A search for ultra-high energy photons with energies above 1 EeV is performed using nine years of data collected by the Pierre Auger Observatory in hybrid operation mode. An unprecedented separation ...power between photon and hadron primaries is achieved by combining measurements of the longitudinal air-shower development with the particle content at ground measured by the fluorescence and surface detectors, respectively. Only three photon candidates at energies 1 - 2 EeV are found, which is compatible with the expected hadron-induced background. Upper limits on the integral flux of ultra-high energy photons of 0.038, 0.010, 0.009, 0.008 and 0.007 km\(^{-2}\) sr\(^{-1}\) yr\(^{-1}\) are derived at 95% C.L. for energy thresholds of 1, 2, 3, 5 and 10 EeV. These limits bound the fractions of photons in the all-particle integral flux below 0.14%, 0.17%, 0.42%, 0.86% and 2.9%. For the first time the photon fraction at EeV energies is constrained at the sub-percent level. The improved limits are below the flux of diffuse photons predicted by some astrophysical scenarios for cosmogenic photon production. The new results rule-out the early top-down models \(-\) in which ultra-high energy cosmic rays are produced by, e.g., the decay of super-massive particles \(-\) and challenge the most recent super-heavy dark matter models.
In Parkinson's disease, striatal dopamine depletion produces profound alterations in the neural activity of the cortico-basal ganglia motor loop, leading to dysfunctional motor output and ...parkinsonism. A key regulator of motor output is the balance between excitation and inhibition in the primary motor cortex, which can be assessed in humans with transcranial magnetic stimulation techniques. Despite decades of research, the functional state of cortical inhibition in Parkinson's disease remains uncertain. Towards resolving this issue, we applied paired-pulse transcranial magnetic stimulation protocols in 166 patients with Parkinson's disease (57 levodopa-naïve, 50 non-dyskinetic, 59 dyskinetic) and 40 healthy controls (age-matched with the levodopa-naïve group). All patients were studied OFF medication. All analyses were performed with fully automatic procedures to avoid confirmation bias, and we systematically considered and excluded several potential confounding factors such as age, gender, resting motor threshold, EMG background activity and amplitude of the motor evoked potential elicited by the single-pulse test stimuli. Our results show that short-interval intracortical inhibition is decreased in Parkinson's disease compared to controls. This reduction of intracortical inhibition was obtained with relatively low-intensity conditioning stimuli (80% of the resting motor threshold) and was not associated with any significant increase in short-interval intracortical facilitation or intracortical facilitation with the same low-intensity conditioning stimuli, supporting the involvement of cortical inhibitory circuits. Short-interval intracortical inhibition was similarly reduced in levodopa-naïve, non-dyskinetic and dyskinetic patients. Importantly, intracortical inhibition was reduced compared to control subjects also on the less affected side (n = 145), even in de novo drug-naïve patients in whom the less affected side was minimally symptomatic (lateralized Unified Parkinson's Disease Rating Scale part III = 0 or 1, n = 23). These results suggest that cortical disinhibition is a very early, possibly prodromal feature of Parkinson's disease.
Background
The negative consequences of prescription opioid misuse and opioid use disorder make it relevant to identify factors associated with this problem in individuals with chronic pain. This ...cross‐sectional study aimed at identifying subgroups of people with chronic pain based on their psychological profiles, prescription opioid misuse, craving, and withdrawal.
Methods
The sample comprised 185 individuals with chronic pain. We performed hierarchical cluster analysis on impulsivity, anxiety sensitivity, pain acceptance, pain intensity, opioid misuse, craving, and withdrawal.
Results
The four‐cluster solution was the optimal one. Misuse, craving, and anxiety sensitivity were higher among people in the Severe‐problems cluster than among people in the other three clusters. Withdrawal was the highest in the High‐withdrawal cluster. Impulsivity was higher among people in the Severe‐problems and High‐withdrawal clusters than those in the Moderate‐problems and Mild‐problems clusters. Pain acceptance was higher among people in the Mild‐problems cluster than among people in the other three clusters. Anxiety sensitivity and misuse were higher among people in the Moderate‐problems cluster than among people in the Mild‐problems cluster.
Conclusions
These results support that impulsivity, anxiety sensitivity, and pain acceptance are useful constructs to identify subgroups of people with chronic pain according to their level of prescription opioid misuse, craving, and withdrawal. The results of this study may help in selecting the early intervention most suitable for each of the identified profiles.
Significance
The psychological profile of individuals with chronic pain, prescription opioid misuse, craving, and withdrawal is characterized by fearing anxiety‐related symptoms due to the catastrophic interpretation of such symptoms and reacting impulsively to negative moods. In contrast, participants with high pain acceptance had less prescription opioid misuse, craving, and withdrawal. The profiles identified in this study could help clinicians select targets for intervention among profiles with similar needs and facilitate early interventions to prevent opioid misuse onset or aggravation.
