Cost-effectiveness of infant vaccination with RIX4414 (Rotarix) in the UK.

This study estimated the cost-effectiveness of infant rotavirus vaccination with Rotarix in the UK, taking into account community rotavirus infections that do not present to the healthcare system. A Markov model compared the costs and outcomes of vaccination versus no vaccination in a hypothetical birth cohort of children followed over a lifetime, from a societal perspective and the perspective of the National Health Service (NHS). The model estimated costs and quality-adjusted life-years (QALYs) lost due to death, hospitalisation, general practitioner (GP) consultation, emergency attendance and calls to NHS Direct for rotavirus infection in children aged <5 years. Time lost from work and parents' travel costs were also included in the societal perspective. The base case cost-effectiveness ratio for vaccination compared with no vaccination was pound23,298/QALY from the NHS perspective and pound11,459 from the societal perspective. In sensitivity analysis, the most important parameters were hospitalisation cost and number of GP consultations. Addition of Rotarix to the paediatric vaccination schedule would be a cost-effective policy option in the UK at the threshold range ( pound20,000-30,000/QALY) currently adopted by the National Institute for Health and Clinical Excellence

Asymptotic information leakage under one-try attacks

We study the asymptotic behaviour of (a) information leakage and (b) adversary’s error probability in information hiding systems modelled as noisy channels. Specifically, we assume the attacker can make a single guess after observing n independent executions of the system, throughout which the secret information is kept fixed. We show that the asymptotic behaviour of quantities (a) and (b) can be determined in a simple way from the channel matrix. Moreover, simple and tight bounds on them as functions of n show that the convergence is exponential. We also discuss feasible methods to evaluate the rate of convergence. Our results cover both the Bayesian case, where a prior probability distribution on the secrets is assumed known to the attacker, and the maximum-likelihood case, where the attacker does not know such distribution. In the Bayesian case, we identify the distributions that maximize the leakage. We consider both the min-entropy setting studied by Smith and the additive form recently proposed by Braun et al., and show the two forms do agree asymptotically. Next, we extend these results to a more sophisticated eavesdropping scenario, where the attacker can perform a (noisy) observation at each state of the computation and the systems are modelled as hidden Markov models

Efficient template attacks

This is the accepted manuscript version. The final published version is available from http://link.springer.com/chapter/10.1007/978-3-319-08302-5_17.Template attacks remain a powerful side-channel technique to eavesdrop on tamper-resistant hardware. They model the probability distribution of leaking signals and noise to guide a search for secret data values. In practice, several numerical obstacles can arise when implementing such attacks with multivariate normal distributions. We propose efficient methods to avoid these. We also demonstrate how to achieve significant performance improvements, both in terms of information extracted and computational cost, by pooling covariance estimates across all data values. We provide a detailed and systematic overview of many different options for implementing such attacks. Our experimental evaluation of all these methods based on measuring the supply current of a byte-load instruction executed in an unprotected 8-bit microcontroller leads to practical guidance for choosing an attack algorithm.Omar Choudary is a recipient of the Google Europe Fellowship in Mobile Security, and this research is supported in part by this Google Fellowship

Efficient Entropy Estimation for Mutual Information Analysis Using B-Splines

International audienceThe Correlation Power Analysis (CPA) is probably the most used side-channel attack because it seems to fit the power model of most standard CMOS devices and is very efficiently computed. However, the Pearson correlation coefficient used in the CPA measures only linear statistical dependences where the Mutual Information (MI) takes into account both linear and nonlinear dependences. Even if there can be simultaneously large correlation coefficients quantified by the correlation coefficient and weak dependences quantified by the MI, we can expect to get a more profound understanding about interactions from an MI Analysis (MIA). We study methods that improve the non-parametric Probability Density Functions (PDF) in the estimation of the entropies and, in particular, the use of B-spline basis functions as pdf estimators. Our results indicate an improvement of two fold in the number of required samples compared to a classic MI estimation. The B-spline smoothing technique can also be applied to the rencently introduced Cramér-von-Mises test

KLEIN: A New Family of Lightweight Block Ciphers

Resource-efficient cryptographic primitives become fundamental for realizing both security and efficiency in embedded systems like RFID tags and sensor nodes. Among those primitives, lightweight block cipher plays a major role as a building block for security protocols. In this paper, we describe a new family of lightweight block ciphers named KLEIN, which is designed for resource-constrained devices such as wireless sensors and RFID tags. Compared to the related proposals, KLEIN has advantage in the software performance on legacy sensor platforms, while in the same time its hardware implementation can also be compact

