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Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer's disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases.

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn’s disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.

Abstract Background Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA. Methods This was a prospective case–control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Results Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed z-score ≤ − 1 (at least borderline–mild impairment) in ≥ 2 cognitive domains, 14% performed z-score ≤ − 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = − 0.37, 95% confidence intervals [− 0.61, − 0.12]), verbal (MD = − 0.34 [− 0.62, − 0.07]), and visual/constructive functions (MD = − 0.26 [− 0.47, − 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = − 0.44 [− 0.82, − 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance. Conclusions In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue. Trial registration ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.

Abstract Background Systems ensuring continuity of care through the treatment chain improve outcomes for traumatic brain injury (TBI) patients. Non-neurosurgical acute care trauma hospitals are central in providing care continuity in current trauma systems, however, their role in TBI management is understudied. This study aimed to investigate characteristics and care pathways and identify factors associated with interhospital transfer to neurotrauma centers for patients with isolated moderate-to-severe TBI primarily admitted to acute care trauma hospitals. Methods A population-based cohort study from the national Norwegian Trauma Registry (2015–2020) of adult patients (≥ 16 years) with isolated moderate-to-severe TBI (Abbreviated Injury Scale [AIS] Head ≥ 3, AIS Body

Abstract Positron emission tomography (PET) constitutes a functional imaging technique that is harnessed to probe biological processes in vivo. PET imaging has been used to diagnose and monitor the progression of diseases, as well as to facilitate drug development efforts at both preclinical and clinical stages. The wide applications and rapid development of PET have ultimately led to an increasing demand for new methods in radiochemistry, with the aim to expand the scope of synthons amenable for radiolabeling. In this work, we provide an overview of commonly used chemical transformations for the syntheses of PET tracers in all aspects of radiochemistry, thereby highlighting recent breakthrough discoveries and contemporary challenges in the field. We discuss the use of biologicals for PET imaging and highlight general examples of successful probe discoveries for molecular imaging with PET – with a particular focus on translational and scalable radiochemistry concepts that have been entered to clinical use.

Introduction. Dietary supplements with vitamin and calcium are recommended to nursing home residents in Denmark, but adherence to the recommendation is low. In a previous part of this study, we reported improved adherence by means of The Model for Improvement leading to increased awareness and change of workflows at two nursing homes. However, potential effects of this improved adherence are unknown. Objective. The objective of this substudy was to investigate if the improved adherence to the recommendation affected vitamin D status, muscle strength, and physical functioning of the residents. Methods. This was a 20-week quasiexperimental study involving 40 residents from two Danish nursing homes. Baseline and endpoint measurements took place in October 2021 and March 2022, respectively. Outcomes were number of residents taking vitamin D and calcium supplements; vitamin D status; handgrip strength; and physical functioning with timed-up-and-go test and 30-second chair stand test. Results. Prevalence of vitamin D supplement users increased from 45 to 78% (mean dose 41 μg) and of calcium supplement users from 40 to 72% (mean dose 769 mg) (both P=0.002). Among those having blood sampled at both baseline and endpoint (n = 30), mean vitamin D status increased from 66.6 ± 31.7 nmol/L to 82.8 ± 26.3 nmol/L (P

Malignant melanoma is a highly immunogenic tumour, and the immune profile significantly influences cancer development and response to immunotherapy. The peripheral immune profile may identify high risk patients. The current study showed reduced levels of CD4+ T cells and increased levels of CD8+ T cells in peripheral blood from malignant melanoma patients compared with controls. Percentages of peripheral CD56dimCD16+ NK cells were reduced and CD56brightCD16−KIR3+ NK cells were increased in malignant melanoma patients. Late stage malignant melanoma was correlated with low levels of CD4+ T cells and high levels of CD56brightCD16−KIR3+ NK cells. Finally, high levels of Tregs in peripheral blood were correlated with poor overall survival and disease-free survival. The results indicate that changes in specific immune cell subsets in peripheral blood samples from patients at the time of diagnosis may be potential biomarkers for prognosis and survival. Further studies will enable clarification of independent roles in tumour pathogenesis.

