Showing papers by "Memorial University of Newfoundland published in 2015"

Minimum Information about a Biosynthetic Gene cluster.

Abstract: A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.

The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

Abstract: The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

Whole-genome sequencing of quartet families with autism spectrum disorder

Abstract: Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for hundreds of susceptibility loci. Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics.

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder

Abstract: Importance The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. Objective To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. Design, Setting, and Participants The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). Exposures All probands underwent CMA, with WES performed for 95 proband-parent trios. Main Outcomes and Measures The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. Results Of 258 probands, 24 (9.3%, 95% CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95% CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. For CMA, the proportion of children with a positive test result was 7 of 168 (4.2%, 95% CI, 1.7%-8.4%) in the essential group, 4 of 37 (10.8%, 95% CI, 3.0%-25.4%) in the equivocal group, and 13 of 53 (24.5%, 95% CI, 13.8%-38.3%) in the complex group ( P P = .02). Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95% CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined molecular diagnostic yield was 6.3% (95% CI, 1.7%-15.2%) in the essential group (4/64 children), 28.6% (95% CI, 3.7%-71.0%) in the equivocal group (2/7 children), and 37.5% (95% CI, 18.8%-59.4%) in the complex group (9/24 children; 3-group comparison, P = .001). The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). Conclusions and Relevance Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.

Reinventing residual reserves in the sea: are we favouring ease of establishment over need for protection?

Abstract: As systems of marine protected areas (MPAs) expand globally, there is a risk that new MPAs will be biased toward places that are remote or unpromising for extractive activities, and hence follow the trend of terrestrial protected areas in being ‘residual’ to commercial uses. Such locations typically provide little protection to the species and ecosystems that are most exposed to threatening processes. There are strong political motivations to establish residual reserves that minimize costs and conflicts with users of natural resources. These motivations will likely remain in place as long as success continues to be measured in terms of area (km2) protected. The global pattern of MPAs was reviewed and appears to be residual, supported by a rapid growth of large, remote MPAs. The extent to which MPAs in Australia are residual nationally and also regionally within the Great Barrier Reef (GBR) Marine Park was also examined. Nationally, the recently announced Australian Commonwealth marine reserves were found to be strongly residual, making almost no difference to ‘business as usual’ for most ocean uses. Underlying this result was the imperative to minimize costs, but without the spatial constraints of explicit quantitative objectives for representing bioregions or the range of ecological features in highly protected zones. In contrast, the 2004 rezoning of the GBR was exemplary, and the potential for residual protection was limited by applying a systematic set of planning principles, such as representing a minimum percentage of finely subdivided bioregions. Nonetheless, even at this scale, protection was uneven between bioregions. Within-bioregion heterogeneity might have led to no-take zones being established in areas unsuitable for trawling with a risk that species assemblages differ between areas protected and areas left available for trawling. A simple four-step framework of questions for planners and policy makers is proposed to help reverse the emerging residual tendency of MPAs and maximize their effectiveness for conservation. This involves checks on the least-cost approach to establishing MPAs in order to avoid perverse outcomes. © 2014 The Authors. Aquatic Conservation: Marine and Freshwater Ecosystems published by John Wiley & Sons, Ltd.

Barriers to Goals of Care Discussions With Seriously Ill Hospitalized Patients and Their Families: A Multicenter Survey of Clinicians

Abstract: Importance Seriously ill hospitalized patients have identified communication and decision making about goals of care as high priorities for quality improvement in end-of-life care. Interventions to improve care are more likely to succeed if tailored to existing barriers. Objective To determine, from the perspective of hospital-based clinicians, (1) barriers impeding communication and decision making about goals of care with seriously ill hospitalized patients and their families and (2) their own willingness and the acceptability for other clinicians to engage in this process. Design, Setting, and Participants Multicenter survey of medical teaching units of nurses, internal medicine residents, and staff physicians from participating units at 13 university-based hospitals from 5 Canadian provinces. Main Outcomes and Measures Importance of 21 barriers to goals of care discussions rated on a 7-point scale (1 = extremely unimportant; 7 = extremely important). Results Between September 2012 and March 2013, questionnaires were returned by 1256 of 1617 eligible clinicians, for an overall response rate of 77.7% (512 of 646 nurses [79.3%], 484 of 634 residents [76.3%], 260 of 337 staff physicians [77.2%]). The following family member–related and patient-related factors were consistently identified by all 3 clinician groups as the most important barriers to goals of care discussions: family members’ or patients’ difficulty accepting a poor prognosis (mean [SD] score, 5.8 [1.2] and 5.6 [1.3], respectively), family members’ or patients’ difficulty understanding the limitations and complications of life-sustaining treatments (5.8 [1.2] for both groups), disagreement among family members about goals of care (5.8 [1.2]), and patients’ incapacity to make goals of care decisions (5.6 [1.2]). Clinicians perceived their own skills and system factors as less important barriers. Participants viewed it as acceptable for all clinician groups to engage in goals of care discussions—including a role for advance practice nurses, nurses, and social workers to initiate goals of care discussions and be a decision coach. Conclusions and Relevance Hospital-based clinicians perceive family member–related and patient-related factors as the most important barriers to goals of care discussions. All health care professionals were viewed as playing important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication and decision making about goals of care.