LRRK2 secretion in exosomes is regulated by 14-3-3

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset Parkinson's disease (PD). Emerging evidence suggests a role for LRRK2 in the endocytic pathway. Here, we show that LRRK2 is released in extracellular microvesicles (i.e. exosomes) from cells that natively express LRRK2. LRRK2 localizes to collecting duct epithelial cells in the kidney that actively secrete exosomes into urine. Purified urinary exosomes contain LRRK2 protein that is both dimerized and phosphorylated. We provide a quantitative proteomic profile of 1673 proteins in urinary exosomes and find that known LRRK2 interactors including 14-3-3 are some of the most abundant exosome proteins. Disruption of the 14-3-3 LRRK2 interaction with a 14-3-3 inhibitor or through acute LRRK2 kinase inhibition potently blocks LRRK2 release in exosomes, but familial mutations in LRRK2 had no effect on secretion. LRRK2 levels were overall comparable but highly variable in urinary exosomes derived from PD cases and age-matched controls, although very high LRRK2 levels were detected in some PD affected cases. We further characterized LRRK2 exosome release in neurons and macrophages in culture, and found that LRRK2-positive exosomes circulate in cerebral spinal fluid (CSF). Together, these results define a pathway for LRRK2 extracellular release, clarify one function of the LRRK2 14-3-3 interaction and provide a foundation for utilization of LRRK2 as a biomarker in clinical trial

measuring the cost of a pediatric vaccine administration in the uk

Abstract The administration of a vaccine dose involves a series of activities prior to and on the day of vaccine delivery. Total vaccination cost should include the cost of each activity, which is often not done or poorly reported. To calculate those costs a field study was performed in 6 United Kingdom (UK) sites (General Practitioner (GP) practices) during a 4-month period (April–June 2015). First, a workflow map of all the relevant vaccine-related activities per site was obtained through interviews. Second, time estimates for activities happening prior to the vaccination day were obtained through interviews and associated costs were calculated. A prospective, non-interventional study using Time & Motion (T&M) methodology was used to measure time for activities happening on the day of vaccination. Consumables, wastage, and guardian time were also collected. Third, the time for each task and for all tasks combined during the T&M study was analyzed using a random intercept model to account for site effect. Hundred and twenty-three T&M observations with approximately 20 per site were collected and were equally stratified by vaccination visit during the first year of a baby's life. Total cost per visit was £11.9 (site range: £8.6–£17.0) when supply cost and time for activities prior to the vaccination day were included. Time per dose administrated was 7.1 min (site range: 5.7–9.2) and the associated cost was £4.3 (site range: £3.1–£6.2). The study demonstrates an accurate reflection of the time and cost involved in a vaccine dose administration in a pediatric setting in the UK. The amount measured is consistent with the current National Health Services fee schedule

Practical Improvements of Profiled Side-Channel Attacks on a Hardware Crypto-Accelerator

Abstract. This article investigates the relevance of the theoretical frame-work on profiled side-channel attacks presented by F.-X. Standaert et al. at Eurocrypt 2009. The analyses consist in a case-study based on side-channel measurements acquired experimentally from a hardwired crypto-graphic accelerator. Therefore, with respect to previous formal analyses carried out on software measurements or on simulated data, the inves-tigations we describe are more complex, due to the underlying chip’s architecture and to the large amount of algorithmic noise. In this dif-ficult context, we show however that with an engineer’s mindset, two techniques can greatly improve both the off-line profiling and the on-line attack. First, we explore the appropriateness of different choices for the sensitive variables. We show that a skilled attacker aware of the regis-ter transfers occurring during the cryptographic operations can select the most adequate distinguisher, thus increasing its success rate. Sec-ond, we introduce a method based on the thresholding of leakage data to accelerate the profiling or the matching stages. Indeed, leveraging on an engineer’s common sense, it is possible to visually foresee the shape of some eigenvectors thereby anticipating their estimation towards their asymptotic value by authoritatively zeroing weak components containing mainly non-informational noise. This method empowers an attacker, in that it saves traces when converging towards correct values of the secret. Concretely, we demonstrate a 5 times speed-up in the on-line phase of the attack.

A MAC Mode for Lightweight Block Ciphers

status: accepte

Levodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats

Background Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition. Methodology/Principal Findings Quantitative real-time polymerase chain reaction (PCR) was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH) was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes. Conclusions/Significance TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease.Morris K. Udall Center for Excellence in Parkinson’s Research at MGH/MITNational Institutes of Health (U.S.) (NIH NS38372)American Parkinson Disease Association, Inc.University of Alabama at BirminghamMassachusetts General HospitalNational Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIDDK/NIH grant R01 DK58148)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NINDS/NIH grant NS045231)Stanley H. and Sheila G. Sydney FundMichael J. Fox Foundation for Parkinson's Researc