Transformation of organic microcontaminants (OMCs) during wastewater treatments results in the generation of transformation products (TPs), which can be more persistent than parent compounds. Due to ...reuse of reclaimed wastewater (RWW) for crop irrigation, OMCs and TPs are released in soils being capable to translocate to crops. Furthermore, OMCs are also susceptible to transformation once they reach the soil or crops. The recalcitrant antiepileptic carbamazepine (CBZ) and some of its frequently reported TPs have been found in agricultural systems. However, there is no knowledge about the fate in reuse practices of multiple CBZ TPs that can be formed during wastewater treatment processes. For the first time, this work presents a study of the behavior of CBZ TPs generated after a conventional Ultraviolet-C (UVC) treatment in an agricultural environment. The UVC-treated water was used for the irrigation of lettuces grown under controlled conditions. The latter was compared to the fate of TPs generated in the peat and plant by irrigation with non-treated water containing CBZ. A suspect screening strategy was developed to identify the TPs using liquid chromatography coupled to quadrupole-time-of-flight (LC-QTOF-MS). The results revealed the presence of 24 TPs, 22 in UVC-treated water, 11 in peat and 9 in lettuce leaves. 4 of the TPs identified in peat (iminostilbene, TP 271B, TP 285A-B); and 3 in leaves (10–11 dihydrocarbamazepine, TP 271A-B) were not previously reported in soils or edible parts of crops, respectively. Comparing the TPs found in peat and lettuces derived from both irrigation conditions, no significant differences regarding TPs formation or occurrence were observed. UVC treatment did not contribute to the formation of different TPs than those generated by transformation or metabolism of CBZ in peat or plant material. This research improves the current knowledge on the fate of CBZ TPs in agricultural systems because of reuse practices.
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•Determination CBZ TPs in agricultural environment by suspect screening LC-QTOF-MS.•A total 24 CBZ TPs were identified, 22 in UVC treated water, 11 in peat and 9 in lettuces.•The suspect screening strategy allowed the confirmation of 7 CBZ TPs in samples.•Reported for the first time 4 CBZ TPs in soil and 3 in edible parts of crops.•No different TPs were identified in lettuce and peat samples irrigated under the different experimental conditions.
A lab scale study has evidenced the potential translocation of non-previously reported CBZ TPs in a lettuce crop irrigated with UVC-treated water which contained CBZ.
Restoration and preservation of coastal dunes is urgently needed because of the increasingly rapid loss and degradation of these ecosystems because of many human activities. These activities alter ...natural processes and coastal dynamics, eliminate topographic variability, fragment, degrade or eliminate habitats, reduce diversity and threaten endemic species. The actions of coastal dune restoration that are already taking place span contrasting activities that range from revegetating and stabilizing the mobile substrate, to removing plant cover and increasing substrate mobility. Our goal was to review how the relative progress of the actions of coastal dune restoration has been assessed, according to the ecosystem attributes outlined by the Society of Ecological Restoration: namely, integrity, health and sustainability and that are derived from the ecological theory of succession. We reviewed the peer reviewed literature published since 1988 that is listed in the ISI Web of Science journals as well as additional references, such as key books. We exclusively focused on large coastal dune systems (such as transgressive and parabolic dunefields) located on natural or seminatural coasts. We found 150 articles that included “coastal dune”, “restoration” and “revegetation” in areas such as title, keywords and abstract. From these, 67 dealt specifically with coastal dune restoration. Most of the studies were performed in the USA, The Netherlands and South Africa, during the last two decades. Restoration success has been assessed directly and indirectly by measuring one or a few ecosystem variables. Some ecosystem attributes have been monitored more frequently (ecosystem integrity) than others (ecosystem health and sustainability). Finally, it is important to consider that ecological succession is a desirable approach in restoration actions. Natural dynamics and disturbances should be considered as part of the restored system, to improve ecosystem integrity, health and sustainability.
•Restoration of coastal dunes is needed because of the impact of human activities.•Coastal dune restoration can be contrasting: re-vegetation and de-vegetation.•We explored how the success of these restoration actions has been analyzed.•We contrasted restoration with the ecological theory of natural succession.•Ecosystem integrity was monitored more frequently than health and sustainability.
Objective
To describe health‐related quality of life (HRQOL) and physical function in patients with early axial spondyloarthritis (SpA) and to assess their associations with disease activity and ...radiographic damage.
Methods
This was a cross‐sectional study drawing upon baseline data of axial SpA patients (Assessment of SpondyloArthritis international Society criteria) from the ESPERANZA cohort. Linear regression analyses were used to evaluate the associations between disease activity and radiographic damage (spine and sacroiliac joints) with HRQOL, physical function, and spinal mobility.