Ecdysteroid molting hormone synthesis is directed by a pair of molting glands or Y-organs (YOs), and this synthesis is inhibited by molt-inhibiting hormone (MIH). MIH is a member of the crustacean hyperglycemic hormone (CHH) neuropeptide superfamily, which includes CHH and insect ion transport peptide (ITP). It is hypothesized that the MIH receptor is a Class A (Rhodopsin-like) G protein-coupled receptor (GPCR). The YO of the blackback land crab, Gecarcinus lateralis, expresses 49 Class A GPCRs, three of which (Gl-CHHR-A9, -A10, and -A12) were provisionally assigned as CHH-like receptors. CrusTome, a transcriptome database assembled from 189 crustaceans and 12 ecdysozoan outgroups, was used to deorphanize candidate MIH/CHH GPCRs, relying on sequence homology to three functionally characterized ITP receptors (BNGR-A2, BNGR-A24, and BNGR-A34) in the silk moth, Bombyx mori. Phylogenetic analysis and multiple sequence alignments across major taxonomic groups revealed extensive expansion and diversification of crustacean A2, A24, and A34 receptors, designated CHH Family Receptor Candidates (CFRCs). The A2 clade was divided into three subclades; A24 clade was divided into five subclades; and A34 was divided into six subclades. The subclades were distinguished by conserved motifs in extracellular loop (ECL) 2 and ECL3 in the ligand-binding region. Eleven of the 14 subclades occurred in decapod crustaceans. In G. lateralis, seven CFRC sequences, designated Gl-CFRC-A2α1, -A24α, -A24β1, -A24β2, -A34α2, -A34β1, and -A34β2, were identified; the three A34 sequences corresponded to Gl-GPCR-A12, -A9, and A10, respectively. ECL2 in all the CFRC sequences had a two-stranded β-sheet structure similar to human Class A GPCRs, whereas the ECL2 of decapod CFRC-A34β1/β2 had an additional two-stranded β-sheet. We hypothesize that this second β-sheet on ECL2 plays a role in MIH/CHH binding and activation, which will be investigated further with functional assays.

With increasing anthropogenic activities, freshwater ecosystems around the world are becoming increasingly affected by various pressures, including eutrophication, overfishing, and irrational stocking, which may have a negative impact on the food web structure. Despite the extensive research and proposed management measures for eutrophic lakes, there are only few analysis on long-term monitoring data regarding fishery resources. Additionally, there is a lack of evaluation and prediction of the effectiveness of current fish management policies. To remedy this, we analyzed long-term monitoring data from Lake Taihu, China, a severely eutrophicated lake with a skewed fish size structure exhibiting dominance of small individuals. We first constructed 14 Ecopath models to investigate how trophic interactions and biomass fluxes changed from 2007 to 2020. Subsequently, the Ecosim model was used to predict how the biomass of fish and the ecosystem network respond to the initiated 10-years fishing ban. Our results demonstrate long-term changes in fish biomass and ecosystem stability. The analyses revealed that 1) the biomass development in different feeding types of fish is controlled by human activities (mainly catches and stocking) and trophic interactions and 2) the rate of decline in ecosystem network stability slows down during the fishing ban. The primary focus of this study was to fill the gap in long-term serial studies of fish monitoring data and ecosystem stability in the lake and, for the first time, to predict the outcome of the fishing ban from an ecosystem perspective using the Ecosim model. Overall, our results emphasize the importance of rational stocking and fishing policies and provide a better understanding of the changes in the ecological dynamics in Lake Taihu of relevance for the management and restoration of the lake.

Inspired by Erling’s abiding interest in variational linguistics, our contribution aims at exploring two interesting, yet rather unexplored, cases of grammaticalization processes – i.e. the grammaticalization and subsequent actualization (Andersen 2001a, 2008) of the preposition vu (‘since’) and the conjunction vu que (‘given’) in French. Our paper is intended to investigate these items, which are found in French from the Middle French period, in order to consider whether they are introduced “from above” or “from below”. Most frequently, innovations start from below, i.e. in unmarked contexts.1 In Modern French the preposition vu is mainly found in legal texts, whereas vu que seems to have spread from legal texts to other registers. This suggests a diachronic process starting from above. We intend to investigate this question by use of diverse corpora including administrative language, novels, historical texts, and web-language, focusing on the role of diachronic, diaphasic (text type), and diamesic variation parameters.

