In fluvial networks, some confluences are associated with tributary-driven aggradation where coarse sediment is stored, downstream sediment connectivity is interrupted and substantial hydraulic and ...morphological heterogeneity is generated. To the extent that biological diversity is supported by physical diversity, it has been proposed that the distribution and frequency of tributary-driven aggradation is important for the magnitude and spatial structure of river biodiversity. Relevant ideas are formulated within the Link Discontinuity Concept and the Network Dynamics Hypothesis, but many of the issues raised by these conceptual models have not been systematically evaluated. This paper first tests an automated method for predicting the likelihood of tributary-driven aggradation in three large drainage networks in the Rocky Mountain foothills, Canada. The method correctly identified approximately 75% of significant tributary confluences and 97% of insignificant confluences. The method is then used to evaluate two hypotheses of the Network Dynamics Hypothesis: that linear-shaped basins are more likely to show a longitudinal, downstream decline in tributary-driven aggradation; and that larger and more compact basins contain more confluences with a high probability of impact. The use of a predictive model that included a measure of tributary basin sediment delivery, rather than symmetry ratio alone, mediated the outcomes somewhat, but as anticipated, the number of significant confluences increased with basin size and basin shape was a strong control of the number and distribution of significant confluences. Doubling basin area led to a 1.9-fold increase in the number of significant confluences and compact basins contained approximately twice as many significant confluences per unit channel length as linear basins. In compact basins, significant confluences were more widely distributed, whereas in linear basins they were concentrated in proximal reaches. Interesting outstanding issues include the possibility of using spatially-distributed sediment routing models to predict tributary-driven confluence aggradation and the need to gather ecological data sufficient to properly test for increases in local and network-scale biodiversity associated with significant confluences and their network-scale controls.
•A method for predicting the likelihood of tributary-driven confluence aggradation is evaluated.•Tests of the Network Dynamics Hypothesis are undertaken across several thousand confluences.•Compact-shaped basins contain twice as many significant confluences as linear basins.•Doubling basin area almost doubles the number of significant confluences.•Basin morphometry affects sediment connectivity, riverscape heterogeneity and biodiversity.
Herpes simplex virus type 1, or HSV-1, is a widespread human pathogen that replicates in epithelial cells of the body surface and then establishes latent infection in peripheral neurons. When HSV-1 ...replicates, viral progeny must be efficiently released to spread infection to new target cells. Viral spread occurs via two major routes. In cell-cell spread, progeny virions are delivered directly to cellular junctions, where they infect adjacent cells. In cell-free release, progeny virions are released into the extracellular milieu, potentially allowing the infection of distant cells. Cell-cell spread of HSV-1 has been well studied and is known to be important for in vivo infection and pathogenesis. In contrast, HSV-1 cell-free release has received less attention, and its significance to viral biology is unclear. Here, I review the mechanisms and regulation of HSV-1 cell-free virion release. Based on knowledge accrued in other herpesviral systems, I argue that HSV-1 cell-free release is likely to be tightly regulated in vivo. Specifically, I hypothesize that this process is generally suppressed as the virus replicates within the body, but activated to high levels at sites of viral reactivation, such as the oral mucosa and skin, in order to promote efficient transmission of HSV-1 to new human hosts.
Deposition of fine sediment that fills interstitial spaces in streambed substrates is widely acknowledged to have significant negative effects on macroinvertebrate communities, but the temporal ...consistency of clogging effects is less well known. In this study the effects of experimentally enhanced fine sediment content on aquatic invertebrates were examined over 126days in two lowland UK streams. Taxonomic approaches indicated significant differences in macroinvertebrate community structure associated with sediment treatment (clean or sedimented substrates), although the effects were variable on some occasions. The degree of separation between clean and sedimented communities was strong within seven of the nine sampling periods with significant differences in community composition being evident. EPT taxa and taxon characterised as sensitive to fine sediment demonstrated strong responses to enhanced fine sediment loading. Faunal traits also detected the effects of enhanced fine sediment loading but the results were not as consistent or marked. More widely, the study highlights the temporal dynamics of sedimentation effects upon macroinvertebrate communities and the need to consider faunal life histories when examining the effects of fine sediment loading pressures on lotic ecosystems.
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•Fine sediment effects on macroinvertebrate traits and assemblages were examined.•Analysis of taxonomic community structure identified strong fine sediment effects.•Effects of sediment loading on community structure were not temporally consistent.•Faunal traits performed poorly in characterising fine sediment effects.•Taxon life cycles probably influence the effect of fine sediment load.
For the purposes of meta-analysis and network meta-analysis, the use of standard outcome measures is ideal. In OA research, the WOMAC was developed as an OA-specific measure of disability. It ...includes a pain subscale. In 1994 a consensus meeting recommended the use of WOMAC as a primary measure of efficacy in OA. In the context of a review of the efficacy of physical interventions for the relief of the pain of OA of the knee, we investigated the use of WOMAC.
A systematic review (December 2009-January 2010) identified trials that used the WOMAC outcome. These were investigated for correct use and clear reporting of the WOMAC pain subscale and the WOMAC index.
The WOMAC pain subscale was used in 45% of the 134 trials. Reporting of the exact method of administering the WOMAC pain subscale was poor in many cases: in 53% of trials the reporting of the type of WOMAC scale used was inadequate; the score range was reported ambiguously in 38% of trials, with a further 10% being completely unclear. Similar less than optimal reporting of the WOMAC index was found.
Poor reporting of both the WOMAC pain subscale and the WOMAC index resulted in significant uncertainty in the interpretation of the results of individual trials and limited their contribution to evidence synthesis. Improved adherence with the standard use of the WOMAC scoring system, with clear reporting of it in trials of OA of the knee should be encouraged.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a ...generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4- and KMT2A-rearranged subtypes separate into CEBPA/FLT3- or NFATC4-expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes.
Automated medical technology is becoming an integral part of routine anesthetic practice. Automated technologies can improve patient safety, but may create new workflows with potentially surprising ...adverse consequences and cognitive errors that must be addressed before these technologies are adopted into clinical practice. Industries such as aviation and nuclear power have developed techniques to mitigate the unintended consequences of automation, including automation bias, skill loss, and system failures. In order to maximize the benefits of automated technology, clinicians should receive training in human–system interaction including topics such as vigilance, management of system failures, and maintaining manual skills. Medical device manufacturers now evaluate usability of equipment using the principles of human performance and should be encouraged to develop comprehensive training materials that describe possible system failures. Additional research in human–system interaction can improve the ways in which automated medical devices communicate with clinicians. These steps will ensure that medical practitioners can effectively use these new devices while being ready to assume manual control when necessary and prepare us for a future that includes automated health care.
An integral part of the antiviral innate immune response is the APOBEC3 family of single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and ...-independent activities. Viruses have evolved mechanisms to counteract these enzymes, such as HIV-1 Vif-mediated formation of a ubiquitin ligase to degrade virus-restrictive APOBEC3 enzymes. A new example is Epstein-Barr virus (EBV) ribonucleotide reductase (RNR)-mediated inhibition of cellular APOBEC3B (A3B). The large subunit of the viral RNR, BORF2, causes A3B relocalization from the nucleus to cytoplasmic bodies and thereby protects viral DNA during lytic replication. Here, we use coimmunoprecipitation and immunofluorescence microscopy approaches to ask whether this mechanism is shared with the closely related gammaherpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) and the more distantly related alphaherpesvirus herpes simplex virus 1 (HSV-1). The large RNR subunit of KSHV, open reading frame 61 (ORF61), coprecipitated multiple APOBEC3s, including A3B and APOBEC3A (A3A). KSHV ORF61 also caused relocalization of these two enzymes to perinuclear bodies (A3B) and to oblong cytoplasmic structures (A3A). The large RNR subunit of HSV-1, ICP6, also coprecipitated A3B and A3A and was sufficient to promote the relocalization of these enzymes from nuclear to cytoplasmic compartments. HSV-1 infection caused similar relocalization phenotypes that required ICP6. However, unlike the infectivity defects previously reported for BORF2-null EBV, ICP6 mutant HSV-1 showed normal growth rates and plaque phenotypes. Combined, these results indicate that both gamma- and alphaherpesviruses use a conserved RNR-dependent mechanism to relocalize A3B and A3A and furthermore suggest that HSV-1 possesses at least one additional mechanism to neutralize these antiviral enzymes.
The APOBEC3 family of DNA cytosine deaminases constitutes a vital innate immune defense against a range of different viruses. A novel counterrestriction mechanism has recently been uncovered for the gammaherpesvirus EBV, in which a subunit of the viral protein known to produce DNA building blocks (ribonucleotide reductase) causes A3B to relocalize from the nucleus to the cytosol. Here, we extend these observations with A3B to include a closely related gammaherpesvirus, KSHV, and a more distantly related alphaherpesvirus, HSV-1. These different viral ribonucleotide reductases also caused relocalization of A3A, which is 92% identical to A3B. These studies are important because they suggest a conserved mechanism of APOBEC3 evasion by large double-stranded DNA herpesviruses. Strategies to block this host-pathogen interaction may be effective for treating infections caused by these herpesviruses.
Children and adolescents with medical conditions present special issues with respect to participation in athletic activities. The pediatrician can play an important role in determining whether a ...child with a health condition should participate in certain sports by assessing the child's health status, suggesting appropriate equipment or modifications of sports to decrease the risk of injury, and educating the athlete, parent(s) or guardian, and coach regarding the risks of injury as they relate to the child's condition. This report updates a previous policy statement and provides information for pediatricians on sports participation for children and adolescents with medical conditions.
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