On the Security of Balanced Encoding Countermeasures

Most cryptographic devices should inevitably have a resistance against the threat of side channel attacks. For this, masking and hiding schemes have been proposed since 1999. The security validation of these countermeasures is an ongoing research topic, as a wider range of new and existing attack techniques are tested against these countermeasures. This paper examines the side channel security of the balanced encoding countermeasure, whose aim is to process the secret key-related data under a constant Hamming weight and/or Hamming distance leakage. Unlike previous works, we assume that the leakage model coefficients conform to a normal distribution, producing a model with closer fidelity to real-world implementations. We perform analysis on the balanced encoded PRINCE block cipher with simulated leakage model and also an implementation on an AVR board. We consider both standard correlation power analysis (CPA) and bit-wise CPA. We confirm the resistance of the countermeasure against standard CPA, however, we find with a bit-wise CPA that we can reveal the key with only a few thousands traces.

Targeting FPGA DSP Slices for a Large Integer Multiplier for Integer Based FHE

Homomorphic encryption offers potential for secure cloud computing. However due to the complexity of homomorphic encryption schemes, performance of implemented schemes to date have been unpractical. This work investigates the use of hardware, specifically Field Programmable Gate Array (FPGA) technology, for implementing the building blocks involved in somewhat and fully homomorphic encryption schemes in order to assess the practicality of such schemes. We concentrate on the selection of a suitable multiplication algorithm and hardware architecture for large integer multiplication, one of the main bottlenecks in many homomorphic encryption schemes. We focus on the encryption step of an integer-based fully homomorphic encryption (FHE) scheme. We target the DSP48E1 slices available on Xilinx Virtex 7 FPGAs to ascertain whether the large integer multiplier within the encryption step of a FHE scheme could fit on a single FPGA device. We find that, for toy size parameters for the FHE encryption step, the large integer multiplier fits comfortably within the DSP48E1 slices, greatly improving the practicality of the encryption step compared to a software implementation. As multiplication is an important operation in other FHE schemes, a hardware implementation using this multiplier could also be used to improve performance of these schemes.

Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)

Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".

Doxorubicin induces the cleavage of Poly (ADP-ribose) polymerase, a marker of programmed cell death (apoptosis) in mouse cardiomyocytes

Cancer is one of the leading causes of death in the world. Despite this, a growing number of people are surviving the disease due to medical advancements and the development of numerous new therapies. Doxorubicin, a chemotherapeutic agent, is a widely-used and successful first-line anti-tumour treatment. However, the established toxic and deleterious effects of the drug on the cardiovascular system confer increased risk of congestive heart failure, thereby necessitating the use of reduced doxorubicin doses. In order to investigate how these events are initiated, mouse cardiomyocytes (HL-1) were treated in vitro with varying concentrations of doxorubicin (0.5-4.0 µmol/L). Following treatment (24h), a marked level of cell death was observed in comparison to untreated cardiomyocytes; the level of death appeared to correlate with the concentration of the drug used. Western blotting revealed the cleavage of full length Poly (ADP-ribose) polymerase (PARP) into 89 and 24kDa fragments, a process which is instrumental in triggering programmed cell death/apoptosis. Importantly, results suggested that this event may be independent of caspase 3 cleavage and thus activation. A number of previous studies have reported a functional role for both Mitofusin-2 (Mfn2) and NADPH oxidase 2 (Nox2) in the cardiotoxic response. Given that PARP cleavage is a validated indicator of cellular apoptosis, these results clearly indicate that this marker could be used in future studies when determining if depletion of the above proteins would cause a reduction in or eradicate the pro-apoptotic action of this agent on cardiomyocytes. Such investigations may lead to significant developments in ensuring that doxorubicin can achieve its full therapeutic anti-tumour potential without causing the subsequent deleterious effects on the cardiovascular system.

INVESTIGATING THE ROLE OF NOX NADPH OXIDASE SIGNALLING IN CELL MIGRATION AND ANGIOGENESIS OF ENDOTHELIAL COLONY-FORMING CELLS

Introduction. Endothelial colony-forming cells (ECFCs) hold great cytotherapeutic potential for ischaemic disease. Emerging evidence supports a key role for NADPH oxidases in underlying angiogenic processes of these and other endothelial cells. Aims. To study the influence of Nox NADPH oxidases on the pro-angiogenic function of ECFCs. Methods. Human ECFCs isolated from umbilical cord blood were treated with pro-oxidant PMA and assessed in vitro, both under basal conditions and after siRNA knockdown of Nox4, a key endothelial NADPH oxidase isoform, alongside primary mature human aortic endothelial cells (HAoECs) for comparison, using an established scratch-wound assay as the functional end-point. Results. PMA (500nM for 8h) increased cell migration (control 18.6±2.8, PMA 32.7±6.6% wound closure; n=6, P<0.05) in a superoxide-dependent manner, as indicated by attenuation of this effect in the presence of PEG-SOD. Although HAoEC migration in response to PMA also tended to increase, this did not reach statistical significance. Notably, cell migration at 16h was reduced by Nox4 knockdown in ECFCs (control siRNA 53.4±3.5, Nox4 siRNA 35.1±4.9% closure; n=3, P<0.05), but not in HAoECs, whilst the pro-migratory effect of PMA in ECFCs was potentiated after Nox4 knockdown (control siRNA 53.4±3.5, +PMA 61.5±3.2% closure; n=3, P=NS; Nox4 siRNA 35.1±4.9, +PMA 53.0±4.9% closure; n=3, P<0.05). Conclusion. ECFC migration is enhanced by low concentrations of superoxide, to a greater extent compared to mature endothelial cells, and appears to be at least partly dependent upon NADPH oxidase, including a specific role for Nox4. Although, the precise contribution of endothelial Nox NADPH oxidases isoforms remains to be determined, it is clear that these findings may have significant implications for potential ECFC-based therapies for ischaemic disease, which is associated with an oxidative microenvironment.