Nutrient management is a global challenge for protecting water bodies from eutrophication and for retaining and sustainably recycling phosphorus within the biosphere. This challenge is especially important for water resource recovery facilities (WRRFs) in jurisdictions that limit nutrient loads in plant effluent. A microalgae-based biofilm platform has been designed, constructed, and tested to remove phosphorus and nitrogen from anaerobic digester (AD) effluent filtrate through cultivating biomass and inducing the precipitation of a mineral called struvite (NH₄MgPO₄ · 6H₂O) using a rotating algae biofilm reactor (RABR). RABRs function by rotating a growth substratum through nutrient rich water and then into the atmosphere, immersing microalgae in both sunlight and water. Photosynthesis is utilized in RABR operation to enhance struvite formation by increasing the pH value within the biofilm through the uptake of carbon dioxide from solution. Measurements of pH trended higher with depth through the biofilm when exposed to light confirming the function of photosynthesis in increasing pH and, as a consequence, struvite formation. In addition, reducing RPM allows more time for water to evaporate through exposure of the biofilm to the atmosphere and provides a management option to exceed struvite solubility product. Struvite precipitation was predicted based on chemical analysis and MINTEQ modeling of ADE, was confirmed using Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy, and quantified by determining ash content. Increase in pH within the biofilm was confirmed as photosynthetic photon flux density increased. While struvite precipitation and removal from wastewater is conventionally accomplished through physicochemical methods, this research is the first report of struvite enhanced formation through algae biofilm-based photosynthesis processes.

AbstractIn head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM). The hOBs were exposed to ionizing γ-irradiation in single doses of 2, 6 or 10 Gy. Twenty-one days post-irradiation, cell nuclei and collagen production were quantified. Cytotoxicity and indicators of differentiation were measured and compared to unirradiated controls. Radiation with backscatter from titanium significantly reduced the number of hOBs but increased the alkaline phosphatase activity in both types of medium when adjusted to the relative cell number on day 21. Irradiated hOBs on the TiF-surface produced similar amounts of collagen as unirradiated controls when cultured in DM. The majority of osteogenic biomarkers significantly increased on day 21 when the hOBs had been exposed to 10 Gy, while the opposite or no effect was observed after lower doses. High doses reinforced with backscatter from titanium resulted in smaller but seemingly more differentiated subpopulations of osteoblasts.

Abstract Background Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case–control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing. Methods An individually matched (sex and age) prospective case–control study comparing patients with recent-onset depression to healthy controls. CSF was analyzed with the Mesoscale V-PLEX Neuroinflammation Panel 1. Outcomes: comparisons of analyte levels in the CSF between groups with interleukin (IL)-6 and IL-8 as primary outcomes and 23 other cytokines as secondary outcomes. Results We included 106 patients (84.0% outpatients) with recent-onset depression and 106 healthy controls. There were no significant differences in the primary outcomes IL-6 (relative mean difference (MD): 1.10; 95% confidence interval (CI) 0.93–1.30; p = 0.276) or IL-8 levels (MD: 1.05; 95% CI 0.96–1.16; p = 0.249) relative to healthy controls. IL-4 was 40% higher (MD: 1.40; 95% CI 1.14–1.72; p = 0.001), monocyte chemoattractant protein (MCP)-1 was 25% higher (MD: 1.25; 95% CI 1.06–1.47; p = 0.009) and macrophage inflammatory protein (MIP)-1β was 16% higher (MD: 1.16; 95% CI 1.02–1.33; p = 0.025) in patients with depression relative to healthy controls. However, only IL-4 was significantly elevated after correction for multiple testing of secondary outcomes (p = 0.025). Conclusion We found no significant differences in CSF levels of the co-primary outcomes IL-6 and IL-8, however, the higher CSF levels of IL-4, MCP-1 and MIP-1β among patients with recent-onset depression compared to healthy controls indicate a potential role of these cytokines in the neuroinflammatory response to depression.

Drinking water is closely related to human health, disease and mortality, and contaminated drinking water causes 485,000 deaths from diarrhea each year worldwide. China has been facing increasingly severe water scarcity due to both water shortages and poor water quality. Ensuring safe and clean drinking water is a great challenge and top priority, especially for China with 1.4 billion people. In China, more than 4000 centralized drinking water sources including rivers, lakes and reservoirs, and groundwater have been established to serve urban residents. However, there is little knowledge on the percentage, serving population and water quality of three centralized drinking water source types. We collected nationwide centralized drinking water sources data and serving population data covering 395 prefecture-level and county-level cities and water quality data in the two most populous provinces (Guangdong and Shandong) to examine their contribution and importance. Geographically, the drinking water source types can be classified into three clear regions exhibiting apparent differences in the respective contributions of rivers, lakes and reservoirs, and groundwater. We further found that overall, lakes and reservoirs account for 40.6% of the centralized drinking water sources vs. river (30.8%) and groundwater (28.6%) in China. Lakes and reservoirs are particularly important in the densely populated eastern region, where they are used as drinking water sources by 51.0% of the population (318 million). Moreover, the contribution to the drinking water supply from lakes and reservoirs is increasing due to their better water quality and many cross-regional water transfer projects. These results will be useful for the government to improve and optimize the establishment of centralized drinking water sources, which provide safe and clean drinking water in China to safeguard people's lives and health and realize sustainable development goals.

