Search

Aims: Current follow-up for head and neck cancer (HNC) is ineffective, expensive and fails to address patients' needs. The PETNECK2 trial will compare a new model of patient-initiated follow-up (PIFU) with routine scheduled follow-up. This article reports UK clinicians' views about HNC follow-up and PIFU, to inform the trial design. Materials and Methods: Online focus groups with surgeons (ear, nose and throat/maxillofacial), oncologists, clinical nurse specialists and allied health professionals. Clinicians were recruited from professional bodies, mailing lists and personal contacts. Focus groups explored views on current follow-up and acceptability of the proposed PIFU intervention and randomised controlled trial design (presented by the study co-chief investigator), preferences, margins of equipoise, potential organisational barriers and thoughts about the content and format of PIFU. Data were interpreted using inductive thematic analysis. Results: Eight focus groups with 34 clinicians were conducted. Clinicians highlighted already known limitations with HNC follow-up – lack of flexibility to address the wide-ranging needs of HNC patients, expense and lack of evidence – and agreed that follow-up needs to change. They were enthusiastic about the PETNECK2 trial to develop and evaluate PIFU but had concerns that PIFU may not suit disengaged patients and may aggravate patient anxiety/fear of recurrence and delay detection of recurrence. Anticipated issues with implementation included ensuring a reliable route back to clinic and workload burden on nurses and allied health professionals. Conclusions: Clinicians supported the evaluation of PIFU but voiced concerns about barriers to help-seeking. An emphasis on patient engagement, psychosocial issues, symptom reporting and reliable, quick routes back to clinic will be important. Certain patient groups may be less suited to PIFU, which will be evaluated in the trial. Early, meaningful, ongoing engagement with clinical teams and managers around the trial rationale and recruitment process will be important to discourage selective recruitment and address risk-averse behaviour and potential workload burden.

The observed scaling violations of the nucleon structure functionF 2 and $$\bar q$$ have been analysed in the framework of perturbative QCD to determine the shape and magnitude of the gluon distribution. The data are in good agreement with leading order QCD, and the simultaneous use ofF 2 and $$\bar q$$ structure functions permits, for the first time, a reliable determination of the gluon structure function.

CD4+ T cell differentiation requires metabolic reprogramming to fulfil the bioenergetic demands of proliferation and effector function, and enforce specific transcriptional programmes1-3. Mitochondrial membrane dynamics sustains mitochondrial processes4, including respiration and tricarboxylic acid (TCA) cycle metabolism5, but whether mitochondrial membrane remodelling orchestrates CD4+ T cell differentiation remains unclear. Here we show that unlike other CD4+ T cell subsets, T helper 17 (TH17) cells have fused mitochondria with tight cristae. T cell-specific deletion of optic atrophy 1 (OPA1), which regulates inner mitochondrial membrane fusion and cristae morphology6, revealed that TH17 cells require OPA1 for its control of the TCA cycle, rather than respiration. OPA1 deletion amplifies glutamine oxidation, leading to impaired NADH/NAD+ balance and accumulation of TCA cycle metabolites and 2-hydroxyglutarate-a metabolite that influences the epigenetic landscape5,7. Our multi-omics approach revealed that the serine/threonine kinase liver-associated kinase B1 (LKB1) couples mitochondrial function to cytokine expression in TH17 cells by regulating TCA cycle metabolism and transcriptional remodelling. Mitochondrial membrane disruption activates LKB1, which restrains IL-17 expression. LKB1 deletion restores IL-17 expression in TH17 cells with disrupted mitochondrial membranes, rectifying aberrant TCA cycle glutamine flux, balancing NADH/NAD+ and preventing 2-hydroxyglutarate production from the promiscuous activity of the serine biosynthesis enzyme phosphoglycerate dehydrogenase (PHGDH). These findings identify OPA1 as a major determinant of TH17 cell function, and uncover LKB1 as a sensor linking mitochondrial cues to effector programmes in TH17 cells.

Heterochromatin has essential functions in maintaining chromosome structure, in protecting genome integrity and in stabilizing gene expression programs. Heterochromatin is often nucleated by underlying DNA repeat sequences, such as major satellite repeats (MSR) and long interspersed nuclear elements (LINE). In order to establish heterochromatin, MSR and LINE elements need to be transcriptionally competent and generate non-coding repeat RNA that remain chromatin associated. We explored whether these heterochromatic RNA, similar to DNA and histones, may be methylated, particularly for 5-methylcytosine (5mC) or methyl-6-adenosine (m6A). Our analysis in mouse ES cells identifies only background level of 5mC but significant enrichment for m6A on heterochromatic RNA. Moreover, MSR transcripts are a novel target for m6A RNA modification, and their m6A RNA enrichment is decreased in ES cells that are mutant for Mettl3 or Mettl14, which encode components of a central RNA methyltransferase complex. Importantly, MSR transcripts that are partially deficient in m6A RNA methylation display impaired chromatin association and have a reduced potential to form RNA:DNA hybrids. We propose that m6A modification of MSR RNA will enhance the functions of MSR repeat transcripts to stabilize mouse heterochromatin.