EFFECTS OF ENVIRONMENTAL ANTIOXIDANTS ON PRO-ANGIOGENIC ROS SIGNALLING IN ENDOTHELIAL COLONY FORMING CELLS IN VITRO

Introduction. Endothelial colony-forming cells (ECFCs) hold great cytotherapeutic potential for ischaemic disease. Whilst increasing evidence supports a key role for reactive oxygen species (ROS), specifically those derived from Nox NADPH oxidases, in the underlying angiogenic processes of these and other endothelial cells, such studies investigating the role of redox signalling may be hampered by the standard inclusion of antioxidant agents in endothelial cell media, such as phenol red. Aims. To study the effects of antioxidants present in culture media on pro-angiogenic function of ECFCs in vitro. Methods. Human ECFCs isolated from umbilical cord blood were maintained in media with and without antioxidant components (EGM2 and phenol red-free DMEM, respectively) prior to treatment with pro-oxidant PMA and assessment of their in vitro migratory capacity using a scratch-wound assay to measure pro-angiogenic activity. Results. Our previous work in our group indicated that PMA (500nM) increased ECFC migration in a both a superoxide and NADPH oxidase-dependent manner (control 18.6±2.8, PMA 32.7±6.6% wound closure; n=6, P<0.05), as indicated by attenuation with PEG-SOD and VAS2870. However, inconsistencies in the data generated under varying experimental conditions led us to hypothesise that antioxidant agents in the standard ECFC media may be influencing these effects. Indeed, a direct comparison of cell migration between ECFCs incubated in EGM2 DMEM demonstrated a clear trend towards higher migration in the latter (EGM2 9.0±4.5, DMEM 22.7±6.4%; n=3, P=NS). Similar to our previous EGM2 studies, cell migration was potentiated by PMA (control 11.6±1.6, PMA 25.1±2.8%; n=3, P<0.05), but at a lower dose (100nM), which is consistent with a reduction in media antioxidants. Notably, this response was attenuated by VAS2870 (PMA 37.6±7.3, PMA+VAS2870 10.3±2.9%; n=6, P<0.05), underlining a likely role for Nox NADPH oxidases. Conclusion. Taken together, these data indicate that ECFC migration is sensitive to different endothelial cell growth media, which appears to be dependent upon their antioxidant content. Although further experiments, such as quantification of cellular superoxide generation by dihydroethidium fluorescence may be required to confirm a specific role for antioxidants, such blunting of ROS signalling in vitro is clearly an important consideration which may significantly impact upon data interpretation.

Closed circuit rebreathing to achieve inert gas wash-in for multiple breath wash-out

Multiple breath wash-out (MBW) testing requires prior wash-in of inert tracer gas. Wash-in efficiency can be enhanced by a rebreathing tracer in a closed circuit. Previous attempts to deploy this did not account for the impact of CO2 accumulation on patients and were unsuccessful. We hypothesised that an effective rebreathe wash-in could be delivered and it would not alter wash-out parameters. Computer modelling was used to assess the impact of the rebreathe method on wash-in efficiency. Clinical testing of open and closed circuit wash-in–wash-out was performed in healthy controls and adult patients with cystic fibrosis (CF) using a circuit with an effective CO2 scrubber and a refined wash-in protocol. Wash-in efficiency was enhanced by rebreathing. There was no difference in mean lung clearance index between the two wash-in methods for controls (6.5 versus 6.4; p=0.2, n=12) or patients with CF (10.9 versus 10.8; p=0.2, n=19). Test time was reduced by rebreathe wash-in (156 versus 230 s for CF patients, p<0.001) and both methods were well tolerated. End wash-in CO2 was maintained below 2% in most cases. Rebreathe–wash-in is a promising development that, when correctly deployed, reduces wash-in time and facilitates portable MBW testing. For mild CF, wash-out outcomes are equivalent to an open circuit.

