Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-11CPK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO ...PET for RA imaging, second generation TSPO tracers 11CDPA-713 and 18FDPA-714 have recently been evaluated pre-clinically showing better imaging characteristics.
A clinical proof of concept study to evaluate 11CDPA-713 and 18FDPA-714 to visualize arthritis in RA patients.
RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of 18FDPA-714, 11CDPA-713 and/or (R)-11CPK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison.
Clinically active arthritis was present in 110 hand joints (2-17 pp). Arthritic joints were visualized with both 11CDPA-713 and 18FDPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for 11CDPA-713 than for 18FDPA-714, the latter being not significantly different from (R)-11CPK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-11CPK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for 11CDPA-713.
11CDPA-713 and 18FDPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for 11CDPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.
BACKGROUND AND AIMS: We investigated whether spatial differences in belowground niches between shallow- and deep-rooted species result in increased resource uptake and drought resistance in ...agricultural grassland communities. MATERIAL AND METHODS: We injected the tracers ¹⁵N and rubidium (Rb) into the soil and measured tracer uptake from 5 and 35 cm soil depth in monocultures and mixtures containing shallow-rooted (Lolium perenne, non-legume; Trifolium repens, legume) and deep-rooted (Cichorium intybus, non-legume; Trifolium pratense, legume) species, grown under drought or control conditions. RESULTS: Deep-rooted species had a higher proportional uptake of both tracers from 35 cm soil depth than shallow-rooted species (p < 0.001). Under drought conditions, all species enhanced their proportional tracer uptake from the deeper soil layer (p < 0.004) and species with a high proportional ¹⁵N uptake from the deeper soil layer were more drought resistant. Total community uptake of Rb was significantly higher in mixed communities than monocultures (p < 0.007); however, this diversity effect was the result of mixing legumes with non-legumes and not the result of mixing deep- with shallow-rooted species. CONCLUSIONS: Clear evidence for spatial niche differences in resource uptake between shallow- and deep-rooted species did not translate into increased resource uptake in mixtures. Resource uptake from deeper soil layers was found to contribute to adaptation and resistance to drought stress.
Salmonella Newport causes more than an estimated 100 000 infections annually in the United States. In 2002, tomatoes grown and packed on the eastern shore of Virginia contaminated with a ...pan-susceptible S. Newport strain caused illness in 510 patients in 26 states. In July–November 2005, the same strain caused illness in at least 72 patients in 16 states. We conducted a case-control study during the 2005 outbreak, enrolling 29 cases and 140 matched neighbourhood controls. Infection was associated with eating tomatoes (matched odds ratio 9·7, 95% confidence interval 3·3–34·9). Tomatoes were traced back to the eastern shore of Virginia, where the outbreak strain was isolated from pond water used to irrigate tomato fields. Two multistate outbreaks caused by one rare strain, and identification of that strain in irrigation ponds 2 years apart, suggest persistent contamination of tomato fields. Further efforts are needed to prevent produce contamination on farms and throughout the food supply chain.
Background and aims Mixing grasses with N2-fixing legumes benefits grassland yields. We examined if grass/forb/legume mixtures combining species with complementary vertical and temporal nutrient ...capture further promote nutrient yields and improve fertilizer N recovery. Methods Four species differing in N2-fixing ability and in vertical and temporal nutrient capture were grown in monoculture and two- and four-species mixtures. 15N was used to examine vertical complementarity in nutrient capture and fertilizer N recovery. Asynchrony was quantified from the N yield distribution over the year. Results The positive mixture effects on N and P yields (P < 0.001) between species contrasting in vertical and temporal nutrient capture (with same N2-fixing ability) were of a similar magnitude (+45 kg N) as those between N2-fixing and non-fixing species with shallow roots (+52 kg N). Mixture benefits were maximized up to +99 kg N when constituent species differed in N2-fixing ability and vertical and temporal nutrient capture. Species modified their vertical N capture when grown in mixture (niche shift). Remarkably, mixing Trifolium pratense and Cichorium intybus, which were similar in both vertical and temporal nutrient capture, generated negative mixture effects. The 4-species mixture captured as much fertilizer N as the grass monoculture, despite significant abundance of legumes. Conclusions Combining species differing in multiple characteristics for nutrient capture optimizes nutrient capture of non-legume/legume-mixtures.