This study investigated risk factors for school absenteeism in a sample of 983 children in elementary and lower secondary schools in Denmark, using administrative data on absenteeism measured in the year following risk factor measurement. Risk factors were measured by survey (children and teachers) and register data. Two methods of determining importance of risk factors were compared: individual risk factors versus four domains of risk factors (psychological problems, physical problems, school factors, and demographic and family factors). Significant individual risk factors were found in all four domains. When teacher-reports of the children's psychological problems were used, psychological problems was the risk factor domain that predicted school absenteeism best and the school-related factors domain predicted worst. The results highlight the need to distinguish between single risk factors that identify groups of individuals with elevated risk of school absence and the detection of risk factor domains that better predict school absence.

Aquatic plants play a key role in the structuring and functioning of shallow lake ecosystems. However, eutrophication often triggers shifts in plant communities and species diversity, especially in the early stages when the water is still clear. Additionally, water depth is an important factor regulating aquatic plant communities. We conducted a 50-day mesocosm study to investigate how water depth (50 cm and 100 cm) affected the functional traits (vertical expansion versus horizontal colonisation) of 20 aquatic plants under eutrophic clear-water conditions. Among the selected species, the submerged plants Hydrocotyle vulgaris and Limnophila indica exhibited higher plant height or biomass in deeper water, while the emergent plants Myriophyllum aquaticum showed the opposite trend. Additionally, Ludwigia peploides subsp. stipulacea exhibited better vertical growth than the remaining species, and the submerged species Vallisneria denseserrulata had better horizontal colonisation. There was a positive correlation between plant height and rhizome length, indicating the absence of a trade-off between vertical growth and horizontal expansion. Our findings suggest an overall resilience of aquatic plants to varying water depths within our study range and highlight the importance of analysing functional traits when selecting appropriate species in freshwater ecosystem restoration, particularly in the face of climate change-induced water depth fluctuations.

Jumps racing is a form of Thoroughbred horse racing that involves hurdles and steeples and typically longer distances, and heavier weights compared with flat racing, which does not incorporate obstacles. In Australia, jumps racing is carried out only in Victoria, one of eight states and territories. The continuation of jumps racing is contentious due to the higher risk of fatalities, falls and injuries for horses, compared with flat racing. While measures have been introduced by the industry to improve the safety of riders and horses, the rates of fatalities, falls and injuries in horses participating in jumps races have not been collectively reported in Australia since the 2012 to 2014 race seasons. Although information on individual horse fatalities, falls and injuries is published by Racing Victoria in Stewards’ Reports, the data are not aggregated, and so cannot readily be used to assess trends or evaluate the efficacy of safety measures introduced by the industry. The aim of this study was to determine the fatality, fall and injury rates for horses participating in hurdle and steeplechase races in Victoria in the 2022 and 2023 Thoroughbred horse jumps racing seasons compared with horses participating in flat races at the same race meets. Data on horse fatalities, falls and injuries were extracted from the published Racing Victoria race results and Stewards’ Reports for the jumps races (n = 150) and corresponding flat races (n = 157) held at the 38 jumps race meets in Victoria in 2022 and 2023. Overall, horse fatalities, falls and injuries occurred at higher rates in jumps races compared with flat races during the study period. The rate of horse fatalities in jumps races was 3.3 per 1000 starts, with no fatalities in flat races. The rate of horse falls in hurdle races was 24 per 1000 starts and 41.6 per 1000 starts in steeplechase races, comparable with rates previously reported in the 2012 to 2014 seasons. There were no falls in flat races. Horse injuries occurred at a rate of 68.9 per 1000 starts in jumps races compared with 18.8 per 1000 starts in flat races. In hurdle and steeplechase races, veterinary clearance being required following horse injury was 5.4 times (OR 5.4, 95% CI 2.8–10.2) and 7.2 times (OR 7.2, 95% CI 3.3–15.6) more likely, respectively, compared with flat races. The risk of trauma was 4 times more likely in hurdle and steeplechase races (OR 4.8, 95% CI 1.7–13.3 and OR 4.1, 95% CI 1.2–13.4, respectively) and the risk of lameness was increased by 2.5 times in hurdles (OR 2.5, 95% CI 1.2–5.2) and 5.1 times in steeplechase races (OR 5.1, 95% CI 2.3–11.5), compared with flat races. These findings support concerns about the welfare of horses involved in jumps racing and of the need for further safety measures to reduce these risks.