Results
In total, 259 patients were included. The mean ± SD age was 32.2 ± 6.9 years, disease duration was 13.3 ± 6.8 months, Ankylosing Spondylitis Quality of Life score was 5.9 ± 4.8, Bath Ankylosing Spondylitis Functional Index score was 2.4 ± 2.3, Bath Ankylosing Spondylitis Metrology Index score was 1.4 ± 1.3, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was 3.8 ± 2.3, C‐reactive protein (CRP) level was 9.7 ± 13.2 mg/liter, and Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI‐s) score was 1.7 ± 1.6. HRQOL was mainly associated with disease activity on univariate analysis (β values for BASDAI 0.646, patient global visual analog scale VAS 0.641, night back pain VAS 0.598, physician VAS 0.560, and CRP level 0.275; P < 0.01 for all), whereas the association with radiographic damage was weaker (standardized β for BASRI‐s 0.142; P < 0.05). On multivariate models, HRQOL only remained significantly associated with disease activity (standardized β for BASDAI 0.330; P < 0.01, and physician VAS 0.205 and night back pain VAS 0.210; P = 0.01). Similarly, physical function was associated with disease activity and radiographic damage on univariate analysis, but only with disease activity (BASDAI β 0.466; P < 0.01) on multivariate analysis. However, spinal mobility was associated with radiographic damage in both univariate and multivariate analyses.
Conclusion
Patients with axial SpA already have impaired quality of life and physical function, albeit mildly, at the beginning of their disease course. Both outcomes are mainly associated with disease activity in these patients.
Background
Scholar photoprotection campaigns are among the most effective strategies for preventing skin cancer. Analysis of the target population constitutes a valuable starting point for the ...implementation of primary prevention strategies. Our aim is to study photoprotection habits, attitudes and knowledge among a Spanish school community.
Methods
Descriptive cross-sectional study targeting schoolchildren, parents and teachers at 20 schools in the area of the Costa del Sol Health Agency in southern Spain. Two population-specific, validated questionnaires were used: the CHRESI (for children aged 0–10 years) and CHACES Questionnaire(for adults and adolescents aged > 11 years). We collected demographic data, skin colour, skin phototype, sunburn episodes, sun exposure and photoprotection practices, attitudes and knowledge.
Results
1728 questionnaires were analyzed (22% parents, 14.5% teachers, 44.8% adolescents and 18.6% children). The average ages were 8 years (children), 16 years (adolescents), 39 years (teachers) and 42 years (parents). Globally, the predominant features were: male sex (52%), Spanish nationality (92%) and phototypes II–III (61%). Children, followed by adolescents, reported the highest exposure to the sun, both in frequency and in duration. Adolescents had the higher rate of sunburn (75%), followed by parents/teachers (54.1%) and children (44.1%). Children and their parents were the most likely to adopt photoprotection measures, while adolescents presented more risky attitudes. Knowledge regarding photoprotection was acceptable (6.9/10).
Conclusions
This study highlights the need to improve photoprotection knowledge, habits and attitudes among our target population. Scholars, parents and teachers in our area should be addressed in campaigns to promote healthy sun exposure habits, thus reducing skin cancer-related morbidity and mortality in this region.
SPROUTY-2 (SPRY2) is a modulator of tyrosine kinase receptor signaling with receptor- and cell type-dependent inhibitory or enhancing effects. Studies on the action of SPRY2 in major cancers are ...conflicting and its role remains unclear. Here we have dissected SPRY2 action in human colon cancer. Global transcriptomic analyses show that SPRY2 downregulates genes encoding tight junction proteins such as claudin-7 and occludin and other cell-to-cell and cell-to-matrix adhesion molecules in human SW480-ADH colon carcinoma cells. Moreover, SPRY2 represses LLGL2/HUGL2, PATJ1/INADL and ST14, main regulators of the polarized epithelial phenotype, and ESRP1, an epithelial-to-mesenchymal transition (EMT) inhibitor. A key action of SPRY2 is the upregulation of the major EMT inducer ZEB1, as these effects are reversed by ZEB1 knock-down by means of RNA interference. Consistently, we found an inverse correlation between the expression level of claudin-7 and those of SPRY2 and ZEB1 in human colon tumors. Mechanistically, ZEB1 upregulation by SPRY2 results from the combined induction of ETS1 transcription factor and the repression of microRNAs (miR-200 family, miR-150) that target ZEB1 RNA. Moreover, SPRY2 increased AKT activation by epidermal growth factor, whereas AKT and also Src inhibition reduced the induction of ZEB1. Altogether, these data suggest that AKT and Src are implicated in SPRY2 action. Collectively, these results show a tumorigenic role of SPRY2 in colon cancer that is based on the dysregulation of tight junction and epithelial polarity master genes via upregulation of ZEB1. The dissection of the mechanism of action of SPRY2 in colon cancer cells is important to understand the upregulation of this gene in a subset of patients with this neoplasia that have poor prognosis.
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