Grafius and Anderson

It is widely assumed that, among detritivorous stream invertebrates, shredders facilitate collectors through their role in producing particles from coarser detritus. While this hypothesis is plausible, we argue that it has not been adequately tested. It has not even been clear what information would be necessary or sufficient to document such an interaction. We outline the evidence which we believe must be sought: it must be established that collectors are particle-limited, that shredder activity produces particles, that shredder activity enhances collector performance, and that the mechanism for this enhancement lies in particle production and not some other process. We review available data that bear on these propositions, and describe a straightforward experiment which could unambiguously test the shredder-collector facilitation hypothesis. Invertebrate faunas of forest streams are often dominated by detritivores which feed on organic matter derived largely from leaf litter. Two major functional groups can be distinguished among them: shredders, which consume coarse particulate organic matter (CPOM), and collectors, which consume fine particles (FPOM) filtered from the water column or gathered from sediments. Shredders process CPOM and produce particles as they feed, and it is widely believed that shredders facilitate collectors as a result of this particle production (e.g. These putative shredder-collector interactions are important for at least three reasons. First, on a local scale, effects of shredders on collector performance have obvious consequences for productivity throughout stream food webs. These effects are likely to have ecological and economic implications beyond the stream itself. For instance, increased collector growth should allow greater productivity of stream fish, which in turn will benefit terrestrial piscivores and commercial and sports fisheries. In addition, the emergent adults of stream collectors can be a major resource for terrestrial and aerial insectivores, and some are also important pests -for instance, black flies. Second, on a much larger spatial scale, shredder-collector facilitation (at the level of whole functional groups) is a major element of the River Continuum Concep

Roundtable debate: Controversies in the management of the septic patient – desperately seeking consensus

Despite continuous advances in technologic and pharmacologic management, the mortality rate from septic shock remains high. Care of patients with sepsis includes measures to support the circulatory system and treat the underlying infection. There is a substantial body of knowledge indicating that fluid resuscitation, vasopressors, and antibiotics accomplish these goals. Recent clinical trials have provided new information on the addition of individual adjuvant therapies. Consensus on how current therapies should be prescribed is lacking. We present the reasoning and preferences of a group of intensivists who met to discuss the management of an actual case. The focus is on management, with emphasis on the criteria by which treatment decisions are made. It is clear from the discussion that there are areas where there is agreement and areas where opinions diverge. This presentation is intended to show how experienced intensivists apply clinical science to their practice of critical care medicine

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

The Impact of Alkaliphilic Biofilm Formation on the Release and Retention of Carbon Isotopes from Nuclear Reactor Graphite

¹⁴C is an important consideration within safety assessments for proposed geological disposal facilities for radioactive wastes, since it is capable of re-entering the biosphere through the generation of ¹⁴C bearing gases. The irradiation of graphite moderators in the UK gas-cooled nuclear power stations has led to the generation of a significant volume of ¹⁴C-containing intermediate level wastes. Some of this ¹⁴C is present as a carbonaceous deposit on channel wall surfaces. Within this study, the potential of biofilm growth upon irradiated and ¹³C doped graphite at alkaline pH was investigated. Complex biofilms were established on both active and simulant samples. High throughput sequencing showed the biofilms to be dominated by Alcaligenes sp at pH 9.5 and Dietzia sp at pH 11.0. Surface characterisation revealed that the biofilms were limited to growth upon the graphite surface with no penetration of the deeper porosity. Biofilm formation resulted in the generation of a low porosity surface layer without the removal or modification of the surface deposits or the release of the associated ¹⁴C/¹³C. Our results indicated that biofilm formation upon irradiated graphite is likely to occur at the pH values studied, without any additional release of the associated ¹⁴C

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

A Transcription Factor Map as Revealed by a Genome-Wide Gene Expression Analysis of Whole-Blood mRNA Transcriptome in Multiple Sclerosis

Background: Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls. Methodology/Principal Findings: We have used two different analytical methodologies: a non-standard differential expression analysis and a differential co-expression analysis, which have converged on a significant number of regulatory motifs that are statistically overrepresented in genes that are either differentially expressed (or differentially co-expressed) in cases and controls (e.g., V$KROX_Q6, p-value ,3.31E-6; V$CREBP1_Q2, p-value ,9.93E-6, V$YY1_02, p-value ,1.65E-5). Conclusions/Significance: Our analysis uncovered a network of transcription factors that potentially dysregulate several genes in MS or one or more of its disease subtypes. The most significant transcription factor motifs were for the Early Growth Response EGR/KROX family, ATF2, YY1 (Yin and Yang 1), E2F-1/DP-1 and E2F-4/DP-2 heterodimers, SOX5, and CREB and ATF families. These transcription factors are involved in early T-lymphocyte specification and commitment as well as in oligodendrocyte dedifferentiation and development, both pathways that have significant biological plausibility in MS causation

Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10−8) near FTO (P = 3.72 × 10−23), TMEM18 (P = 3.24 × 10−17), MC4R (P = 4.41 × 10−17), TNNI3K (P = 4.32 × 10−11), SEC16B (P = 6.24 × 10−9), GNPDA2 (P = 1.11 × 10−8) and POMC (P = 4.94 × 10−8) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10−5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different age

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genome-Wide Association for Abdominal Subcutaneous and Visceral Adipose Reveals a Novel Locus for Visceral Fat in Women

Samuli Ripatti ja Jaakko Kaprio työryhmien jäseniä, joita yht. 304.Peer reviewe

Joint registry approach for identification of outlier prostheses

Background and purposeJoint Replacement Registries play a significant role in monitoring arthroplasty outcomes by publishing data on survivorship of individual prostheses or combinations of prostheses. The difference in outcomes can be device- or non-device-related, and these factors can be analyzed separately. Although registry data indicate that most prostheses have similar outcomes, some have a higher than anticipated rate of revision when compared to all other prostheses in their class. This report outlines how the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) has developed a method to report prostheses with a higher than expected rate of revision. These are referred to as "outlier" prostheses.Material and methodsSince 2004, the AOANJRR has developed a standardized process for identifying outliers. This is based on a 3-stage process consisting of an automated algorithm, an extensive analysis of individual prostheses or combinations by registry staff, and finally a meeting involving a panel from the Australian Orthopaedic Association Arthroplasty Society. Outlier prostheses are listed in the Annual Report as (1) identified but no longer used in Australia, (2) those that have been re-identified and that are still used, and (3) those that are being identified for the first time.Results78 prostheses or prosthesis combinations have been identified as being outliers using this approach (AOANJRR 2011 Annual Report). In addition, 5 conventional hip prostheses were initially identified, but after further analysis no longer met the defined criteria. 1 resurfacing hip prosthesis was initially identified, subsequently removed from the list, and then re-identified the following year when further data were available. All unicompartmental and primary total knee prostheses identified as having a higher than expected rate of revision have continued to be re-identified.InterpretationIt is important that registries use a transparent and accountable process to identify an outlier prosthesis. This paper describes the development, implementation, assessment, and impact of the approach used by the Australian Registry.Richard N de Steiger, Lisa N Miller, David C Davidson, Philip Ryan and Stephen E Grave