Computing Local Sensitivities of Counting Queries with Joins

Local sensitivity of a query Q given a database instance D, i.e. how much the output Q(D) changes when a tuple is added to D or deleted from D, has many applications including query analysis, outlier detection, and in differential privacy. However, it is NP-hard to find local sensitivity of a conjunctive query in terms of the size of the query, even for the class of acyclic queries. Although the complexity is polynomial when the query size is fixed, the naive algorithms are not efficient for large databases and queries involving multiple joins. In this paper, we present a novel approach to compute local sensitivity of counting queries involving join operations by tracking and summarizing tuple sensitivities -- the maximum change a tuple can cause in the query result when it is added or removed. We give algorithms for the sensitivity problem for full acyclic join queries using join trees, that run in polynomial time in both the size of the database and query for an interesting sub-class of queries, which we call 'doubly acyclic queries' that include path queries, and in polynomial time in combined complexity when the maximum degree in the join tree is bounded. Our algorithms can be extended to certain non-acyclic queries using generalized hypertree decompositions. We evaluate our approach experimentally, and show applications of our algorithms to obtain better results for differential privacy by orders of magnitude.Comment: To be published in Proceedings of the 2020 ACM SIGMOD International Conference on Management of Dat

Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study

Background Carbapenems are frequently the last line of defence in serious infections due to multidrug-resistant Gram-negative bacteria, but their use is threatened by the growing prevalence of carbapenemase-producing pathogens. Ceftazidime-avibactam is a potential new agent for use in such infections. We aimed to assess the efficacy, safety, and tolerability of ceftazidime-avibactam compared with best available therapy in patients with complicated urinary tract infection or complicated intra-abdominal infection due to ceftazidime-resistant Gram-negative pathogens. Methods REPRISE was a pathogen-directed, international, randomised, open-label, phase 3 trial that recruited patients from hospitals across 16 countries worldwide. Eligible patients were aged 18–90 years with complicated urinary tract infection or complicated intra-abdominal infection caused by ceftazidime-resistant Enterobacteriaceae or Pseudomonas aeruginosa. Patients were randomised (1:1) to 5–21 days of treatment with either ceftazidime-avibactam (a combination of 2000 mg ceftazidime plus 500 mg avibactam, administered via a 2-h intravenous infusion every 8 h) or best available therapy. The primary endpoint was clinical response at the test-of-cure visit, 7–10 days after last infusion of study therapy, analysed in all patients who had at least one ceftazidime-resistant Gram-negative pathogen, as confirmed by the central laboratory, and who received at least one dose of study drug. Safety endpoints were assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01644643. Findings Between Jan 7, 2013, and Aug 29, 2014, 333 patients were randomly assigned, 165 to ceftazidime-avibactam and 168 to best available therapy. Of these, 154 assigned to ceftazidime-avibactam (144 with complicated urinary tract infection and ten with complicated intra-abdominal infection) and 148 assigned to best available therapy (137 with complicated urinary tract infection and 11 with complicated intra-abdominal infection) were analysed for the primary outcome. 163 (97%) of 168 patients in the best available therapy group received a carbapenem, 161 (96%) as monotherapy. The overall proportions of patients with a clinical cure at the test-of-cure visit were similar with ceftazidime-avibactam (140 [91%; 95% CI 85·6–94·7] of 154 patients) and best available therapy (135 [91%; 85·9–95·0] of 148 patients). 51 (31%) of 164 patients in the ceftazidime-avibactam group and 66 (39%) of 168 in the best available therapy group had an adverse event, most of which were mild or moderate in intensity. Gastrointestinal disorders were the most frequently reported treatment-emergent adverse events with both ceftazidime-avibactam (21 [13%] of 164 patients) and best available therapy (30 [18%] of 168 patients). No new safety concerns were identified for ceftazidime-avibactam. Interpretation These results provide evidence of the efficacy of ceftazidime-avibactam as a potential alternative to carbapenems in patients with ceftazidime-resistant Enterobacteriaceae and P aeruginosa. Funding AstraZeneca

The PER model of abstract non-interference

Abstract. In this paper, we study the relationship between two models of secure information flow: the PER model (which uses equivalence relations) and the abstract non-interference model (which uses upper closure operators). We embed the lattice of equivalence relations into the lattice of closures, re-interpreting abstract non-interference over the lattice of equivalence relations. For narrow abstract non-interference, we show non-interference it is strictly less general. The relational presentation of abstract non-interference leads to a simplified construction of the most concrete harmless attacker. Moreover, the PER model of abstract noninterference allows us to derive unconstrained attacker models, which do not necessarily either observe all public information or ignore all private information. Finally, we show how abstract domain completeness can be used for enforcing the PER model of abstract non-interference

Circular and leakage resilient public-key encryption under subgroup indistinguishability (or: Quadratic residuosity strikes back)

