Precise Null Pointer Analysis Through Global Value Numbering

Precise analysis of pointer information plays an important role in many static analysis techniques and tools today. The precision, however, must be balanced against the scalability of the analysis. This paper focusses on improving the precision of standard context and flow insensitive alias analysis algorithms at a low scalability cost. In particular, we present a semantics-preserving program transformation that drastically improves the precision of existing analyses when deciding if a pointer can alias NULL. Our program transformation is based on Global Value Numbering, a scheme inspired from compiler optimizations literature. It allows even a flow-insensitive analysis to make use of branch conditions such as checking if a pointer is NULL and gain precision. We perform experiments on real-world code to measure the overhead in performing the transformation and the improvement in the precision of the analysis. We show that the precision improves from 86.56% to 98.05%, while the overhead is insignificant.Comment: 17 pages, 1 section in Appendi

Propagation of an Earth-directed coronal mass ejection in three dimensions

Solar coronal mass ejections (CMEs) are the most significant drivers of adverse space weather at Earth, but the physics governing their propagation through the heliosphere is not well understood. While stereoscopic imaging of CMEs with the Solar Terrestrial Relations Observatory (STEREO) has provided some insight into their three-dimensional (3D) propagation, the mechanisms governing their evolution remain unclear due to difficulties in reconstructing their true 3D structure. Here we use a new elliptical tie-pointing technique to reconstruct a full CME front in 3D, enabling us to quantify its deflected trajectory from high latitudes along the ecliptic, and measure its increasing angular width and propagation from 2-46 solar radii (approximately 0.2 AU). Beyond 7 solar radii, we show that its motion is determined by an aerodynamic drag in the solar wind and, using our reconstruction as input for a 3D magnetohydrodynamic simulation, we determine an accurate arrival time at the Lagrangian L1 point near Earth.Comment: 5 figures, 2 supplementary movie

The role of lumbar puncture in children with suspected central nervous system infection

BACKGROUND: The use of the lumbar puncture in the diagnosis of central nervous system infection in acutely ill children is controversial. Recommendations have been published but it is unclear whether they are being followed. METHODS: The medical case notes of 415 acute medical admissions in a children's hospital were examined to identify children with suspected central nervous system infection and suspected meningococcal septicaemia. We determined whether lumbar punctures were indicated or contraindicated, whether they had been performed, and whether the results contributed to the patients' management. RESULTS: Fifty-two children with suspected central nervous system infections, and 43 with suspected meningococcal septicaemia were identified. No lumbar punctures were performed in patients with contraindications, but only 25 (53%) of 47 children with suspected central nervous system infection and no contraindications received a lumbar puncture. Lumbar puncture findings contributed to the management in 18 (72%) of these patients, by identifying a causative organism or excluding bacterial meningitis. CONCLUSION: The recommendations for undertaking lumbar punctures in children with suspected central nervous system infection are not being followed because many children that should receive lumbar punctures are not getting them. When they are performed, lumbar puncture findings make a useful contribution to the patients' management

An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

Illness perceptions and explanatory models of viral hepatitis B & C among immigrants and refugees: a narrative systematic review.

© 2015 Owiti et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.BACKGROUND: Hepatitis B and C (HBV, HCV) infections are associated with high morbidity and mortality. Many countries with traditionally low prevalence (such as UK) are now planning interventions (screening, vaccination, and treatment) of high-risk immigrants from countries with high prevalence. This review aimed to synthesise the evidence on immigrants' knowledge of HBV and HCV that might influence the uptake of clinical interventions. The review was also used to inform the design and successful delivery of a randomised controlled trial of targeted screening and treatment. METHODS: Five databases (PubMed, CINHAL, SOCIOFILE, PsycINFO & Web of Science) were systematically searched, supplemented by reference tracking, searches of selected journals, and of relevant websites. We aimed to identify qualitative and quantitative studies that investigated knowledge of HBV and HCV among immigrants from high endemic areas to low endemic areas. Evidence, extracted according to a conceptual framework of Kleinman's explanatory model, was subjected to narrative synthesis. We adapted the PEN-3 model to categorise and analyse themes, and recommend strategies for interventions to influence help-seeking behaviour. RESULTS: We identified 51 publications including quantitative (n = 39), qualitative (n = 11), and mixed methods (n = 1) designs. Most of the quantitative studies included small samples and had heterogeneous methods and outcomes. The studies mainly concentrated on hepatitis B and ethnic groups of South East Asian immigrants residing in USA, Canada, and Australia. Many immigrants lacked adequate knowledge of aetiology, symptoms, transmission risk factors, prevention strategies, and treatment, of hepatitis HBV and HCV. Ethnicity, gender, better education, higher income, and English proficiency influenced variations in levels and forms of knowledge. CONCLUSION: Immigrants are vulnerable to HBV and HCV, and risk life-threatening complications from these infections because of poor knowledge and help-seeking behaviour. Primary studies in this area are extremely diverse and of variable quality precluding meta-analysis. Further research is needed outside North America and Australia

Oligomerization of the E. coli Core RNA Polymerase: Formation of (α2ββ'ω)2–DNA Complexes and Regulation of the Oligomerization by Auxiliary Subunits

In this work, using multiple, dissimilar physico-chemical techniques, we demonstrate that the Escherichia coli RNA polymerase core enzyme obtained through a classic purification procedure forms stable (α2ββ'ω)2 complexes in the presence or absence of short DNA probes. Multiple control experiments indicate that this self-association is unlikely to be mediated by RNA polymerase-associated non-protein molecules. We show that the formation of (α2ββ'ω)2 complexes is subject to regulation by known RNA polymerase interactors, such as the auxiliary SWI/SNF subunit of RNA polymerase RapA, as well as NusA and σ70. We also demonstrate that the separation of the core RNA polymerase and RNA polymerase holoenzyme species during Mono Q chromatography is likely due to oligomerization of the core enzyme. We have analyzed the oligomeric state of the polymerase in the presence or absence of DNA, an aspect that was missing from previous studies. Importantly, our work demonstrates that RNA polymerase oligomerization is compatible with DNA binding. Through in vitro transcription and in vivo experiments (utilizing a RapAR599/Q602 mutant lacking transcription-stimulatory function), we demonstrate that the formation of tandem (α2ββ'ω)2–DNA complexes is likely functionally significant and beneficial for the transcriptional activity of the polymerase. Taken together, our findings suggest a novel structural aspect of the E. coli elongation complex. We hypothesize that transcription by tandem RNA polymerase complexes initiated at hypothetical bidirectional “origins of transcription” may explain recurring switches of the direction of transcription in bacterial genomes

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD

The role of cranial CT in the investigation of meningitis

More patients with meningitis are undergoing CT and the number of inappropriate requests are increasing. There are few abnormal CT scans presenting a contraindication for lumbar puncture and the majority of these patients usually have clinical signs to suggest raised intracranial pressure

Towards successful coordination of electronic health record based-referrals: a qualitative analysis

<p>Abstract</p> <p>Background</p> <p>Successful subspecialty referrals require considerable coordination and interactive communication among the primary care provider (PCP), the subspecialist, and the patient, which may be challenging in the outpatient setting. Even when referrals are facilitated by electronic health records (EHRs) (<it>i.e</it>., e-referrals), lapses in patient follow-up might occur. Although compelling reasons exist why referral coordination <it>should </it>be improved, little is known about which elements of the complex referral coordination process should be targeted for improvement. Using Okhuysen & Bechky's coordination framework, this paper aims to understand the barriers, facilitators, and suggestions for improving communication and coordination of EHR-based referrals in an integrated healthcare system.</p> <p>Methods</p> <p>We conducted a qualitative study to understand coordination breakdowns related to e-referrals in an integrated healthcare system and examined work-system factors that affect the timely receipt of subspecialty care. We conducted interviews with seven subject matter experts and six focus groups with a total of 30 PCPs and subspecialists at two tertiary care Department of Veterans Affairs (VA) medical centers. Using techniques from grounded theory and content analysis, we identified organizational themes that affected the referral process.</p> <p>Results</p> <p>Four themes emerged: lack of an institutional referral policy, lack of standardization in certain referral procedures, ambiguity in roles and responsibilities, and inadequate resources to adapt and respond to referral requests effectively. Marked differences in PCPs' and subspecialists' communication styles and individual mental models of the referral processes likely precluded the development of a <it>shared </it>mental model to facilitate coordination and successful referral completion. Notably, very few barriers related to the EHR were reported.</p> <p>Conclusions</p> <p>Despite facilitating information transfer between PCPs and subspecialists, e-referrals remain prone to coordination breakdowns. Clear referral policies, well-defined roles and responsibilities for key personnel, standardized procedures and communication protocols, and adequate human resources must be in place before implementing an EHR to facilitate referrals.</p