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•Intensification scenarios increased absolute N emissions compared to baseline.•Intensification scenarios may result in reduced N emission intensity.•Mitigation methods ameliorate ...increased emissions associated with intensification.•Mitigation methods may not offset absolute increase in N loss due to intensification.
Increased global demand for dairy produce and the abolition of EU milk quotas have resulted in expansion in dairy production across Europe and particularly in Ireland. Simultaneously, there is increasing pressure to reduce the impact of nitrogen (N) losses to air and groundwater on the environment. In order to develop grassland management strategies for grazing systems that meet environmental targets and are economically sustainable, it is imperative that individual mitigation measures for N efficiency are assessed at farm system level. To this end, we developed an excel-based N flow model simulating an Irish grass-based dairy farm, to evaluate the effect of farm management on N efficiency, N losses, production and economic performance. The model was applied to assess the effect of different strategies to achieve the increased production goals on N utilization, N loss pathways and economic performance at farm level. The three strategies investigated included increased milk production through increased grass production, through increased concentrate feeding and by applying a high profit grass-based system. Additionally, three mitigation measures; low ammonia emission slurry application, the use of urease and nitrification inhibitors and the combination of both were applied to the three strategies. Absolute N emissions were higher for all intensification scenarios (up to 124 kg N ha−1) compared to the baseline (80 kg N ha−1) due to increased animal numbers and higher feed and/or fertiliser inputs. However, some intensification strategies showed the potential to reduce the emissions per ton milk produced for some of the N-loss pathways. The model showed that the assessed mitigation measures can play an important role in ameliorating the increased emissions associated with intensification, but may not be adequate to entirely offset absolute increases. Further improvements in farm N use efficiency and alternatives to mineral fertilisers will be required to decouple production from reactive N emissions.
Abstract Introduction Gaining regular insight into the nature and severity of distress by a psychosocial nurse coupled with referral to psychosocial and/or paramedical healthcare provider(s) is an ...experimental supportive care approach. We sought to examine the effects of this approach on quality of life (QoL), patient's mood and satisfaction, end-of-life care and survival in patients with lung cancer. Methods Patients with newly diagnosed or recurrent lung cancer starting systemic therapy were randomly assigned to receive usual care or the experimental approach. Patients were followed up at 1, 7, 13 and 25 weeks after randomisation with the EORTC-QLQ-C30, the European Quality of Life-5D, the Hospital Anxiety and Depression Scale and the Patient Satisfaction Questionnaire-III. Primary outcome was the mean change in the EORTC-QLQ-C30 global QoL-score between 1 and 25 weeks. Results A total of 223 patients were randomised of whom 111 (50%) completed all four assessments (44% in the usual care group versus 55% in the experimental group). No significant difference was found in the mean change global QoL-score (−2.4, 95% CI: 12.1–7.2; P = 0.61), nor in the other patient-reported outcomes. Fewer patients in the experimental group received chemotherapy shortly before the end-of-life, and median survival was comparable (10.3 versus 10.1 months, P = 0.62). Of the 112 dropouts, 33 died and 79 discontinued participation for other reasons. Conclusions This supportive care approach neither improved QoL nor other patient-reported outcomes in patients with lung cancer. However, it reduced the use of chemotherapy shortly before the end of life. Possibly, (late) side effects of systemic therapy may have obscured effects of our intervention on QoL. Clinical trial registration NTR3540.