30th Annual Cryptology Conference, Santa Barbara, CA, USA, August 15-19, 2010. ProceedingsThe main results of this work are new public-key encryption schemes that, under the quadratic residuosity (QR) assumption (or Paillier’s decisional composite residuosity (DCR) assumption), achieve key-dependent message security as well as high resilience to secret key leakage and high resilience to the presence of auxiliary input information. In particular, under what we call the subgroup indistinguishability assumption, of which the QR and DCR are special cases, we can construct a scheme that has: • Key-dependent message (circular) security. Achieves security even when encrypting affine functions of its own secret key (in fact, w.r.t. affine “key-cycles” of predefined length). Our scheme also meets the requirements for extending key-dependent message security to broader classes of functions beyond affine functions using previous techniques of Brakerski et al. or Barak et al. • Leakage resiliency. Remains secure even if any adversarial low-entropy (efficiently computable) function of the secret key is given to the adversary. A proper selection of parameters allows for a “leakage rate” of (1 − o(1)) of the length of the secret key. • Auxiliary-input security. Remains secure even if any sufficiently hard to invert (efficiently computable) function of the secret key is given to the adversary. Our scheme is the first to achieve key-dependent security and auxiliary-input security based on the DCR and QR assumptions. Previous schemes that achieved these properties relied either on the DDH or LWE assumptions. The proposed scheme is also the first to achieve leakage resiliency for leakage rate (1 − o(1)) of the secret key length, under the QR assumption. We note that leakage resilient schemes under the DCR and the QR assumptions, for the restricted case of composite modulus product of safe primes, were implied by the work of Naor and Segev, using hash proof systems. However, under the QR assumption, known constructions of hash proof systems only yield a leakage rate of o(1) of the secret key length.Microsoft Researc

Plucked human hair as a tissue in which to assess pharmacodynamic end points during drug development studies

We have demonstrated the feasibility of detecting and quantifying six cell-cycle-related nuclear markers (Ki67, pRb, p27, phospho-p27 (phosphorylated p27), phospho-pRb (phosphorylated pRb), phospho-HH3 (phosphorylated histone H3)) in plucked human scalp and eyebrow hair. Estimates of the proportion of plucked hairs that are lost or damaged during processing plus the intra- and intersubject variability of each nuclear marker with these techniques are provided to inform sizing decisions for intervention studies with drugs potentially impacting on these markers in the future

Assessing proliferation, cell-cycle arrest and apoptotic end points in human buccal punch biopsies for use as pharmacodynamic biomarkers in drug development

Easily accessible normal tissues expressing the same molecular site(s) of drug action as malignant tissue offer an enhanced potential for early proof of anticancer drug mechanism and estimation of the biologically effective dose. Studies were undertaken in healthy male volunteers to assess the tolerability of single and multiple (four in 24 h) 3 mm punch biopsies of the buccal mucosa, and to determine the feasibility of detecting and quantifying a range of proliferation, cell-cycle arrest and apoptosis markers by immunohistochemistry (IHC) for use as potential pharmacodynamic (PD) end points. The biopsy procedure was well tolerated with 100% of volunteers stating that they would undergo single (n=10) and multiple (n=12) biopsies again. Total retinoblastoma protein (pRb), phosphorylated pRb (phospho-pRb), total p27, phosphorylated p27 (phospho-p27), phosphorylated-histone H3 (phospho-HH3), p21, p53, Cyclin A, Cyclin E, Ki67 all produced good signal detection, but M30, cleaved caspase 3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling did not. Total pRb, phospho-pRb, total p27 and phospho-p27 were quantified further in a multiple biopsy study to allow components of variability to be addressed to inform future sizing decisions on intervention studies. Neither site of biopsy within the oral cavity, nor the nominal time of biopsy had any significant impact on any of the four markers expression levels. Inter- and intrasubject coefficients of variation (CVs) that could be used to size future intervention studies for pRb, phospho-pRb, total p27 and phospho-p27 were 14, 19, 18 and 16%; and 18, 29, 25 and 19%, respectively. In conclusion, quantitation of such markers in 3 mm buccal punch biopsies would be suitable to explore as PD end points within intervention studies of drugs acting on these pathways

Bayesian Mode Regression

This article has been made available through the Brunel Open Access Publishing Fund.Like mean, quantile and variance, mode is also an important measure of central tendency of a distribution. Many practical questions, particularly in the analysis of big data, such as \Which element (gene or le or signal) is the most typical one among all elements in a network?" are directly related to mode. Mode regression, which provides a convenient summary of how the regressors a ect the conditional mode, is totally di erent from other models based on conditional mean or conditional quantile or conditional variance. Some inference methods for mode regression exist but none of them is from the Bayesian perspective. This paper introduces Bayesian mode regression by exploring three different approaches, including their theoretic properties. The proposed approacher are illustrated using simulated datasets and a real data set

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16INK4a and p14ARF. Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene

Dose-effect study of Gelsemium sempervirens in high dilutions on anxiety-related responses in mice

Introduction This study was designed to investigate the putative anxiolytic-like activity of ultra-low doses of Gelsemium sempervirens (G. sempervirens), produced according to the homeopathic pharmacopeia. Methods Five different centesimal (C) dilutions of G. sempervirens (4C, 5C, 7C, 9C and 30C), the drug buspirone (5 mg/kg) and solvent vehicle were delivered intraperitoneally to groups of ICR-CD1 mice over a period of 9 days. The behavioral effects were assessed in the open-field (OF) and light\u2013dark (LD) tests in blind and randomized fashion. Results Most G. sempervirens dilutions did not affect the total distance traveled in the OF (only the 5C had an almost significant stimulatory effect on this parameter), indicating that the medicine caused no sedation effects or unspecific changes in locomotor activity. In the same test, buspirone induced a slight but statistically significant decrease in locomotion. G. sempervirens showed little stimulatory activity on the time spent and distance traveled in the central zone of the OF, but this effect was not statistically significant. In the LD test, G. sempervirens increased the % time spent in the light compartment, an indicator of anxiolytic-like activity, with a statistically significant effect using the 5C, 9C and 30C dilutions. These effects were comparable to those of buspirone. The number of transitions between the compartments of the LD test markedly increased with G. sempervirens 5C, 9C and 30C dilutions. Conclusion The overall pattern of results provides evidence that G. sempervirens acts on the emotional reactivity of mice, and that its anxiolytic-like effects are apparent, with a non-linear relationship, even at high dilutions