Embracing Tensions in Corporate Sustainability A Review of Research From Win-Wins and Trade-Offs to Paradoxes and Beyond

Abstract: Corporate sustainability is rife with tensions as firms seek to balance often divergent economic, social, and environmental goals. To assess how tensions have been addressed in past research and to...

Modelling of pitting corrosion in marine and offshore steel structures – A technical review

Abstract: Corrosion is a major cause of structural deterioration in marine and offshore structures. It affects the life of process equipment and pipelines, and can result in structural failure, leakage, product loss, environmental pollution and the loss of life. Pitting corrosion is regarded as one of the most hazardous forms of corrosion for marine and offshore structures. The total loss of the structure might be very small, but local rate of attack can be very large and can lead to early catastrophic failure. Pitting corrosion is a localized accelerated dissolution of metal that occurs as a result of a breakdown in the protective passive film on the metal surface. It has been studied for many years; however, the structural failure due to pit characteristics is still not fully understood. Accurate pit depth measurements, precise strength assessment techniques, risk analysis due to pitting, and the mathematical relationship of the environmental factors that causes pitting failure are also factors, which need further understanding. Hence this paper focuses on these issues. It reviews and analyses the current understanding of the pitting corrosion mechanism and investigates all possible factors that can cause pitting corrosion. Furthermore, different techniques employed by scientists and researchers to identify and model the pitting corrosion are also reviewed and analysed. Future work should involve an in-depth scientific study of the corrosion mechanism and an engineering predictive model is recommended in order to assess failure, and thereby attempt to increase the remaining life of offshore assets.

Short on Time: Intertemporal Tensions in Business Sustainability

Abstract: This inductive study of five firms in Alberta's oil sands examines how organizations attend to the intertemporal tensions between the short term and long term that are inherent in business sustainability. Grounding our insights in organizational responses to the climate change issue, we find that firms that juxtapose the short term and long term also confront the tension between business and society. These firms are, therefore, more likely to recognize the complexity of climate change and the need for integrated, multidimensional solutions. These insights contribute to prior research in business sustainability.

Foam Rolling for Delayed-Onset Muscle Soreness and Recovery of Dynamic Performance Measures

Abstract: Context: After an intense bout of exercise, foam rolling is thought to alleviate muscle fatigue and soreness (ie, delayed-onset muscle soreness [DOMS]) and improve muscular performance. Potentially, foam rolling may be an effective therapeutic modality to reduce DOMS while enhancing the recovery of muscular performance. Objective: To examine the effects of foam rolling as a recovery tool after an intense exercise protocol through assessment of pressure-pain threshold, sprint time, change-of-direction speed, power, and dynamic strength-endurance. Design: Controlled laboratory study. Setting: University laboratory. Patients or Other Participants: A total of 8 healthy, physically active males (age = 22.1 ± 2.5 years, height = 177.0 ± 7.5 cm, mass = 88.4 ± 11.4 kg) participated. Intervention(s): Participants performed 2 conditions, separated by 4 weeks, involving 10 sets of 10 repetitions of back squats at 60% of their 1-repetition maximum, followed by either no foam rolling or 20 minutes of foam rolling imme...

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1.

Abstract: Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.

CHERI: A Hybrid Capability-System Architecture for Scalable Software Compartmentalization

Abstract: CHERI extends a conventional RISC Instruction-Set Architecture, compiler, and operating system to support fine-grained, capability-based memory protection to mitigate memory-related vulnerabilities in C-language TCBs. We describe how CHERI capabilities can also underpin a hardware-software object-capability model for application compartmentalization that can mitigate broader classes of attack. Prototyped as an extension to the open-source 64-bit BERI RISC FPGA soft-core processor, Free BSD operating system, and LLVM compiler, we demonstrate multiple orders-of-magnitude improvement in scalability, simplified programmability, and resulting tangible security benefits as compared to compartmentalization based on pure Memory-Management Unit (MMU) designs. We evaluate incrementally deployable CHERI-based compartmentalization using several real-world UNIX libraries and applications.

Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

Abstract: Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

A review on the pyrolysis of woody biomass to bio-oil: focus on kinetic models.

Abstract: The thermal decomposition of woody biomass in the absence of oxygen, or pyrolysis, is a series of complex reactions involving hundreds of compounds. The species of residue, form of residue (bark, sawdust, and other residues), age, storage conditions, among other factors, will impact the composition of the residue which in turn impacts the pyrolytic reactions. The reaction rates must be understood to optimize the pyrolysis reactor. However, the determination of intrinsic kinetics in this system is complex (both due to feedstock composition and the nature of reactions at pyrolysis temperatures) and as such the approach has been to use an overall reaction rate or series of simplified reactions. In this study, a review of large scale pyrolysis process units, reactor mathematical models, mechanisms for conversion of woody biomass and overview of heat of pyrolysis is presented. In addition, the presented kinetic models have been compared to experimental data obtained from pyrolysis of different liginocellulosic biomass (i.e. sawdust, bark, and wood chips) in a lab-scale tube furnace reactor, to determine the “best” kinetic model for the fast pyrolysis of sawmill residues. The results show that the chemical percolation devolatilization model (Lewis et al. Energy Fuels 2013; 27:942–953. doi:10.1021/ef3018783) predicts the pyrolysis products most accurately. Furthermore, the competitive model (Chan et al. Fuel 1985; 64:1505–1513. doi:10.1016/0016-2361(85)90364-3) shows very good agreement for bio-oil experimental data. Although the pyrolysis of biomass has been widely investigated in recent decades, the models have some limitations which could limit their application to a broad spectrum of feedstock and pyrolysis operating conditions.

Nonequilibrium clumped isotope signals in microbial methane

Abstract: Methane is a key component in the global carbon cycle, with a wide range of anthropogenic and natural sources. Although isotopic compositions of methane have traditionally aided source identification, the abundance of its multiply substituted "clumped" isotopologues (for example, (13)CH3D) has recently emerged as a proxy for determining methane-formation temperatures. However, the effect of biological processes on methane's clumped isotopologue signature is poorly constrained. We show that methanogenesis proceeding at relatively high rates in cattle, surface environments, and laboratory cultures exerts kinetic control on (13)CH3D abundances and results in anomalously elevated formation-temperature estimates. We demonstrate quantitatively that H2 availability accounts for this effect. Clumped methane thermometry can therefore provide constraints on the generation of methane in diverse settings, including continental serpentinization sites and ancient, deep groundwaters.

The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists

Abstract: Purpose and scope The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translation and development of best practices for clinical genome-wide sequencing for genetic diagnosis of monogenic diseases in Canada; it does not address the clinical application of this technology in other fields such as molecular investigation of cancer or for population screening of healthy individuals. Methods of statement development Two multidisciplinary groups consisting of medical geneticists, clinical laboratory geneticists, genetic counsellors, ethicists, lawyers and genetic researchers were assembled to review existing literature and guidelines on genome-wide sequencing for clinical genetic diagnosis in the context of monogenic diseases, and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. Results and conclusions Recommendations include (1) clinical genome-wide sequencing is an appropriate approach in the diagnostic assessment of a patient for whom there is suspicion of a significant monogenic disease that is associated with a high degree of genetic heterogeneity, or where specific genetic tests have failed to provide a diagnosis; (2) until the benefits of reporting incidental findings are established, we do not endorse the intentional clinical analysis of disease-associated genes other than those linked to the primary indication; and (3) clinicians should provide genetic counselling and obtain informed consent prior to undertaking clinical genome-wide sequencing. Counselling should include discussion of the limitations of testing, likelihood and implications of diagnosis and incidental findings, and the potential need for further analysis to facilitate clinical interpretation, including studies performed in a research setting. These recommendations will be routinely re-evaluated as knowledge of diagnostic and clinical utility of clinical genome-wide sequencing improves. While the document was developed to direct practice in Canada, the applicability of the statement is broader and will be of interest to clinicians and health jurisdictions internationally.

Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study.

Abstract: Background Safe and effective therapies are needed for pediatric patients with psoriasis. Objective The purpose of this study was to evaluate ustekinumab in patients age 12 to 17 years who had moderate-to-severe psoriasis. Methods Patients (n = 110) were randomly assigned to ustekinumab standard dosing (SD; 0.75 mg/kg [≤60 kg], 45 mg [>60-≤100 kg], and 90 mg [>100 kg]) or half-standard dosing (HSD; 0.375 mg/kg [≤60 kg], 22.5 mg [>60-≤100 kg], and 45 mg [>100 kg]) at weeks 0 and 4 and every 12 weeks or placebo at weeks 0 and 4 with crossover to ustekinumab SD or HSD at week 12. Clinical assessments included the proportion of patients achieving a Physician's Global Assessment of cleared/minimal (PGA 0/1), at least 75% improvement in Psoriasis Area and Severity Index (PASI 75), and at least 90% in PASI (PASI 90). Adverse events (AEs) were monitored through week 60. Results At week 12, 67.6% and 69.4% of patients receiving ustekinumab HSD and SD, respectively, achieved PGA 0/1 versus 5.4% for placebo ( P P Limitations The study was small relative to adult trials. Conclusions In this patient population (12–17 years), the standard ustekinumab dose provided response comparable to that in adults with no unexpected AEs through 1 year.

