Intel TDX Demystified: A Top-Down Approach

Intel Trust Domain Extensions (TDX) is a new architectural extension in the 4th Generation Intel Xeon Scalable Processor that supports confidential computing. TDX allows the deployment of virtual machines in the Secure-Arbitration Mode (SEAM) with encrypted CPU state and memory, integrity protection, and remote attestation. TDX aims to enforce hardware-assisted isolation for virtual machines and minimize the attack surface exposed to host platforms, which are considered to be untrustworthy or adversarial in the confidential computing's new threat model. TDX can be leveraged by regulated industries or sensitive data holders to outsource their computations and data with end-to-end protection in public cloud infrastructure. This paper aims to provide a comprehensive understanding of TDX to potential adopters, domain experts, and security researchers looking to leverage the technology for their own purposes. We adopt a top-down approach, starting with high-level security principles and moving to low-level technical details of TDX. Our analysis is based on publicly available documentation and source code, offering insights from security researchers outside of Intel

Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis

Background: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. Methods: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45000 children younger than 5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January, 2011. In Kilifi, there was a three-dose catch-up campaign for infants (aged \u3c1 \u3eyear) and a two-dose catch-up campaign for children aged 1–4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. Findings: Between May 1, 2002 and March 31, 2015, 44771 children aged 2–143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses’ strikes. In 2002–03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2–59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2–11 months had received at least two doses of PCV10 and 23298 (62·3%) of 37416 children aged 12–59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologicallyconfirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32–0·86), 0·73 (0·54–0·97), and 0·63 (0·31–1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100000; this value was reduced by 329 per 100000 at the point of PCV10 introduction. Interpretation: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10

Remote attestation of SEV-SNP confidential VMs using e-vTPMs

Departing from "your data is safe with us" model where the cloud infrastructure is trusted, cloud tenants are shifting towards a model in which the cloud provider is not part of the trust domain. Both silicon and cloud vendors are trying to address this shift by introducing confidential computing - an umbrella term that provides mechanisms for protecting the data in-use through encryption below the hardware boundary of the CPU, e.g., Intel Software Guard Extensions (SGX), AMD secure encrypted virtualization (SEV), Intel trust domain extensions (TDX), etc. In this work, we design and implement a virtual trusted platform module (vTPM) that virtualizes the hardware root-of-trust without requiring to trust the cloud provider. To ensure the security of a vTPM in a provider-controlled environment, we leverage unique isolation properties of the SEV-SNP hardware and a novel approach to ephemeral TPM state management. Specifically, we develop a stateless ephemeral vTPM that supports remote attestation without persistent state. This allows us to pair each confidential VM with a private instance of a vTPM that is completely isolated from the provider-controlled environment and other VMs. We built our prototype entirely on open-source components - Qemu, Linux, and Keylime. Though our work is AMD-specific, a similar approach could be used to build remote attestation protocol on other trusted execution environments (TEE).Comment: 12 pages, 4 figure

Evaluating the impact of an intervention to increase uptake of modern contraceptives among adolescent girls (15-19 years) in Nigeria, Ethiopia and Tanzania: the Adolescents 360 quasi-experimental study protocol.

INTRODUCTION: Nigeria, Ethiopia and Tanzania have some of the highest teenage pregnancy rates and lowest rates of modern contraceptive use among adolescents. The transdisciplinary Adolescents 360 (A360) initiative being rolled out across these three countries uses human-centred design to create context-specific multicomponent interventions with the aim of increasing voluntary modern contraceptive use among girls aged 15-19 years. METHODS: The primary objective of the outcome evaluation is to assess the impact of A360 on the modern contraceptive prevalence rate (mCPR) among sexually active girls aged 15-19 years. A360 targets different subpopulations of adolescent girls in the three countries. In Northern Nigeria and Ethiopia, the study population is married girls aged 15-19 years. In Southern Nigeria, the study population is unmarried girls aged 15-19 years. In Tanzania, both married and unmarried girls aged 15-19 years will be included in the study. In all settings, we will use a prepopulation and postpopulation-based cross-sectional survey design. In Nigeria, the study design will also include a comparison group. A one-stage sampling design will be used in Nigeria and Ethiopia. A two-stage sampling design will be used in Tanzania. Questionnaires will be administered face-to-face by female interviewers aged between 18 and 26 years. Study outcomes will be assessed before the start of A360 implementation in late 2017 and approximately 24 months after implementation in late 2019. ETHICS AND DISSEMINATION: Findings of this study will be widely disseminated through workshops, conference presentations, reports, briefings, factsheets and academic publications

Conformational Change in the Chromatin Remodelling Protein MENT

Chromatin condensation to heterochromatin is a mechanism essential for widespread suppression of gene transcription, and the means by which a chromatin-associated protein, MENT, induces a terminally differentiated state in cells. MENT, a protease inhibitor of the serpin superfamily, is able to undergo conformational change in order to effect enzyme inhibition. Here, we sought to investigate whether conformational change in MENT is ‘fine-tuned’ in the presence of a bound ligand in an analogous manner to other serpins, such as antithrombin where such movements are reflected by a change in intrinsic tryptophan fluorescence. Using this technique, MENT was found to undergo structural shifts in the presence of DNA packaged into nucleosomes, but not naked DNA. The contribution of the four Trp residues of MENT to the fluorescence change was mapped using deconvolution analysis of variants containing single Trp to Phe mutations. The analysis indicated that the overall emission spectra is dominated by a helix-H tryptophan, but this residue did not dominate the conformational change in the presence of chromatin, suggesting that other Trp residues contained in the A-sheet and RCL regions contribute to the conformational change. Mutagenesis revealed that the conformational change requires the presence of the DNA-binding ‘M-loop’ and D-helix of MENT, but is independent of the protease specificity determining ‘reactive centre loop’. The D-helix mutant of MENT, which is unable to condense chromatin, does not undergo a conformational change, despite being able to bind chromatin, indicating that the conformational change may contribute to chromatin condensation by the serpin

Challenges and opportunities in evaluating programmes incorporating human-centred design: lessons learnt from the evaluation of Adolescents 360.

