connected hubs. However, many studies have ignored that many networks in addition to their topological connectivity may be organised either logically or spatially in a hierarchical system which may significantly change their response to perturbations. In this paper we explore if hierarchical network models exhibit significantly different higher-order topological characteristics compared to other network structures and how this impacts on their resilience to a number of different failure types. This is achieved by investigating a suite of synthetic networks as well as a suite of ‘real world’ spatial infrastructure networks

The Athletic Profile of Fast Bowling in Cricket : A Review

Cricket is a global sport played in over 100 countries with elite performers attracting multimillion dollar contracts. Therefore, performers maintaining optimum physical fitness and remaining injury free is important. Fast bowlers have a vital position in a cricket team, and there is an increasing body of scientific literature that has reviewed this role over the past decade. Previous research on fast bowlers has tended to focus on biomechanical analysis and injury prevention in performers. However, this review aims to critically analyze the emerging contribution of physiological-based literature linked to fast bowling in cricket, highlight the current evidence related to simulated and competitive in-match performance, and relate this practically to the conditioning coach. Furthermore, the review considers limitations with past research and possible avenues for future investigation. It is clear with the advent of new applied mobile monitoring technology that there is scope for more ecologically valid and longitudinal exploration capturing in-match data, providing quantification of physiological workloads, and analysis of the physical demands across the differing formats of the game. Currently, strength and conditioning specialists do not have a critical academic resource with which to shape professional practice, and this review aims to provide a starting point for evidence in the specific areaPeer reviewedFinal Accepted Versio

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative

Covalent targeting of the vacuolar H+-ATPase activates autophagy via mTORC1 inhibition.

Autophagy is a lysosomal degradation pathway that eliminates aggregated proteins and damaged organelles to maintain cellular homeostasis. A major route for activating autophagy involves inhibition of the mTORC1 kinase, but current mTORC1-targeting compounds do not allow complete and selective mTORC1 blockade. Here, we have coupled screening of a covalent ligand library with activity-based protein profiling to discover EN6, a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase, which activates mTORC1 via the Rag guanosine triphosphatases. EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. Consistently, EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner. Our results provide insight into how the v-ATPase regulates mTORC1, and reveal a unique approach for enhancing cellular clearance based on covalent inhibition of lysosomal mTORC1 signaling

Bayesian Methods for Analysis and Adaptive Scheduling of Exoplanet Observations

We describe work in progress by a collaboration of astronomers and statisticians developing a suite of Bayesian data analysis tools for extrasolar planet (exoplanet) detection, planetary orbit estimation, and adaptive scheduling of observations. Our work addresses analysis of stellar reflex motion data, where a planet is detected by observing the "wobble" of its host star as it responds to the gravitational tug of the orbiting planet. Newtonian mechanics specifies an analytical model for the resulting time series, but it is strongly nonlinear, yielding complex, multimodal likelihood functions; it is even more complex when multiple planets are present. The parameter spaces range in size from few-dimensional to dozens of dimensions, depending on the number of planets in the system, and the type of motion measured (line-of-sight velocity, or position on the sky). Since orbits are periodic, Bayesian generalizations of periodogram methods facilitate the analysis. This relies on the model being linearly separable, enabling partial analytical marginalization, reducing the dimension of the parameter space. Subsequent analysis uses adaptive Markov chain Monte Carlo methods and adaptive importance sampling to perform the integrals required for both inference (planet detection and orbit measurement), and information-maximizing sequential design (for adaptive scheduling of observations). We present an overview of our current techniques and highlight directions being explored by ongoing research.Comment: 29 pages, 11 figures. An abridged version is accepted for publication in Statistical Methodology for a special issue on astrostatistics, with selected (refereed) papers presented at the Astronomical Data Analysis Conference (ADA VI) held in Monastir, Tunisia, in May 2010. Update corrects equation (3

Cabazitaxel in platinum pre-treated patients with locally advanced or metastatic transitional cell carcinoma who developed disease progression after platinum based chemotherapy : results of the phase II CAB-B1 trial

There is a paucity of chemotherapy options for patients with urothelial cancers who have relapsed following platinum based chemotherapy (CT). CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had recurred after receiving platinum based treatment. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes included Progression Free Survival (PFS) and Overall Survival (OS). Between January 2013 and October 2016, 20 patients were randomised (10 on each arm). BSC included paclitaxel CT for 9 patients and radiotherapy for 1 patient. 8 patients completed 6 cycles of CT (3 on CAB; 5 on BSC). 2 patients had an ORR on CAB and 1 patient on BSC. Median OS was 5.8 months (95% confidence interval (CI) 0.7-14.6) for CAB patients and 7.5 months (95% CI 1.0-10.8) for BSC patients. Median PFS was 4.8 months (95% CI 0.7-8.3) for CAB patients and 3.7 months (95% CI 1.0-7.0) for BSC patients. CAB-B1 successfully reached the efficacy target for 1st stage, showing that there could be a role for CAB in these patients

Networks and the epidemiology of infectious disease

The science of networks has revolutionised research into the dynamics of interacting elements. It could be argued that epidemiology in particular has embraced the potential of network theory more than any other discipline. Here we review the growing body of research concerning the spread of infectious diseases on networks, focusing on the interplay between network theory and epidemiology. The review is split into four main sections, which examine: the types of network relevant to epidemiology; the multitude of ways these networks can be characterised; the statistical methods that can be applied to infer the epidemiological parameters on a realised network; and finally simulation and analytical methods to determine epidemic dynamics on a given network. Given the breadth of areas covered and the ever-expanding number of publications, a comprehensive review of all work is impossible. Instead, we provide a personalised overview into the areas of network epidemiology that have seen the greatest progress in recent years or have the greatest potential to provide novel insights. As such, considerable importance is placed on analytical approaches and statistical methods which are both rapidly expanding fields. Throughout this review we restrict our attention to epidemiological issues

Bioharness multivariable monitoring device. Part I: Validity

The BioharnessTM monitoring system may provide physiological information on human performance but there is limited information on its validity. The objective of this study was to assess the validity of all 5 BioharnessTM variables using a laboratory based treadmill protocol. 22 healthy males participated. Heart rate (HR), Breathing Frequency (BF) and Accelerometry (ACC) precision were assessed during a discontinuous incremental (0- 12 km·h-1) treadmill protocol. Infra-red skin temperature (ST) was assessed during a 45 min-1 sub-maximal cycle ergometer test, completed twice, with environmental temperature controlled at 20 ±0.1 °C and 30 ± 0.1 °C. Posture (P) was assessed using a tilt table moved through 160°. Adopted precision of measurement devices were; HR: Polar T31 (Polar Electro), BF: Spirometer (Cortex Metalyser), ACC: Oxygen expenditure (Cortex Metalyser), ST: Skin thermistors (Grant Instruments), P:Goniometer (Leighton Flexometer). Strong relationships (r = .89 to .99, p \u3c 0.01) were reported for HR, BF, ACC and P. Limits of agreement identified differences in HR (-3.05±32.20 b·min-1), BF (-3.46 ± 43.70 br·min-1) and P (0.20 ± 2.62°). ST established a moderate relationships (-0.61 ± 1.98 °C; r = 0.76, p \u3c 0.01). Higher velocities on the treadmill decreased the precision of measurement, especially HR and BF. Global results suggest that the BioharressTM is a valid multivariable monitoring device within the laboratory environment