Honest Majority Multi-Prover Interactive Arguments

Interactive arguments, and their (succinct) non-interactive and zero-knowledge counterparts, have seen growing deployment in real world applications in recent years. Unfortunately, for large and complex statements, concrete proof generation costs can still be quite expensive. While recent work has sought to solve this problem by outsourcing proof computation to a group of workers in a privacy preserving manner, current solutions still require each worker to do work on roughly the same order as a single-prover solution. We introduce the Honest Majority Multi-Prover (HMMP) model for interactive arguments. In these arguments, we distribute prover computation among $M$ collaborating, but distrusting, provers. All provers receive the same inputs and have no private inputs, and we allow any $t < M/2$ provers to be statically corrupted before generation of public parameters, and all communication is done via an authenticated broadcast channel. In contrast with the recent works of Ozdemir and Boneh (USENIX \u2722) and Dayama et al. (PETS \u2722), we target prover efficiency over privacy. We show that: (1) any interactive argument where the prover computation is suitably divisible into $M$ sub-computations can be transformed into an interactive argument in the HMMP model; and (2) arguments that are obtained via compiling polynomial interactive oracle proofs with polynomial commitment schemes admit HMMP model constructions that experience a (roughly) $1/M$ speedup over a single-prover solution. The transformation of (1) preserves computational (knowledge) soundness, zero-knowledge, and can be made non-interactive via the Fiat-Shamir transformation. The constructions of (2) showcase that there are efficiency gains in proof distribution when privacy is not a concern

Effects of Spinal Fusion for Idiopathic Scoliosis on Lower Body Kinematics During Gait

Objectives The purpose of this study was to compare gait among patients with scoliosis undergoing posterior spinal fusion and instrumentation (PSFI) to typically developing subjects and determine if the location of the lowest instrumented vertebra impacted results. Summary of Background Data PSFI is the standard of care for correcting spine deformities, allowing the preservation of body equilibrium while maintaining as many mobile spinal segments as possible. The effect of surgery on joint motion distal to the spine must also be considered. Very few studies have addressed the effect of PSFI on activities such as walking and even fewer address how surgical choice of the lowest instrumented vertebra (LIV) influences possible motion reduction. Methods Individuals with scoliosis undergoing PSFI (n = 38) completed gait analysis preoperatively and at postoperative years 1 and 2 along with a control group (n = 24). Comparisons were made with the control group at each time point and between patients fused at L2 and above (L2+) versus L3 and below (L3–). Results The kinematic results of the AIS group showed some differences when compared to the Control Group, most notably decreased range of motion (ROM) in pelvic tilt and trunk lateral bending. When comparing the LIV groups, only minor differences were observed, and the results showed decreased coronal trunk and pelvis ROM at the one-year visit and decreased hip rotation ROM at the two-year visit in the L3– group. Conclusions Patients with AIS showed decreased ROM preoperatively with further decreases postoperatively. These changes remained relatively consistent following the two-year visit, indicating that most kinematic changes occurred in the first year following surgery. Limited functional differences between the two LIV groups may be due to the lack of full ROM used during normal gait, and future work could address tasks that use greater ROM

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Gait Deviations in Children With Osteogenesis Imperfecta Type I

Background: Osteogenesis imperfecta (OI) is a congenital connective tissue disorder often characterized by orthopaedic complications that impact normal gait. As such, mobility is of particular interest in the OI population as it is associated with multiple aspects of participation and quality of life. The purpose of the current study was to identify and describe common gait deviations in a large sample of individuals with type I OI and speculate the etiology with a goal of improving function. Methods: Gait analysis was performed on 44 subjects with type I (11.7±3.08 y old) and 30 typically developing controls (9.54±3.1 y old ). Spatial temporal, kinematic, and kinetic gait data were calculated from the Vicon Plug-in-Gait Model. Musculoskeletal modeling of the muscle tendon lengths (MTL) was done in OpenSim 3.3 to evaluate the MTL of the gastrocnemius and gluteus maximus. The gait deviation index, a dimensionless parameter that evaluates the deviation of 9 kinematic gait parameters from a control database, was also calculated. Results: Walking speed, single support time, stride, and step length were lower and double support time was higher in the OI group. The gait deviation index score was lower and external hip rotation angle was higher in the OI group. Peak hip flexor, knee extensor and ankle plantarflexor moments, and power generation at the ankle were lower in the OI group. MTL analysis revealed no significant length discrepancies between the OI group and the typically developing group. Conclusions: Together, these findings provide a comprehensive description of gait characteristics among a group of individuals with type I OI. Such data inform clinicians about specific gait deviations in this population allowing clinicians to recommend more focused interventions. Level of Evidence: Level III—case-control study

Genomic characterization and phylogenetic analysis of Salmonella enterica serovar Javiana