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci.

Abstract: Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susce ...

Resonant scattering of outer zone relativistic electrons by multiband EMIC waves and resultant electron loss time scales

Abstract: To improve our understanding of the role of electromagnetic ion cyclotron (EMIC) waves in radiation belt electron dynamics, we perform a comprehensive analysis of EMIC wave-induced resonant scattering of outer zone relativistic (>0.5 MeV) electrons and resultant electron loss time scales with respect to EMIC wave band, L shell, and wave normal angle model. The results demonstrate that while H+-band EMIC waves dominate the scattering losses of ~1–4 MeV outer zone relativistic electrons, it is He+-band and O+-band waves that prevail over the pitch angle diffusion of ultrarelativistic electrons at higher energies. Given the wave amplitude, EMIC waves at higher L shells tend to resonantly interact with a larger population of outer zone relativistic electrons and drive their pitch angle scattering more efficiently. Obliquity of EMIC waves can reduce the efficiency of wave-induced relativistic electron pitch angle scattering. Compared to the frequently adopted parallel or quasi-parallel model, use of the latitudinally varying wave normal angle model produces the largest decrease in H+-band EMIC wave scattering rates at pitch angles ~5 MeV. At a representative nominal amplitude of 1 nT, EMIC wave scattering produces the equilibrium state (i.e., the lowest normal mode under which electrons at the same energy but different pitch angles decay exponentially on the same time scale) of outer belt relativistic electrons within several to tens of minutes and the following exponential decay extending to higher pitch angles on time scales from <1 min to ~1 h. The electron loss cone can be either empty as a result of the weak diffusion or heavily/fully filled due to approaching the strong diffusion limit, while the trapped electron population at high pitch angles close to 90° remains intact because of no resonant scattering. In this manner, EMIC wave scattering has the potential to deepen the anisotropic distribution of outer zone relativistic electrons by reshaping their pitch angle profiles to “top-hat.” Overall, H+-band and He+-band EMIC waves are most efficient in producing the pitch angle scattering loss of relativistic electrons at ~1–2 MeV. In contrast, the presence of O+-band EMIC waves, while at a smaller occurrence rate, can dominate the scattering loss of 5–10 MeV electrons in the entire region of the outer zone, which should be considered in future modeling of the outer zone relativistic electron dynamics.

Signal identification for emerging intelligent radios: classical problems and new challenges

Abstract: Signal identification, which initially found applications in electronic warfare and spectrum monitoring and surveillance, has been recently considered for commercial communications in the context of software defined and cognitive radios. In this article, I present a snapshot of the status of signal identification algorithms, starting from a general description of maximum likelihood (ML) and feature based (FB) approaches to a more detailed discussion of a practical methodology using cyclostationarity-based features. I discuss the cyclostationarity-based features of various signals and the criteria of decision for their identification, while considering classical problems of identifying single carrier linearly digitally (SCLD) modulated signals, as well as new challenges posed by the identification of orthogonal frequency division multiplexing (OFDM), SC frequency domain equalization (SC-FDE), and multiple-transmit antenna signals. I conclude the article with remarks on practical solutions to signal identification and open research issues.

Presentation and management of osteoporosis presenting in association with pregnancy or lactation.

Abstract: In this review, we summarize our current understanding of the pathophysiology of fragility fractures that occur for the first time during pregnancy and lactation, and provide guidance on appropriate investigations and treatment strategies. Most affected women will have had no prior bone density reading, and so the extent of bone loss that may have occurred during pregnancy or lactation is uncertain. During pregnancy, intestinal calcium absorption doubles in order to meet the fetal demand for calcium, but if maternal intake of calcium is insufficient to meet the combined needs of the mother and baby, the maternal skeleton will undergo resorption during the third trimester. During lactation, several hormonal changes, independent of maternal calcium intake, program a 5–10 % loss of trabecular mineral content in order to provide calcium to milk. After weaning the baby, the maternal skeleton is normally restored to its prior mineral content and strength. This physiological bone resorption during reproduction does not normally cause fractures; instead, women who do fracture are more likely to have additional secondary causes of bone loss and fragility. Transient osteoporosis of the hip may affect one or both femoral heads during pregnancy but it involves localized edema and not skeletal resorption. Case reports have described the use of calcitonin, bisphosphonates, strontium ranelate, teriparatide, vertebroplasty, and kyphoplasty to treat post-partum vertebral fractures. However, the need for such treatments is uncertain given that a progressive increase in bone mass subsequently occurs in most women who present with a fracture during pregnancy or lactation.

Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases

Abstract: Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.