Adolescents 360 (A360) is a four-year initiative (2016-2020) to increase 15-19-year-old girls' use of modern contraception in Nigeria, Ethiopia and Tanzania. The innovative A360 approach is led by human-centred design (HCD), combined with social marketing, developmental neuroscience, public health, sociocultural anthropology and youth engagement 'lenses', and aims to create context-specific, youth-driven solutions that respond to the needs of adolescent girls. The A360 external evaluation includes a process evaluation, quasi-experimental outcome evaluation, and a cost-effectiveness study. We reflect on evaluation opportunities and challenges associated with measuring the application and impact of this novel HCD-led design approach. For the process evaluation, participant observations were key to capturing the depth of the fast-paced, highly-iterative HCD process, and to understand decision-making within the design process. The evaluation team had to be flexible and align closely with the work plan of the implementers. The HCD process meant that key information such as intervention components, settings, and eligible populations were unclear and changed over outcome evaluation and cost-effectiveness protocol development. This resulted in a more time-consuming and resource-intensive study design process. As much time and resources went into the creation of a new design approach, separating one-off "creation" costs versus those costs associated with actually implementing the programme was challenging. Opportunities included the potential to inform programmatic decision-making in real-time to ensure that interventions adequately met the contextualized needs in targeted areas. Robust evaluation of interventions designed using HCD, a promising and increasingly popular approach, is warranted yet challenging. Future HCD-based initiatives should consider a phased evaluation, focusing initially on programme theory refinement and process evaluation, and then, when the intervention program details are clearer, following with outcome evaluation and cost-effectiveness analysis. A phased approach would delay the availability of evaluation findings but would allow for a more appropriate and tailored evaluation design

Equivalence testing of a newly developed interviewer-led telephone script for the EORTC QLQ-C30

Purpose The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core Questionnaire (QLQ-C30) is a widely used generic self-report measure of health-related quality of life (HRQOL) for cancer patients. However, no validated voice script for interviewer-led telephone administration was previously available. The aim of this study was to develop a voice script for interviewer administration via telephone. Methods Following guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) PRO Mixed Modes Good Research Practices Task Force, a randomised cross-over equivalence study, including cognitive debriefing, was conducted to assess equivalence between paper and telephone administration modes. Assuming an expected intraclass correlation coefficient (ICC) of 0.70 and a minimally acceptable level of 0.50, a sample size of 63 was required. Results Cognitive interviews with five cancer patients found the voice script to be clear and understandable. Due to a protocol deviation in the first wave of testing, only 26 patients were available for analyses. A second wave of recruitment was conducted, adding 37 patients (n = 63; mean age 55.48; 65.1% female). Total ICCs for mode comparison ranged from 0.72 (nausea and vomiting, 95% CI 0.48–0.86) to 0.90 (global health status/QoL, 95% CI 0.80–0.95; pain, 95% CI 0.79–0.95; constipation, 95% CI 0.80–0.95). For paper first administration, all ICCs were above 0.70, except nausea and vomiting (ICC 0.55; 95% CI 0.24–0.76) and financial difficulties (ICC 0.60; 95% CI 0.31–0.79). For phone first administration, all ICCs were above 0.70. Conclusions The equivalence testing results support the voice script’s validity for administration of the QLQ-C30 via telephone

The REFOLD database: a tool for the optimization of protein expression and refolding

A large proportion of proteins expressed in Escherichia coli form inclusion bodies and thus require renaturation to attain a functional conformation for analysis. In this process, identifying and optimizing the refolding conditions and methodology is often rate limiting. In order to address this problem, we have developed REFOLD, a web-accessible relational database containing the published methods employed in the refolding of recombinant proteins. Currently, REFOLD contains >300 entries, which are heavily annotated such that the database can be searched via multiple parameters. We anticipate that REFOLD will continue to grow and eventually become a powerful tool for the optimization of protein renaturation. REFOLD is freely available at

Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion

Heavy-light, absent-present: rethinking the 'weight' of imprisonment.

Since King and McDermott (1995), following Downes (1988), defined the psychological oppressiveness of incarceration in terms of 'weight', little has been written about the 'weight of imprisonment'. None the less, it is generally assumed that prisons that are 'light' are preferable to those that are 'heavy' - in part because of an assumption among many penologists that power, and its application, is dangerous and antagonistic. This article does not dispute that 'heavy' prisons are undesirable. Its argument is that there can also be dangers if prisons are excessively light. Many of these dangers are linked to the under-use of power. The tone and quality of prison life depends on the combined effects of institutional weight with the 'absence' or 'presence' of staff power. Drawing on prisoners' descriptions of their experiences in public and private sector prisons, and their assessments of important aspects of their quality of life, the article outlines what these concepts mean in practice. The authors develop a four-quadrant framework for conceptualizeng penal legitimacy and the experience of penal authority.The empirical research on which this article draws was funded by the Economic and Social Research Council (RES-062-23-0212).This is the accepted version of the following article: Crewe B, Liebling A, Hulley S, The British Journal of Sociology 2014, 65: 387–410, which has been published in final form at http://dx.doi.org/10.1111/1468-4446.1208