Aims During the first days after harvest of Lolium perenne L., N remobilized from roots and stubble forms the main N source for regrowth. Low N uptake from the soil during this period may lead to N ...loss if N fertilizer is applied too soon. Furthermore, temporary N deprivation has been found to stimulate root growth. We therefore hypothesized that a strategic delay in N application after harvest may improve N-use efficiency of L. perenne grassland by increasing root biomass and reducing N loss. Methods In a laboratory and field experiment with L. perenne, we delayed N fertilizer application after harvest for 0,3,6,9 and 12 days, repeated this for up to six harvest cycles, and determined effects on herbage yield, herbage N uptake and root biomass. Results In both experiments, delaying N application for up to 12 days had no significant effect on root biomass or total herbage N uptake, but it significantly reduced total herbage yield in the laboratory experiment. Total yield tended to be highest when N application was delayed for 3 days. Two growth periods in the field experiment showed significantly higher N uptake when N application was delayed, possibly due to rainfallinduced N losses in the treatments with shorter delay. Conclusions Our results do not provide evidence that delaying N application improves N-use efficiency of L. perenne grassland by increasing root biomass. However, strategic timing of N fertilizer application based on rainfall forecasts could contribute to improve N-use efficiency by reducing N losses from leaching and denitrification.
To advance understanding of the heterogeneity in the course of ADHD, joint symptom trajectories of inattention and hyperactivity-impulsivity from childhood to young adulthood were modelled and ...associated with genetic, demographic, and clinical characteristics. Data were obtained from the NeuroIMAGE cohort which includes 485 individuals with ADHD, their 665 siblings, and 399 typically developing children. Trajectories were based on scores of the Conners Parent Rating Scale Revised and estimated over seven homogeneous age bins (from 5 to 28 years) using parallel process latent class growth analysis on data collected across 2–4 time points. Multilevel multinomial logistic regression was used to identify characteristics that differentiated between the derived classes. A seven-class solution revealed “severe combined stable” (4.8%), “severe combined decreasing” (13%), “severe inattentive stable” (4.8%), “moderate combined increasing” (7.5%), “moderate combined decreasing” (12.7%), “stable mild” (12.9%), and “stable low” (44.3%) classes. Polygenic risk for depression, ADHD diagnosis, ADHD medication use, IQ, comorbid symptom levels (foremost oppositional behaviour), and functional impairment levels differentiated classes with similar ADHD symptom levels in childhood but a diverging course thereafter. The course of ADHD is highly heterogeneous, with stable, decreasing, and increasing trajectories. Overall, severe symptom levels in childhood are associated with elevated-to-severe symptom levels in adolescence and young adulthood, despite substantial symptom reductions. Beyond symptom severity in childhood, genetic, demographic, and clinical characteristics distinguish the heterogeneous course.
The results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed ...the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence.
We recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF inhibition, verbal (VWM) and visuospatial working memory (VsWM). Data were analysed using generalized estimating equations (GEEs).
Parental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents.
The core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children 'grow out' of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.
There are very few studies on the long-term outcome of children and adolescents with ADHD-combined type in Europe. The objective of the present study is to assess the 6-year outcome (including ...pharmacological treatment) of a large cohort of participants with ADHD-combined type (
N
= 347, mean age 11.4 years) in late adolescence and early adulthood. At study entry and follow-up (mean age 17.4 years), participants were comprehensively assessed on ADHD and comorbid disorders by structured psychiatric interviews and multi-informant questionnaires. Overall functioning was assessed by the Children’s Global Assessment Scale. The retention rate was 75.6 %. The majority of participants (86.5 %) persisted in a DSM-5 ADHD diagnosis, 8.4 % had a subthreshold diagnosis, and 5.1 % remitted from the disorder at follow-up. Comorbidities decreased strongly; oppositional defiant disorder: 58 > 31 %, conduct disorder: 19 > 7 %. At follow-up, mood- and anxiety disorders were virtually non-existent following strict criteria (1–3 %). Percentage of children having had pharmacological treatment at any time increased from 79 to 91 %. On the Children’s Global Assessment Scale, 48.5 % of participants were still functionally impaired at follow-up. Parental ADHD, higher ADHD symptom severity at baseline and higher parent-reported impairment at baseline positively predicted current ADHD symptom severity (
R
2
= 20.9 %). Younger baseline age, higher ADHD symptom severity at baseline and higher parent-reported impairment at baseline were positively associated with poorer overall functioning (
R
2
= 17.8 %). Pharmacological treatment had no (beneficial) impact on either ADHD symptom severity or overall functioning. Results confirm that ADHD is largely persistent into late adolescence with severity and family history for the disorder as important risk factors.
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