The Secondary Education and Social Change (SESC) research project team at the University of Cambridge collaborated with four secondary school history teachers to produce resource packs for teaching Key Stage 3 pupils about post-war British social history through the history of secondary education. In this article, Chris Jeppesen explains the focus of the project and the design of the resource packs. He makes a case for teaching post-war British social history and shows the value of education as a lens through which to do so. Hannah Cusworth and Molly Navey, two of the teachers involved, offer their evaluation of the collaborative experience and the design and impact of the resources.

Educational developers in universities and colleges design, develop, and deliver courses and programs for professors and teaching assistants (TAs) to support teaching and learning in postsecondary institutions. These courses and programs, however, are often not accredited, so the Educational Developers Caucus (EDC) created a working group to explore the appetite for a Canadian accreditation process, and then design and implement a framework. This article summarizes the working group's outcomes, and reports on an initial evaluation of their impact, arguing for their contribution to enhancing the quality of faculty and TA development courses and programs and, thereby, of teaching and learning.

Does participation in a reflective teaching development program transform educators? In a three-year teaching development program, faculty met in small interdisciplinary groups with peer facilitators and used online resources to complement their learning activities. The first two cohorts of participants found that involvement in a teaching development program encouraged them to develop self-reflective practices that they viewed as positively impacting their teaching. While valuing the collaborative and collegial relationships created through program participation, as these supported their individual growth and development, faculty also identified challenges that created barriers to their participation in the program.

Patients with localized non-small cell lung cancer (NSCLC) considered unfit for surgery are at substantially increased risk of venous thromboembolism. Radiotherapy may further increase this risk. We aim to investigate the impact of stereotactic body radiotherapy (SBRT) on thrombin generation and platelet aggregation. We included 110 patients with localized NSCLC treated with SBRT. Blood samples were obtained prior to SBRT, immediately after SBRT completion, and 4-6 weeks following SBRT. Ex vivo and in vivo thrombin generations were analyzed using a calibrated automated thrombogram and commercial enzyme-linked immunosorbent assays. Platelet aggregation was evaluated using multiple electrode aggregometry. No significant differences were found in ex vivo or in vivo thrombin generation between blood samples before and immediately after SBRT treatment. Platelet aggregation was lower immediately after SBRT than before SBRT (TRAP: P = 0.04 and ASPI: P = 0.02) but remained within the reference interval. SBRT did not affect in vivo and ex vivo thrombin generation or platelet aggregation. SBRT did not cause prothrombotic changes in the coagulation in this study population of SBRT-treated patients with localized NSCLC.

Rotifers are one of the most important functional groups in lentic freshwaters, and mainly structured by predation or competition from crustaceans and food availability from phytoplankton. Their functional traits involving in defense and food utilization provides insights into the functional diversity and assembly of their communities. Tropical urban reservoirs are commonly subjected to intense fish culture and strong eutrophication, and rotifers become the dominant component of the zooplankton communities and play an important role in ecosystem functioning. Knowledge about the functional diversity and functional redundancy of rotifers is therefore of relevance for effective ecosystem management. In tropical reservoirs, we hypothesized that functional diversity and redundancy of rotifer communities are synergistically affected by top-down and bottom-up effects, and that they strongly change seasonally with environmental conditions at local scale as well as with connectivity between reservoirs at regional scale. To test these hypotheses, we investigated the seasonal dynamics of taxonomic and functional diversities in twenty-five tropical urban reservoirs. Traits of rotifers mainly associated with body size, feeding behavior, and defensive strategies were used to explore the drivers of functional diversity and functional redundancy. We found that, at the local scale, both taxonomic alpha and functional alpha diversities of rotifers increased from the wet to the dry season, whereas the functional alpha redundancy showed no significant change. Crustacean abundance (top-down effect) and phytoplankton biomass (bottom-up effect) were the dominant variables explaining the variation of taxonomic and functional alpha diversities. At the regional scale, both the taxonomic and the functional beta diversities of rotifer communities decreased from the wet to the dry season. However, functional beta redundancy increased, accompanied by a reduction in environmental distance, i.e., biological and physicochemical distance. Thus, weakened environmental heterogeneity and strengthened homogenization of biological selection resulted in a more similar functional trait composition than a more similar taxonomic composition between reservoirs.