Establishing realistic targets for fish community composition is needed to assess the effectiveness of river restoration projects. We used environmental DNA (eDNA) metabarcoding with MiFish primers to obtain estimates of fish community composition across 17 sites upstream, downstream and within a restoration mitigation project area (Kaihotsu– Kasumi) located in the Shigenobu River system, Ehime Prefecture, Japan. We evaluate the benefits of using eDNA to quickly, sensitively, and extensively gather data to establish existing fish community composition in the restoration area, as well as potential future short-term, medium-term, and long-term targets of species assemblages that could realistically emerge following dispersal into the project area from upstream and downstream populations. We compare results from eDNA metabarcoding with species lists obtained from contemporaneous capture surveys and historical information. Nonmetric multidimensional scaling plots of community composition obtained from eDNA surveys showed that the Kaihotsu–Kasumi restoration area and surrounding river reaches were divided into three clusters: upper reaches, middle and lower reaches, and estuarine reaches. The Kaihotsu– Kasumi restoration area sites were included in the group containing the middle and lower reaches of the inflow and outflow rivers that were near the restoration area. We detected a total of twenty-six species in this group, twenty-one native species and five non-native species. Therefore, these native species were considered suitable as short-term target species with high potential for dispersal into Kaihotsu–Kasumi restoration area. By comparison, only 14 species would have been selected as target species based on capture surveys and historical literature. One factor increasing the resolution of our eDNA surveys was our ability to identify the presence of intraspecific lineages of Misgurnus anguillicaudatus (Clades A and B), which were missed by the capture surveys. These results indicate that the eDNA metabarcoding method can provide more comprehensive and realistic short-term target species estimates than capture surveys, as well as provide higher resolution monitoring through intraspecific lineage detection.

Environmental DNA (eDNA) has emerged as a potentially powerful tool for use in conservation and resource management, including for tracking the recolonization dynamics of fish populations. We used eDNA to assess the effectiveness of dam removal to restore fish passage on the Elwha River in Washington State (USA). Using a suite of 11 species‐specific eDNA polymerase chain reaction (PCR) assays, we showed that most targeted anadromous species (five Pacific Salmon species and Pacific Lamprey) were able to pass upstream of both former dam sites. Multiscale occupancy modeling showed that the timing and spatial extent of recolonization differed among species during the four years of post‐dam removal monitoring. More abundant species like Chinook Salmon and Coho Salmon migrated farther into the upper portions of the watershed than less abundant species like Pink Salmon and Chum Salmon. Sampling also allowed assessment of potamodromous fish species. Bull Trout and Rainbow Trout, ubiquitous species in the watershed, were detected at all sampling locations. Environmental DNA from Brook Trout, a non‐native species isolated between the dams prior to dam removal, was detected downstream of Elwha dam but rarely upstream of the Glines Canyon Dam suggested that the species has not expanded its range appreciably in the watershed following dam removal. We found that eDNA was an effective tool to assess the response of fish populations to large‐scale dam removal on the Elwha River.

Environmental DNA (eDNA) analysis offers a promising tool for rapid and early detection of aquatic plant invasive species, but currently suffers from substantial unknowns that limit its wid...

Integrating solid-state quantum emitters with nanophotonic resonators is essential for efficient spin-photon interfacing and optical networking applications. While diamond color centers have proven to be excellent candidates for emerging quantum technologies, their integration with optical resonators remains challenging. Conventional approaches based on etching resonators into diamond often negatively impact color center performance and offer low device yield. Here, we developed an integrated photonics platform based on templated atomic layer deposition of TiO2 on diamond membranes. Our fabrication method yields high-performance nanophotonic devices while avoiding etching wavelength-scale features into diamond. Moreover, this technique generates highly reproducible optical resonances and can be iterated on individual diamond samples, a unique processing advantage. Our approach is suitable for a broad range of both wavelengths and substrates and can enable high-cooperativity interfacing between cavity photons and coherent defects in diamond or silicon carbide, rare earth ions, or other material systems., 13 pages, 4 figures, 1 table

Tissue nanotransfection (TNT) is an electromotive gene transfer technology that was developed to achieve tissue reprogramming in vivo. This protocol describes how to fabricate the required hardware, commonly referred to as a TNT chip, and use it for in vivo TNT. Silicon hollow-needle arrays for TNT applications are fabricated in a standardized and reproducible way. In

Landscape perspectives in riverine ecology have been undertaken increasingly in the last 30 years, leading aquatic ecologists to develop a diverse set of approaches for conceptualizing, mapping and understanding ‘riverscapes’. Spatiotemporally explicit perspectives of rivers and their biota nested within the socio-ecological landscape now provide guiding principles and approaches in inland fisheries and watershed management. During the last two decades, scientific literature on riverscapes has increased rapidly, indicating that the term and associated approaches are serving an important purpose in freshwater science and management. We trace the origins and theoretical foundations of riverscape perspectives and approaches and examine trends in the published literature to assess the state of the science and demonstrate how they are being applied to address recent challenges in the management of riverine ecosystems. We focus on approaches for studying and visualizing rivers and streams with remote sensing, modelling and sampling designs that enable pattern detection as seen from above (e.g. river channel, floodplain, and riparian areas) but also into the water itself (e.g. aquatic organisms and the aqueous environment). Key concepts from landscape ecology that are central to riverscape approaches are heterogeneity, scale (resolution, extent and scope) and connectivity (structural and functional), which underpin spatial and temporal aspects of study design, data collection and analysis. Mapping of physical and biological characteristics of rivers and floodplains with high-resolution, spatially intensive techniques improves understanding of the causes and ecological consequences of spatial patterns at multiple scales. This information is crucial for managing river ecosystems, especially for the successful implementation of conservation, restoration and monitoring programs. Recent advances in remote sensing, field-sampling approaches and geospatial technology are making it increasingly feasible to collect high-resolution data over larger scales in space and time. We highlight challenges and opportunities and discuss future avenues of research with emerging tools that can potentially help to overcome obstacles to collecting, analysing and displaying these data. This synthesis is intended to help researchers and resource managers understand and apply these concepts and approaches to address real-world problems in freshwater management.

Life-cycle models combine several strengths for estimating population parameters and biological reference points of harvested species and are particularly useful for those exhibiting distinct habitat shifts and experiencing contrasting environments. Unfortunately, time series data are often limited to counts of adult abundance and harvest. By incorporating data from other populations and by dynamically linking the life-history stages, Bayesian life-cycle models can be used to estimate stage-specific productivities and capacities as well as abundance of breeders that produce maximum sustained yield (MSY). Using coho salmon (Oncorhynchus kisutch) as our case study, we show that incorporating information on marine survival variability from nearby populations can improve model estimates and affect management parameters such as escapement at MSY. We further show that the expected long-term average yield of a fishery managed for a spawner escapement target that produces MSY strongly depends on the average marine survival. Our results illustrate the usefulness of incorporating information from other sources and highlight the importance of accounting for variation in marine survival when making inferences about the management of Pacific salmon.

One of the desired outcomes of dam decommissioning and removal is the recovery of aquatic and riparian ecosystems. To investigate this common objective, we synthesized information from empirical studies and ecological theory into conceptual models that depict key physical and biological links driving ecological responses to removing dams. We define models for three distinct spatial domains: upstream of the former reservoir, within the reservoir, and downstream of the removed dam. Emerging from these models are response trajectories that clarify potential pathways of ecological transitions in each domain. We illustrate that the responses are controlled by multiple causal pathways and feedback loops among physical and biological components of the ecosystem, creating recovery trajectories that are dynamic and nonlinear. In most cases, short-term effects are typically followed by longer-term responses that bring ecosystems to new and frequently predictable ecological condition, which may or may not be similar to what existed prior to impoundment.

Improving heat insulation in microelectromechanical system based thermal-type infrared sensor is crucial to increase its performance. The concept of phonon engineering allows us to change material thermal conductivity by several orders of magnitudes, which can be a potential technique for thermal management of such microelectronic devices. Here, we introduced a phononic crystal structure in a prototype thermopile sensor to investigate the effectiveness of phonon engineering. We demonstrate that ultrafine phononic crystal structure, which was consisted of through-holes periodically arranged at 38 nm, resulted in ten-fold reduction in Si thermal conductivity. This led to improvement of the sensitivity of IR detection by a factor of ten. In addition, our phononic crystal could suppress thermal conductivity while maintaining the electrical conductivity, which enable us to increase the noise equivalent temperature difference by 5.6 times. The present study demonstrates great potential of phonon engineering for infrared sensor technology to reach for smaller pixel size and lower device cost.

We measured food availability and diet composition of juvenile salmonids over multiple years and seasons before and during the world’s largest dam removal on the Elwha River, Washington State. We conducted these measurements over three sediment-impacted sections (the estuary and two sections of the river downstream of each dam) and compared these to data collected from mainstem tributaries not directly affected by the massive amount of sediment released from the reservoirs. We found that sediment impacts from dam removal significantly reduced invertebrate prey availability, but juvenile salmon adjusted their foraging so that the amount of energy in diets was similar before and during dam removal. This general pattern was seen in both river and estuary habitats, although the mechanisms driving the change and the response differed between habitats. In the estuary, the dietary shifts were related to changes in invertebrate assemblages following a hydrological transition from brackish to freshwater caused by sediment deposition at the river’s mouth. The loss of brackish invertebrate species caused fish to increase piscivory and rely on new prey sources such as plankton. In the river, energy provided to fish by Ephemeroptera, Plecoptera, and Trichoptera taxa before dam removal was replaced first by terrestrial invertebrates, and then by sediment-tolerant taxa such as Chironomidae. The results of our study are consistent with many others that have shown sharp declines in invertebrate density during dam removal. Our study further shows how those changes can move through the food web and affect fish diet composition, selectivity, and energy availability. As we move further along the dam removal response trajectory, we hypothesize that food web complexity will continue to increase as annual sediment load now approaches natural background levels, anadromous fish have recolonized the majority of the watershed between and above the former dams, and revegetation and microhabitats continue to develop in the estuary.

Integrating solid-state quantum emitters with nanophotonic resonators is essential for efficient spin-photon interfacing and optical networking applications. While diamond color centers have proven to be excellent candidates for emerging quantum technologies, their integration with optical resonators remains challenging. Conventional approaches based on etching resonators into diamond often negatively impact color center performance and offer low device yield. Here, we developed an integrated photonics platform based on templated atomic layer deposition of TiO

We measured food availability and diet composition of juvenile salmonids over multiple years and seasons before and during the world’s largest dam removal on the Elwha River, Washington State. We conducted these measurements over three sediment-impacted sections (the estuary and two sections of the river downstream of each dam) and compared these to data collected from mainstem tributaries not directly affected by the massive amount of sediment released from the reservoirs. We found that sediment impacts from dam removal significantly reduced invertebrate prey availability, but juvenile salmon adjusted their foraging so that the amount of energy in diets was similar before and during dam removal. This general pattern was seen in both river and estuary habitats, although the mechanisms driving the change and the response differed between habitats. In the estuary, the dietary shifts were related to changes in invertebrate assemblages following a hydrological transition from brackish to freshwater caused by sediment deposition at the river’s mouth. The loss of brackish invertebrate species caused fish to increase piscivory and rely on new prey sources such as plankton. In the river, energy provided to fish by Ephemeroptera, Plecoptera, and Trichoptera taxa before dam removal was replaced first by terrestrial invertebrates, and then by sediment-tolerant taxa such as Chironomidae. The results of our study are consistent with many others that have shown sharp declines in invertebrate density during dam removal. Our study further shows how those changes can move through the food web and affect fish diet composition, selectivity, and energy availability. As we move further along the dam removal response trajectory, we hypothesize that food web complexity will continue to increase as annual sediment load now approaches natural background levels, anadromous fish have recolonized the majority of the watershed between and above the former dams, and revegetation and microhabitats continue to develop in the estuary.

Developing fast, cost-effective assessments of wild animal abundance is an important goal for many researchers, and environmental DNA (eDNA) holds much promise for this purpose. However, the quantitative relationship between species abundance and the amount of DNA present in the environment is likely to vary substantially among taxa and with ecological context. Here, we report a strong quantitative relationship between eDNA concentration and the abundance of spawning sockeye salmon in a small stream in Alaska, USA, where we took temporally- and spatially-replicated samples during the spawning period. This high-resolution dataset suggests that (1) eDNA concentrations vary significantly day-to-day, and likely within hours, in the context of the dynamic biological event of a salmon spawning season; (2) eDNA, as detected by species-specific quantitative PCR probes, seems to be conserved over short distances (tens of meters) in running water, but degrade quickly over larger scales (ca. 1.5 km); and (3) factors other than the mere presence of live, individual fish — such as location within the stream, live/dead ratio, and water temperature — can affect the eDNA-biomass correlation in space or time. A multivariate model incorporating both biotic and abiotic variables accounted for over 75% of the eDNA variance observed, suggesting that where a system is well-characterized, it may be possible to predict species' abundance from eDNA surveys, although we underscore that species- and system-specific variables are likely to limit the generality of any given quantitative model. Nevertheless, these findings provide an important step toward quantitative applications of eDNA in conservation and management.

Habitat diversity and heterogeneity play a fundamental role in structuring ecological communities. Dam emplacement and removal can fundamentally alter habitat characteristics, which in turn can affect associated biological communities. Beginning in the early 1900s, the Elwha and Glines Canyon dams in Washington, USA, withheld an estimated 30 million tonnes of sediment from river, coastal, and nearshore habitats. During the staged removal of these dams—the largest dam removal project in history—over 14 million tonnes of sediment were released from the former reservoirs. Our interdisciplinary study in coastal habitats—the first of its kind—shows how the physical changes to the river delta and estuary habitats during dam removal were linked to responses in biological communities. Sediment released during dam removal resulted in over a meter of sedimentation in the estuary and over 400 m of expansion of the river mouth delta landform. These changes increased the amount of supratidal and intertidal habitat, but also reduced the influx of seawater into the pre-removal estuary complex. The effects of these geomorphic and hydrologic changes cascaded to biological systems, reducing the abundance of macroinvertebrates and fish in the estuary and shifting community composition from brackish to freshwater-dominated species. Vegetation did not significantly change on the delta, but pioneer vegetation increased during dam removal, coinciding with the addition of newly available habitat. Understanding how coastal habitats respond to large-scale human stressors—and in some cases the removal of those stressors—is increasingly important as human uses and restoration activities increase in these habitats. This article is protected by copyright. All rights reserved.

Dam removal is widely used as an approach for river restoration in the United States. The increase in dam removals—particularly large dams—and associated dam-removal studies over the last few decades motivated a working group at the USGS John Wesley Powell Center for Analysis and Synthesis to review and synthesize available studies of dam removals and their findings. Based on dam removals thus far, some general conclusions have emerged: (1) physical responses are typically fast, with the rate of sediment erosion largely dependent on sediment characteristics and dam-removal strategy; (2) ecological responses to dam removal differ among the affected upstream, downstream, and reservoir reaches; (3) dam removal tends to quickly reestablish connectivity, restoring the movement of material and organisms between upstream and downstream river reaches; (4) geographic context, river history, and land use significantly influence river restoration trajectories and recovery potential because they control broader physical and ecological processes and conditions; and (5) quantitative modeling capability is improving, particularly for physical and broad-scale ecological effects, and gives managers information needed to understand and predict long-term effects of dam removal on riverine ecosystems. Although these studies collectively enhance our understanding of how riverine ecosystems respond to dam removal, knowledge gaps remain because most studies have been short (< 5 years) and do not adequately represent the diversity of dam types, watershed conditions, and dam-removal methods in the U.S.

Background Azathioprine (AZA) is an immunosuppressive drug, which is metabolised in the liver and kidneys into 6-thioguanine- the form responsible for the therapeutic effect. Despite its anti-inflammatory, antibacterial and immunomodulating properties, azathioprine has also dose-related side effects, such as bone marrow suppression, liver damage and pancreatitis. The purpose of this study was to assess the usefulness of monitoring the concentration of azathioprine metabolites: 6-tioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in the group of paediatric patients with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). Methods The clinical data of 46 paediatric patients (24 girls) with IBD and AIH, aged 8–17 years, hospitalised in the Department of Gastroenterology, who had undergone a blood examination for AZA metabolites concentration, were analysed. Results Initial mean dose of azathioprine was 1.23 mg/kg/day in IBD and 1.16 mg/kg/day in AIH. In 30% of patients, the concentrations of 6-TG and 6-MMP were within the normal range. Forty-eight per cent of patients required a dose change due to: elevated 6-TG concentration (32.6%) or underdosage (15.4%). After modification the mean dose was 1.16 mg/kg/day in IBD and 0.85 mg/kg/day in AIH. In 10.7 % of patients, the concentrations of 6-TG and 6 MMP were below the proper range, in the same percentage of patients metabolites were undetectable. Conclusion In a significant number of cases monitoring the concentration of AZA metabolites indicated the necessity to reduce the dose of AZA allowing to achieve the therapeutic optimum and prevent serious side effects. Receiving undetectable concentration of metabolites is a sign of non-compliance. The final doses of AZA were found to be lower than the recommended doses. Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels is a good strategy that can be used to optimise IBD and AIH therapeutics.

Completed SPIRIT (2013) checklist. (DOC 137 kb)

Supplementary information, providing additional information about the main trial outcome measures, as well as brain imaging sub-study recruitment, outcome measures and data analysis. (DOCX 3944 kb)

Resource competition between animals is influenced by a number of factors including the species, size and relative abundance of competing individuals. Stream-dwelling animals often experience variably available food resources, and some employ territorial behaviors to increase their access to food. We investigated the factors that affect dominance between resident, non-native brook trout and recolonizing juvenile coho salmon in the Elwha River, WA, USA, to see if brook trout are likely to disrupt coho salmon recolonization via interference competition. During dyadic laboratory feeding trials, we hypothesized that fish size, not species, would determine which individuals consumed the most food items, and that species would have no effect. We found that species, not size, played a significant role in dominance; coho salmon won 95% of trials, even when only 52% the length of their brook trout competitors. As the pairs of competing fish spent more time together during a trial sequence, coho salmon began to con...

Sediment pulses can cause widespread, complex changes to rivers and coastal regions. Quantifying landscape response to sediment-supply changes is a long-standing problem in geomorphology, but the unanticipated nature of most sediment pulses rarely allows for detailed measurement of associated landscape processes and evolution. The intentional removal of two large dams on the Elwha River (Washington, USA) exposed ~30 Mt of impounded sediment to fluvial erosion, presenting a unique opportunity to quantify source-to-sink river and coastal responses to a massive sediment-source perturbation. Here we evaluate geomorphic evolution during and after the sediment pulse, presenting a 5-year sediment budget and morphodynamic analysis of the Elwha River and its delta. Approximately 65% of the sediment was eroded, of which only ~10% was deposited in the fluvial system. This restored fluvial supply of sand, gravel, and wood substantially changed the channel morphology. The remaining ~90% of the released sediment was transported to the coast, causing ~60 ha of delta growth. Although metrics of geomorphic change did not follow simple time-coherent paths, many signals peaked 1–2 years after the start of dam removal, indicating combined impulse and step-change disturbance responses.

Lampreys have a worldwide distribution, are functionally important to ecological communities and serve significant roles in many cultures. In Pacific coast drainages of North America, lamprey populations have suffered large declines. However, lamprey population status and trends within many areas of this region are unknown and such information is needed for advancing conservation goals. We developed two quantitative PCR-based, aquatic environmental DNA (eDNA) assays for detection of Pacific Lamprey (Entosphenus tridentatus) andLampetraspp, using locked nucleic acids (LNAs) in the probe design. We used these assays to characterize the spatial distribution of lamprey in 18 watersheds of Puget Sound, Washington, by collecting water samples in spring and fall. Pacific Lamprey andLampetraspp were each detected in 14 watersheds and co-occurred in 10 watersheds. Lamprey eDNA detection rates were much higher in spring compared to fall. Specifically, the Pacific Lamprey eDNA detection rate was 3.5 times higher in spring and theLampetraspp eDNA detection rate was 1.5 times higher in spring even though larval lamprey are present in streams year-round. This significant finding highlights the importance of seasonality on eDNA detection. Higher stream discharge in the fall likely contributed to reduced eDNA detection rates, although seasonal life history events may have also contributed. These eDNA assays differentiate Pacific Lamprey andLampetraspp across much of their range along the west coast of North America. Sequence analysis indicates the Pacific Lamprey assay also targets otherEntosphenusspp and indicates theLampetraspp assay may have limited or no capability of detectingLampetrain some locations south of the Columbia River Basin. Nevertheless, these assays will serve as a valuable tool for resource managers and have direct application to lamprey conservation efforts, such as mapping species distributions, occupancy modeling, and monitoring translocations and reintroductions.

Dam removal is becoming an increasingly common tool to restore rivers. What would it take to replace lost electricity from removed hydroelectric dams with solar power?

Understanding landscape responses to sediment supply changes constitutes a fundamental part of many problems in geomorphology, but opportunities to study such processes at field scales are rare. The phased removal of two large dams on the Elwha River, Washington, exposed 21 ± 3 million m3, or ~ 30 million tonnes (t), of sediment that had been deposited in the two former reservoirs, allowing a comprehensive investigation of watershed and coastal responses to a substantial increase in sediment supply. Here we provide a source-to-sink sediment budget of this sediment release during the first two years of the project (September 2011–September 2013) and synthesize the geomorphic changes that occurred to downstream fluvial and coastal landforms. Owing to the phased removal of each dam, the release of sediment to the river was a function of the amount of dam structure removed, the progradation of reservoir delta sediments, exposure of more cohesive lakebed sediment, and the hydrologic conditions of the river. The greatest downstream geomorphic effects were observed after water bodies of both reservoirs were fully drained and fine (silt and clay) and coarse (sand and gravel) sediments were spilling past the former dam sites. After both dams were spilling fine and coarse sediments, river suspended-sediment concentrations were commonly several thousand mg/L with ~ 50% sand during moderate and high river flow. At the same time, a sand and gravel sediment wave dispersed down the river channel, filling channel pools and floodplain channels, aggrading much of the river channel by ~ 1 m, reducing river channel sediment grain sizes by ~ 16-fold, and depositing ~ 2.2 million m3 of sand and gravel on the seafloor offshore of the river mouth. The total sediment budget during the first two years revealed that the vast majority (~ 90%) of the sediment released from the former reservoirs to the river passed through the fluvial system and was discharged to the coastal waters, where slightly less than half of the sediment was deposited in the river-mouth delta. Although most of the measured fluvial and coastal deposition was sand-sized and coarser (> 0.063 mm), significant mud deposition was observed in and around the mainstem river channel and on the seafloor. Woody debris, ranging from millimeter-size particles to old-growth trees and stumps, was also introduced to fluvial and coastal landforms during the dam removals. At the end of our two-year study, Elwha Dam was completely removed, Glines Canyon Dam had been 75% removed (full removal was completed 2014), and ~ 65% of the combined reservoir sediment masses—including ~ 8 Mt of fine-grained and ~ 12 Mt of coarse-grained sediment—remained within the former reservoirs. Reservoir sediment will continue to be released to the Elwha River following our two-year study owing to a ~ 16 m base level drop during the final removal of Glines Canyon Dam and to erosion from floods with larger magnitudes than occurred during our study. Comparisons with a geomorphic synthesis of small dam removals suggest that the rate of sediment erosion as a percent of storage was greater in the Elwha River during the first two years of the project than in the other systems. Comparisons with other Pacific Northwest dam removals suggest that these steep, high-energy rivers have enough stream power to export volumes of sediment deposited over several decades in only months to a few years. These results should assist with predicting and characterizing landscape responses to future dam removals and other perturbations to fluvial and coastal sediment budgets.

The Elwha River restoration project, in Washington State, includes the largest dam-removal project in United States history to date. Starting September 2011, two nearly century-old dams that collectively contained 21 ± 3 million m3 of sediment were removed over the course of three years with a top-down deconstruction strategy designed to meter the release of a portion of the dam-trapped sediment. Gauging with sediment-surrogate technologies during the first two years downstream from the project measured 8,200,000 ± 3,400,000 tonnes of transported sediment, with 1,100,000 and 7,100,000 t moving in years 1 and 2, respectively, representing 3 and 20 times the Elwha River annual sediment load of 340,000 ± 80,000 t/y. During the study period, the discharge in the Elwha River was greater than normal (107% in year 1 and 108% in year 2); however, the magnitudes of the peak-flow events during the study period were relatively benign with the largest discharge of 292 m3/s (73% of the 2-year annual peak-flow event) early in the project when both extant reservoirs still retained sediment. Despite the muted peak flows, sediment transport was large, with measured suspended-sediment concentrations during the study period ranging from 44 to 16,300 mg/L and gauged bedload transport as large as 24,700 t/d. Five distinct sediment-release periods were identified when sediment loads were notably increased (when lateral erosion in the former reservoirs was active) or reduced (when reservoir retention or seasonal low flows and cessation of lateral erosion reduced sediment transport). Total suspended-sediment load was 930,000 t in year 1 and 5,400,000 t in year 2. Of the total 6,300,000 ± 3,200,000 t of suspended-sediment load, 3,400,000 t consisted of silt and clay and 2,900,000 t was sand. Gauged bedload on the lower Elwha River in year 2 of the project was 450,000 ± 360,000 t. Bedload was not quantified in year 1, but qualitative observations using bedload-surrogate instruments indicated detectable bedload starting just after full removal of the downstream dam. Using comparative studies from other sediment-laden rivers, the total ungauged fraction of

Systematic breeding of polled Fleckvieh (Simmental) cattle in Bavaria dates back until 1974 when the first polled cow was purchased for breeding purposes. Until 1985 three polled bulls and two more polled dams were purchased and from 1984 on the first homozygous bulls were produced via embryo transfer. Until 1990 the polled allele was only common in beef strains of the Fleckvieh breed. At the beginning of the 1990s the first polled alleles were introduced into the dairy herd of the State Research Farm in Grub. This research farm acted as the nucleus for the introgression of the polled allele in the dual-purpose lines of the Fleckvieh breed. Since 2003 polled calves in all herds under milk recording were systematically recorded and the polled phenotype was regularly examined by employees of the Bavarian State Research Institute for Agriculture. At the same time a systematic cooperation with Bavarian herdbook organizations and AI-stations was established. Between 2000 and 2011 in total 193 polled bulls were raised at the Bavarian State Research Institute for Agriculture (LfL), of which 37 entered AI-stations. Currently the dual-purpose population of Fleckvieh comprises 7055 polled cows and 175 polled AI-sires. In 2013 and 2014 approximately 22,000 and 32,000 polled calves were born per year. The analysis of relationships showed that the polled bulls are less related to the horned population and that until now the introgression has caused negligible amounts of additional inbreeding. It is expected that in 2021 the proportion of polled cows in the Fleckvieh dual-purpose population will be at 10.5% of all cows if the progression of polledness continues linearly. However, it can be expected that the progression will accelerate due to the new possibilities offered by genomic preselection of polled AI-bulls. First experiences with genomically preselected polled bulls show a very good acceptance among breeders.

Dam removal in the United States is increasing as a result of structural concerns, sedimentation of reservoirs, and declining riverine ecosystem conditions. The removal of the 32 m Elwha and 64 m Glines Canyon dams from the Elwha River in Washington, U.S.A., was the largest dam removal project in North American history. During the 3 yr of dam removal—from September 2011 to August 2014—more than ten million cubic meters of sediment was eroded from the former reservoirs, transported downstream, and deposited throughout the lower river, river delta, and nearshore waters of the Strait of Juan de Fuca. Water quality data collected in the estuary complex at the mouth of the Elwha River document how conditions in the estuary changed as a result of sediment deposition over the 3 yr the dams were removed. Rapid and large-scale changes in estuary conditions—including salinity, depth, and turbidity—occurred 1 yr into the dam removal process. Tidal propagation into the estuary ceased following a large sediment deposition event that began in October 2013, resulting in decreased salinity, and increased depth and turbidity in the estuary complex. These changes have persisted in the system through dam removal, significantly altering the structure and functioning of the Elwha River estuary ecosystem.

Analytical tools are needed in riverine science and management to bridge the gap between GIS and statistical packages that were not designed for the directional and dendritic structure of streams. We introduce linbin, an R package developed for the analysis of riverscapes at multiple scales. With this software, riverine data on aquatic habitat and species distribution can be scaled and plotted automatically with respect to their position in the stream network or—in the case of temporal data—their position in time. The linbin package aggregates data into bins of different sizes as specified by the user. We provide case studies illustrating the use of the software for (1) exploring patterns at different scales by aggregating variables at a range of bin sizes, (2) comparing repeat observations by aggregating surveys into bins of common coverage, and (3) tailoring analysis to data with custom bin designs. Furthermore, we demonstrate the utility of linbin for summarizing patterns throughout an entire ...

This is the first study that connects pharmacokinetics of tolperisone with genetic polymorphism of the enzymes involved in its metabolism in human. We aimed to identify the influence of polymorphism of two main enzymes (CYP2D6 and CYP2C19) on pharmacokinetic profile of parent drug.In a single-dose study, 28 healthy Caucasian male volunteers received an oral dose of 150 mg of tolperisone. The subjects were genotyped with respect to CYP2D6 and CYP2C19 enzymes. Plasma was sampled for up to 12 h post dose, followed by quantification of tolperisone by a fully validated HPLC-tandem mass spectrometry (MS/MS) method. The pharmacokinetic parameters were estimated using a non-compartmental method and compared statistically at level p0.05 across the genotyped groups.High variability (exceeded 100%) of main bioavailability parameters (AUCt, AUC(inf), C(max)) was observed in the whole group of subjects. An essential difference in the pharmacokinetics of tolperisone of quick metabolizers whose genotype expressed wild homozygote CYP2D6 *1/*1 with respect to heterozygous *1/*4 and *1/*5 subjects was demonstrated. The mean AUC(inf) was 2.1- and 3.4-fold higher in *1/*4 and *1/*5, respectively, than in *1/*1 subjects. In case of Cmax, the differences were greater and reached maximally 3.8 times (mean values 54.00, 98.85, and 205.20 ng/mL for CYP2D6 *1/*1, *1/*4, and *1/*5, respectively). Values of the parameters for the one subject that expressed *4/*4 genotype were even 8.5 times higher than in subjects with extensive or intermediate phenotype. Although CYP2C19 *1/*2 subjects had higher AUCt, AUC(inf), and Cmax values than *1/*1, no statistically significant differences were observed. Oral clearance (CL/F) significantly decreased by 65.7% in heterozygous *1/*2 relative to homozygous *1/*1 extensive metabolizers.In this study, we first demonstrated the effect of CYP2D6 polymorphism on pharmacokinetics of tolperisone in Caucasian subjects. The contribution of CYP2C19 enzyme seems to be less important.

A substantial increase in fluvial sediment supply relative to transport capacity causes complex, large-magnitude changes in river and floodplain morphology downstream. Although sedimentary and geomorphic responses to sediment pulses are a fundamental part of landscape evolution, few opportunities exist to quantify those processes over field scales. We investigated the downstream effects of sediment released during the largest dam removal in history, on the Elwha River, Washington, USA, by measuring changes in riverbed elevation and topography, bed sediment grain size, and channel planform as two dams were removed in stages over two years. As 10.5 million t (7.1 million m3) of sediment was released from two former reservoirs, downstream dispersion of a sediment wave caused widespread bed aggradation of ~ 1 m (greater where pools filled), changed the river from pool–riffle to braided morphology, and decreased the slope of the lowermost river. The newly deposited sediment, which was finer than most of the pre-dam-removal bed, formed new bars (largely pebble, granule, and sand material), prompting aggradational channel avulsion that increased the channel braiding index by almost 50%. As a result of mainstem bed aggradation, floodplain channels received flow and accumulated new sediment even during low to moderate flow conditions. The river system showed a two- to tenfold greater geomorphic response to dam removal (in terms of bed elevation change magnitude) than it had to a 40-year flood event four years before dam removal. Two years after dam removal began, as the river had started to incise through deposits of the initial sediment wave, ~ 1.2 million t of new sediment (~ 10% of the amount released from the two reservoirs) was stored along 18 river km of the mainstem channel and 25 km of floodplain channels. The Elwha River thus was able to transport most of the released sediment to the river mouth. The geomorphic alterations and changing bed sediment grain size along the Elwha River have important ecological implications, affecting aquatic habitat structure, benthic fauna, salmonid fish spawning and rearing potential, and riparian vegetation. The response of the river to dam removal represents a unique opportunity to observe and quantify fundamental geomorphic processes associated with a massive sediment influx, and also provides important lessons for future river-restoration endeavors.

The coastal marine ecosystem near the Elwha River was altered by a massive sediment influx-over 10 million tonnes-during the staged three-year removal of two hydropower dams. We used time series of bathymetry, substrate grain size, remotely sensed turbidity, scuba dive surveys, and towed video observations collected before and during dam removal to assess responses of the nearshore subtidal community (3 m to 17 m depth). Biological changes were primarily driven by sediment deposition and elevated suspended sediment concentrations. Macroalgae, predominantly kelp and foliose red algae, were abundant before dam removal with combined cover levels greater than 50%. Where persistent sediment deposits formed, macroalgae decreased greatly or were eliminated. In areas lacking deposition, macroalgae cover decreased inversely to suspended sediment concentration, suggesting impacts from light reduction or scour. Densities of most invertebrate and fish taxa decreased in areas with persistent sediment deposition; however, bivalve densities increased where mud deposited over sand, and flatfish and Pacific sand lance densities increased where sand deposited over gravel. In areas without sediment deposition, most invertebrate and fish taxa were unaffected by increased suspended sediment or the loss of algae cover associated with it; however, densities of tubeworms and flatfish, and primary cover of sessile invertebrates increased suggesting benefits of increased particulate matter or relaxed competition with macroalgae for space. As dam removal neared completion, we saw evidence of macroalgal recovery that likely owed to water column clearing, indicating that long-term recovery from dam removal effects may be starting. Our results are relevant to future dam removal projects in coastal areas and more generally to understanding effects of increased sedimentation on nearshore subtidal benthic communities.