Towards Understanding and Harnessing the Potential of Clause Learning

Efficient implementations of DPLL with the addition of clause learning are the fastest complete Boolean satisfiability solvers and can handle many significant real-world problems, such as verification, planning and design. Despite its importance, little is known of the ultimate strengths and limitations of the technique. This paper presents the first precise characterization of clause learning as a proof system (CL), and begins the task of understanding its power by relating it to the well-studied resolution proof system. In particular, we show that with a new learning scheme, CL can provide exponentially shorter proofs than many proper refinements of general resolution (RES) satisfying a natural property. These include regular and Davis-Putnam resolution, which are already known to be much stronger than ordinary DPLL. We also show that a slight variant of CL with unlimited restarts is as powerful as RES itself. Translating these analytical results to practice, however, presents a challenge because of the nondeterministic nature of clause learning algorithms. We propose a novel way of exploiting the underlying problem structure, in the form of a high level problem description such as a graph or PDDL specification, to guide clause learning algorithms toward faster solutions. We show that this leads to exponential speed-ups on grid and randomized pebbling problems, as well as substantial improvements on certain ordering formulas

Energy-efficient precoding in multicell networks with full-duplex base stations

© 2017, The Author(s). This paper considers multi-input multi-output (MIMO) multicell networks, where the base stations (BSs) are full-duplex transceivers, while uplink and downlink users are equipped with multiple antennas and operate in a half-duplex mode. The problem of interest is to design linear precoders for BSs and users to optimize the network’s energy efficiency. Given that the energy efficiency objective is not a ratio of concave and convex functions, the commonly used Dinkelbach-type algorithms are not applicable. We develop a low-complexity path-following algorithm that only invokes one simple convex quadratic program at each iteration, which converges at least to the local optimum. Numerical results demonstrate the performance advantage of our proposed algorithm in terms of energy efficiency

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity.

Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation

Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe

Consent for orthopaedic trauma surgery during the COVID-19 pandemic

INTRODUCTION: The COVID-19 pandemic has brought a series of new challenges to the management of surgical patients. The consent process relies on a foundation of open and non-coerced discussion between clinician and patient, which includes all the potential risks of surgery. This must be updated to incorporate the additional risks of surgery during the pandemic including infection with the SARS-CoV-2 and increased risks of complications with the potential requirement for intensive care support. AIM: The aim of this multi-cycle quality improvement project was to ensure all patients were fully informed of the risks of developing COVID-19 and the possible need for intensive care unit (ICU) support. METHODS: We investigated the quality of the consent process for patients undergoing surgery for trauma at our major trauma centre. Our baseline data collection included a review of all orthopaedic trauma consent forms over a 4-week period in March 2020. We subsequently undertook three further Plan-Do-Study-Act (PDSA) cycles over separate 4-week periods. First, in June 2020, after education measures and presentation of baseline data, second in July 2020 after further education and regular digital reminders were sent to staff, and third in September 2021 after the implementation of an electronic consent form. RESULTS: At baseline, only 2.6% of consent forms mentioned the risk of COVID-19 and none mentioned the risk of requiring ITU support. Through three PDSA cycles this increased to 97% of cases where consent forms displayed the additional risks of COVID-19 and the potential need for ITU admission. CONCLUSION: Our quality improvement project improved the informed consent procedure at our trust. By incorporating these additional risks into the template of an electronic consent form, we hope to achieve sustained improvement in practice

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Long-Term Immune Response to SARS-CoV-2 Infection and Vaccination in Children and Adolescents

BACKGROUND: This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents. METHODS: Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed. RESULTS: N antibody levels reached a median of 84.10 U/ml (IQR: 20.2, 157.7) cutoff index (COI) ~ 6 months post-infection and increased slightly to a median of 85.25 (IQR: 28.0, 143.0) COI at 12 months post-infection. Peak S antibody levels were reached at a median of 2500 U/mL ~6 months post-vaccination and remained for ~12 months (mean 11.6 months, SD 1.20). CONCLUSIONS: This analysis provides evidence of robust durability of nucleocapsid and spike antibodies in a large pediatric sample up to 12 months post-infection/vaccination. This information can inform pediatric SARS-CoV-2 vaccination schedules. IMPACT: This study provided evidence of robust durability of both nucleocapsid and spike antibodies in a large pediatric sample up to 12 months after infection. Little is known about the long-term durability of natural and vaccine-induced SARS-CoV-2 antibodies in the pediatric population. Here, we determined the durability of anti-SARS-CoV-2 spike (S-test) and nucleocapsid protein (N-test) in children/adolescents after SARS-CoV-2 infection and/or vaccination lasts at least up to 12 months. This information can inform future SARS-CoV-2 vaccination schedules in this age group