Stocking of filter-feeding fish (mainly Hypophthalmichthys molitrix and Aristichthys nobilis) is a common method used in lakes and reservoirs in (sub)tropical China to control phytoplankton, but the results are ambiguous and lack long-term data to support. We analysed a decade (2010-2020) of monitoring data from a subtropical plateau reservoir, southwest China, to which filter-feeding fish were stocked annually. We found that the total phytoplankton biomass, cyanobacteria biomass and average individual mass of phytoplankton decreased significantly during the study period despite absence of nutrient concentration reduction. However, the grazing pressure of zooplankton on phytoplankton also decreased markedly as judged from changes in the ratio of zooplankton biomass to phytoplankton biomass and Daphnia proportion of total zooplankton biomass. This is likely a response to increasing predation on zooplankton by the stocked fish. Our results also indicated that water temperature, total phosphorus and water level promoted phytoplankton growth. Our results revealed that filter-feeding fish contributed to the decline in the biomass of phytoplankton but that it also had a strong negative effect on the grazing pressure of zooplankton on phytoplankton, even in this deep reservoir where zooplankton may have a better chance of survival through vertical migration. The particular strong effect on zooplankton is most likely due to imbalance of stocking and harvesting of fish. In the management of eutrophic reservoirs, the reduction of external nutrient loading should have highest priority. In highland (low temperature) deep-water eutrophic reservoirs, stocking of filter-feeding fish may help to control filamentous phytoplankton provided that the fish stocking is properly managed. The optimal stocking intensity of filter-feeding fish that can help control phytoplankton in such reservoirs without excessive impact on large-bodied zooplankton is a topic for further elucidation, however.

Introduction: Circulating fetal cells isolated from maternal blood can be used for prenatal testing, representing a safe alternative to invasive testing. The present study investigated the potential of cell-based noninvasive prenatal testing (NIPT) for diagnosing monogenic disorders dependent on the mode of inheritance.Methods: Maternal blood samples were collected from women opting for prenatal diagnostics for specific monogenic disorders (N = 7). Fetal trophoblasts were enriched and stained using magnetic activated cell sorting and isolated by fluorescens activated single-cell sorting. Individual cells were subject to whole genome amplification, and cells of fetal origin were identified by DNA-profiling using short tandem repeat markers. The amplified fetal DNA was input for genetic testing for autosomal dominant-, autosomal recessive-, X-linked and repeat expansion disorders by direct variant analysis and haplotyping. The cell-based NIPT results were compared with those of invasive testing.Results: In two cases at risk of skeletal dysplasia, caused by variants in the FGFR3 gene (autosomal dominant disorders), cell-based NIPT correctly stated an affected fetus, but allelic dropout of the normal alleles were observed in both cases. Cell-based NIPT gave an accurate result in two cases at risk of autosomal recessive disorders, where the parents carried either different diastrophic dysplasia causing variants in the SLC26A2 gene or the same cystic fibrosis disease-causing variant in the CFTR gene. Cell-based NIPT accurately identified an affected male fetus in a pregnancy at risk of Duchenne muscular dystrophy (DMD gene, X-linked recessive disorders). In two cases at risk of the myotonic dystrophy type 1 (DMPK gene, repeat expansion disorder), cell-based NIPT correctly detected an affected and an unaffected fetus, respectively.Discussion: Circulating fetal cells can be used to detect both maternally- and paternally inherited monogenic disorders irrespective of the type of variant, however, the risk of allelic dropout must be considered. We conclude that the clinical interpretation of the cell-based NIPT result thus varies depending on the disorders’ mode of inheritance.

Coastal eutrophication is a prevalent threat to the healthy functioning of ecosystems globally. While degraded water quality can be detected by monitoring oxygen, nutrient concentrations, and algal abundance, establishing regulatory guidelines is complicated by a lack of baseline data (e.g., pre-Anthropocene). We use historical carbon and nitrogen isoscapes over ~300 years from sediment cores to reconstruct spatial and temporal changes in nutrient dynamics for a central California estuary, Elkhorn Slough, where development and agriculture dramatically enhanced nutrient inputs over the past century. We found strong contrasts between current sediment stable isotopes and those from the recent past, demonstrating shifts exceeding those in previously studied eutrophic estuaries and substantial increases in nutrient inputs. Comparisons of contemporary with historical isoscapes also revealed that nitrogen sources shifted from a historical marine-terrestrial gradient with higher δ15N near the inlet to amplified denitrification at the head and mouth of the modern estuary driven by increased N inputs. Geospatial analysis of historical data suggests that an increase in fertilizer application – rather than population growth or increases in the extent of cultivated land – is chiefly responsible for increasing nutrient loads during the 20th century. This study demonstrates the ability of isotopic and stoichiometric maps to provide important perspectives on long-term shifts and spatial patterns of nutrients that can be used to improve management of nutrient pollution.

Variation in hydrological connectivity (HC) between rivers and lakes gives rise to periodic large water level fluctuation (WLF) in river-connected lakes (RCL). However, how WLF shapes the material cycling and concomitant trophodynamics of RCL remain unclear. Here we evaluated the resource availability, relative contributions of autochthonous and allochthonous carbon sources (by Bayesian mixing models) and trophic structure (using δ13C and δ15N) of Lake Poyang, the largest freshwater lake in China, during different hydrological periods. Terrestrial C3 plants in the aquatic/terrestrial transition zones (ATTZ) were the main supporter of aquatic consumers all year round. Compared with historical data, the contributions of autochthonous production to aquatic food webs were low. This is primarily ascribed to the influences of hydrological regimes in that the operation of Three Gorges Dam and HC changed the rhythm of WLF in Lake Poyang, restricting the production of aquatic vegetation and epiphytic algae. Most common fish species indicated higher trophic positions (TPs) during the dry than wet season, but only eleven of thirty-six common species showed a statistically significant increase (p

There is a lack of reliable and valid PTSD tests for young children that cannot read or are weak readers. The semi-projective cartoon test, “Darryl”, which is read aloud, is a measure that appeals to this age group. The test has been applied in both clinical and epidemiological studies.

In the first datafied pandemic, the production of interactive Covid-19 data maps was intensified by state institutions and corporate media. Maps have been used by states and citizens to understand the advance and retreat of the contagion and monitor vaccine rates. However, the visualisations being used are often based on non-comparable data types across countries, leading to visual misrepresentations. Many pandemic data visualisations have consequently had a negative impact on public debate, contributing to an infodemic of disinformation that has stigmatised marginalised groups and detracted from social justice objectives. Counter to such hegemonic mapping, counter-data maps, produced by marginalised groups, have revealed hidden inequalities, supporting calls for intersectional health justice. This article investigates the ways in which various intersectional global communities have appropriated data, produced counter-data maps, unveiled hidden social realities, and generated more authentic social meanings through emergent counter-data mapping imaginaries. We use a comparative multi-case study, based on a multi case-study of three Covid-19 data mapping projects, namely Data for Black Lives (US), Indigenous Emergency (Brazil), and CityLab maps (global). Our findings indicate that counter-data mapping imaginaries are deeply embedded in community-oriented notions of spatiality and relationality. Moreover, the cartographic process tends to reflect alternative imaginaries through four key dimensions of data mapping practice—objectives, uses, production, and ownership. We argue that counter-data mapping is the new frontier of digital media activism and community communication, as it extends the projects of data justice and community media activism, generating new practices in the activist repertoire of communicative action.

Background: It is known that poppy seeds may contain opiates naturally, i.e. morphine and codeine. Morphine and codeine, however, are also commonly used drugs. Drug tests in urine being positive for opiates are sometimes explained by the consumption of poppy seeds in the form of baked goods. In such cases it can be challenging to determine what was actually ingested. The aim of this study was to examine the amount of poppy seeds needed to be ingested to yield positive opiate results with our analytical methods. Material and methods: In all, 16 volunteers divided into 4 groups (A-D) ate poppy seeds from either (A) 1-4 rolls, (B) 1-4 crisp breads, (C) spice jar (48 grams) or (D) spice bag (48 grams). Urine samples collected during the following 24 hours were analyzed with immunological screening method and specific chromatographic method (LC-MSMS). Results: No samples from group A and B were positive with the immunological method, but one subject in group B (4 crisp breads) was positive for morphine with the chromatographic method. In groups C and D all subjects had two or more positive tests measured with immunological and chromatographic method. There were significant differences in measured levels between groups C and D. No samples contained higher concentration of codeine than morphine in this study. Interpretation: Consumption of poppy seeds can yield positive test results for opiates, depending on the quantity of poppy seeds consumed. Consumption of the same amount of poppy seeds can produce very different levels of opiates depending on the type and origin of the seeds ingested.

Sune Moeller Skov-Jeppesen,1,2 Nicky Anúel Petersen,1 Knud Bonnet Yderstraede,2,3 Boye L Jensen,4 Claus Bistrup,2,5 Lars Lund1,2 1Department of Urology, Odense University Hospital, Odense, Denmark; 2Clinical Institute, University of Southern Denmark, Odense, Denmark; 3Department of Endocrinology, Odense University Hospital, Odense, Denmark; 4Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; 5Department of Nephrology, Odense University Hospital, Odense, DenmarkCorrespondence: Sune Moeller Skov-Jeppesen, Department of Urology, Odense University Hospital, Sdr. Boulevard 29, Odense, 5000, Denmark, Tel +45 51210911, Fax +45 65411726, Email sun_mjep@hotmail.comBackground: Low-intensity extracorporeal shockwave therapy (LI-ESWT) has been suggested as a treatment for vascular diseases such as ischemic heart disease, diabetic foot ulcers, and erectile dysfunction. Primarily, LI-ESWT is known for its ability to stimulate angiogenesis and activation of stem cells in target tissues. Application of LI-ESWT in chronic progressive renal diseases is a novel area. The aim of the present review was to summarize available data on the effects of LI-ESWT used in the setting of renal diseases.Methods: We systematically searched PubMed, Medline, and Embase databases for relevant studies. Our review included the results from preclinical animal experiments and clinical research.Results: Eleven animal studies and one clinical study were included in the review. In the animal studies, LI-ESWT was used for the treatment of hypertensive nephropathy (n=1), diabetic nephropathy (n=1), or various types of ischemic renal injury (ie, artery occlusion, reperfusion injury) (n=9). The clinical study was conducted in a single-arm cohort as a Phase 1 study with patients having diabetic nephropathy. In animal studies, the application of LI-ESWT was associated with several effects: LI-ESWT led to increased VEGF and endothelial cell proliferation and improved vascularity and perfusion of the kidney tissue. LI-ESWT reduced renal inflammation and fibrosis. LI-ESWT caused only mild side effects in the clinical study, and, similarly, there were no signs of kidney injury after LI-ESWT in the animal studies.Conclusion: LI-ESWT, as a non-invasive treatment, reduces the pathological manifestations (inflammation, capillary rarefaction, fibrosis, decreased perfusion) associated with certain types of renal disease. The efficacy of renal LI-ESWT needs to be confirmed in randomized clinical trials.Keywords: review, kidney disease, extracorporeal shockwave therapy, ESWT

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M4) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M4 positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M4 PET ligand that allows the non-invasive visualization of M4 in the brain. Structure–activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 ― a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [18F]12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [18F]12 for the M4-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [18F]12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [18F]12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [18F]12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M4 PET radioligand with promising attributes. The availability of a clinically validated M4 PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

Shallow lakes have long been considered an example of alternative equilibria in ecological systems. Here, the authors combine empirical data and simulations to show that the relationship of shallow lake chlorophyll-a with nutrient enrichment does not fit the theory of alternative stable states.

Secchi disk depth (SDD) is a simple but particularly important indicator for characterizing the overall water quality status and assessing the long-term dynamics of water quality for diverse global waters. For this reason, countless efforts have been made to collect SDD data from the field and through remote sensing systems. Many empirical and semianalytical algorithms have been proposed to estimate SDD from different satellite images for a specific or regional water. However, the construction of a robust global SDD estimation model is still challenging due to the nonlinear response of SDD to optical properties and the complex physical and biogeochemical processes of different waters. Therefore, machine learning methods to better interpret nonlinear processes were used to improve remote sensing estimations of SDD for global lakes and reservoirs based on a global matchup dataset from Landsat TM (N = 4099), ETM+ (N = 2420), and OLI (N = 1249) covering in situ SDD from 0.01 m to over 18 m. Overall, extreme gradient boosting (XGBoost) and random forest (RF) had better SDD retrievals than back propagation neural network, support vector regression, empirical and quasi-analytical models showing high precision with mean relative error of approximately 30% and good agreements with the long-term in situ SDD in different waters with various optical properties. Our results can support long-term global-level water quality evaluation and thus making informed decisions about development policy.

The authors find that the insulin receptor forms dynamic clusters during insulin signaling and that these clusters become dysfunctional in insulin resistance. This dysfunction is partially rescued by metformin, a drug used to treat type 2 diabetes.