Salmonella enterica serovar Javiana is the fourth most reported serovar of laboratory-confirmed human Salmonella infections in the U.S. and in Tennessee (TN). Although Salmonella ser. Javiana is a common cause of human infection, the majority of cases are sporadic in nature rather than outbreak-associated. To better understand Salmonella ser. Javiana microbial population structure in TN, we completed a phylogenetic analysis of 111 Salmonella ser. Javiana clinical isolates from TN collected from Jan. 2017 to Oct. 2018. We identified mobile genetic elements and genes known to confer antibiotic resistance present in the isolates, and performed a pan-genome-wide association study (pan-GWAS) to compare gene content between clades identified in this study. The population structure of TN Salmonella ser. Javiana clinical isolates consisted of three genetic clades: TN clade I (n = 54), TN clade II (n = 4), and TN clade III (n = 48). Using a 5, 10, and 25 hqSNP distance threshold for cluster identification, nine, 12, and 10 potential epidemiologically-relevant clusters were identified, respectively. The majority of genes that were found to be over-represented in specific clades were located in mobile genetic element (MGE) regions, including genes encoding integrases and phage structures (91.5%). Additionally, a large portion of the over-represented genes from TN clade II (44.9%) were located on an 87.5 kb plasmid containing genes encoding a toxin/antitoxin system (ccdAB). Additionally, we completed phylogenetic analyses of global Salmonella ser. Javiana datasets to gain a broader insight into the population structure of this serovar. We found that the global phylogeny consisted of three major clades (one of which all of the TN isolates belonged to) and two cgMLST eBurstGroups (ceBGs) and that the branch length between the two Salmonella ser. Javiana ceBGs (1,423 allelic differences) was comparable to those from other serovars that have been reported as polyphyletic (929–2,850 allelic differences). This study demonstrates the population structure of TN and global Salmonella ser. Javiana isolates, a clinically important Salmonella serovar and can provide guidance for phylogenetic cluster analyses for public health surveillance and response

Insufficient Anthrax Lethal Toxin Neutralization Is Associated with Antibody Subclass and Domain Specificity in the Plasma of Anthrax-Vaccinated Individuals

Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from Bacillus anthracis spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing, and/or antibody titers that wane over time, necessitating annual boosters. To study individuals with such poor responses, we examine the properties of anti-PA in a subset of vaccinated individuals that make significant quantities of antibody but are still unable to neutralize toxin. In this cohort, characterized by poorly neutralizing antibody, we find that increased IgG4 to IgG1 subclass ratios, low antibody avidity, and insufficient antibody targeting domain 4 associate with improper neutralization. Thus, future vaccines and vaccination schedules should be formulated to improve these deficiencies

Phylogenetic Analysis Reveals Source Attribution Patterns for Campylobacter spp. in Tennessee and Pennsylvania

Campylobacteriosis is the most common bacterial foodborne illness in the United States and is frequently associated with foods of animal origin. The goals of this study were to compare clinical and non-clinical Campylobacter populations from Tennessee (TN) and Pennsylvania (PA), use phylogenetic relatedness to assess source attribution patterns, and identify potential outbreak clusters. Campylobacter isolates studied (n = 3080) included TN clinical isolates collected and sequenced for routine surveillance, PA clinical isolates collected from patients at the University of Pennsylvania Health System facilities, and non-clinical isolates from both states for which sequencing reads were available on NCBI. Phylogenetic analyses were conducted to categorize isolates into species groups and determine the population structure of each species. Most isolates were C. jejuni (n = 2132, 69.2%) and C. coli (n = 921, 29.9%), while the remaining were C. lari (0.4%), C. upsaliensis (0.3%), and C. fetus (0.1%). The C. jejuni group consisted of three clades; most non-clinical isolates were of poultry (62.7%) or cattle (35.8%) origin, and 59.7 and 16.5% of clinical isolates were in subclades associated with poultry or cattle, respectively. The C. coli isolates grouped into two clades; most non-clinical isolates were from poultry (61.2%) or swine (29.0%) sources, and 74.5, 9.2, and 6.1% of clinical isolates were in subclades associated with poultry, cattle, or swine, respectively. Based on genomic similarity, we identified 42 C. jejuni and one C. coli potential outbreak clusters. The C. jejuni clusters contained 188 clinical isolates, 19.6% of the total C. jejuni clinical isolates, suggesting that a larger proportion of campylobacteriosis may be associated with outbreaks than previously determined

Phylogenetic Analysis Reveals Source Attribution Patterns for <i>Campylobacter</i> spp. in Tennessee and Pennsylvania

Campylobacteriosis is the most common bacterial foodborne illness in the United States and is frequently associated with foods of animal origin. The goals of this study were to compare clinical and non-clinical Campylobacter populations from Tennessee (TN) and Pennsylvania (PA), use phylogenetic relatedness to assess source attribution patterns, and identify potential outbreak clusters. Campylobacter isolates studied (n = 3080) included TN clinical isolates collected and sequenced for routine surveillance, PA clinical isolates collected from patients at the University of Pennsylvania Health System facilities, and non-clinical isolates from both states for which sequencing reads were available on NCBI. Phylogenetic analyses were conducted to categorize isolates into species groups and determine the population structure of each species. Most isolates were C. jejuni (n = 2132, 69.2%) and C. coli (n = 921, 29.9%), while the remaining were C. lari (0.4%), C. upsaliensis (0.3%), and C. fetus (0.1%). The C. jejuni group consisted of three clades; most non-clinical isolates were of poultry (62.7%) or cattle (35.8%) origin, and 59.7 and 16.5% of clinical isolates were in subclades associated with poultry or cattle, respectively. The C. coli isolates grouped into two clades; most non-clinical isolates were from poultry (61.2%) or swine (29.0%) sources, and 74.5, 9.2, and 6.1% of clinical isolates were in subclades associated with poultry, cattle, or swine, respectively. Based on genomic similarity, we identified 42 C. jejuni and one C. coli potential outbreak clusters. The C. jejuni clusters contained 188 clinical isolates, 19.6% of the total C. jejuni clinical isolates, suggesting that a larger proportion of campylobacteriosis may be associated with outbreaks than previously determined