Scalar conservation laws with nonconstant coefficients with application to particle size segregation in granular flow

Granular materials will segregate by particle size when subjected to shear, as occurs, for example, in avalanches. The evolution of a bidisperse mixture of particles can be modeled by a nonlinear first order partial differential equation, provided the shear (or velocity) is a known function of position. While avalanche-driven shear is approximately uniform in depth, boundary-driven shear typically creates a shear band with a nonlinear velocity profile. In this paper, we measure a velocity profile from experimental data and solve initial value problems that mimic the segregation observed in the experiment, thereby verifying the value of the continuum model. To simplify the analysis, we consider only one-dimensional configurations, in which a layer of small particles is placed above a layer of large particles within an annular shear cell and is sheared for arbitrarily long times. We fit the measured velocity profile to both an exponential function of depth and a piecewise linear function which separates the shear band from the rest of the material. Each solution of the initial value problem is non-standard, involving curved characteristics in the exponential case, and a material interface with a jump in characteristic speed in the piecewise linear case

The practical implications of using standardized estimation equations in calculating the prevalence of chronic kidney disease

BACKGROUND: Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) guidelines have focused on the utility of using the modified four-variable MDRD equation (now traceable by isotope dilution mass spectrometry IDMS) in calculating estimated glomerular filtration rates (eGFRs). This study assesses the practical implications of eGFR correction equations on the range of creatinine assays currently used in the UK and further investigates the effect of these equations on the calculated prevalence of CKD in one UK regionMETHODS: Using simulation, a range of creatinine data (30-300 micromol/l) was generated for male and female patients aged 20-100 years. The maximum differences between the IDMS and MDRD equations for all 14 UK laboratory techniques for serum creatinine measurement were explored with an average of individual eGFRs calculated according to MDRD and IDMS &lt; 60 ml/min/1.73 m(2) and 30 ml/min/1.73 m(2). Similar procedures were applied to 712,540 samples from patients &gt; or = 18 years (reflecting the five methods for serum creatinine measurement utilized in Northern Ireland) to explore, graphically, maximum differences in assays. CKD prevalence using both estimation equations was compared using an existing cohort of observed data.RESULTS: Simulated data indicates that the majority of laboratories in the UK have small differences between the IDMS and MDRD methods of eGFR measurement for stages 4 and 5 CKD (where the averaged maximum difference for all laboratory methods was 1.27 ml/min/1.73 m(2) for females and 1.59 ml/min/1.73 m(2) for males). MDRD deviated furthest from the IDMS results for the Endpoint Jaffe method: the maximum difference of 9.93 ml/min/1.73 m(2) for females and 5.42 ml/min/1.73 m(2) for males occurred at extreme ages and in those with eGFR &gt; 30 ml/min/1.73 m(2). Observed data for 93,870 patients yielded a first MDRD eGFR &lt; 60 ml/min/1.73 m(2) in 2001. 66,429 (71%) had a second test &gt; 3 months later of which 47,093 (71%) continued to have an eGFR &lt; 60 ml/min/1.73 m(2). Estimated crude prevalence was 3.97% for laboratory detected CKD in adults using the MDRD equation which fell to 3.69% when applying the IDMS equation. Over 95% of this difference in prevalence was explained by older females with stage 3 CKD (eGFR 30-59 ml/min/1.73 m(2)) close to the stage 2 CKD (eGFR 60-90 ml/min/1.73 m(2)) interface.CONCLUSIONS: Improved accuracy of eGFR is obtainable by using IDMS correction especially in the earlier stages of CKD 1-3. Our data indicates that this improved accuracy could lead to reduced prevalence estimates and potentially a decreased likelihood of onward referral to nephrology services particularly in older females.</p

Comparative efficacy versus effectiveness of initial antiretroviral therapy in clinical trials versus routine care

BACKGROUND: The applicability of clinical trial findings (efficacy) to the routine care setting (effectiveness) may be limited because of study eligibility criteria and volunteer bias. Although well-chronicled in many conditions, the efficacy versus effectiveness of antiretroviral therapy (ART) remains understudied. METHODS: A retrospective study of the University of Alabama at Birmingham 1917 Clinic Cohort evaluated ART-naive patients who started ART from 1 January 2000 through 31 December 2006. Patients received ART through clinical trials or routine care. Multivariable logistic and linear regression models were fit to evaluate factors associated with virological failure (virological failure was defined as a viral load \u3e50 copies/mL) and change from baseline CD4+ cell count 6 and 12 months after ART initiation. Sensitivity analyses evaluated the impact of missing data on outcomes. RESULTS: Among 570 patients starting ART during the study period, 121 (21%) enrolled in clinical trials, and 449 (79%) received ART via routine care. ART receipt through routine care was not associated with viral failure at either 6 months (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.54-1.86) or 12 months (OR, 1.56; 95% CI, 0.80-3.05) in primary analyses. No statistically significant differences in CD4+ cell count responses at 6 and 12 months were observed. CONCLUSIONS: Although marked differences in efficacy versus effectiveness have been observed in the therapeutic outcomes of other conditions, our analyses found no evidence of such divergence among our patients who initiated antiretroviral therapy for human immunodeficiency virus infection

How paradata can illuminate technical, social and professional role changes between the Poverty in the UK (1967/1968) and Poverty and Social Exclusion in the UK (2012) surveys

© 2016, The Author(s). This article brings together analyses of the micro paradata ‘by-products’ from the 1967/1968 Poverty in the United Kingdom (PinUK) and 2012 Poverty and Social Exclusion in the UK (PSE) surveys to explore changes in the conditions of production over this 45year period. We highlight technical, social and professional role continuities and changes, shaped by the institutionalisation of survey researchers, the professionalization of the field interviewer, and economisation. While there are similarities between the surveys in that field interviewers were and are at the bottom of the research hierarchy, we demonstrate an increasing segregation between the core research team and field interviewers. In PinUK the field interviewers are visible in the paper survey booklets; through their handwritten notes on codes and in written marginalia they can ‘talk’ to the central research team. In PSE they are absent from the computer mediated data, and from communication with the central team. We argue that, while there have been other benefits to field interviewers, their relational labour has become less visible in a shift from the exercise of observational judgement to an emphasis on standardisation. Yet, analyses of what field interviewers actually do show that they still need to deploy the same interpersonal skills and resourcefulness to secure and maintain interviews as they did 45years previously

Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied–despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term ‘prebiotic’ by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups