Tailoring the sampling time of single-sample GFR measurement according to expected renal function: a multisite audit

BackgroundThe 2018 BNMS Glomerular Filtration Rate (GFR) guidelines recommend a single-sample technique with the sampling time dictated by the expected renal function, but this is not known with any accuracy before the test. We aimed to assess whether the sampling regime suggested in the guidelines is optimal, and determine the expected error in GFR result if the sample time is chosen incorrectly. We can then infer the degree of flexibility in the sampling regime.Methods Data from 8946 patients referred for GFR assessment at 6 different hospitals for a variety of indications were reviewed. The difference between the single-sample (Fleming) GFR result at each sample time and the slope-intercept GFR result at each hospital was calculated. A second dataset of 775 studies from one hospital with nine samples collected from 5 minutes to 8 hours post injection was analysed to provide a reference GFR to which the single sample results were compared.Results Recommended single-sample times have been revised: for estimated GFR above 80 ml/min/1.73m2 a 2 hour sample is recommended, giving mean difference from slope-intercept GFR of -2.08 ml/min/1.73m2 (1333 GFR tests included). Between 30 and 80 ml/min/1.73m2 a 4 hour sample is recommended, giving a 1.95 ml/min/1.73m2 mean difference (2057 GFR tests included). The standard deviation of the differences is 3.50 ml/min/1.73m2 at 2 hours and 2.56 ml/min/1.73m2 at 4 hours for GFR results in the recommended range. It is 5.81 ml/min/1.73m2 at 2 hours and 5.70 ml/min/1.73m2 at 4 hours for GFR results outside the recommended range. ConclusionThe results of this multisite study demonstrate a reassuringly wide range of sample times for an acceptably accurate single-sample GFR result. Modified recommended single-sample times have been proposed in line with the results, and the reported errors for both sample times can be used for error analysis of a mistimed sample.

Post-outbreak surveillance strategies to support proof of freedom from foot-and-mouth disease

Whilst emergency vaccination may help contain foot-and-mouth disease in a previously FMD-free country, its use complicates post-outbreak surveillance and the recovery of FMD-free status. A structured surveillance program is required that can distinguish between vaccinated and residually infected animals, and provide statistical confidence that the virus is no longer circulating in previously infected areas.Epidemiological models have been well-used to investigate the potential benefits of emergency vaccination during a control progam and when/where/whom to vaccinate in the face of finite supplies of vaccine and personnel. Less well studied are post-outbreak issues such as the management of vaccinated animals and the implications of having used vaccination during surveillance regimes to support proof-of-freedom. This paper presents enhancements to the Australian Animal Disease Model (AADIS) that allow comparisons of different post-outbreak surveillance sampling regimes for establishing proof-of-freedom from FMD.A case study is provided that compares a baseline surveillance sampling regime (derived from current OIE guidelines), with an alternative less intensive sampling regime. It was found that when vaccination was not part of the control program, a reduced sampling intensity significantly reduced the number of samples collected and the cost of the post-outbreak surveillance program, without increasing the risk of missing residual infected herds.

Construction and Monte Carlo Estimation of Wavelet Frames Generated by a Reproducing Kernel

We introduce a construction of multiscale tight frames on general domains. The frame elements are obtained by spectral filtering of the integral operator associated with a reproducing kernel. Our construction extends classical wavelets as well as generalized wavelets on both continuous and discrete non-Euclidean structures such as Riemannian manifolds and weighted graphs. Moreover, it allows to study the relation between continuous and discrete frames in a random sampling regime, where discrete frames can be seen as Monte Carlo estimates of the continuous ones. Pairing spectral regularization with learning theory, we show that a sample frame tends to its population counterpart, and derive explicit finite-sample rates on spaces of Sobolev and Besov regularity. Our results prove the stability of frames constructed on empirical data, in the sense that all stochastic discretizations have the same underlying limit regardless of the set of initial training samples.

Distribution and Public Health Significance of Vibrio Pathogens Recovered from Selected Treated Effluents in the Eastern Cape Province, South Africa

Treated sewage harbours pathogenic microbes, such as enteric bacteria and protozoa, are capable of causing several diseases. Some of these are emerging pathogens sometimes recovered in the absence of common water quality indicator organisms. The possibility of selected treatments plants serving as momentary reservoirs of Vibrio pathogens during a non-outbreak period was assessed. The occurrence and diversity of Vibrio pathogens were monitored for one year (December 2016 to November 2017) in the treated effluents and upstream and downstream areas of the receiving water bodies of two wastewater treatment plants (WWTPs), designated AL and TS. Physicochemical parameters of TS and AL WWTPs’ water samples were analysed using a multi-parameter meter (Hanna, model HI 9828, Padova, Italy) and a turbidimeter (HACH, model 2100P, Johannesburg, South Africa). Water samples were augmented with alkaline peptone water and cultured on thiosulfate citrate bile salts sucrose agar at 37 °C for 24 h. The recovered probable pathogens were confirmed via PCR amplification, using primers specific for Vibrio species of public health significance. The distribution of Vibrio species positively and significantly (p < 0.01) correlated with turbidity (r = 0.630), temperature (r = 0.615), dissolved oxygen (r = 0.615), pH (r = 0.607), biological oxygen demand (r = 0.573), total dissolved solid (r = 0.543), total suspended solid (r = 0.511), electrical conductivity (r = 0.499), residual chlorine (r = 0.463) and salinity (r = 0.459). The densities of Vibrio species were found to be significantly higher (p < 0.05) in effluents from both AL and TS WWTPs than upstream and downstream of the receiving rivers across the sampling regime. Furthermore, the maximum Vibrio species density across the sampling regime were observed during the warmer Summer and Spring season. Moreover, six medically important Vibrio species were detected in the water samples, indicating that the methods employed were efficient in revealing that WWTPs are potential reservoirs of Vibrio pathogens, which could pose a substantial public health risk if the receiving water is used for domestic purposes. Our findings further strengthen existing calls for the inclusion of emerging bacterial pathogens, including Vibrio species, as water quality indicators by the South African Department of Water Affairs. Hence, we recommend regular monitoring of treated effluents and receiving water bodies to ensure early control of potential outbreaks of vibriosis and cholera.

Tracking an Auto-Regressive Process with Limited Communication per Unit Time

Samples from a high-dimensional first-order auto-regressive process generated by an independently and identically distributed random innovation sequence are observed by a sender which can communicate only finitely many bits per unit time to a receiver. The receiver seeks to form an estimate of the process value at every time instant in real-time. We consider a time-slotted communication model in a slow-sampling regime where multiple communication slots occur between two sampling instants. We propose a successive update scheme which uses communication between sampling instants to refine estimates of the latest sample and study the following question: Is it better to collect communication of multiple slots to send better refined estimates, making the receiver wait more for every refinement, or to be fast but loose and send new information in every communication opportunity? We show that the fast but loose successive update scheme with ideal spherical codes is universally optimal asymptotically for a large dimension. However, most practical quantization codes for fixed dimensions do not meet the ideal performance required for this optimality, and they typically will have a bias in the form of a fixed additive error. Interestingly, our analysis shows that the fast but loose scheme is not an optimal choice in the presence of such errors, and a judiciously chosen frequency of updates outperforms it.

Effects of stream permanence on stonefly (Insecta, Plecoptera) community structure at Mammoth Cave National Park, Kentucky, USA

Stoneflies (Plecoptera) are often associated with inhabiting cold perennial streams, but many species also inhabit intermittent streams that experience reduced or lack of flow during summer and autumn. In this study, the influence of stream permanence on stonefly assemblage composition and spatial distribution at Mammoth Cave National Park, Kentucky, USA, was addressed, based on a 14 month sampling regime from the fullest range of stream sizes and habitable flow regions available. Adult stoneflies were collected monthly from 43 sites at the Park plus an additional two sites at the near-adjacent Western Kentucky University Green River Preserve. Collections were done from December 2018–November 2019 using a standard timed protocol with beating sheets for adults and once in December 2019–January 2020 for larvae. Stream sites were assigned one of five category types: perennial spring runs, perennial spring seeps, upland perennial streams, perennial riverine and summer dry runs. In total, 34 species were collected. The most prominent difference in stonefly community structure was between spring runs, spring seeps and summer dry streams vs. upland perennial streams. Approximately 88% of species collected had univoltine-fast life cycles and 79% likely had an extended period of egg or larval diapause. Due to the predominance of small upland perennial and summer dry streams, species commonly typically found in larger lotic systems are fundamentally filtered out of the region due to the lack of available habitats. Species able to survive in intermittent habitats do so by life history adaptations including to survive desiccation as larvae or eggs.

Can eDNA metabarcoding offer a catchment-based approach for biodiversity monitoring?

In previous studies eDNA metabarcoding has been demonstrated as a viable tool for catchment-level biodiversity sampling in rivers (Deiner et al. 2016). However, questions still remain over the appropriate sampling protocol for large spatial scale sampling. River reaches are composed of multiple habitats with species composition varying from one to the next (Costa and Melo 2007). Therefore, how many spatial replicates are needed to reliably represent the river network? Is the previously used approach to sample at every river confluence (Deiner et al. 2016) sufficient or is more needed? These questions were addressed using a case study in the headwaters of the Cound Brook, a tributary to the River Severn in Shropshire, UK. Two sub-catchments of the Cound Brook were used. One sub-catchment had a sample taken at the most downstream point before the confluence. Additionally, a sample at the upstream extent of the same sub-catchment was taken to estimate any correlation between the species found at the beginning of the river reach and at the end. Another sub-catchment also had the same up- and downstream sample design. However, in between was a systemic sampling regime every 500 m. This is to test if increasing the spatial resolution gave significantly different results to the sparser sampling regime. At each sample location, a 1 L water sample was sequentially filtered through membranes of three different mesh sizes: 5µm, 0.45µm and 0.2µm. Sequential filtering was performed because DNA resides in two forms in the environment (Civade et al. 2017), within whole cells (cellular DNA) and outside of cells (extracellular). The theory is that the coarser filters predominantly collect cellular DNA and the finer filters collect predominantly extracellular DNA of increasingly smaller fragment lengths. Consequently, sequential filtering could represent DNA degradation in the environment (Fig. 1). Also, Turner et al. 2014 suggested that the larger particles could determine very recent or local organisms. Therefore, we hypothesised that the DNA collected by the coarser filters would represent local diversity and the DNA collected by the finer filters would reflect biodiversity further upstream. Initial results suggest sequential filtering through the 5µm and 0.45µm filters caught detectable levels of eDNA where the 0.2µm did not catch enough to show up through gel electrophoresis. The relevance of the initial finding suggests that if we only used a 5µm filter the data collected at 0.45µm could have been discarded. Further investigations of any differences in species compositions between filters and the relationships to other sampling locations is still to be determined. This ongoing research is intended to determine the appropriate sampling protocol for a large-scale biodiversity assessment regime combining eDNA metabarcoding and species distribution modelling.

Towards rectifying limitations on species delineation in dusky salamanders (Desmognathus: Plethodontidae): An ecoregion-drainage sampling grid reveals additional cryptic clades

Dusky salamanders (Desmognathus) constitute a large, species-rich group within the family Plethodontidae, and though their systematic relationships have been addressed extensively, most studies have centered on particular species complexes and therefore offer only piecemeal phylogenetic perspective on the genus. Recent work has revealed Desmognathus to be far more clade rich—35 reciprocally monophyletic clades versus 22 recognized species—than previously imagined, results that, in turn, provide impetus for additional survey effort within clades and across geographic areas thus far sparsely sampled. We conceived and implemented a sampling regime combining level IV ecoregions and independent river drainages to yield a geographic grid for comprehensive recovery of all genealogically exclusive clades. We sampled over 550 populations throughout the distribution of Desmognathus in the eastern United States of America and generated mitochondrial DNA sequence data (mtDNA; 1,991 bp) for 536 specimens. A Bayesian phylogenetic reconstruction of the resulting haplotypes revealed forty-five reciprocally monophyletic clades, eleven of which have never been included in a comprehensive phylogenetic reconstruction, and an additional three not represented in any molecular systematic survey. Although general limitations associated with mtDNA data preclude new species delineation, we profile each of the 45 clades and assign names to 10 new clades (following a protocol for previous clade nomenclature). We also redefine several species complexes and erect new informal species complexes. Our dataset, which contains topotypic samples for nearly every currently recognized species and most synonymies, will offer a robust framework for future efforts to delimit species within Desmognathus.

How to characterise shared space use networks

ABSTRACTStudying the social behaviour of small or cryptic species often relies on constructing space-sharing networks from sparse point-based observations of individuals. Such an approach assumes that individuals that have greater shared space use will also interact more. However, there is very little guidance on how much data are required to construct meaningful space-sharing networks, or on how to interpret the relationships generated from such networks. In this study, we quantify the robustness of space-sharing networks to different sampling regimes, providing much needed guidance for informing the choice of sampling regime when designing studies to accurately quantify space sharing. We then describe the characteristics of space use in a wild population of field voles (Microtus agrestis), and use this empirical dataset to develop a new method for generating shared space use networks which are generally more strongly correlated with the real network, differ less from the real network and are more powerful to detect effects present in the real network. Our method pools data among individuals to estimate a general home range profile for a given set of individuals.Combining these profiles with the individual-level observation data then allows us to better estimate their overlap in space and requires less data. Our new method provides the potential to generate meaningful space-sharing networks, and in doing so, to address a range of key questions in ecology and evolution, even when point-based observations of individuals are sparse.