Lattice-based Encryption Over Standard Lattices in Hardware

Lattice-based cryptography has gained credence recently as a replacement for current public-key cryptosystems, due to its quantum-resilience, versatility, and relatively low key sizes. To date, encryption based on the learning with errors (LWE) problem has only been investigated from an ideal lattice standpoint, due to its computation and size efficiencies. However, a thorough investigation of standard lattices in practice has yet to be considered. Standard lattices may be preferred to ideal lattices due to their stronger security assumptions and less restrictive parameter selection process. In this paper, an area-optimised hardware architecture of a standard lattice-based cryptographic scheme is proposed. The design is implemented on a FPGA and it is found that both encryption and decryption fit comfortably on a Spartan-6 FPGA. This is the first hardware architecture for standard lattice-based cryptography reported in the literature to date, and thus is a benchmark for future implementations.
Additionally, a revised discrete Gaussian sampler is proposed which is the fastest of its type to date, and also is the first to investigate the cost savings of implementing with lamda_2-bits of precision. Performance results are promising in comparison to the hardware designs of the equivalent ring-LWE scheme, which in addition to providing a stronger security proof; generate 1272 encryptions per second and 4395 decryptions per second.

Metabolically-inactive glucagon-like peptide-1(9-36)amide confers selective protective actions against post-myocardial infarction remodelling

BACKGROUND: Glucagon-like peptide-1 (GLP-1) therapies are routinely used for glycaemic control in diabetes and their emerging cardiovascular actions have been a major recent research focus. In addition to GLP-1 receptor activation, the metabolically-inactive breakdown product, GLP-1(9-36)amide, also appears to exert notable cardiovascular effects, including protection against acute cardiac ischaemia. Here, we specifically studied the influence of GLP-1(9-36)amide on chronic post-myocardial infarction (MI) remodelling, which is a major driver of heart failure progression.

METHODS: Adult female C57BL/6 J mice were subjected to permanent coronary artery ligation or sham surgery prior to continuous infusion with GLP-1(9-36)amide or vehicle control for 4 weeks.

RESULTS: Infarct size was similar between groups with no effect of GLP-1(9-36)amide on MI-induced cardiac hypertrophy, although modest reduction of in vitro phenylephrine-induced H9c2 cardiomyoblast hypertrophy was observed. Whilst echocardiographic systolic dysfunction post-MI remained unchanged, diastolic dysfunction (decreased mitral valve E/A ratio, increased E wave deceleration rate) was improved by GLP-1(9-36)amide treatment. This was associated with modulation of genes related to extracellular matrix turnover (MMP-2, MMP-9, TIMP-2), although interstitial fibrosis and pro-fibrotic gene expression were unaltered by GLP-1(9-36)amide. Cardiac macrophage infiltration was also reduced by GLP-1(9-36)amide together with pro-inflammatory cytokine expression (IL-1β, IL-6, MCP-1), whilst in vitro studies using RAW264.7 macrophages revealed global potentiation of basal pro-inflammatory and tissue protective cytokines (e.g. IL-1β, TNF-α, IL-10, Fizz1) in the presence of GLP-1(9-36)amide versus exendin-4.

CONCLUSIONS: These data suggest that GLP-1(9-36)amide confers selective protection against post-MI remodelling via preferential preservation of diastolic function, most likely due to modulation of infiltrating macrophages, indicating that this often overlooked GLP-1 breakdown product may exert significant actions in this setting which should be considered in the context of GLP-1 therapy in patients with cardiovascular disease.

A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy

Background and AimsTo compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy.MethodsEndoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathological parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines.ResultsA total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, p<0.001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending upon which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies.ConclusionsChoice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.

Physical rehabilitation interventions for adult patients during critical illness: an overview of systematic reviews

Background Physical rehabilitation interventions aim to ameliorate the effects of critical illness-associated muscle dysfunction in survivors. We conducted an overview of systematic reviews (SR) evaluating the effect of these interventions across the continuum of recovery.

Methods Six electronic databases (Cochrane Library, CENTRAL, DARE, Medline, Embase, and Cinahl) were searched. Two review authors independently screened articles for eligibility and conducted data extraction and quality appraisal. Reporting quality was assessed and the Grading of Recommendations Assessment, Development and Evaluation approach applied to summarise overall quality of evidence.

Results Five eligible SR were included in this overview, of which three included meta-analyses. Reporting quality of the reviews was judged as medium to high. Two reviews reported moderate-to-high quality evidence of the beneficial effects of physical therapy commencing during intensive care unit (ICU) admission in improving critical illness polyneuropathy/myopathy, quality of life, mortality and healthcare utilisation. These interventions included early mobilisation, cycle ergometry and electrical muscle stimulation. Two reviews reported very low to low quality evidence of the beneficial effects of electrical muscle stimulation delivered in the ICU for improving muscle strength, muscle structure and critical illness polyneuropathy/myopathy. One review reported that due to a lack of good quality randomised controlled trials and inconsistency in measuring outcomes, there was insufficient evidence to support beneficial effects from physical rehabilitation delivered post-ICU discharge.

Conclusions Patients derive short-term benefits from physical rehabilitation delivered during ICU admission. Further robust trials of electrical muscle stimulation in the ICU and rehabilitation delivered following ICU discharge are needed to determine the long-term impact on patient care. This overview provides recommendations for design of future interventional trials and SR.