Attacking FHE-based applications by software fault injections

The security of fully homomorphic encryption is often studied at the primitive level, and a lot of questions remain open when the cryptographer needs to choose between incompatible options, like IND- CCA1 security versus circular security or search-to-decision reduction. The aim of this report is to emphasize the well known (and often under- estimated) fact that the ability to compute every function, which is the most desired feature of Homomorphic Encryption schemes, is also their main weakness. We show that it can be exploited to perform very realistic attacks in the context of secure homomorphic computations in the cloud. In order to break a fully homomorphic system, the cloud provider who runs the computation will not target the primitive but the overall system. The attacks we describe are a combination between safe-errors attacks (well known in the smart cards domain) and reaction attacks, they are easy to perform and they can reveal one secret key bit per query. Furthermore, as homomorphic primitives gets improved, and become T times faster with K times smaller keys, these attacks become KT times more practical. Our purpose is to highlight the fact, that if a semantically-secure model is in general enough to design homomorphic primitives, additional protections need to be adopted at a system level to secure cloud applications. We do not attack a specific construction but the entire idea of homomorphic encryption, by pointing out all the possible targets of this attack (encrypted data, bootstrapping keys, trans-ciphering keys, etc.). We also propose some possible countermeasures (or better precautions) in order to prevent the loss of information

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Table_1_Prevalence and cost of sickle cell disease in France: real-world analysis using data from the Echantillon Généraliste des Bénéficiaires.DOCX

Sickle cell disease (SCD) is a genetic disorder of the hemoglobin resulting in chronic anemia, hemolysis, and vaso-occlusions. Its treatment mostly relies on hydroxycarbamide, transfusions, and stem cell transplantation. This study aimed at describing the epidemiology and management of SCD in adolescent and adult patients in France. This was a retrospective study performed among SCD patients aged ≥12 years between 2016 and 2018 and controls. SCD patients were matched on a 1:3 ratio with a group of individuals with no diagnosis of SCD, referred as control group. The matching of SCD patients and controls was a direct matching based on age, sex, CMU-c status (which corresponds to free-of-charge complementary coverage for people with low resources) and geographical region of residence. SCD patients and their matched controls were followed-up for the same amount of time by adjusting controls’ follow-up period to that of the associated patients. This study used claims data from the French representative 1/97th sample of health data system. The main outcomes were the patients’ characteristics and treatments received, healthcare consumptions and related costs among SCD cases and controls. Between 2016 and 2018, 151 patients with ≥6 months of follow-up were identified out of the total population of 732,164 individuals. SCD prevalence extrapolated to the entire population [95% CI] was 19,502 [19,230, 19,778] in 2018. The median (Q1–Q3) age at inclusion date was 37.0 (25.0–48.0) years, with 69.5% of patients being female. The mean (SD) reimbursed cost over follow-up was €24,310 (89,167), mostly represented by hospitalization costs accounting for €21,156 (86,402). A switch in SCD management was observed with age, as younger patients presented more frequent hospitalizations and acute procedures, while older ones had more frequent medical visits and paramedical care. Mean (SD) annual costs were €25,680 (91,843) and vs. €3,227 (23,372) for patients and controls, respectively (p < 0.001), representing an extra cost of almost €150 million over the entire SCD population. This study highlighted the important costs related to SCD and the related medical need with treatment alternatives, which could be filled by the emergence of new therapies.</p

Economic impact of clinical pharmaceutical activities in hospital wards: A systematic review

International audienceThe positive impact of clinical pharmacy services (CPS) in improving clinical outcomes such as reduction of drug related problems is well demonstrated. Despite these results, the deployment of these activities is not systematically observed in the hospital setting.Objectives: This systematic review first aimed to describe existing evidence regarding economic evaluation of ward-based CPS focusing on the entire treatment of a patient in a hospital setting. Secondly, the quality of economic evaluations of existing evidence was assessed.Methods: A comprehensive literature search was performed in PubMed/Medline, Science Direct and the NHS Economic Evaluation databases from January 2000 to March 2019. English or French language articles describing an economic evaluation of ward-based CPS on inpatients in hospital settings were included. Articles not describing a single study, dealing with a CPS not considering the entire medication regimen of the patient or presenting both inpatient and outpatient CPS were excluded. Selected articles were analyzed according to Drummond's check-list for assessing economic evaluations.Results: Forty-one studies were included. About one third were American publications. CPS implemented in ICU represented about half of the selected articles. Pharmacist-to-bed ratios varied according to countries and care unit type with the most favorable ratios in ICU and in American studies. Cost-avoidance was mostly used to express economic impact and ranged from €1579 to €3,089 328. Studies yielding the greater economic impact were conducted in the USA with implementation of full-time equivalents pharmacists or establishing of collaborative practice agreements. Only 6 articles dealt correctly with at least 7 of the 10 Drummond's checklist assessment criteria.Conclusion: This review suggests that the existing evidence is not sufficient to conclude to a positive economic impact of CPS conducted according to clinical pharmacy guidelines. Funding resources, remuneration of clinical pharmacy activities and provision of standardized national clinical and economic databases appear to be essential evolutions to improve CPS development

World J Urol

PURPOSE: To describe the incidence, management, and survival outcomes of patients with muscle-invasive urothelial carcinoma (MIUC) undergoing radical surgery (RS) in France. METHODS: We relied on a non-interventional real-world retrospective study based on French National Hospitalization Database. Adults with MIUC with a first RS between 2015 and 2020 were selected. Subpopulations of patients with RS performed in 2015 and 2019 (pre-COVID-19) were extracted, according to cancer site: muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Disease-free and overall survival (DFS, OS - Kaplan-Meier) were assessed on the 2015 subpopulation. RESULTS: Between 2015 and 2020, 21,295 MIUC patients underwent a first RS. Of them, 68.9% had MIBC, 28.9% UTUC, and 2.2% both cancers. Apart from fewer men among UTUC (70.2%) than MIBC patients (90.1%), patients' demographic (mean age ~ 73 years) and clinical characteristics were similar whatever the cancer site or year of first RS. In 2019, RS alone was the most frequent treatment, occurring in 72.3% and 92.6% in MIBC and UTUC, respectively. Between 2015 and 2019, neoadjuvant use rate increased from 13.8% to 22.2% in MIBC, and adjuvant use rate increased from 3.7% to 6.3% in UTUC. Finally, median [95% confidence interval] DFS times were 16.0 [14.0-18.0] and 27.0 [23.0-32.0] months among MIBC and UTUC, respectively. CONCLUSION: Among patients with resected MIUC annually, RS alone remained the main treatment. Neoadjuvant and adjuvant use increased between 2015 and 2019. Nonetheless, MIUC remains of poor prognosis, highlighting an unmet medical need, notably among patients at high risk of recurrence

Genetic Background of the Sickle Cell Disease Pediatric Population of Dakar, Senegal, and Characterization of a Novel Frameshift β -Thalassemia Mutation [ HBB : c.265_266del; p.Leu89Glufs*2]

International audienc

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response